BridgeBio Oncology Therapeutics, Inc. 10-K

10-K Table of Contents w UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission File Number 001-41955 BRIDGEBIO ONCOLOGY THERAPEUTICS, INC. (Exact name of Registrant as specified in its Charter) Delaware 39-3690783 (State or other jurisdiction of incorporation or organization) (I.R.S. Employer Identification No.) 256 E. Grand Avenue , Suite 104 South San Francisco , CA 94080 (Address of principal executive offices) (Zip Code) Registrant’s telephone number, including area code: (650) 405-4770 Securities registered pursuant to Section 12(b) of the Act: Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, par value $0.0001 per share BBOT The Nasdaq Global Market Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. YES ☐ NO ☒ Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. YES ☐ NO ☒ Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. YES ☒ NO ☐ Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). YES ☒ NO ☐ Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act. Large accelerated filer ☐ Accelerated filer ☐ Non-accelerated filer ☒ Smaller reporting company ☒ Emerging growth company ☒ If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐ Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐ If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐ Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐ Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). YES ☐ NO ☒ The aggregate market value of the voting and non-voting common equity held by non-affiliates of the Registrant, based on the closing price of the shares of common stock on the Nasdaq Global Market on August 13, 2025 was approximately $ 465,152,172 . Shares of the Registrant’s Common Stock held by each executive officer and director and by each other person who may be deemed an affiliate of the Registrant have been excluded from this computation. The determination of affiliate status for this purpose is not necessarily a conclusive determination for other purposes. The number of shares of Registrant’s Common Stock outstanding as of March 2, 2026 was 80,032,823 . DOCUMENTS INCORPORATED BY REFERENCE Specified portions of the registrant’s definitive Proxy Statement to be issued in conjunction with the Registrant’s 2026 Annual Meeting of Stockholders, which is expected to be filed not later than 120 days after the Registrant’s fiscal year ended December 31, 2025, are incorporated by reference into Part III of this Annual Report on Form 10-K. Except as expressly incorporated by reference, the Registrant’s Proxy Statement shall not be deemed to be a part of this Annual Report on Form 10‑K. Table of Contents BridgeBio Oncology Therapeutics, Inc. 2025 Form 10-K Annual Report Table of Contents Page PART I Item 1. Business 1 Item 1A. Risk Factors 42 Item 1B. Unresolved Staff Comments 98 Item 1C. Cybersecurity 98 Item 2. Properties 99 Item 3. Legal Proceedings 99 Item 4. Mine Safety Disclosures 99 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 100 Item 6. [Reserved] 100 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 101 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 114 Item 8. Financial Statements and Supplementary Data 115 Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 144 Item 9A. Controls and Procedures 144 Item 9B. Other Information 145 Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 145 PART III Item 10. Directors, Executive Officers and Corporate Governance 146 Item 11. Executive Compensation 146 Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 146 Item 13. Certain Relationships and Related Transactions, and Director Independence 146 Item 14. Principal Accounting Fees and Services 146 PART IV Item 15. Exhibits, Financial Statement Schedules 147 Item 16. Form 10-K Summary 147 Exhibit Index 148 Signatures 151 i Table of Contents EXPLANATORY NOTE On August 11, 2025 (the “Closing Date”), Helix Acquisition Corp. II (“Helix”), a Cayman Islands exempted company which domesticated as a Delaware corporation in August 2025, consummated a series of transactions that resulted in the combination of Helix II Merger Sub, Inc., a Delaware corporation and a wholly-owned subsidiary of Helix (“Merger Sub”), and TheRas, Inc. (d/b/a BridgeBio Oncology Therapeutics), a Delaware corporation (“Legacy BBOT”), pursuant to a Business Combination Agreement, dated February 28, 2025, as amended on June 17, 2025 (the “Business Combination Agreement”), by and among Helix, Merger Sub and Legacy BBOT, as described further below. Pursuant to the terms of the Business Combination Agreement, a business combination between Helix and Legacy BBOT was effected through the merger of Merger Sub with and into Legacy BBOT, with Legacy BBOT surviving the merger as a wholly-owned subsidiary of Helix (the “Business Combination”), following the approval by shareholders of Helix at the extraordinary general meeting of the shareholders of Helix held on August 4, 2025 (the “Special Meeting”). Following the consummation of the Business Combination, Helix was renamed “BridgeBio Oncology Therapeutics, Inc.” In this Annual Report on Form 10-K (“Form 10-K”), the terms “we,” “us,” “our,” and the “Company” generally refer to Helix Acquisition Corp. II prior to the Business Combination and BridgeBio Oncology Therapeutics, Inc. following the Business Combination, unless the context specifically indicates otherwise. References to “BBOT” include Legacy BBOT prior to the Business Combination and BridgeBio Oncology Therapeutics, Inc. following the Business Combination. Some of the information contained in this section or set forth elsewhere in this Form 10-K, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS This Form 10-K contains forward‑looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward‑looking statements involve substantial risks, uncertainties and assumptions. All statements in this Form 10‑K, other than statements of historical fact, including, without limitation, statements regarding our strategy, future operations, future operating expenses, future financial position, future revenue, projected costs, prospects, plans, intentions, expectations, goals and objectives may be forward‑looking statements. The words “anticipates,” “approximately,” “believes,” “could,” “designed,” “estimates,” “expects,” “goal,” “intends,” “may,” “objective,” “plans,” “potential,” “predicts,” “projects,” “pursuing,” “seeks,” “should,” “will,” “would” and similar expressions (including the negatives thereof) are intended to identify forward‑looking statements, although not all forward‑looking statements contain these identifying words. The forward-looking statements in this report include, but are not limited to, statements about: • expectations related to the success, cost and timing of product development activities, including timing of initiation, completion and data readouts for clinical trials and the potential approval of our product candidates, including the progress and results of the ONKORAS-101, BREAKER-101 and KONQUER-101 clinical trials; • the clinical and therapeutic potential of BBO-8520, BBO-10203 and BBO-11818; • the size and growth potential of the markets for our product candidates; • the therapeutic and curative potential of our product candidates; • projected financial information, anticipated growth rate and market opportunities; • our ability to maintain the listing of our Common Stock on Nasdaq; • potential liquidity and trading volatility of our Common Stock; • our ability to raise financing in the future; • success in retaining or recruiting, or changes required in, officers, key employees or directors; • our ability to obtain and maintain regulatory approval of current and potential future product candidates; • our ability to obtain and maintain intellectual property protection for our technologies and our product candidates; • the rate and degree of market acceptance of current and any potential future product candidates; • regulatory developments in the United States and international jurisdictions; • potential liability lawsuits and penalties related to our technologies, product candidates and current and future relationships with third parties; • our ability to attract and retain key scientific and management personnel; ii Table of Contents • our ability to effectively manage the growth of operations; • our ability to compete effectively with existing competitors and new market entrants; • our ability to implement and maintain effective internal controls; • the impact of supply chain disruptions; • unfavorable global economic conditions, including inflationary pressures, market volatility, acts of war and civil and political unrest; and • other factors detailed under the section entitled “Risk Factors” in this Form 10-K. Any forward-looking statements in this Form 10-K reflect our current views with respect to future events or to our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under Part I, Item 1A. Risk Factors and elsewhere in this Form 10-K. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future. This Form 10-K also contains estimates, projections and other information concerning our industry, our business, and the markets for certain diseases, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained this industry, business, market and other data from reports, research surveys, studies and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data and similar sources. RISK FACTOR SUMMARY Below is a summary of the principal factors that make an investment in our common stock speculative or risky. This summary does not address all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the heading “Risk Factors” and should be carefully considered, together with other information in this Annual Report on Form 10-K and our other filings with the U.S. Securities and Exchange Commission, or the SEC, before making investment decisions regarding our common stock. • We have a limited operating history, have not completed any clinical trials, have no products approved for commercial sale, have never commercialized a product, and have not generated any revenue, which may make it difficult for investors to evaluate our current business and likelihood of success and viability. • Our ability to generate revenue and achieve profitability depends significantly on our ability to achieve our objectives relating to the discovery, development and commercialization of our product candidates. If we are unable to advance our product candidates through development, obtain regulatory approval and ultimately commercialize such product candidates, or experience significant delays in doing so, our business will be materially harmed. • We may require additional capital to finance our operations. If we are unable to raise such capital when needed, or on acceptable terms, we may be forced to delay, reduce or eliminate one or more of our research and drug development programs, future commercialization efforts, product development or other operations. • Our preclinical studies and clinical trials may fail to adequately demonstrate the safety and efficacy of any of our product candidates, which would prevent or delay development, regulatory approval and commercialization. • Any delays in the commencement or completion, or any termination or suspension, of our current, planned or future clinical trials could result in increased costs, delay or limit our ability to generate revenue and adversely affect our commercial prospects. • The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; interim, preliminary and topline data from our preclinical studies and clinical trials that we announce or publish from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data; and the results of our clinical trials may not satisfy the requirements of the FDA, EMA or other comparable foreign regulatory authorities. iii Table of Contents • The regulatory approval processes of the FDA, EMA and other comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable. • Our product candidates may cause significant adverse events, toxicities or other undesirable adverse events when used alone or in combination with other approved products or investigational new drugs that may result in a safety profile that could prevent regulatory approval, prevent market acceptance, limit their commercial potential or result in significant negative consequences. • We currently rely on third parties to supply and manufacture preclinical and clinical drug supplies, and we intend to rely on third parties to produce commercial supplies of any approved product, which increases the risk that we will not have sufficient quantities of these product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts. • We face substantial competition which may result in others discovering, developing or commercializing products before or more successfully than we do. • Any product candidates we develop may become subject to unfavorable third-party coverage and reimbursement practices, as well as pricing regulations. • Our business entails a significant risk of product liability. • Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in others, and even if our product candidates receive regulatory approval, they will be subject to significant post-marketing regulatory requirements and oversight. • We may seek certain designations for our product candidates, but we might not receive such designations, and even if we do, such designations may not lead to a faster development or regulatory review or approval process. • We are or may become subject to stringent privacy laws, information security laws, regulations, policies and contractual obligations related to data privacy and security. • Our success is highly dependent on our ability to attract, hire and retain highly skilled executive officers and employees. • If we are unable to obtain, maintain and enforce patent protection for our technology and product candidates, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize technology and products similar or identical to our. • Patent terms may not protect our competitive position for an adequate amount of time. • We may become involved in lawsuits to protect or enforce our patent or other intellectual property rights, which could be expensive, time-consuming and unsuccessful. • We rely on third parties to conduct our preclinical studies and clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials, research and studies. • There may not be an active trading market for our Common Stock, which may make it difficult to sell shares of our Common Stock. • Future sales, or the perception of future sales, by us or our stockholders in the public market could cause the market price for our securities to decline. • We have identified a material weakness in our internal controls over financial reporting in the past. • We have increased costs as a result of operating as a public company, and our management devotes substantial time to related compliance initiatives. • We are currently in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by a new U.S. presidential administration and accompanying regulatory activities and economic policies and events related thereto, ongoing military conflicts and geopolitical instability and inflation and interest rates. iv Table of Contents PART I Item 1. Bus iness. Overview BBOT is a clinical-stage biotechnology company with the mission of transforming the lives of patients with cancers driven by RAS and PI3Kα, the two most frequently mutated oncogenes. Aberrant RAS signaling drives uncontrolled tumor growth in some of the deadliest cancers, including lung, breast, pancreas and colon cancer. This can come from mutations in RAS itself, which underlie approximately 30% of all human cancers, or from RAS-mediated overactivation of PI3Kα. Our goal is to provide meaningful benefit to patients by designing and developing new therapies to achieve high levels of target inhibition against these oncogenic drivers while maintaining a favorable tolerability profile. Our pipeline consists of three orally bioavailable small molecule inhibitors that were designed and optimized within BBOT with the goal to provide patients with significant benefit over standard of care. Additionally, we believe BBOT has the opportunity to provide further benefit to patients with KRAS mutant tumors through combination of our inhibitors. We believe our pipeline has the opportunity to address a large number of patients afflicted with metastatic cancer. BBO-8520 (direct KRAS G12C ON/OFF) and BBO-11818 (direct panKRAS ON/OFF) programs target KRAS — the most mutated oncogene. KRAS is a small GTPase protein that acts like a molecular switch, toggling between the GTP-bound active “ON” state, and the GDP-bound inactive “OFF” state. Oncogenic mutations in KRAS disrupt the normal equilibrium of the two states, resulting in a dramatic increase in the proportion of the “ON” state, and ultimately activating pathways that result in uncontrolled cell growth and cancer progression. The majority of KRAS mutations occur in codon 12. In NSCLC, KRAS G12C mutation are present in approximately 15% of patients. In 2021, the FDA approved the first therapeutic that specifically targets KRAS G12C. However, this first-generation drug and others like it exclusively target the “OFF” state, which renders them susceptible to adaptive resistance, which may limit their efficacy and durability. In addition, patients treated with “OFF” state inhibitors experience significant toxicities which is worse when combined with immune checkpoint inhibitors (ICI). In contrast, BBO-8520, our orally bioavailable dual KRAS G12C “ON/OFF” inhibitor, directly engages both states of the mutant protein. We believe BBO-8520’s next-gen mechanism of action and degree of potency can provide significant benefit to patients with KRAS G12C-driven NSCLC — both as monotherapy and in combination with other therapies. ONKORAS-101 is an ongoing Phase 1 study evaluating BBO-8520 alone and in combination with pembrolizumab in subjects with locally advanced and unresectable or metastatic NSCLC with a KRAS G12C mutation. We disclosed BBO-8520 clinical data in January 2026, where BBO-8520 showed differentiated efficacy, safety and pharmacokinetics with best-in-class potential. We expect to share additional clinical data from ONKORAS-101 in the second half of 2026. BBO-11818, is an orally bioavailable pan KRAS “ON/OFF” inhibitor designed to bind directly to the target. It is able to bind to KRAS G12D, G12V, G12C and WT KRAS with picomolar affinity. In KRAS mutant cells, BBO-11818 has shown low nanomolar potency with greater than 500-fold selectivity for KRAS over H- and NRAS. Like BBO-8520, BBO-11818 was designed to inhibit KRAS in both its “ON” and “OFF” states. We believe these properties will enable BBO-11818 to achieve optimal target inhibition to 1 Table of Contents provide significant benefit to patients with tumors driven by these oncogenes while maintaining a favorable tolerability profile. The KONQUER-101 trial is a currently ongoing phase 1 study evaluating the safety and preliminary antitumor activity of BBO-11818 in heavily pretreated subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. Preliminary BBO-11818 monotherapy data is encouraging as we have observed anti-tumor activity with a favorable and differentiated safety profile. We expect to share additional clinical data from KONQUER-101 in the second half of 2026. PI3Kα is involved in many aspects of cell physiology, including growth, differentiation, survival and migration. It also plays an important role in glucose homeostasis through direct activation of its catalytic subunit, p110a, by insulin and IGF-1. In addition to its role in physiologic processes, an oncogenic form of PI3Kα (encoded by the PIK3CA gene) as well as activating mutations in PIK3CA were identified over 20 years ago. As such, oncology drug discovery and development have explored inhibition of the kinase activity of the p110a catalytic subunit to block PI3Ka signaling. Unfortunately, all of these initial efforts have been hampered to varying degrees by undesired hyperglycemia and hyperinsulinemia side effects as they cannot adequately block oncogenic signaling without effects on glucose homeostasis. More recently, direct binding and activation of PI3Kα by RAS proteins has been described in tumorigenesis. Additionally, several studies in mice have shown that selective blocking of RAS activation of PI3Kα can slow tumor growth without interfering with glucose homeostasis. We set out to discover a small molecule that can block RAS activation of PI3Kα with the goal of inhibiting oncogenic signaling while avoiding hyperglycemia and hyperinsulinemia. If successful, we may be able to achieve high levels of target inhibition in patients while maintaining a favorable tolerability profile. BBO-10203, our RAS:PI3Kα Breaker, is an oral drug candidate that targets the RAS-binding domain of PI3Kα, preventing its activation by HRAS, NRAS, and KRAS in tumors. BBO-10203’s mechanism of action can inhibit PI3Ka signaling in tumors and avoid hyperglycemia and hyperinsulinemia in preclinical models. This stems from the simple fact that insulin signaling does not rely on RAS proteins to mediate glucose uptake. Thus far, we have observed activity in preclinical models and settings where RAS or PI3Kα is known to play a role in tumorigenesis, such as tumors with oncogenic mutations in KRAS or PIK3CA. However, an important additional feature of BBO-10203 is that it is agnostic to the mutational status of RAS and PIK3CA, i.e. BBO-10203 can work in settings where either or both are wild-type. For example, we have observed activity in preclinical models with amplified or overexpressing HER2. In non-clinical testing, BBO-10203 has elicited significant tumor growth inhibition in multiple tumor types as monotherapy, and shown promising activity in combination with HER2 inhibitors, mutant KRAS inhibitors, ER antagonists, CDK4/6 inhibitors, and chemotherapy. BREAKER-101 is an ongoing Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of BBO-10203 as monotherapy and in combination with trastuzumab, fulvestrant ± ribociclib, or FOLFOX + bevacizumab in patients with locally advanced or metastatic HER2+ breast cancer (BC), HR+/HER2- BC and KRAS mutant colorectal cancer (CRC). We disclosed the preliminary clinical data from BREAKER-101 study in January 2026. BBO-10203 showed differentiated safety profile as compared to other PI3Ka-targeting agents with no hyperglycemia observed. We expect to share additional data from the trial in the second half of 2026. In addition, we plan to initiate internal combinations with BBO-8520 and BBO-11818 this year. BBOT is developing three precision oncology assets to serve patients with tumors driven by the two most prevalent oncogenes. We believe each has the potential to deliver meaningful benefit by achieving high levels of target inhibition while maintaining a favorable safety profile. In addition, BBOT is well positioned to develop combination therapies from within our own pipeline to inhibit both the MAPK and PI3Kα-AKT pathways simultaneously in patients with KRAS mutant tumors. While this has been a major goal in the field for over 20 years, the inability of other inhibitors to distinguish between tumor and wild-type cells has historically resulted in unacceptable toxicity. We aim to succeed where others have failed, due to BBO-10203’s unique mechanism of action that takes advantage of RAS’ distinct role in tumors. By inhibiting any RAS-driven activation of PI3Kα, BBO-10203 blocks oncogenic signaling while avoiding hyperglycemia. The fact that BBO-10203 has the potential to provide benefit and avoid hyperglycemia in WT PIK3CA setting is key to our combination approaches, as RAS and PIK3CA are very rarely co-mutated in human cancer. Hence, we will evaluate the combination of BBO-10203 and BBO-8520, and the combination of BBO-10203 and BBO-11818. Strategy At BBOT, we are accelerating scientific and medical breakthroughs with the goal of delivering well-tolerated, safe medicines with greater efficacy to people facing the deadliest cancers. We focus on patients with RAS- and PI3Kα-driven malignancies, including lung, breast, colorectal and pancreatic cancers. With deep expertise in small molecule targeted oncology, our team understands that maximizing target inhibition is critical to providing significant benefit to patients with oncogene-addicted tumors, requiring novel mechanisms of action and precise inhibitor design. Using state-of-the-art structure-based drug design, BBOT is advancing two approaches to achieve this goal. 2 Table of Contents First, we have designed KRAS inhibitors that bind the protein directly with high affinity, resulting in inhibition of both the ON and OFF states. By coupling ON-state inhibition — the form of KRAS that drives tumorigenesis — with high affinity, we believe we can achieve maximal suppression of oncogenic signaling in KRAS-driven tumors. Second, we have designed highly selective PI3Kα inhibitors that exclusively block RAS-dependent signaling. This approach enables inhibition of RAS-driven PI3Kα tumorigenesis while preserving PI3Kα signaling directly activated by growth factor receptors. With this selective mechanism, we believe our RAS:PI3Kα breakers may achieve high levels of inhibition of RAS-dependent PI3Kα signaling while minimizing side effects associated with PI3Kα kinase inhibitors, such as hyperglycemia. Developing these inhibitors both as monotherapy and in combination has the potential to provide meaningful benefit to patients by safely delivering high-level inhibition of oncogenic signaling. Overview of BBO-8520 Program Preclinical BBO-8520 is a direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRAS G12C. KRAS G12C is an oncogenic mutation that leads to insensitivity to GTPase activating protein (GAP)– mediated hydrolysis, which significantly increases the proportion of KRAS G12C in the ON state and promotes tumor cell growth. Currently approved inhibitors of KRAS G12C bind and inhibit the OFF-form only. The mechanism of action of these inhibitors is through sequestering the OFF-form and preventing it from cycling to the ON-form. Tumor cells can adapt to this mechanism of action rather easily by activating receptor protein tyrosine kinases (RTKs) upstream of KRAS and by increasing de novo protein production through mutant allele amplification. Activation of RTKs activates SOS pushing KRAS into its ON -form where OFF-only inhibitors cannot bind. Amplification of the mutant allele also leads to increased ON-form protein as there is ten times more GTP than GDP in the cells. To prevent fast adaptation through the above -mentioned mechanisms and to achieve optimal target coverage of the KRAS G12C driver oncogene, new generation inhibitors must inhibit the ON-form of KRAS G12C. To address this critical gap in target coverage by approved OFF -only inhibitors, we have designed BBO-8520 to be a direct, covalent dual inhibitor of both OFF- and ON- forms of KRAS G12C. Biochemical studies using MALDI-TOF show that while the OFF-only inhibitors effectively modify GDP-bound KRAS G12C, they are unable to modify the GTP-bound form. In contrast, MALDI-TOF demonstrates that BBO- 8520 modifies KRAS G12C whether it is bound to GDP or GTP. The ability to modify GTP-bound KRAS G12C provides BBO-8520 with a differentiating mechanism of action that functions by blocking effector binding instead of just trapping the OFF -form. Effector binding blockade is only possible with inhibitors that target the ON-form as this is the only form of KRAS G12C that binds effector. BBO-8520 binds to the same switch II pocket and takes advantage of the same cysteine 12 mutant residue as OFF-only inhibitors. Head-to-head in vitro comparisons of potency, measured as kinact/Ki, show that BBO-8520 is almost three times more active than the most active OFF -only inhibitor, divarasib, and adds strong affinity against the ON-form of the protein which is completely absent in the OFF-only inhibitors. Notably, we were able to demonstrate activity in these studies against the ON -form while maintaining the selectivity of the molecule. Global cysteine proteomics shows that BBO-8520 is very specific for KRAS G12C with no significant binding to other cysteine containing proteins. 3 Table of Contents BBO-8520 has shown rapid (within 30 minutes) engagement of Cys-12 in the KRAS G12C mutant MIA PaCa-2 and SW1463 cell lines, leading to KRAS G12C covalent modification and strong pERK signal suppression, consistent with its dual (ON/OFF) mechanism of action. This early effect appears to only be achievable by engaging KRAS G12C (ON) as we have not observed it with sotorasib and adagrasib even at 5× higher concentrations (100 nmol/L). Peak downregulation of the MAPK signaling pathway was observed within the first 2 hours and lasted for at least 24 hours in both cell lines. A time course of pERK inhibition using HTRF, as a complementary method, in both MIA PaCa-2 and SW1463 cells confirmed the rapid and sustained inhibition of ERK phosphorylation by BBO-8520. To better understand the potency and selectivity of BBO-8520 in malignant cells, we have profiled BBO-8520 in a panel of approximately 50 cancer cell lines harboring either wild-type or mutant KRAS (G12C, G12D, G12S, G12V, and G13D) or a BRAFV600E mutation. BBO -8520 compared favorably against sotorasib and adagrasib in both the ERK phosphorylation inhibition and 3D viability assays, displaying better than 10 -fold gain in potency, in its results of head-to-head testing. Comparison with RMC-6291, a tricomplex KRAS G12C ON inhibitor, in six KRAS G12C cell lines showed a similar degree of inhibition for both compounds. BBO-8520 demonstrated selectivity for KRAS G12C over other KRAS codon 12 mutations approximately 50 to 500-fold selectivity and approximately 500 to 30,000-fold for 3D viability, and wild-type KRAS (>1,600-fold for pERK and >450-fold for 3D viability) and has no demonstrable activity in the BRAFV600E mutant cell line A375 (>10,000 -nmol/L IC50 for pERK and 3D viability). BBO-8520 also demonstrated inhibition of pAKT signaling in some KRASG12C cell lines with IC50 below 10 nmol/L. In vivo activity was also studied in the NSCLC heterozygous KRAS G12C model NCI-H358. Orally administered BBO-8520, once daily for 28 days at 0.3, 1, 3, or 10 mg/kg resulted in tumor growth inhibition of 20% (0.3 mg/kg) and 71% (1 mg/kg), and mean tumor regressions of 19% (3 mg/kg) and 100% (10 mg/kg), in mice. The ED50 was 0.6 mg/kg, and ED90 was 1.6 mg/kg. Tumors from 1/10 and 10/10 mice in the 3- and 10-mg/kg BBO-8520 groups, respectively, had complete regressions. When the activity of BBO-8520 at the 3 mg/kg dose was compared to divarasib’s 5 mg/kg dose, which is equivalent to the clinically determined recommended phase 2 dose of 400 mg, we observed that BBO-8520 was able to achieve better or similar activity with about a tenth of the free drug exposure. We believe BBO-8520 is able to achieve similar effects at a much lower free drug concentration because of its ability to inhibit all KRAS G12C (ON/OFF). Inhibition of the ON-form may allow BBO-8520 to decouple PK from PD, meaning that drug does not have to be present all the time to capture the cycling of KRAS G12C as required by OFF-only inhibitors. We believe the ability to provide optimal target coverage at lower free drug concentration could significantly reduce the toxicities observed in patients as both monotherapy and in combination with anti-PD-1 antibodies. If BBO-8520 is able to achieve better tolerability in combination with anti-PD-1 antibodies, the combination could provide first line metastatic NSCLC patients a better option than OFF inhibitors where liver toxicity has been observed and is a concern. 4 Table of Contents To assess BBO-8520’s ability to combine with anti-PD-1 antibodies, we have generated preclinical data in two syngeneic mouse models with limited sensitivity to anti-PD-1 reagents. Using both a subcutaneous model and a liver metastasis model, the combination of BBO-8520 and anti-PD-1 antibodies produced strong anti-tumor activity with favorable durability. Clinical The ONKORAS-101 Phase 1 study is currently enrolling patients with non-small cell lung cancer (NSCLC) carrying KRAS G12C mutation as monotherapy and in combination with pembrolizumab (NCT06343402). We disclosed encouraging updated clinical data in January 2026. As of November 15, 2025, a 65% (11/17) objective response rate (ORR) was observed in NSCLC patients with a KRAS G12C mutation across all dose levels, including 10 PRs and one complete response (CR). 5 Table of Contents Responses appear durable with a 6-month progression-free survival (PFS) of 68% and 83% of patients with at least 6-month follow-up remaining on treatment greater than 6 months. In this interim readout, BBO-8520 has shown a generally tolerable, manageable and potentially differentiated safety profile with no dose-limiting toxicities, no grade 3 or higher liver toxicity, and only low frequency and low grade, transient, and clinically asymptomatic liver enzyme elevations. There were no grade ≥4 treatment-related adverse events (TRAEs); and no treatment-related serious adverse events (TRSAEs). Nausea, vomiting, and diarrhea were the most common TRAEs. 6 Table of Contents BBO-8520 in combination with pembrolizumab showed promising efficacy in both first line and previously treated patients with NSCLC KRAS G12C. Each efficacy evaluable patient (n=8) experienced a tumor reduction regardless of PD-L1 status, and 3 out of 3 front-line patients and 2 out of 5 patients previously treated with KRAS G12C inhibitor(s) achieved a PR. . BBO-8520 was generally well tolerated from 200 mg to 500 mgin combination with pembrolizumab. Potentially, the safety profile is best-in-class with a differentiated liver toxicity profile. In 15 patients, only one instance of AST/ALT elevation was observed which was considered by the principal investigator to mainly be due to co-medications. This favorable combination safety profile was achieved using active BBO-8520 dose levels. 7 Table of Contents BBO-8520’s ON state inhibition enables efficacy with relatively lower exposure resulting in superior therapeutic index compared to OFF inhibitors. BBO-8520 exposure is approximately dose proportional achieving predicted efficacious levels at 200 mg and above. Importantly, compared with systemic exposure of BBO-8520 500 mg QD, exposures of adagrasib/sotorasib are >700 fold higher, MK1084/D3S-001 are >150 fold higher and olomorasib/divarasib are >10 fold higher. BBO-8520’s markedly lower exposure compared with OFF-state inhibitors is consistent with an ON-state mechanism that creates a favorable PK/PD profile. We believe the high potency, promising efficacy achieved with low exposure and generally tolerable differentiated safety profile, may position BBO-8520 as the combination agent of choice with pembrolizumab for patients with KRAS G12C mutant NSCLC. Our data demonstrate that BBO-8520 can be well combined with pembrolizumab at highly active dose levels. This contrasts with what is has been reported with “OFF” state inhibitors. “OFF” inhibitors have had to significantly reduce their dose to sub-optimal levels when combined with pembrolizumab due to liver toxicity. Even at the sub-optimal dose levels, patients experienced grade 3 toxicities from 30% to 70%. In comparison, we believe BBO-8520 is well positioned to potentially differentiate in earlier settings where safety is critical. 8 Table of Contents Encouraging early efficacy signals were seen in patients with KRASG12C and STK11 and/or KEAP1 co-mutants, where all five initial patients achieved a PR. This is a highly resistant patient population for which there is currently no effective therapy. Opportunities Lung cancer is among the most common cancers in the United States, with an annual estimated incidence of approximately 235,000 in 2024. Non-small cell lung cancer (NSCLC) accounts for approximately 87% of diagnosed lung cancer cases and approximately 10% of these patients have KRAS G12C mutations. Current FDA-approved therapies targeting KRAS G12C mutations in NSCLC include Sotorasib, which received accelerated approval in 2021, and Adagrasib, which received accelerated approval in 2022. Both of these therapies are indicated for second-line monotherapy treatment in the metastatic setting and target the OFF state of the KRAS protein. Additionally, both therapies have modest efficacy compared to other precision oncology medicines, with an ORR of approximately 40% and a median PFS of approximately 6 months based on phase 3 trials and have suffered from grade 3+ toxicities in some patients. By targeting both the ON and OFF states of KRAS G12C with strong affinity, we believe BBO-8520 has the potential to improve clinical outcomes for patients with KRAS G12C NSCLC. BBOT aims to offer BBO-8520 to NSCLC patients who carry KRAS G12C mutation across settings of the disease either as monotherapy or in combination with other agents such as immunotherapy and other candidates in BBOT’s internal pipeline. 9 Table of Contents Overview of BBO-11818 Program Preclinical KRAS is one of the most commonly mutated oncogenes in human cancers, with mutations found in approximately 11% to 15% of all cancers. It is particularly prevalent in lung, colorectal, and pancreatic cancers, where mutations occur in about 30%, 40%, and 90% of cases, respectively. The most common KRAS mutations occur at codon 12, accounting for 81% of all KRAS mutations. The most frequent mutations are KRASG12D (glycine to aspartate), which accounts for 33%, and KRASG12V (glycine to valine), which accounts for 23%. Every year, over 90,000 patients in the United States are diagnosed with cancers harboring KRASG12D or KRASG12V mutations. These mutations result in a significantly increased abundance of the active GTP-bound state of KRAS, disrupting the normal GAP-mediated cycling of GTP to GDP. This persistent activation leads to continuous downstream signaling, driving tumor cell growth and contributing to oncogenesis. BBO-11818 is a selective, orally bioavailable non-covalent dual ON/OFF panKRAS inhibitor. Its discovery was facilitated by the structure-based drug design from our KRAS G12C inhibitor program that produced BBO-8520. It is designed to target KRAS G12D and G12V mutations, two of the three most common KRAS mutations in human cancers. BBO-11818 effectively binds both the inactive GDP-bound (OFF) and active GTP-bound (ON) forms of KRAS, exhibiting high affinity and specificity for KRAS over other RAS isoforms like HRAS and NRAS. In SPR assays, the KD value for the (OFF)-form of KRAS G12D is in the sub nanomolar range. In contrast, KD values for HRAS and NRAS are significantly higher, demonstrating the compound’s specificity for KRAS. BBO-11818 has also been shown to disrupt the interaction between KRAS and its effector RAF1, demonstrating strong affinity for the GTP-bound (ON) form of KRAS, which we believe is a key attribute to achieve optimal target coverage. In cellular assays, BBO-11818 exhibited inhibition of pERK and cell viability in a range of cancer cell lines harboring KRAS mutations. The EC50 values for pERK inhibition in a series of KRAS G12D and G12V-mutant cell lines ranged from sub nanomolar to low double digit nanomolar potency. Importantly, BBO -11818 demonstrated similar activity in reducing cell viability in KRASG12D, KRASG12V, and KRASG12C -mutant cell lines, with EC50 values as low as 0.244 nM. The potency of BBO-11818 in the short-term signaling assay was consistent with what was observed in the long-term 3D-viability assay, a characteristic seen as important in translating the activity of mutant KRAS inhibitors to in vivo tumor models and clinical studies. Cell-based data using NRAS and BRAF mutant cell lines showed insensitivity to BBO-11818, reinforcing the compound’s high selectivity for KRAS mutations. 10 Table of Contents The high affinity, potency and selectivity of BBO-11818 for KRAS mutant cell lines have translated well into in vivo efficacy in animal models of human cancers. BBO-11818 exhibited robust in vivo antitumor activity in KRASG12D- and KRASG12V-driven CDX models of CRC, PDAC, and NSCLC. BBO-11818 showed a clear dose response in all three models with significant tumor regressions shown at the 100 mg/kg BID dose level in the KRAS G12D setting and stasis in the KRAS G12V setting. In the HPAC CDX model of KRAS G12D PDAC, BBO-11818 achieved ED50 of 9.0 mg/kg BID and an ED90 of 30.1 mg/kg BID. A significant focus in the development of BBO-11818 is combinations with other targeted therapies to overcome resistance mechanisms and potentially enhance clinical activity. We believe BBOT is uniquely positioned to deliver the combination of co-inhibition of the MAPK and PI3Ka/Akt pathways with a therapeutic index. Consistent with our data showing the strong interaction between our KRAS G12C inhibitor with our BBO-10203 RAS:PI3Kα inhibitor, the combination of BBO-11818 with BBO-10203 in the PDAC Capan-2 CDX model (KRAS G12V) showed significant tumor volume regressions in the combination treatment. Notably, MOA studies demonstrated that BBO-11818 had tumor intrinsic effects on decreasing cell proliferation and increasing apoptosis, and 11 Table of Contents that the combination of BBO-11818 and BBO-10203 led to an antitumor benefit likely due to further reduction tumor cell proliferation and increase in apoptosis in this model. Combining BBO-11818 with cetuximab, an anti-EGFR monoclonal antibody, in the LS513 model of KRAS G12D-driven CRC, led to synergy in a 2D cellular viability assay, suppression of the long-term growth of cells in a clonogenic assay, and robust 57% mean tumor regression in an efficacy study, which surpassed the antitumor effects of either compound alone. We believe this combination may be particularly beneficial for CRC patients with KRAS G12D or KRAS G12V mutations, as it targets the feedback activation of EGFR signaling, which can mediate resistance to KRAS inhibition. 12 Table of Contents The immunosuppressive nature of KRAS-mutant tumors prompted exploration of combining KRAS inhibitors with ICIs. In the CT26 syngeneic mouse model of KRAS G12D CRC, the combination of BBO-11818 and anti- PD-1 significantly prolonged survival compared to both monotherapy treatments alone and led to 44% of the mice having complete tumor regressions. These preclinical findings provide support to the evaluation of BBO-11818 as both monotherapy and in combination particularly with EGFR inhibitors, ICIs, or PI3Ka inhibitors. We believe these combination approaches have the potential to overcome resistance mechanisms and offer superior therapeutic outcomes for patients with KRAS G12D and KRAS G12V mutations, paving the way for further clinical benefit. Clinical KONQUER-101 (NCT06917079) is an open- label, multi-center, Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BBO-11818 alone and in combination with pembrolizumab, pembrolizumab cis/carboplatin and pemetrexed, or cetuximab in subjects with locally advanced unresectable or metastatic KRAS mutant solid tumors. We anticipate that additional clinical data from this study will be available in the second half of 2026. As of December 10, 2025, BBO-11818 demonstrated encouraging early anti-tumor activity across dose levels and tumor types, including a PR in a patient with pancreatic ductal adenocarcinoma (PDAC) with a 56% tumor reduction, as well as tumor reductions at higher dose levels. The response was unconfirmed at the time of data cutoff but was subsequently confirmed. 13 Table of Contents BBO-11818 monotherapy treatment (n=13) appeared generally tolerable with no DLTs. TRAEs were largely gastrointestinal-related. 14 Table of Contents BBO-11818 demonstrated approximately dose-proportional exposure with 600 mg BID covering G12D and G12V mutant alleles. Opportunities We intend to develop BBO-11818 primarily in KRAS G12D and KRAS G12V mutant NSCLC, CRC, and PDAC. Lung cancer had an annual estimated incidence in the U.S. of approximately 235,000 in 2024. Non-small cell lung cancer (NSCLC) accounts for approximately 87% of diagnosed lung cancer cases and approximately 8% of patients have KRAS G12D and KRAS G12V mutations. As of 2024, there were an estimated 153,000 patients with colorectal cancer in the U.S. Approximately 15% of patients have KRAS G12D mutations and approximately 10% of patients have KRAS G12V mutations. As of 2024, there were an estimated 66,000 incident pancreatic cancer patients in the U.S., with approximately 90% of these patients presenting with pancreatic ductal adenocarcinoma. Of these patients, approximately 40% have KRAS G12D mutations and 29% have KRAS G12V mutations. There are currently no targeted therapies approved for KRAS G12D and KRAS G12V mutations. If approved, we believe BBO- 11818 may offer an improved product profile over current standard of care. In NSCLC, commercial opportunities include combination with immune-oncology agents such as pembrolizumab with and without platinum-based chemotherapy regimens in the first line, as well as monotherapy potential and combination with our RAS:PI3Ka Breaker BBO-10203 in 2L+ metastatic populations. CRC commercial opportunities include combination with chemotherapy and bevacizumab in 1L populations, as well as monotherapy potential and combination with BBO-10203 or EGFR antibodies. The commercial opportunity in PDAC includes combinations with chemotherapy regimens as well as monotherapy potential and combination with BBO-10203. Overview of BBO-10203 Program Preclinical Phosphoinositide 3-kinases function in many aspects of cell physiology, including growth, differentiation, survival, and migration. PI3Ka is regulated by receptor tyrosine kinases and contributes to insulin homeostasis. The catalytic subunit of PI3Kα, p110α (encoded by the PIK3CA gene), is recruited to activated receptors through its direct interaction with the PI3Kα regulatory subunit p85, or in the case of insulin and insulin-like growth factor 1 (IGF-1), through p85 binding to insulin receptor substrate (IRS) proteins. Deletion of p110a causes embryonic lethality, whereas mice heterozygous for p110a survive but are glucose intolerant and suffer from hyperinsulinemia and hyperphagia, among other phenotypes associated with defective insulin signaling. An oncogenic form of PI 3-kinase a (PIK3CA) was discovered in an avian retrovirus, and activating mutations in PIK3CA were later identified in human tumors. These mutations occur in 24-46% of endometrial cancers, 20-32% of breast cancers, 20-27% of bladder cancers, and at notable frequencies in most other cancer types. Canonical RAS proteins bind directly to PI3-kinases but with lower affinity than to RAF kinases. Oncogenic RAS proteins activate PI3Ka when over-expressed. The ability to bind and activate PI3Ka gives mutant RAS the ability to co-activate both the MAPK and PI3K/AKT pathways leading to its strong tumorigenic activity. 15 Table of Contents Disrupting RAS-PI3Kα interaction through mutations T208D and K227A in the PI3Kα RAS-binding domain (RBD) severely impairs tumor formation driven by KRAS-G12D. Systemic disruption of RAS-PI3Kα interaction in mice is well tolerated and does not provoke hyperglycemia. Tumors driven by oncogenic mutants of EGFR regress after genetic disruption of RAS-PI3Ka binding, and neo-angiogenesis is impaired. These findings indicate that RAS binding to PI3Ka is not essential in normal cells, or for insulin homeostasis, but is vital for tumor formation and maintenance. The hypothesis for the BBO-10203 program is that if we could mimic the effect of these two point mutations in the RBD domain of PI3Kα with a small molecule, we could recapitulate the benefits on the efficacy without the limitations of potential safety signals. BBO-10203 is a covalent small molecule that binds to the RBD of PI3Kα. It is specific for PI3Kα, does not inhibit the kinase activity of PI3Kα, blocks K-, H-, & NRAS from binding to PI3Kα, and it is agnostic to the mutational status of either RAS or PI3Kα. This mutation agnostic feature is important because more than 90% of human mutant RAS tumors are PI3Kα wild-type. Therefore, recently developed selective inhibitors of mutant PI3Kα cannot be combined with mutant KRAS inhibitors. BBO-10203 has single digit nanomolar affinity for the PI3Kα RBD and has shown the ability to potently inhibit signaling. 16 Table of Contents Pharmacology experiments using mouse models with BBO-10203 showed that significant inhibition of pAKT could be achieved by disrupting the interaction between PI3Kα and RAS. In a pharmacodynamic model, increasing doses of BBO-10203 were inversely correlated with pAKT levels, reaching maximal inhibition of approximately 81%. Importantly, this inhibition of pAKT resulted in 44% tumor regression as monotherapy when BBO-10203 was dosed daily, orally, for 28 days. As predicted by the genetic experiments, BBO-10203 treatment did not result in hyperglycemia. In a glucose tolerance test in male mice, BBO-10203, at three times the dose required to elicit tumor regressions, did not induce hyperglycemia when compared to the PI3Kα kinase inhibitor, alpelisib. This trait has the potential to differentiate BBO-10203 from all PI3Kα/Akt pathway inhibitors. In the context of human tumors, PI3Kα mutations are mostly found within breast cancers. BBO-10203 as monotherapy, or in combination with standard of care, showed significant tumor growth inhibition in three PI3Kα mutant preclinical breast cancer models. In these models, which include both HER2 overexpressing and ER+ models, BBO-10203 showed tumor growth inhibition consistent with its GI arrest mechanism of action. Interestingly, when combined with standard of care inhibitors like trastuzumab, fulvestrant and palbociclib, BBO-10203 showed significantly better preclinical activity than these single agents alone. 17 Table of Contents In combination with mutant KRAS inhibitors, BBO-10203 presents a unique opportunity to co-inhibit both the MAPK and PI3Kα signaling pathways. As previously mentioned, a key attribute of mutant RAS is that it can co-activate the MAPK and PI3Kα/Akt pathways. Tumors driven by mutant KRAS can be targeted with new generation KRAS inhibitors (such as BBO-8520 and BBO-11818) resulting in strong MAPK pathway inhibition. This effect drives reactivation of the PI3Kα/AKT pathway for cell survival and resistance. In the presence of a mutant KRAS inhibitor, reactivation of PI3Kα/AKT is driven by WT RAS (K-, H-, or N-). As BBO-10203 is agnostic to the RAS isoform and/or mutation status, we believe it is the ideal therapeutic candidate to inhibit PI3Kα/AKT pathway reactivation in KRAS mutant tumors. The combination of BBO-10203 with our KRAS G12C inhibitor BBO-8520 has shown that strong preclinical activity is achievable by inhibiting both pathways. In three different xenograft models with KRAS G12C mutations, the combination of both agents was significantly better than either alone. This is true whether the model is inherently sensitive or resistant to BBO-8520 monotherapy. In the clinically relevant H2122 xenograft model, which displays a KEAP1 mutation, the combination of BBO-8520 and BBO-10203 resulted in significantly better effects than either agent alone. Importantly, this combination led to significant decrease in cell proliferation and to increase in cellular apoptosis and was well tolerated in tumor bearing mice with no differences in body weight versus the vehicle group. 18 Table of Contents Clinical BREAKER-101 is a multicenter, open-label, Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of BBO-10203 as monotherapy and in combination with trastuzumab, fulvestrant ± ribociclib, or FOLFOX + bevacizumab in patients with locally advanced or metastatic HER2+ breast cancer (BC), HR+/HER2- BC and KRAS mutant colorectal cancer (CRC). BREAKER-101 has completed Phase 1a monotherapy dose escalation enrollment. Combination cohorts with fulvestrant in HR+ HER2- PIK3CA mutant BC, with trastuzmab in HER2+ BC and with FOLFOX + bevacizumab in KRAS mutant CRC are enrolling. Additional data from the study are expected to be available in the second half of 2026. BBO-10203 in combination with BBO-8520 and BBO-11818 in KRAS mutant tumors are planned this year. 19 Table of Contents As of December 10, 2025, the BBO-10203 safety profile has demonstrated the potential to be highly differentiated compared to previously reported data on other PI3Ka-targeting agents. There were no DLTs; no grade ≥3 TRAEs except for one incidence of asymptomatic hypokalemia (lab abnormality); no dose reductions; and no TRSAEs. Importantly, without restrictions on baseline enrollment HbA1c status or glucose levels, no hyperglycemia of any grade was observed, consistent with preclinical findings BBO-10203 also achieved target systemic exposure and rapid full target engagement. Clinical benefit was observed in patients with CRC (>80% 3L+) and HR+ BC who were previously heavily treated and tumor reductions were observed in some patients. Based on safety, pharmacokinetics and target engagement, 500 mg QD has been selected as the recommended for expansion. 20 Table of Contents Opportunities BBO-10203 is being developed in hormone receptor-positive PIK3CA mutant breast cancer in combination with HR-directed therapies and CDK4/6 inhibitors, HER2-positive breast cancer in combination with HER2-directed biologics, and KRAS G12X non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC) in combination with KRAS inhibitors. Breast cancer is among the most common cancers in the U.S. with an annual estimated incidence of approximately 314,000 in 2024. Approximately 14% of patients have HER2+ breast cancer while 70% of patients have HR+/HER2- breast cancer with 40% of HR+/HER2- breast cancer patients presenting with PIK3CA mutations. Lung cancer is among the most common cancers with an annual estimated incidence in the U.S. of approximately 235,000 in 2024. Non-small cell lung cancer (NSCLC) accounts for approximately 87% of diagnosed lung cancer cases and approximately 15% of these patients have KRAS G12C mutations and approximately 8% of patients have KRAS G12D and KRAS G12V mutations. As of 2024, there were an estimated 153,000 patients with colorectal cancer in the U.S. Approximately 15% of patients have KRAS G12D mutations and approximately 10% of patients have KRAS G12V mutations. As of 2024, there were an estimated 66,000 pancreatic cancer patients in the U.S., with approximately 90% of these patients presenting with pancreatic ductal adenocarcinoma. Of these patients, approximately 40% have KRAS G12D mutations and 29% have KRAS G12V mutations. Intellectual Property We pursue a layered intellectual property strategy, including by securing and/or filing for patents, trademarks, and trade secret rights, to protect our drug candidates. Our commercial success depends in large part on our ability to protect our intellectual property rights, including our ability to obtain and maintain patent protection in the U.S. and other countries for our drug candidates, to operate without infringing valid and enforceable patents and proprietary rights of others, and to defend and enforce our intellectual property rights, in particular our patent rights. We seek to protect our proprietary position by filing, in the U.S. and certain other countries, patent applications that cover the composition of matter of our drug candidates, their methods of use and related discoveries, technologies, inventions and improvements that may be commercially important to our business. We may also rely on trade secrets and know-how to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. We also intend to take advantage of regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions where available. We have three drug candidates in our KRAS and PI3K programs. Given the early stage of development of our drug candidates, we cannot be certain that any of our intellectual property rights will provide protection for any drug candidate that may ultimately be commercialized. Our patent portfolio consists of patent applications co-owned with Lawrence Livermore National Security, LLC and Frederick National Laboratory for Cancer Research, operated by Leidos Biomedical Research, Inc., and Company-owned patent applications. As of December 31, 2025, our patent portfolio consists of patent applications filed in the United States and in foreign jurisdictions such as Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Eurasia, Europe, Hong Kong, India, Indonesia, Israel, Japan, Republic of Korea, Malaysia, Mexico, New Zealand, Peru, Philippines, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, Ukraine, and Vietnam, directed to, for example, compositions of matter and methods of use related to our drug candidates. Of these, BBOT has 11 patent families directed to KRAS inhibitor compounds and 1 patent family each directed to methods of treatment 21 Table of Contents with BBO-8520 or BBO-11818. Of these, BBOT has 4 patent families directed to compounds disrupting RAS-PI3Kα interaction and 5 patent families directed to methods of treatment with BBO-10203 alone or in combination with other therapeutic agents. The term of any patents that issue from our U.S. and foreign patent applications will vary in accordance with the laws of each jurisdiction but is typically 20 years from the earliest non-provisional filing date. In the United States, the patent term may be shortened if a patent is terminally disclaimed over another patent that expires earlier. The term of a U.S. patent may be lengthened by patent term adjustment if there are administrative delays by the USPTO in examining and granting a patent. Any patents that may issue in the future from our pending patent applications are projected to expire between 2042 and 2046, unless extended or otherwise adjusted. The patent positions for biotechnology and pharmaceutical companies like us are generally uncertain and can involve complex legal, scientific and factual issues. Changes in either the patent laws or their interpretation in the U.S. and other countries may diminish our ability to protect our investigational products and enforce the patent rights that we own and could affect the value of such intellectual property and the business. With respect to our intellectual property, we cannot guarantee that the patent applications we are currently pursuing or may file in the future will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors. Our competitors may independently develop similar investigational products or technologies that are outside the scope of the rights granted under any patents that may issue. We cannot be sure that any patents granted to us will be commercially useful in protecting our products or their methods of use or manufacture. Moreover, even issued patents do not guarantee us the right to commercialize our products. For example, third parties may have blocking patents that could be used to prevent us from commercializing or manufacturing our investigational products. In addition, the coverage claimed in a patent application may be significantly reduced before a patent is granted, and its scope can be reinterpreted and even challenged after issuance. As a result, we cannot guarantee that any of our products will be protected or remain protectable by enforceable patents. Moreover, any patents that we license or may own in the future may be challenged, circumvented, or invalidated by third parties. In addition, because of the extensive time required for clinical development and regulatory review of a product candidate we may develop, it is possible that, before our product candidate can be commercialized successfully, any related patents may expire or remain in force for only a short period following commercial launch, thereby limiting the protection such patent would afford the applicable product and any competitive advantage such patent may provide. Because of the extensive time required for development, testing and regulatory review of an investigational product, it is possible that, before a product can be commercialized, any patent protection for such product may expire or remain in force for only a short period following commercialization, thereby reducing the commercial advantage the patent provides. In the U.S., the term of a patent covering an FDA-approved product may, in certain cases, be eligible for a patent term extension (“PTE”) under the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act”) as compensation for the loss of patent term during the FDA regulatory review process. The period of extension may be up to five years but cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval. Only one patent among those eligible for an extension may be extended and the amount of available extension to any PTE-eligible patent depends on a variety of factors, including the date on which the patent issues and certain dates related to the regulatory review period. Similar extensions may be available in Europe and in certain other jurisdictions to extend the term of a patent that covers an approved product. While we intend to seek patent term extensions in any jurisdictions where they are available to us, there is no guarantee that the applicable authorities, including the FDA or the USPTO, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions. We cannot be sure that any patents will issue from any pending or future patent applications. Even if patents do issue, we cannot be sure that the claims of these patents will be held valid or enforceable by a court of law or governmental agency, will provide us with any significant protection against competitive products, or will afford us a commercial advantage over competitive products. For example: • we might not have been the first to file patent applications for the inventions covered by our pending patent applications and any patents that issue therefrom; • others may independently develop similar or alternative technologies without infringing our intellectual property rights; • some or all of our pending patent applications may not result in issued patents or the claims that issue may be narrow in scope and not provide us with a competitive advantage; • any patents that issue from any of our pending patent applications may be challenged by a third party and invalidated; • any patents that issue from our pending patent applications may be subject to post-grant proceedings, oppositions or other administrative or court proceedings that may result in a reduction in their scope or their loss altogether; • we may not develop proprietary technologies or investigational products that are patentable; and • the patents of others may prevent us from discovering, developing or commercializing our investigational products. 22 Table of Contents The defense and prosecution of intellectual property infringement suits, post-grant proceedings, oppositions and related legal and administrative proceedings are costly, time-consuming to pursue and divert resources. The outcome of these types of proceedings is uncertain and could significantly harm our business. The development of our investigational products and the commercialization of any resulting drugs may be impacted by patents of other companies or by companies engaged in the development of competitive programs or those with significantly greater resources. This could result in the expenditure of significant legal fees and management resources. We also rely on trade secrets to protect our technology and product candidates, especially where we do not believe patent protection is appropriate or obtainable. However, trade secrets are often difficult to protect, especially outside of the U.S. While we believe that we use reasonable efforts to protect our trade secrets, our employees, consultants, contractors, partners and other advisors may unintentionally or willfully disclose our trade secrets to others, including competitors. Enforcing a claim that a third party illegally disclosed, obtained or is using our trade secrets would be expensive and time-consuming, and the outcome would be unpredictable. Even if we are able to maintain our trade secrets as confidential, our competitors may independently develop information that is equivalent or similar to our trade secrets. KRAS Portfolio The KRAS patent portfolio consists of eleven patent families, including G12C and G12D KRAS inhibitors and pan-KRAS inhibitors. The G12C portfolio includes patent applications directed to BBO-8520 composition of matter, pharmaceutical compositions thereof, and methods of use in treating diseases mediated by KRAS. Patent applications covering BBO-8520 are pending in the United States and foreign jurisdictions including Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Eurasia, Europe, Hong Kong, India, Indonesia, Israel, Japan, Republic of Korea, Malaysia, Mexico, New Zealand, Peru, Philippines, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, Ukraine, and Vietnam. One patent covering BBO-8520 is granted in the United States. Any patents issuing from these patent applications, if granted, are expected to expire mid-2042, without taking potential patent term adjustments or extensions into account. The pan-KRAS portfolio includes patent applications directed to BBO-11818 composition of matter, pharmaceutical compositions thereof, and methods of use in treating diseases mediated by KRAS. Patent applications covering BBO-11818 are pending in the United States and foreign jurisdictions including Argentina, Australia, Brazil, Canada, China, Europe, Hong Kong, India, Israel, Japan, Republic of Korea, Mexico, New Zealand, South Africa, and Taiwan. Any patents issuing from these patent applications, if granted, are expected to expire mid-2043, not including patent term adjustments and extensions. Other filings in the KRAS portfolio, if granted, are expected to expire between 2042 and 2046, not including patent term adjustments and extensions. PI3K Breaker Portfolio Our PI3K breaker portfolio consists of nine patent families, including patent applications directed to BBO-10203 composition of matter, pharmaceutical compositions thereof, and methods of use in treating diseases associated with interruption of the interaction between a PI3K protein and a RAS protein. Patent applications covering BBO-10203 are pending in the United States and foreign jurisdictions including Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Eurasia, Europe, Hong Kong, India, Indonesia, Israel, Japan, Republic of Korea, Malaysia, Mexico, New Zealand, Peru, Philippines, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, Ukraine, and Vietnam. Any patents issuing from the patent applications, if granted, are expected to expire in February 2043, not including patent term adjustments and extensions. Other filings in the PI3K breaker portfolio, if granted, are expected to expire between 2044 and 2046, not including patent term adjustments and extensions. Combination of a KRAS Inhibitor and a PI3K Breaker We have one patent family directed to the use of a KRAS inhibitor compound in combination with a PI3K breaker compound. Any patents issuing from the patent applications, if granted, are expected to expire in October 2045, not including patent term adjustments and extensions. License and Cooperative Research and Development Agreements LLNS Cooperative Research and Development Agreement On May 22, 2018, BBOT entered into a cooperative research and development agreement with Lawrence Livermore National Security, LLC (“ LLNS ”), as amended by that certain Amendment No. 1 to the cooperative research and development agreement, dated as of December 2, 2019, as further amended by that certain Amendment No. 2 to the cooperative research and development agreement, dated as of May 21, 2021, as further amended by that certain Amendment No. 3 to the cooperative research and development agreement, dated as of June 22, 2022, as further amended by that certain Amendment No. 4 to the cooperative research and development agreement, dated as of December 21, 2023, as extended by that certain No Cost Time Extension Letter, dated as of December 2, 2024, and as further amended by that certain Amendment No. 5 to the cooperative research and development agreement, dated as of May 20, 2025 (collectively, the “ Livermore CRADA ”). Pursuant to the Livermore CRADA, BBOT and LLNS granted each other a royalty-free, 23 Table of Contents nonexclusive, nontransferable, worldwide license to practice (a) such party’s background intellectual property and (b) the inventions of LLNS or BBOT made during the performance of work under the Livermore CRADA (the “ Subject Inventions ”), in each case to the extent needed by the non-granting party to perform its obligations or practice its rights under the Livermore CRADA. BBOT has the exclusive option for a specified period of time to negotiate an exclusive license to LLNS’s Subject Inventions in the field of small molecule KRAS inhibitors. The United States government retains a nonexclusive, nontransferable, irrevocable, paid-up, worldwide license to practice the Subject Inventions. As of December 31, 2025, BBOT has contributed a total value of $28.6 million for the Livermore CRADA, of which $6.5 million was contributed funds-in and $22.1 million was contributed in-kind. The Livermore CRADA will expire in June 2027 unless the parties mutually agree to extend the term. Either party has a right to terminate the CRADA for any reason by providing advanced written notice. The parties’ rights in the Subject Inventions and data survive the expiration of the Livermore CRADA in accordance with the terms therein. PI3K α Breakers Patent License Agreement On July 7, 2022, BBOT entered into a patent license agreement with LLNS, as amended by that certain Amendment One to limited exclusive patent license agreement, dated as of November 18, 2025 (collectively, the “ PI3K α Breakers Patent License Agreement ”) pursuant to which BBOT received a worldwide, exclusive, royalty-bearing, sublicensable (through no more than two tiers) license under certain patent rights relating to the PI3Kα breakers compounds to make, have made, use, import/export, develop, sell, offer to sell, and have sold licensed products and licensed services, and to practice and have practiced licensed methods for all fields of use, subject to certain retained rights by LLNS. Under certain circumstances and subject to restrictions, the United States government reserves the right to a nonexclusive, royalty-free, irrevocable, nontransferable license under the licensed patent rights. BBOT has certain typical diligence obligations under the PI3Kα Breakers Patent License Agreement, including the obligation to use commercially reasonable efforts to develop, manufacture, and sell any licensed method, licensed product or licensed service and file and obtain relevant regulatory applications for the manufacturing, marketing, and sale of licensed products. In addition, BBOT is obligated to use commercially reasonable efforts to meet specific development, regulatory and commercial performance obligations. BBOT made a one-time, non-creditable, non-refundable upfront payment of $0.1 million to LLNS after BBOT entered into the PI3Kα Breakers Patent License Agreement. Additionally, BBOT is obligated to pay LLNS (i) an annual license maintenance fee of a specified amount until the first commercial sale or other exploitation of a licensed method, licensed product or licensed service, (ii) a creditable, tiered, minimum annual royalty in a low-to-mid hundred thousand dollar range after the first commercial sale or other exploitation of a licensed method, licensed product or licensed service, (iii) a low single-digit tiered royalty on sales of licensed products or licensed services, (iv) up to a total of $7.0 million in regulatory and commercialization milestones based upon indication, (v) a mid double-digit percentage in the range of 45% to 55% of certain non-royalty consideration received under a sublicense to a third party, subject to a specified cap, and (vi) an assignment fee of a specified amount. As of December 31, 2025, BBOT has paid an aggregate of $0.4 million to LLNS under the PI3Kα Breakers Patent License Agreement. The term of the PI3Kα Breakers Patent License Agreement will extend until the expiration of the last to expire of the patents and patent applications included within the licensed patent rights, unless earlier terminated. The licensed patent applications, if issued, are expected to expire in 2043. LLNS may terminate the PI3Kα Breakers Patent License Agreement or convert the exclusive license granted to a nonexclusive license upon the occurrence of certain events, including if BBOT materially breaches the PI3Kα Breakers Patent License Agreement or becomes insolvent. LLNS may immediately terminate the PI3Kα Breakers Patent License Agreement or convert the exclusive license granted to a nonexclusive license if BBOT directly or indirectly challenges the validity of any of the licensed patent rights. BBOT may terminate the PI3Kα Breakers Patent License Agreement for any reason by giving written notice to LLNS. KRAS G12C Inhibitors Patent License Agreement On July 7, 2022, BBOT entered into a patent license agreement with LLNS, as amended by that certain Amendment One to limited exclusive patent license agreement, dated as of November 18, 2025 (the “ KRAS G12C Inhibitors Patent License Agreement ”) pursuant to which BBOT received a worldwide, exclusive, royalty-bearing, sublicensable (through no more than two tiers) license under certain patent rights relating to the KRAS G12C inhibitor compounds to make, have made, use, import/export, develop, sell, offer to sell, and have sold licensed products and licensed services, and to practice and have practiced licensed methods for all fields of use, subject to certain retained rights by LLNS. Under certain circumstances and subject to restrictions, the United States government reserves the right to a nonexclusive, royalty-free, irrevocable, nontransferable license under the licensed patent rights. BBOT has certain typical diligence obligations under the KRAS G12C Inhibitors Patent License Agreement, including the obligation to use commercially reasonable efforts to develop, manufacture, and sell any licensed method, licensed product or licensed 24 Table of Contents service and file and obtain relevant regulatory applications for the manufacturing, marketing, and sale of licensed products. In addition, BBOT is obligated to use commercially reasonable efforts to meet specific development, regulatory and commercial performance obligations. BBOT made a one-time, non-creditable, non-refundable upfront payment of less than $0.1 million to LLNS after BBOT entered into the KRAS G12C Inhibitors Patent License Agreement. Additionally, BBOT is obligated to pay LLNS (i) an annual license maintenance fee of a specified amount until the first commercial sale or other exploitation of a licensed method, licensed product or licensed service, (ii) a creditable, tiered, minimum annual royalty in a low-to-mid hundred thousand dollar range after the first commercial sale or other exploitation of a licensed method, licensed product or licensed service, (iii) a low single-digit tiered royalty on sales of licensed products or licensed services, (iv) up to a total of $7.0 million in regulatory and commercialization milestones based upon indication, (v) a mid double-digit percentage in the range of 45% to 55% of certain non-royalty consideration received under a sublicense to a third party, subject to a specified cap, and (vi) an assignment fee of a specified amount. As of December 31, 2025, BBOT has paid $0.4 million to LLNS under the KRAS G12C Inhibitors Patent License Agreement. The term of the KRAS G12C Inhibitors Patent License Agreement will extend until the expiration of the last to expire of the patents and patent applications included within the licensed patent rights, unless earlier terminated. The licensed patent applications, if issued, are expected to expire between 2042-2043. LLNS may terminate the KRAS G12C Inhibitors Patent License Agreement or convert the exclusive license granted to a nonexclusive license upon the occurrence of certain events, including if BBOT materially breaches the KRAS G12C Inhibitors Patent License Agreement or becomes insolvent. LLNS may immediately terminate the KRAS G12C Inhibitors Patent License Agreement or convert the exclusive license granted to a nonexclusive license if BBOT directly or indirectly challenges the validity of any of the licensed patent rights. BBOT may terminate the KRAS G12C Inhibitors Patent License Agreement for any reason by giving written notice to LLNS. Pan-KRAS Inhibitors Agreement On December 20, 2024, BBOT entered into a patent license agreement with LLNS, as amended by that certain Amendment One to limited exclusive patent license agreement, dated as of November 18, 2025 (the “ Pan-KRAS Inhibitors Agreement ”) pursuant to which BBOT received a worldwide, exclusive, royalty-bearing, sublicensable (through no more than two tiers) license, under certain patent rights relating to the Pan-KRAS inhibitor compounds to make, have made, use, import/export, develop, sell, offer to sell, and have sold licensed products and licensed services, and to practice and have practiced licensed methods, limited to the oncology indications, subject to certain retained rights by LLNS. Under certain circumstances and subject to restrictions, the United States government reserves the right to a nonexclusive, royalty-free, irrevocable, nontransferable license under the licensed patent rights. BBOT has certain typical diligence obligations under the Pan-KRAS Inhibitors Agreement, including the obligation to use commercially reasonable efforts to develop, manufacture, and sell any licensed method, licensed product or licensed service and file and obtain relevant regulatory applications for the manufacturing, marketing, and sale of licensed products. In addition, BBOT is obligated to use commercially reasonable efforts to meet specific development, regulatory and commercial performance obligations. BBOT will make a one-time, non-creditable, non-refundable upfront payment of $100,000 to LLNS after BBOT entered into the Pan-KRAS Inhibitors Agreement. Additionally, BBOT is obligated to pay LLNS (i) an annual license maintenance fee of a specified amount until the first commercial sale or other exploitation of a licensed method, licensed product or licensed service, (ii) a creditable, tiered, minimum annual royalty in a low-to-mid hundred thousand dollar range after the first commercial sale or other exploitation of a licensed method, licensed product or licensed service, (iii) a low single-digit tiered royalty on sales of licensed products or licensed services, (iv) up to a total of $7.8 million in regulatory and commercialization milestones based upon indication, (v) a mid double-digit percentage in the range of 45% to 55% of certain non-royalty consideration received under a sublicense to a third party, subject to a specified cap, and (vi) an assignment fee of a specified amount. As of December 31, 2025, BBOT has paid an aggregate of $0.3 million to LLNS under the Pan-KRAS Inhibitors Agreement. The term of the Pan-KRAS Inhibitors Agreement will extend until the expiration of the last to expire of the patents and patent applications included within the licensed patent rights, unless earlier terminated. The licensed patent applications, if issued, are expected to expire between 2042-2044. LLNS may terminate the Pan-KRAS Inhibitors Agreement or convert the exclusive license granted to a nonexclusive license upon the occurrence of certain events, including if BBOT materially breaches the Pan-KRAS Inhibitors Agreement or becomes insolvent. LLNS may immediately terminate the Pan-KRAS Inhibitors Agreement or convert the exclusive license granted to a nonexclusive license if BBOT directly or indirectly challenges the validity of any of the licensed patent rights. BBOT may terminate the Pan-KRAS Inhibitors Agreement for any reason by giving written notice to LLNS. 25 Table of Contents Leidos Cooperative Research and Development Agreement On March 3, 2017, BBOT entered into a cooperative research and development agreement with The Frederick National Laboratory for Cancer Research, operated by Leidos Biomedical Research, Inc. (“ Leidos ”), as amended by that certain Amendment No. 1 to the cooperative research and development agreement dated as of January 19, 2018, as further amended by that certain Amendment No. 2 to the cooperative research and development agreement dated as of January 2, 2019, as further amended by that certain Amendment No. 3 to the cooperative research and development agreement dated as of November 14, 2019, as further amended by that certain Amendment No. 4 to the cooperative research and development agreement dated as of January 13, 2020, as further amended by that certain Amendment No. 5 to the cooperative research and development agreement dated as of September 22, 2021, as further amended by that certain Amendment No. 6 to the cooperative research and development agreement dated as of March 27, 2023, as further amended by that certain Amendment No. 7 to the cooperative research and development agreement dated as of August 20, 2024, as further amended by that certain Amendment No. 8 to the cooperative research and development agreement dated as of September 2, 2025, as further amended by that certain Amendment No. 9 to the cooperative research and development agreement dated as of December 3, 2025, (collectively, the “ Leidos CRADA ”). Pursuant to the Leidos CRADA, Leidos retains the right (a) to utilize any invention of either or both parties conceived or first actually reduced to practice in the performance of work under the Leidos CRADA (“ CRADA Subject Invention ”) that constitutes an improvement to a tangible material not first produced in the performance of the Leidos CRADA that is owned or controlled by BBOT and used in the performance of work under the Leidos CRADA, solely as a research tool for internal, non-profit, pre-clinical research purposes and (b) to any CRADA Subject Invention included within the scope of the retained rights under the exclusive license agreement entered into between BBOT and The Regents of the University of California, San Francisco (“ UCSF ”) dated as of September 28, 2016 (the “ UCSF License Agreement ”). Leidos granted BBOT an exclusive option for a specified period of time to negotiate an exclusive or nonexclusive commercialization license to CRADA Subject Inventions made solely or jointly by Leidos for a field of use that does not exceed the scope of the work committed to under the Leidos CRADA. To the extent required by applicable law, BBOT granted the United States government a nonexclusive, nontransferable, irrevocable, paid -up, worldwide license to practice and have practiced the CRADA Subject Inventions for research and government purposes. As of December 31, 2025, BBOT has paid an aggregate of $15.9 million to Leidos under the Leidos CRADA. The Leidos CRADA expires on September 3, 2026. Either Party has a right to terminate the CRADA upon at least 60 days’ prior written notice. Leidos PLA I On August 5, 2022, BBOT entered into a patent license agreement (the “ Leidos PLA I ”) with Leidos, pursuant to which BBOT received a worldwide, exclusive, royalty-bearing, sublicensable (through multiple tiers) license under certain patent rights relating to the PI3Kα breaker compounds to (i) make and have made, to use and have used, to sell and have sold, to offer to sell, to develop, and to import licensed products and (ii) practice and have practiced any licensed processes, in each case (i) and (ii), for prophylactic, therapeutic, and diagnostic use in humans and animals. The licensed patent rights result from an ongoing research collaboration between BBOT and Leidos, and BBOT may opt to negotiate an exclusive license to any additional inventions resulting from such research collaboration. Under certain circumstances and subject to restrictions, Leidos and the United States government reserve the right to a nonexclusive, royalty-free, irrevocable, nontransferable license under the licensed patent rights. BBOT has certain typical diligence obligations under the Leidos PLA I, including the obligation to use reasonable commercial efforts to bring the licensed products and licensed processes to practical application, and upon the initial transfer of a licensed product or initial practice of a licensed process in exchange for compensation, the obligation to use reasonable commercial efforts to make the licensed products and licensed processes reasonably accessible to the United States public. In addition, BBOT has specific development and regulatory performance milestones to meet. BBOT made a one-time, non-creditable, non-refundable upfront payment of $0.5 million to Leidos after BBOT entered into the Leidos PLA I. Additionally, BBOT is obligated to pay Leidos (i) a non-refundable minimum annual royalty of $150,000 until the initial transfer of a licensed product or initial practice of a licensed process in exchange for compensation, (ii) a low, single-digit royalty on sales of licensed products, (iii) up to a total of (A) $6.75 million in development milestones for the first indication for the first licensed product and (B) $1.875 million in development milestones for the second indication for each licensed product, (iv) a low double-digit percentage in the range of 5% to 15% of certain non-royalty consideration received under a sublicense to a third party, and (v) reimburse Leidos for patenting expenses for the licensed patent rights, if any. In December 2025, the parties amended the Leidos PLA I to include an additional $0.5 million payment for the first indication, triggered by the achievement of a specific development milestone after the amendment date. As of December 31, 2025, BBOT has paid an aggregate of $1.5 million to Leidos under the Leidos PLA I. 26 Table of Contents The term of the Leidos PLA I will extend to the expiration of the last to expire of the licensed patent rights, unless earlier terminated. The licensed patent applications, if issued, are expected to expire in 2034. BBOT has the unilateral right to terminate the Leidos PLA I at any time upon prior written notice to Leidos. Additionally, the Leidos PLA I will terminate if BBOT files a claim that asserts any portion of the licensed patent rights are invalid or unenforceable, unless BBOT withdraws or cause the withdrawal of such claim within a specified period of time. Leidos may terminate the Leidos PLA I in its entirety for BBOT’s material breach that is not remediated within a specified period of time, or upon the occurrence of certain events of BBOT’s insolvency. Further, Leidos has the right to terminate or modify the Leidos PLA I if Leidos determines that BBOT (i) is not using commercially reasonable efforts to develop and commercialize the licensed patent rights, (ii) has not achieved the milestone benchmarks set forth in the Leidos PLA I, or (iii) has willfully made a false statement of, or willfully omitted a material fact in the license application or any report required by the Leidos PLA I. Leidos PLA II On August 5, 2022, BBOT entered into a patent license agreement (the “ Leidos PLA II ”) with Leidos, pursuant to which BBOT received a worldwide, exclusive, royalty-bearing, sublicensable (through multiple tiers) license under patent rights relating to the KRAS G12C inhibitor compounds to (i) make and have made, to use and have used, to sell and have sold, to offer to sell, to develop, and to import licensed products and (ii) practice and have practiced any licensed processes, in each case (i) and (ii), for prophylactic, therapeutic, and diagnostic use in humans and animals. The licensed patent rights result from an ongoing research collaboration between BBOT and Leidos, and BBOT may opt to negotiate an exclusive license to any additional inventions resulting from such research collaboration. Under certain circumstances and subject to restrictions, Leidos and the United States government reserve the right to a nonexclusive, royalty-free, irrevocable, nontransferable license under the licensed patent rights. BBOT has certain typical diligence obligations under the Leidos PLA II, including the obligation to use reasonable commercial efforts to bring the licensed products and licensed processes to practical application, and upon the initial transfer of a licensed product or initial practice of a licensed process in exchange for compensation, the obligation to use reasonable commercial efforts to make the licensed products and licensed processes reasonably accessible to the United States public. In addition, BBOT has specific development and regulatory performance milestones to meet. BBOT made a one-time, non-creditable, non-refundable upfront payment of $0.5 million to Leidos after BBOT entered into the Leidos PLA II. Additionally, BBOT is obligated to pay Leidos (i) a non-refundable minimum annual royalty of $0.15 million until the initial transfer of a licensed product or initial practice of a licensed process in exchange for compensation, (ii) a low, single-digit royalty on sales of licensed products, (iii) up to a total of (A) $6.75 million in development milestones for the first indication for the first licensed product and (B) $1.875 million in development milestones for the second indication for each licensed product, (iv) a low double-digit percentage in the range of 5% to 15% of certain non-royalty consideration received under a sublicense to a third party, and (v) reimburse Leidos for patenting expenses for the licensed patent rights, if any. In December 2025, the parties amended the Leidos PLA II to include an additional $0.5 million payment for the first indication, triggered by the achievement of a specific development milestone after the amendment date. As of December 31, 2025, BBOT has paid an aggregate of $1.5 million to Leidos under the Leidos PLA II. The term of the Leidos PLA II will extend to the expiration of the last to expire of the licensed patent rights, unless earlier terminated. The licensed patent applications, if issued, are expected to expire between 2042-2043. BBOT has the unilateral right to terminate the Leidos PLA II at any time upon prior written notice to Leidos. Additionally, the Leidos PLA II will terminate if BBOT files a claim that asserts any portion of the licensed patent rights are invalid or unenforceable, unless BBOT withdraws or causes the withdrawal of such claim within a specified period of time. Leidos may terminate the Leidos PLA II in its entirety for BBOT’s material breach that is not remediated within a specified period of time, or upon the occurrence of certain events of BBOT’s insolvency. Further, Leidos has the right to terminate or modify the Leidos PLA II if Leidos determines that BBOT (i) is not using commercially reasonable efforts to develop and commercialize the licensed patent rights, (ii) has not achieved the milestone benchmarks set forth in the Leidos PLA II, or (iii) has willfully made a false statement of, or willfully omitted a material fact in the license application or any report required by the Leidos PLA II. Leidos PLA III On December 20, 2023, BBOT entered into a patent license agreement (the “ Leidos PLA III ”) with Leidos, pursuant to which BBOT received a worldwide, exclusive, royalty-bearing, sublicensable (through multiple tiers) license under certain patent rights relating to the Pan -KRAS inhibitor compounds to (i) make and have made, to use and have used, to sell and have sold, to offer to sell, to develop, and to import licensed products and (ii) practice and have practiced any licensed processes, in each case (i) and (ii), for prophylactic, therapeutic, and diagnostic use in humans and animals. The licensed patent rights result from an ongoing research collaboration between BBOT and Leidos, and BBOT may opt to negotiate an exclusive license to any additional inventions resulting 27 Table of Contents from such research collaboration. Under certain circumstances and subject to restrictions, Leidos and the United States government reserve the right to a nonexclusive, royalty-free, irrevocable, nontransferable license under the licensed patent rights. BBOT has certain typical diligence obligations under the Leidos PLA III, including the obligation to use reasonable commercial efforts to bring the licensed products and licensed processes to practical application, and upon the initial transfer of a licensed product or initial practice of a licensed process in exchange for compensation, the obligation to use reasonable commercial efforts to make the licensed products and licensed processes reasonably accessible to the United States public. In addition, BBOT has specific development and regulatory performance milestones to meet. BBOT made a one-time, non-creditable, non-refundable upfront payment of $0.75 million to Leidos after BBOT entered into the Leidos PLA III. Additionally, BBOT is obligated to pay Leidos (i) a non-refundable minimum annual royalty of $0.2 million until the initial transfer of a licensed product or initial practice of a licensed process in exchange for compensation, (ii) a low, single-digit royalty on sales of licensed products, (iii) up to a total of (A) $6.75 million in development milestones for the first indication for the first licensed product and (B) $1.875 million in development milestones for the second indication for each licensed product, (iv) a low double-digit percentage in the range of 5% to 15% of certain non-royalty consideration received under a sublicense to a third party, and (v) reimburse Leidos for patenting expenses for the licensed patent rights, if any. In December 2025, the parties amended the Leidos PLA IIII to include an additional $0.5 million payment for the first indication, triggered by the achievement of a specific development milestone after the amendment date. As of December 31, 2025, BBOT has paid an aggregate of $1.0 million to Leidos under the Leidos PLA III. The term of the Leidos PLA III will extend to the expiration of the last to expire of the licensed patent rights, unless earlier terminated. The licensed patent applications, if issued, are expected to expire between 2042-2044. BBOT has the unilateral right to terminate the Leidos PLA III at any time upon prior written notice to Leidos. Additionally, the Leidos PLA III will terminate if BBOT files a claim that asserts any portion of the licensed patent rights are invalid or unenforceable, unless BBOT withdraws or causes the withdrawal of such claim within a specified period of time. Leidos may terminate the Leidos PLA III in its entirety for BBOT’s material breach that is not remediated within a specified period of time, or upon the occurrence of certain events of BBOT’s insolvency. Further, Leidos has the right to terminate or modify the Leidos PLA III if Leidos determines that BBOT (i) is not using commercially reasonable efforts to develop and commercialize the licensed patent rights, (ii) has not achieved the milestone benchmarks set forth in the Leidos PLA III, or (iii) has willfully made a false statement of, or willfully omitted a material fact in the license application or any report required by the Leidos PLA III. Manufacturing and Supply We currently contract with third parties to manufacture our product candidates and anticipate using third parties for all preclinical, clinical and commercial manufacturing if any of our investigational products obtain marketing approval. We do not own or operate facilities for product manufacturing, packaging, storage and distribution, or testing. We have internal personnel and utilize consultants with extensive technical, manufacturing, analytical, and quality experience to oversee contract manufacturing and testing activities. We believe that this strategy allows us to maintain a more efficient infrastructure by eliminating the need for us to invest in our own manufacturing facilities, equipment and personnel while also enabling us to focus our expertise and resources on the development of our investigational products. Commercialization We intend to retain significant development and commercial rights to our investigational products and, if marketing approval is obtained, to commercialize our investigational products on our own, or potentially with a partner, in the U.S. and other regions. We intend to build the necessary infrastructure and sales, marketing and commercial product distribution capabilities for the U.S., and potentially other regions, following further advancement of our investigational products. Clinical data, the size of the addressable patient population and the size of the commercial infrastructure and manufacturing needs and economics related to the foregoing may all influence or alter our commercialization plans. Competition The pharmaceutical and biotechnology industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. While we believe that our technology, development experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including large pharmaceutical and biotechnology companies, academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for the research, development, manufacturing and commercialization of cancer therapies. Any investigational products that we successfully develop and commercialize will compete with new therapies that may become available in the future. 28 Table of Contents We compete in the segments of the pharmaceutical, biotechnology and other related markets that develop small molecules and drug conjugates as treatments for cancer patients. There are many other companies that have commercialized and/or are developing such treatments for cancer including large pharmaceutical and biotechnology companies, such as AstraZeneca plc, Bristol-Myers Squibb Company, Merck, Pfizer in partnership with Merck KGaA, Regeneron Pharmaceuticals, Inc. in partnership with Sanofi Genzyme and Roche. We are currently developing BBO-8520 in KRAS G12C NSCLC as a KRAS G12C ON/OFF inhibitor. If approved, BBO-8520 would compete with approved KRAS G12C inhibitors Sotorasib and Adagrasib, which target the OFF state of the KRAS G12C protein. There are also a number of other KRAS G12C OFF inhibitor product candidates in clinical development, including Divarasib, Glecirasib, Olomorasib, and Calderasib. In addition, BBO-8520 may compete with Elironrasib, a tricomplex inhibitor of KRAS G12C ON that is currently in early clinical development and FMC -376, a direct inhibitor of KRAS G12C ON/OFF that is currently in early clinical development. BBO-10203 is being developed in hormone receptor-positive PIK3CA mutant breast cancer in combination with HR-directed therapies and CDK4/6 inhibitors, HER2-positive breast cancer in combination with HER2-directed biologics, and we are combining BBO-10203 with chemotherapy and bevacizumab in CRC with KRAS. We are planning to combine with our internal KRASi agents, BBO-8520 and BBO-11818. If approved in the HR+ PIK3CA mut breast cancer setting, BBO-10203 will compete with approved non-mutant-selective PI3Kα inhibitors, Alpelisib and Inavolisib. BBO-10203 may also compete with mutant-selective PI3Kα inhibitors that are currently in clinical development such as STX-478, Zovegalisib, and OKI-219. BBO-10203 may also compete with downstream inhibitors of the PI3Kα pathway such as AKT inhibitor Capivasertib and mTOR inhibitor Everolimus as well as PI3K/mTOR inhibitors such as Gedatolisib. In HER2+ breast cancer, if approved, BBO-10203 may compete with approved small molecule inhibitors of HER2 including Tucatinib, Neratinib, and Lapatinib as well as small molecules inhibitors of HER2 that are currently in clinical development such as ELVN-002, Pyrotinib, Epertinib, IAM-1363, DZD-1516. BBO-11818 is planned to be developed in KRAS G12X mutant solid tumors with a specific focus on KRAS G12D and KRAS G12V mutant tumors in NSCLC, CRC, and PDAC. If approved, BBO-11818 may compete with other pan-KRAS inhibitors currently in clinical or preclinical development such as QTX-3034, BI3706674, QLC1101, PF-07934040, YL-17231, JAB-23400, LY4066434, ABT-200, QTX-3544, BPI-585359, GFH547, ERAS-4001. BBO-11818 may also compete with KRAS G12D inhibitors currently in clinical or preclinical development such as RMC-9805, ASP-3082, HRS-4642, INCB161734, GHF-375, TSN1611, ASP4396, QTX-3046, SHR1127, LY3962673, HBW-012D. BBO-11818 may compete with KRAS G12V inhibitors currently in early clinical development such as RMC-5127. BBO-11818 may also compete with daraxonrasib, a pan-RAS inhibitor currently in clinical development and ERAS-0015, a pan-RAS inhibitor currently in early clinical development. Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved drugs than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and enrolling subjects for our clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. We could see a reduction or elimination of our commercial opportunity if our competitors develop and commercialize products that are safer or more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we or our collaborators may develop. Our competitors also may obtain FDA or foreign regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we or our collaborators are able to enter the market. The key competitive factors affecting the success of all of our investigational products, if approved, are likely to be their degree of efficacy, tolerability profile, convenience and price, the effectiveness of companion diagnostics (if required), the level of biosimilar or generic competition and the availability of reimbursement from government and other third-party payors. Government Regulation Government authorities in the U.S. at the federal, state and local level and in other countries regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of drug and biological products. Generally, before a new drug can be marketed, considerable data demonstrating its quality, safety and efficacy must be obtained, organized into a format specific for each regulatory authority, submitted for review and approved by the regulatory authority. 29 Table of Contents U.S. Drug Development In the U.S., the FDA regulates drugs under the Food, Drug, and Cosmetic Act (“ FDCA ”). Drugs also are subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or post-market may subject an applicant to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, product recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us. Our product candidates are considered small molecule drugs and must be approved by the FDA through the new drug application (“ NDA ”), process before they may be legally marketed in the U.S. The process generally involves the following: • completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with the FDA’s Good Laboratory Practice (“ GLP ”); • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent IRB or ethics committee at each clinical trial site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, GCP requirements and other clinical trial-related protocols and regulations to establish substantial evidence of the safety and efficacy of the investigational product for each proposed indication; • submission to the FDA of an NDA after completion of pivotal trial(s) and other required clinical studies; • determination by the FDA within 60 days of its receipt of an NDA to accept the filing for substantive review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug will be produced to assess compliance with current good manufacturing practice (“ cGMP ”) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; • potential FDA audit of the preclinical study and/or clinical trial sites that generated the data in support of the NDA filing; • FDA review and approval of the NDA, including consideration of the views of any FDA advisory committee, if applicable, prior to any commercial marketing or sale of the drug in the U.S.; and • compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (“REMS”) and the potential requirement to conduct post-approval studies. The data required to support an NDA are generated in two distinct developmental stages: preclinical and clinical. The preclinical and clinical testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for any current and future product candidates will be granted on a timely basis, or at all. Preclinical Studies and IND The preclinical developmental stage generally involves laboratory evaluations of drug chemistry, formulation and stability, as well as studies to evaluate toxicity in animals, which support subsequent clinical testing. The sponsor must submit the results of the preclinical studies, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before human clinical trials may begin. Preclinical studies include laboratory evaluation of product chemistry and formulation, as well as in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations for safety/toxicology studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical studies, among other things, to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence. 30 Table of Contents Clinical Trials The clinical stage of development involves the administration of the investigational product to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirement that all clinical trial subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety and assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND. Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB must also approve the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. There also are requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries. A sponsor who wishes to conduct a clinical trial outside of the U.S. may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of an NDA. When the foreign clinical trial is not conducted under an IND, the sponsor must ensure that the study is conducted in accordance with GCP, including review and approval by an independent ethics committee (IEC) and informed consent from subjects. The GCP requirements are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical trials, as well as the quality and integrity of the resulting data. FDA must also be able to validate the data from the study through an on-site inspection if necessary. An NDA based solely on foreign clinical data meeting U.S. criteria for marketing approval may be approved if (1) the foreign data are applicable to the U.S. population and U.S. medical practice, (2) the studies have been performed by clinical investigators of recognized competence and (3) the FDA is able to validate the data through an onsite inspection or other appropriate means, if deemed necessary. Clinical trials in the U.S. generally are conducted in three sequential phases, known as Phase 1, Phase 2 and Phase 3, which may overlap or be combined. • Phase 1 clinical trials generally involve a small number of healthy volunteers or disease-affected patients who are initially exposed to a single dose and then multiple doses of the product candidate. The primary purpose of these clinical trials is to assess the metabolism, pharmacologic action, tolerability and safety of the drug. • Phase 2 clinical trials involve studies in disease-affected patients to determine the dose and dosing schedule required to produce the desired benefits. At the same time, safety and further pharmacokinetic and pharmacodynamic information is collected, possible adverse effects and safety risks are identified, and a preliminary evaluation of efficacy is conducted. • Phase 3 clinical trials generally involve a large number of patients at multiple sites and are designed to provide the data necessary to demonstrate the effectiveness of the product for its intended use, its safety in use and to establish the overall benefit/risk relationship of the product and provide an adequate basis for product approval. These trials may include comparisons with placebo and/or other comparator treatments. The duration of treatment is often extended to mimic the actual use of a product during marketing. Post-approval trials, sometimes referred to as Phase 4 clinical trials, are conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA. Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA. The sponsor is also responsible for submitting written IND safety reports, including reports of serious and unexpected suspected adverse reactions, findings from other studies suggesting a significant risk to humans exposed to the drug, findings from animal or in vitro testing that suggest a significant risk for human subjects, and any clinically significant increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the clinical trial subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether a trial may move forward at designated checkpoints based on access to certain data from the trial. Concurrent with clinical trials, companies often complete additional animal safety studies and also must develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the product in 31 Table of Contents commercial quantities in accordance with cGMP requirements. The manufacturing process, as performed by the manufacturing facility, must be capable of consistently producing quality batches of our product candidates. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that our product candidates do not undergo unacceptable deterioration over their labeled shelf life. NDA Review Process Following completion of the clinical trials, the results of preclinical studies and clinical trials are submitted to the FDA as part of an NDA, along with proposed labeling, chemistry and manufacturing information to ensure product quality and other relevant data, which is analyzed to assess whether the investigational product is safe and effective for the proposed indicated use or uses. In short, the NDA is a request for approval to market the drug in the U.S. for one or more specified indications and must contain proof of safety and efficacy for a drug. The application must include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings. Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of FDA. FDA approval of an NDA must be obtained before a drug may be legally marketed in the U.S. Under the Prescription Drug User Fee Act (“PDUFA”), as amended, each NDA must be accompanied by a user fee. FDA adjusts the PDUFA user fees on an annual basis. PDUFA also imposes an annual program fee for each marketed human drug. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on NDAs for products designated as orphan drugs, unless the product also includes a non-orphan indication. The FDA reviews all submitted NDAs before it accepts them for filing and may request additional information rather than accepting the NDA for filing. The FDA must make a decision on accepting an NDA for filing within 60 days of receipt. Once the submission is accepted for filing, the FDA begins an in-depth review of the NDA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has 10 months, from the filing date, in which to complete its initial review of a new molecular-entity NDA and respond to the applicant, and six months from the filing date of a new molecular-entity NDA designated for priority review. The FDA may make a decision earlier than the PDUFA goal date or, the review process may be extended by FDA requests for additional information or clarification. Before approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether they comply with cGMP requirements. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. The FDA also may audit data from clinical trials to ensure compliance with GCP requirements. Additionally, the FDA may refer applications for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions, if any. The FDA is not bound by recommendations of an advisory committee, but it considers such recommendations when making decisions on approval. The FDA likely will reanalyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant during the review process. After the FDA evaluates an NDA, it will issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A complete response letter indicates that the review cycle of the application is complete, and the application will not be approved in its present form. A complete response letter usually describes all of the specific deficiencies in the NDA identified by the FDA. The complete response letter may require additional clinical data, additional pivotal Phase 3 clinical trial(s) and/or other significant and time-consuming requirements related to clinical trials, preclinical studies and/or manufacturing. If a complete response letter is issued, the applicant may resubmit the NDA, addressing all of the deficiencies identified in the letter, withdraw the application, or request the opportunity for a hearing. Even if an applicant submits the requested data and information, the FDA may decide that the NDA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data. Orphan Drugs Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the U.S., or more than 200,000 individuals in the U.S. and for which there is no reasonable expectation that the cost of developing and making the product available in the U.S. for this type of disease or condition will be recovered from sales of the product. 32 Table of Contents Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process. If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication for seven years from the date of such approval, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity by means of greater effectiveness, greater safety or providing a major contribution to patient care or in instances of drug supply issues. However, competitors may receive approval of either a different product for the same indication or the same product for a different indication but that could be used off-label in the orphan indication. Orphan drug exclusivity also could block the approval of one of our product candidates for seven years if a competitor obtains approval before we do for the same product, as defined by the FDA, for the same indication we are seeking approval, or if a product candidate is determined to be contained within the scope of the competitor’s product for the same indication. If one of our product candidates designated as an orphan drug receives marketing approval for an indication broader than that which is designated, it may not be entitled to orphan drug exclusivity. Orphan drug status in the European Union has similar, but not identical, requirements and benefits. Expedited Development and Review Programs The FDA has a number of programs intended to facilitate and expedite development and review of new drugs if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition. The fast track program is intended to expedite or facilitate the process for reviewing new drugs that meet certain criteria. Specifically, new drugs are eligible for fast track designation if they are intended to treat a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition. Fast track designation applies to both the product and the specific indication for which it is being studied. The sponsor can request the FDA to designate the product for fast track status any time before receiving NDA approval, but ideally no later than the pre-NDA meeting with the FDA. Any product submitted to the FDA for marketing, including under a fast track program, may be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval. Any product is eligible for priority review if it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness compared to available therapies. Additionally, a drug may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints. The benefits of breakthrough therapy designation include the same benefits as fast track designation, plus intensive guidance from the FDA to ensure an efficient drug development program. Fast track designation, priority review, accelerated approval and breakthrough therapy designation do not change the standards for approval, but may expedite the development or approval process. Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. A product may also be eligible for accelerated approval, if it treats a serious or life-threatening condition and generally provides a meaningful advantage over available therapies. In addition, it must demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality (“IMM”), which is reasonably likely to predict an effect on IMM or other clinical benefit. As a condition of approval, the FDA may require that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials. FDA may withdraw drug approval or require changes to the labeled indication of the drug if confirmatory post-market trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug. Post-approval Requirements Following approval of a new product, the manufacturer and the approved product are subject to continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, requirements to report adverse events and comply with promotion and advertising requirements. Further, if there are any modifications to the drug, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new NDA or NDA supplement, which may require the development of additional data or preclinical studies and clinical trials. If the FDA concludes that a drug shown to be effective can be safely used only if distribution or use is restricted, it may require such post-marketing restrictions as it deems necessary to assure safe use of the product. The FDA may also place other conditions on approvals, including the requirement for REMS, to assure the safe use of the product. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription 33 Table of Contents or dispensing of products. Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing. The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market, or product recalls; • fines, warning letters, or holds on post-approval clinical studies; • refusal of the FDA to approve pending applications or supplements to approved applications; • suspension or revocation of product approvals; • product seizure or detention; • refusal to permit the import or export of products; and • injunctions or the imposition of civil or criminal penalties. FDA regulations require that approved products be manufactured in specific approved facilities and in accordance with cGMP regulations which require, among other things, quality control and quality assurance, the maintenance of records and documentation, and the obligation to investigate and correct any deviations from cGMP. Manufacturers and other entities involved in the manufacture and distribution of approved products, and those supplying products, ingredients, and components of them, are required to register their establishments with the FDA and certain state agencies, and are subject to periodic announced and unannounced inspections by the FDA and certain state agencies for compliance with cGMP requirements and other regulatory requirements. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance. The discovery of violative conditions, including failure to conform to cGMP regulations, could result in enforcement actions. The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability. From time to time, legislation is drafted, introduced, passed in Congress and signed into law that could significantly change the statutory provisions governing the approval, manufacturing, and marketing of products regulated by the FDA. In addition to new legislation, FDA regulations, guidance, and policies are often revised or reinterpreted by the agency in ways that may significantly affect the manner in which pharmaceutical products are regulated and marketed. Other U.S. Regulatory Matters Pharmaceutical manufacturers are subject to various healthcare laws, regulation, and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business. Our conduct, including those of our employees, as well as our business operations and relationships with third parties, including current and future arrangements with healthcare providers, third-party payors, customers, and others may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations, which may constrain the business or financial arrangements and relationships through which we research, as well as, sell, market, and distribute any products for which we obtain marketing approval. The applicable federal, state and foreign healthcare laws and regulations that may affect our ability to operate include, but are not limited to: • Anti-Kickback Statute . The federal Anti-Kickback Statute prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration (including any kickback, bribe or rebate), directly or indirectly, in cash or in kind, to induce or reward or in return for, either the referral of an individual for or the purchase, lease or order of a good, facility, item or service for which payment may be made under a federal healthcare program such as Medicare and Medicaid. Violations are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs. In addition, a claim including items or services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act. 34 Table of Contents • False Claims Laws. The federal false claims and civil monetary penalties laws, including the federal civil False Claims Act (“ FCA ”), impose criminal and civil penalties, including through civil whistleblower or qui tam actions against individuals or entities for, among other things, knowingly presenting or causing to be presented false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties. Pharmaceutical companies can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. • HIPAA. HIPAA imposes criminal and civil liability for, among other things, executing a scheme or making materially false statements in connection with the delivery of or payment for health care benefits, items or services. Additionally, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes obligations on covered entities and their business associates that perform certain functions or activities that involve the use or disclosure of protected health information on their behalf, including mandatory contractual terms and technical safeguards, with respect to maintaining the privacy, security and transmission of individually identifiable health information. • Federal Trade Commission Act. Even when HIPAA does not apply, according to the Federal Trade Commission (“ FTC ”), failing to take appropriate steps to keep consumers’ personal information secure could constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act (“ FTCA ”). The FTC’s current guidance for appropriately securing consumers’ personal information is similar to what is required by the HIPAA security regulations, but this guidance may change in the future, resulting in increased complexity and the need to expend additional resources to ensure we are complying with the FTCA. • The U.S. Federal Physician Payments Sunshine Act. The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or transfers of value made to physicians, other healthcare providers and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members. • Price Reporting Laws. Certain federal and state laws including U.S. federal government price reporting laws, which require manufacturers to calculate and report complex pricing metrics in an accurate and timely manner to government programs. • Analogous State and Foreign Laws. Analogous state and foreign fraud and abuse laws and regulations, such as state anti-kickback and false claims laws, can apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors and are generally broad and are enforced by many different federal and state agencies as well as through private actions. Pricing and rebate programs must also comply with the Medicaid rebate requirements of the U.S. Omnibus Budget Reconciliation Act of 1990 and more recent requirements in the Affordable Care Act. If products are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. Manufacturing, sales, promotion and other activities also are potentially subject to federal and state consumer protection and unfair competition laws. In addition, the distribution of pharmaceutical products is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products. Federal and state consumer protection laws are increasingly being applied by the FTC and states’ attorneys general to regulate the collection, use, storage and disclosure of personal or personally identifiable information, through websites or otherwise, and to regulate the presentation of website content. The FTC has authority to initiate enforcement actions against entities that mislead customers about HIPAA compliance, make deceptive statements about privacy and data sharing in privacy policies, fail to limit third-party use of personal health information, fail to implement policies to protect personal health information or engage in other unfair practices that harm customers or that may violate Section 5(a) of the FTCA, and has brought enforcement actions against companies in the healthcare space in recent years. As a result of regulatory enforcement proceedings, we may be subject to related litigation, settlements or enforcement actions that could include monetary penalties and/or compliance requirements. Many states have laws that protect the privacy and security of sensitive and personal information, including health information, to which BBOT is subject. These laws may be similar to or even more protective than HIPAA and other federal privacy laws. For example, the California Consumer Privacy Act (the “CCPA”) and similar consumer privacy laws in a number of states establish privacy frameworks for covered businesses, including broad definitions of regulated personal information, data privacy rights for consumers residing in the relevant state, special rules on the collection of consumer data from minors, and an enforcement framework for violations and for businesses that fail to implement reasonable security procedures and practices to prevent data breaches. Many of the state laws 35 Table of Contents differ from each other and cover personal information other than protected health information subject to HIPAA, thus complicating compliance efforts and potentially requiring BBOT to incur additional costs and expenses to comply. Furthermore, certain consumer health privacy laws, such as Washington’s My Health My Data Act, which became effective on March 31, 2024 and contains a private right of action, further increase compliance risks and costs. Connecticut and Nevada have also passed similar laws regulating consumer health data. In addition, other states have proposed and/or passed legislation that regulates the privacy and/or security of certain specific types of information. For example, states such as Illinois and Texas have passed laws that regulate biometric data specifically, and enforcement and litigation surrounding such laws has resulted in significant penalties, settlements and awards. The failure to comply with any of these laws or regulatory requirements subjects firms to possible legal or regulatory action. Depending on the circumstances, failure to meet applicable regulatory requirements can result in significant civil, criminal and administrative penalties, including damages, fines, disgorgement, imprisonment, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings, injunctions, requests for recall, seizure of products, total or partial suspension of production, denial or withdrawal of product approvals or refusal to allow a firm to enter into supply contracts, including government contracts. U.S. Patent-Term Restoration and Marketing Exclusivity Depending upon the timing, duration and specifics of FDA approval of any future product candidates, some of our U.S. patents, if issued, may be eligible for limited patent term extension under the Hatch-Waxman Act. The Hatch-Waxman Act permits restoration of the patent term of up to five years as compensation for patent term lost during product development and FDA regulatory review process. Patent-term restoration, however, cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. The patent-term restoration period is generally one-half the time between the effective date of an IND or the issue date of the patent, whichever is later, and the submission date of an NDA plus the time between the submission date of an NDA or the issue date of the patent, whichever is later, and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence. Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. In the future, we may apply for restoration of patent term for our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant NDA. Market exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the U.S. to the first applicant to gain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an abbreviated new drug application (“ANDA”), or a 505(b)(2) NDA submitted by another company for a generic version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement. The FDCA also provides three years of marketing exclusivity for an NDA, 505(b) (2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active agent. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA by another applicant. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness or generate such data themselves. European Union Drug Development Similar to the United States, the various phases of preclinical and clinical research in the European Union are subject to significant regulatory controls. The EU Clinical Trials Directive has been repealed by the Clinical Trials Regulation (EU) No. 536/2014 (“ EU Clinical Trials Regulation ”), which became applicable on 31 January 2022. The EU Clinical Trials Regulation harmonizes the processes for assessment and supervision of clinical trials throughout the EU. The EU Clinical Trials Regulation enables sponsors to submit one online application via a single online platform known as the Clinical Trials Information System (CTIS) for approval to run a clinical trial in several EU Member States, making it more efficient to carry out such multinational trials and for EU Member States to evaluate and authorize such applications together, via the CTIS. 36 Table of Contents Other key benefits of the EU Clinical Trials Regulation include: • improving information-sharing and collective decision-making on clinical trials; • increasing transparency of information on clinical trials; • ensuring high standards of safety for all participants in EU clinical trials. For clinical trials conducted in the EU, sponsors must report suspected unexpected serious adverse reactions through the EudraVigilance system. European Union Drug Review and Approval In the European Economic Area (“ EEA ”), which comprises the Member States of the European Union and three European Free Trade Association States (Norway, Iceland and Liechtenstein), medicinal products can only be commercialized after obtaining a marketing authorization (“ MA ”). There are two types of MAs. • The centralized MA is issued by the European Commission through the centralized procedure, based on the opinion of the Committee for Medicinal Products for Human Use, of the EMA, and is valid throughout the entire territory of the EEA. The centralized procedure is mandatory for certain types of products,such as biotechnology medicinal products, orphan medicinal products, advanced-therapy medicines such as gene-therapy, somatic cell-therapy or tissue-engineered medicines and medicinal products containing a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions and viral diseases. The centralized procedure is optional for products containing a new active substance not yet authorized in the EU, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU. • National MAs, which are issued by the competent authorities of the Member States of the EU and only cover their respective territory, are available for products not falling within the mandatory scope of the centralized procedure. Where a product has already been authorized for marketing in a Member State of the EU, this national MA can be recognized in other EU Member States through the mutual recognition procedure. If the product has not received a national MA in any EU Member State at the time of application, it can be approved simultaneously in various EU Member States through the decentralized procedure. Under the above-described procedures, before granting the MA, the EMA or the competent authorities of the Member States of the EU make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy. Data and Marketing Exclusivity In the EU, new products authorized for marketing, or reference products, qualify for eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization. The data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until 10 years have elapsed from the initial authorization of the reference product in the EU. The 10-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those 10 years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. Orphan Designation In the EU, a medicinal product can be designated as an orphan drug if its sponsor can establish that the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the EU when the application is made, or that the product is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the EU and that, without incentives, it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment in development. For either of these conditions, the applicant must demonstrate that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the EU or, if such method exists, the drug will be of significant benefit to those affected by that condition. 37 Table of Contents In the EU, an application for designation as an orphan product can be made any time prior to the filing of an application for approval to market the product. Marketing authorization for an orphan drug leads to a 10-year period of market exclusivity. During this market exclusivity period, the EMA or the EU Member State competent authorities, cannot accept another application for a marketing authorization, or grant a marketing authorization, for a similar medicinal product for the same indication as the authorized orphan product. The period of market exclusivity may be extended by two years for orphan medicines that have also complied with an agreed pediatric investigational plan. This period may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example because the product is sufficiently profitable not to justify market exclusivity. In very select cases a marketing authorization may be granted to a similar medicinal product for the same indication as an authorized orphan product during the market exclusivity period, such as where there is consent from the marketing authorization holder for the authorized orphan product, inability to supply sufficient quantities of the authorized orphan product, or demonstration of “clinical superiority” by a similar medicinal product to the authorized orphan product. Medicinal products designated as orphan products are eligible for incentives made available by the EU and its Member States to support research into, and the development and availability of, orphan products. All of the aforementioned EU rules are generally applicable in the EEA. The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children). In April 2024, the European Parliament adopted its position on the legislative proposals and, in June 2025, the Council of the European Union adopted its position. A common position on the text has been agreed upon on December 11, 2025, in the context of subsequent inter-institutional trilogue negotiations. The proposed revisions remain to be adopted, and are not expected to become applicable before 2028. Coverage and Reimbursement Sales of our products, if approved, will depend, in part, on the extent to which our products will be covered by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations. There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products. In the U.S., for example, principal decisions about reimbursement for new products are typically made by CMS. CMS decides whether and to what extent a new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding coverage and reimbursement to a substantial degree. However, no uniform policy of coverage and reimbursement for drug products exists. Accordingly, decisions regarding the extent of coverage and amount of reimbursement to be provided for any of our products will be made on a payor-by-payor basis. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Further, such payors are increasingly challenging the price, examining the medical necessity and reviewing the cost effectiveness of medical product candidates. There may be especially significant delays in obtaining coverage and reimbursement for newly approved drugs. Third-party payors may limit coverage to specific product candidates on an approved list, known as a formulary, which might not include all FDA -approved drugs for a particular indication. We may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost effectiveness of our products. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be obtained. Additionally, coverage policies and third party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (“ MMA ”), established the Medicare Part D program to provide a voluntary prescription drug benefit to Medicare beneficiaries. Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities that provide coverage of outpatient prescription drugs. Unlike Medicare Part A and B, Part D coverage is not standardized. While all Medicare drug plans must give at least a standard level of coverage set by Medicare, Part D prescription drug plan sponsors are not required to pay for all covered Part D drugs, and each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level. However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. Any formulary used by a Part D prescription drug plan must be developed and reviewed by a pharmacy and therapeutic committee. Government payment for some of the costs of prescription drugs may increase demand for products for which we receive marketing approval. However, any negotiated prices for our products covered by a Part D prescription drug plan likely will be lower than the prices we might otherwise obtain. Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private third-party payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. 38 Table of Contents In addition, in case a drug product needs companion diagnostics, then companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, will apply to companion diagnostics. In addition, in most foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from country to country. For example, the EU provides options for its Member States to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. An EU Member State may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, products launched in the European Union do not follow price structures of the U.S. and generally prices tend to be significantly lower. Healthcare Reform The U.S. government, state legislatures and foreign governments have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price-controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs. For example, the Affordable Care Act substantially changed the way healthcare is financed by both the government and private insurers, and continues to significantly impact the U.S. pharmaceutical industry. The Affordable Care Act contains provisions that may reduce the profitability of drug products through increased rebates for drugs reimbursed by Medicaid programs, extension of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries and annual fees based on pharmaceutical companies’ share of sales to federal healthcare programs. The Medicaid Drug Rebate Program requires pharmaceutical manufacturers to enter into and have in effect a national rebate agreement with the HHS as a condition for states to receive federal matching funds for the manufacturer’s outpatient drugs furnished to Medicaid patients. The Affordable Care Act made several changes to the Medicaid Drug Rebate Program, including increasing pharmaceutical manufacturers’ rebate liability by raising the minimum basic Medicaid rebate on most branded prescription drugs from 15.1% of average manufacturer price (“ AMP ”), to 23.1% of AMP and adding a new rebate calculation for “line extensions” (i.e., new formulations, such as extended release formulations) of solid oral dosage forms of branded products, as well as potentially impacting their rebate liability by modifying the statutory definition of AMP. The Affordable Care Act also expanded the universe of Medicaid utilization subject to drug rebates by requiring pharmaceutical manufacturers to pay rebates on Medicaid managed care utilization and by enlarging the population potentially eligible for Medicaid drug benefits. Additionally, for a drug product to receive federal reimbursement under the Medicaid or Medicare Part B programs or to be sold directly to U.S. government agencies, the manufacturer must extend discounts to entities eligible to participate in the 340B drug pricing program. The required 340B discount on a given product is calculated based on the AMP and Medicaid rebate amounts reported by the manufacturer. Other legislative changes have been proposed and adopted in the U.S. since the Affordable Care Act was enacted. These changes included the U.S. Budget Control Act of 2011, which among other things, included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, effective April 1, 2013, which, due to subsequent legislative amendments, will stay in effect through 2031 unless additional congressional action is taken. The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. The American Rescue Plan Act of 2021 eliminates the statutory Medicaid drug rebate cap, currently previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024. Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers will be further reduced starting in 2025 absent further legislation. The Inflation Reduction Act of 2022 (the “ IRA ”) also was signed into law in August 2022. The IRA, in part, creates a $2,000 out-of-pocket cap for Medicare Part D beneficiaries, imposes new manufacturer financial liability on all drugs in Medicare Part D, allows the U.S. government to negotiate Medicare Part B and Part D pricing for certain high-cost drugs and biologics without generic or biosimilar competition, requires companies to pay rebates to Medicare for drug prices that increase faster than inflation, and delays the rebate rule that would require pass through of pharmacy benefit manager rebates to beneficiaries. The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program. The effect of IRA on our business and the healthcare industry in general is not yet known. Overall, these new laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our drugs, if approved, and accordingly, our financial operations. With respect to drug pricing reforms proposed by the Trump Administration, CMS released two proposed rules on December 19, 2025 that would introduce most-favored-nation (“ MFN ”) pricing principles into Medicare drug reimbursement. The first proposal, the Global Benchmark for Efficient Drug Pricing Model (“ GLOBE ”) for Medicare Part B, would require manufacturers of specified single source drugs and sole source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting certain spending and eligibility criteria established by CMS. The second proposal, the Guarding U.S. Medicare Against Rising Drug Costs (“ GUARD ”) model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole 39 Table of Contents source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies. As proposed, GLOBE would begin a five-year performance period on October 1, 2026 and GUARD would begin its performance period in 2027. These proposals are likely to face legal challenges that could delay or modify their implementation. Separately, in November 2025, CMS introduced the Generating Cost Reductions For U.S. Medicaid (“ GENEROUS ”) Model, a voluntary MFN-based framework for manufacturers participating in the Medicaid Drug Rebate Program. While participation is optional, the GENEROUS Model could nonetheless influence manufacturer pricing strategies and the broader drug pricing landscape. Additionally, there has been heightened governmental scrutiny recently over the manner in which drug manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for drug products. At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. It is possible that additional governmental action is taken, which may impact our business. We are unable to predict the future course of federal or state healthcare legislation in the U.S. directed at broadening the availability of healthcare and containing or lowering the cost of healthcare. These and any further changes in the law or regulatory framework that reduce our revenue or increase our costs could also have a material and adverse effect on our business, financial condition and results of operations. Facilities Our principal executive office is located in South San Francisco, California, where we lease approximately 11,000 square feet of combined office and lab space under a lease that terminates in April 2030. We believe that these existing facilities will be adequate for our current needs and that suitable additional or alternative space will be available in the future on commercially reasonable terms, if required. Human Capital As of December 31, 2025, we had 92 employees. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good. We recognize that attracting, motivating and retaining talent at all levels is vital to our continued success. Our employees are a significant asset and we aim to create an environment that is equitable, inclusive and representative in which our employees can grow and advance their careers, with the overall goal of developing, expanding and retaining our workforce to support our current pipeline and future business goals. By focusing on employee retention and engagement, we also improve our ability to support our clinical-stage platform, business and operations, and also protect the long-term interests of our securityholders. Our success also depends on our ability to attract, engage and retain a diverse group of employees. Our efforts to recruit and retain a diverse and passionate workforce include providing competitive compensation and benefits packages and ensuring we listen to our employees. We value agility, passion and teamwork, and are building a diverse environment where our employees can thrive and one that inspires exceptional contributions and professional and personal development in order to achieve our mission to significantly change the practice of oncology. Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our Company by motivating such individuals to perform to the best of their abilities and achieve our objectives. We are committed to providing a competitive and comprehensive benefits package to our employees. Our benefits package provides a balance of protection along with the flexibility to meet the individual health and wellness needs of our employees. We plan to continue to develop our efforts related to attracting, retaining and motivating our workforce as we grow and develop and hire more employees. 40 Table of Contents Corporate and Other Information Our business was established in August 2016 by BridgeBio Pharma Inc. (“ BridgeBio Pharma ”) under the name, TheRas, Inc. (“ Legacy BBOT ”). We operated as part of BridgeBio Pharma through April 30, 2024. Legacy BBOT entered into a definitive business combination agreement (“ Business Combination Agreement ”) with Helix Acquisition Corp. II, a publicly traded special purpose acquisition company (“ Helix ”) listed on Nasdaq under the ticker symbol “HLXB.” On August 11, 2025 (the “ Closing” ), Helix II Merger Sub, Inc., a wholly owned subsidiary of Helix, merged with and into Legacy BBOT, with Legacy BBOT surviving the merger as a wholly-owned subsidiary of Helix (“ Merger ”). In connection with the Merger, Helix changed its name to BridgeBio Oncology Therapeutics, Inc., and the combined company became listed on Nasdaq under the new ticker symbol “BBOT” (“ de-SPAC Transaction ”). Our principal executive offices are located at 256 E. Grand Avenue, Suite 104, South San Francisco, CA 94080. Our telephone number is (650) 405-4770. Our web page address is https://bbotx.com . Our investor relations website is located at https://investors.bbotx.com . We make available free of charge on our investor relations website under “SEC Filings” our Annual Reports on Form 10‑K, Quarterly Reports on Form 10‑Q, Current Reports on Form 8‑K, including exhibits, our directors’ and officers’ Section 16 Reports and any amendments to those reports after filing or furnishing such materials to the SEC. References to our website address do not constitute incorporation by reference of the information contained on the website, and the information contained on the website is not part of this document or any other document that we file with or furnish to the SEC. 41 Table of Contents Ite m 1A. Risk Factors. Investing in our common stock involves a high degree of risk. You should carefully read and consider all of the risks described below, as well as the other information in this Form 10-K, including our consolidated financial statements and the related notes and the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” and in other documents we file with the SEC when evaluating our business. The occurrence of any of the events or developments described below could harm our business, financial condition, results of operations and growth prospects. Unless otherwise indicated, references to our business being harmed in these risk factors will include harm to our business, reputation, financial condition, results of operations and future prospects. In such an event, the market price of our common stock could decline, and you may lose all or part of your investment. The risks described below are not intended to be exhaustive and are not the only risks that we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial also may impair our business operations and the market price of our common stock. Risks Related to BBOT’s Financial Position and Need for Additional Capital BBOT has a limited operating history, has not completed any clinical trials, has no products approved for commercial sale and has not generated any revenue, which may make it difficult for investors to evaluate BBOT’s current business and likelihood of success and viability. BBOT is a biopharmaceutical company with a limited operating history upon which investors can evaluate its business and prospects. BBOT was incorporated in August 2016 and commenced significant operations as an independent entity starting in May 2024, has never completed a clinical trial, has no products approved for commercial sale and has never generated any revenue. Drug development is a highly uncertain undertaking and involves a substantial degree of risk. To date, BBOT has devoted substantially all of its resources to research and development activities, including with respect to BBO-8520, BBO-10203 and BBO-11818, and its discovery programs, business planning, establishing and maintaining its intellectual property portfolio, hiring personnel, raising capital and providing general and administrative support for these operations. BBOT has not yet demonstrated its ability to successfully complete clinical trials, obtain marketing approvals, manufacture a commercial-scale product or arrange for a third party to do so on its behalf, or conduct sales and marketing activities necessary for successful product commercialization. As a result, it may be more difficult for investors to evaluate BBOT’s likelihood of success and viability. In addition, BBOT may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors and risks frequently experienced by biopharmaceutical companies at BBOT’s stage of development in rapidly evolving fields. BBOT also expects that, as BBOT advances its product candidates, BBOT will need to transition from a company with a research and development focus to a company capable of supporting commercial activities. BBOT has not yet demonstrated an ability to successfully overcome such risks and difficulties, or to make such a transition. If BBOT does not adequately address these risks and difficulties or successfully make such a transition, its business will suffer. BBOT has incurred significant net losses in each period since its inception, and expects to continue to incur significant net losses for the foreseeable future. BBOT incurred significant net losses in each reporting period since its inception, has not generated any revenue to date and has financed its operations principally through private placements of securities. BBOT’s net losses for the years ended December 31, 2025 and 2024 were $134.0 million and $74.3 million, respectively. As of December 31, 2025, BBOT had an accumulated deficit of $356.6 million. BBOT has not yet completed any clinical trials. As a result, BBOT expects that it will be several years, if ever, before BBOT generates revenue from product sales. Even if BBOT succeeds in receiving marketing approval for and commercializing one or more product candidates, BBOT expects that it will continue to incur substantial research and development and other expenses in order to discover, develop and market additional potential products. BBOT expects to continue to incur significant and increasing expenses and increasing operating losses for the foreseeable future. The net losses BBOT incurs may fluctuate significantly from quarter to quarter such that a period-to-period comparison of BBOT’s results of operations may not be a good indication of future performance. The size of future net losses will depend, in part, on the pace of development activities and the rate of future growth of expenses and BBOT’s ability to generate revenue. BBOT’s prior losses and expected future losses have had and will continue to have an adverse effect on working capital, BBOT’s ability to fund the development of its product candidates and its ability to achieve and maintain profitability and the performance of its stock. 42 Table of Contents BBOT’s ability to generate revenue and achieve profitability depends significantly on its ability to achieve its objectives relating to the discovery, development and commercialization of its product candidates. BBOT relies on its team’s expertise in chemistry, structure-based drug design, oncology drug development, business development and patient-driven approach to develop its product candidates. BBOT’s business depends significantly on the success of its approach and the development and commercialization of the product candidates that BBOT discovers with this approach. BBOT has no products approved for commercial sale and does not anticipate generating any revenue from product sales for the next several years, if ever. BBOT’s ability to generate revenue and achieve profitability depends significantly on its ability to achieve several objectives, including: • successful and timely completion of preclinical and clinical development of BBO-8520, BBO-10203, BBO-11818 and any future product candidates from BBOT’s discovery program • maintaining current and establishing new relationships with contract research organizations (“ CROs ”) and clinical sites for the clinical development of BBO-8520, BBO-10203, BBO-11818 and any future product candidates from BBOT’s current or future discovery programs; • timely receipt of marketing approvals from applicable regulatory authorities for any product candidates for which BBOT successfully completes clinical development; • developing an efficient and scalable manufacturing process for BBOT’s product candidates, including the production of finished products that are appropriately packaged for sale if BBOT’s product candidates obtain marketing approvals; • maintaining current and establishing new commercially viable supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and meet the market demand for BBOT’s product candidates, if approved; • successful commercial launch following any marketing approval, including the development of a commercial infrastructure, whether in-house or with one or more collaborators; • maintaining an acceptable safety profile following any marketing approval of BBOT’s product candidates; • commercial acceptance of BBOT’s product candidates by patients, the medical community and third- party payors, including the willingness of physicians to use BBOT’s product candidates, if approved, in lieu of (or in conjunction with) other approved therapies; • satisfying any required post-marketing approval commitments to applicable regulatory authorities; • identifying, assessing and developing new product candidates; • obtaining, maintaining and expanding patent protection, trade secret protection and regulatory exclusivity, both in the U.S. and internationally; • defending against third-party interference or infringement claims, if any, with respect to BBOT’s intellectual property rights; • entering into, on favorable terms, any collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize BBOT’s product candidates; • obtaining coverage and adequate reimbursement by third-party payors for BBOT’s product candidates, if approved; • addressing any competing therapies and technological and market developments; and • attracting, hiring and retaining qualified personnel. BBOT may never be successful in achieving its objectives and, even if it does, may never generate revenue that is significant or large enough to achieve profitability. If BBOT does achieve profitability, BBOT may not be able to sustain or increase profitability on a quarterly or annual basis. BBOT’s failure to become and remain profitable would decrease the value of the company and could impair BBOT’s ability to maintain or further its research and development efforts, raise additional necessary capital, grow its business and continue its operations. BBOT may require additional capital to finance its operations. If BBOT is unable to raise such capital when needed, or on acceptable terms, BBOT may be forced to delay, reduce or eliminate one or more of its research and drug development programs, future commercialization efforts, product development or other operations. Since inception, BBOT has used substantial amounts of cash to fund its operations, and its expenses will increase substantially in the foreseeable future in connection with its ongoing activities, particularly as BBOT continues the research and development of, initiates additional clinical trials of, and seeks marketing approval for, its product candidates. Developing pharmaceutical products, including 43 Table of Contents conducting preclinical studies and clinical trials, is a very time-consuming, expensive and uncertain process that takes years to complete. Even if one or more of BBOT’s product candidates or any future product candidates that BBOT develops is approved for commercial sale, BBOT anticipates incurring significant costs associated with sales, marketing, manufacturing and distribution activities. BBOT’s expenses could increase beyond expectations if BBOT is required by the FDA, the EMA or other regulatory authorities to perform clinical trials or preclinical studies in addition to those that BBOT currently anticipates. Other unanticipated costs may also arise. Because the design and outcome of BBOT’s clinical trials, including its planned and anticipated clinical trials, are highly uncertain, BBOT cannot reasonably estimate the actual amount of resources and funding that will be necessary to successfully complete the development and commercialization of its product candidates or any future product candidates that it develops. BBOT is currently conducting Phase 1 clinical trials of BBO-8520, BBO-10203 and BBO-11818. BBOT is not permitted to market or promote any product candidate before it receives marketing approval from the FDA, EMA or any comparable foreign regulatory authorities. BBOT is also incurring additional costs associated with operating as a public company. Accordingly, BBOT may need to obtain additional funding in order to continue its operations. BBOT estimates that its existing cash, cash equivalents and short-term marketable securities as of the date of this report will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into early 2028. Advancing the development of BBO-8520, BBO-10203 and BBO-11818 and BBOT’s discovery programs will require a significant amount of capital. BBOT’s existing cash, cash equivalents and marketable securities will not be sufficient to fund all of BBOT’s product candidates through regulatory approval, and BBOT may need to raise additional capital to complete the development and commercialization of its product candidates. BBOT’s estimate as to how long it expects its existing cash, cash equivalents and marketable securities to fund its operations does not include potential product revenue and is based on assumptions that may prove to be wrong, and BBOT could use its available capital resources sooner than currently expected. Changing circumstances, some of which may be beyond BBOT’s control, could cause BBOT to consume capital significantly faster than currently anticipated, and BBOT may need to seek additional funds. BBOT may be required to obtain further funding through public or private equity financings, debt financings, collaborative agreements, licensing arrangements or other sources of financing, which may dilute BBOT’s stockholders or restrict its operating activities. BBOT does not have any committed external source of funds. Adequate additional financing may not be available to BBOT on acceptable terms, or at all. BBOT’s ability to raise additional funds may be adversely impacted by general economic conditions, both inside and outside the U.S., including disruptions to, and instability and volatility in, the credit and financial markets in the U.S. and worldwide, including heightened inflation, interest rate and currency rate fluctuations, and economic slowdown or recession as well as concerns related to public health emergencies, natural disasters or geopolitical events, including civil or political unrest or military conflicts. In addition, market instability and volatility, high levels of inflation and interest rate fluctuations may increase BBOT’s cost of financing or restrict BBOT’s access to potential sources of future liquidity. To the extent that BBOT raises additional capital through the sale of equity or convertible debt securities, each investor’s ownership interests will be diluted, and the terms may include liquidation or other preferences that adversely affect each investor’s rights as a stockholder. Debt financing may result in imposition of debt covenants, increased fixed payment obligations or other restrictions that may affect BBOT’s business. If BBOT raises additional funds through upfront payments or milestone payments pursuant to strategic collaborations with third parties, BBOT may have to relinquish valuable rights to its product candidates or grant licenses on terms that are not favorable to BBOT. In addition, BBOT may seek additional capital due to favorable market conditions or strategic considerations even if BBOT believes it has sufficient funds for its current or future operating plans. BBOT’s failure to raise capital as and when needed or on acceptable terms would have a negative impact on its financial condition and its ability to pursue its business strategy, and BBOT may have to delay, reduce the scope of, suspend or eliminate one or more of its research or drug development programs, clinical trials or future commercialization efforts. Risks Related to BBOT’s Product Development, Regulatory Approval and Commercialization BBOT’s future prospects are substantially dependent on the advancement of its product candidates. If BBOT is unable to advance its product candidates through development, obtain regulatory approval and ultimately commercialize such product candidates, or experience significant delays in doing so, BBOT’s business will be materially harmed. BBOT is currently conducting Phase 1 clinical trials of BBO-8520, BBO-10203 and BBO-11818. BBOT’s ability to generate product revenue, which BBOT does not expect will occur for many years, if ever, will depend heavily on the successful clinical development and eventual commercialization of one or more product candidates. BBOT is not permitted to market or promote any product candidate before BBOT receives marketing approval from the FDA, EMA or any comparable foreign regulatory authorities, and BBOT may never receive such marketing approvals. 44 Table of Contents The success of BBOT’s product candidates will depend on several factors, including the following: • successful and timely completion of preclinical studies; • submission of INDs in the U.S. and CTAs and/or comparable applications outside the U.S. for regulatory authority review and agreement to proceed with BBOT’s clinical trials; • successful initiation and completion of clinical trials; • successful and timely patient selection and enrollment in and completion of clinical trials; • maintaining and establishing relationships with CROs and clinical sites for the clinical development of BBOT’s product candidates both in the U.S. and internationally; • maintaining and growing an organization of scientific, medical and other professionals who can develop and commercialize BBOT’s product candidates; • the frequency and severity of adverse events in clinical trials; • obtaining positive data that support demonstration of efficacy, safety and tolerability profiles and durability of effect for BBOT’s product candidates that are satisfactory to the FDA, EMA or any comparable foreign regulatory authority for marketing approval; • the timely receipt of marketing approvals from applicable regulatory authorities; • the timely identification, development and approval of companion diagnostic tests, if required; • the extent of any required post-marketing approval commitments to applicable regulatory authorities; • the maintenance of existing or the establishment of new supply arrangements with third-party drug product suppliers and manufacturers for clinical development and, if approved, commercialization of BBOT’s product candidates; • obtaining and maintaining patent protection, trade secret protection and regulatory exclusivity, both in the U.S. and internationally; • the protection of BBOT’s rights in its intellectual property portfolio; • establishing sales, marketing and distribution capabilities and the successful launch of commercial sales of BBOT’s product candidates if and when approved for marketing, whether alone or in collaboration with others; • maintaining an acceptable safety profile following any marketing approval; • commercial acceptance by patients, the medical community and third-party payors, including the willingness of physicians to use BBOT’s product candidates, if approved, in lieu of (or in conjunction with) other approved therapies; • BBOT’s ability to compete with other therapies; and • BBOT’s ability to address any potential delays resulting from factors related to public health emergencies, natural disasters or geopolitical events. BBOT does not have complete control over many of these factors, including certain aspects of preclinical and clinical development and the regulatory submission process, potential threats to BBOT’s intellectual property rights and the manufacturing, marketing, distribution and sales efforts of any future collaborator. If BBOT is not successful with respect to one or more of these factors in a timely manner or at all, BBOT could experience significant delays or an inability to successfully commercialize any product candidates from its lead programs, which would materially harm its business. If BBOT does not receive marketing approvals for such product candidates, BBOT may not be able to continue its operations. BBOT’s preclinical studies and clinical trials may fail to adequately demonstrate the safety and efficacy of any of its product candidates, which would prevent or delay development, regulatory approval and commercialization. Before obtaining marketing approval from the FDA, EMA or other comparable foreign regulatory authorities for the sale of BBOT’s product candidates, BBOT must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that its product candidates are both safe and effective for use in each target indication. Preclinical and clinical testing is expensive, difficult to design and implement, can take many years to complete and the ultimate outcome is uncertain. Failure can occur at any time during the preclinical study and clinical trial processes, there is a high risk of failure, and BBOT may never succeed in developing marketable products. 45 Table of Contents BBOT may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent receipt of marketing approval or BBOT’s ability to commercialize its product candidates, including: • failure of BBOT’s product candidates in preclinical studies or clinical trials to demonstrate safety and efficacy; • receipt of feedback from regulatory authorities that requires BBOT to modify the design of its clinical trials; • negative or inconclusive clinical trial results that may require BBOT to conduct additional clinical trials or abandon certain research, discovery and/or drug development programs; • the number of patients required for clinical trials being larger than anticipated, enrollment in these clinical trials being slower than anticipated, particularly if there are other trials enrolling the same or overlapping precisely targeted patient populations, or participants dropping out of these clinical trials at a higher rate than anticipated; • third-party contractors failing to comply with regulatory requirements or meet their contractual obligations to BBOT in a timely manner, or at all; • the suspension or termination of BBOT’s clinical trials for various reasons, including non-compliance with regulatory requirements or a finding that BBOT’s product candidates have undesirable adverse events or other unexpected characteristics or risks; • the cost of clinical trials of BBOT’s product candidates being greater than anticipated; • the supply or quality of BBOT’s product candidates or other materials necessary to conduct clinical trials of BBOT’s product candidates being insufficient or inadequate; and • regulators revising the requirements for approving BBOT’s product candidates. If BBOT is required to conduct additional clinical trials or other testing of its product candidates beyond those that BBOT is currently contemplating, if BBOT is unable to successfully complete clinical trials of its product candidates or other testing in a timely manner, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, BBOT may incur unplanned costs, be delayed in seeking and obtaining marketing approval, if BBOT receives such approval at all, receive more limited or restrictive marketing approval, be subject to additional post-marketing testing requirements or have the drug removed from the market after obtaining marketing approval. BBOT’s discovery and development activities are focused on precision oncology to treat RAS-dependent cancers, which is a rapidly evolving area of science, and the approach BBOT is taking to discover and develop drugs may never lead to approved or marketable products. The discovery and development of precision oncology therapeutics for patients with RAS-dependent cancers is an emerging field, and the scientific discoveries that form the basis for BBOT’s efforts to discover and develop product candidates are evolving. The scientific evidence to support the feasibility of developing product candidates based on these discoveries is both preliminary and limited. Although BBOT believes, based on BBOT’s preclinical work and clinical trials to date, that BBOT’s product candidates can inhibit RAS, clinical results may not confirm this hypothesis or may only confirm it for certain tumor types. The patient populations for BBOT’s product candidates are limited to those with KRAS and PI3Ka mutations and HER2 amplification and may not be completely defined but are substantially smaller than the general treated cancer population, and BBOT will need to screen and identify these targeted patients. Successful identification of patients is dependent on several factors, including evaluation of patient biopsies and blood samples, which may require the use of companion diagnostic tests. Furthermore, even if BBOT is successful in identifying patients, BBOT cannot be certain that the resulting patient populations for each mutation will be large enough to allow BBOT to successfully obtain approval for each mutation type and commercialize BBOT’s product candidates and achieve profitability. BBOT does not know if its approach of focusing on treating patients with RAS-dependent cancers will be successful, and if its approach is unsuccessful, BBOT’s business will suffer. Any delays in the commencement or completion, or any termination or suspension, of BBOT’s current, planned or future clinical trials could result in increased costs to BBOT, delay or limit BBOT’s ability to generate revenue and adversely affect BBOT’s commercial prospects. Before BBOT can initiate clinical trials of any product candidate in any indication, BBOT must submit the results of preclinical studies to the FDA, EMA or other comparable foreign regulatory authorities along with other information, including information about the product candidate’s chemistry, manufacturing and controls and its proposed clinical trial protocol, as part of an IND or similar regulatory submission under which BBOT must receive authorization to proceed with clinical development. The FDA, EMA or other comparable foreign regulatory authorities may require BBOT to conduct additional preclinical studies for any product candidate before they allow BBOT to initiate clinical trials under any IND, CTA or comparable application which may lead to additional delays and increase the costs of BBOT’s preclinical development programs. 46 Table of Contents Before obtaining marketing approval from the FDA of BBO-8520, BBO-10203, BBO-11818 or of any other future product candidate in any indication, BBOT must conduct extensive clinical studies to demonstrate safety and efficacy. Clinical testing is expensive, time consuming and uncertain as to outcome. In addition, BBOT expects to rely in part on preclinical, clinical and quality data generated by BBOT’s CROs and other third parties for regulatory submissions for BBOT’s product candidates. While BBOT has or will have agreements governing these third parties’ services, BBOT has limited influence over their actual performance. If these third parties do not make data available to BBOT, or, if applicable, make regulatory submissions in a timely manner, in each case pursuant to BBOT’s agreements with them, BBOT’s development programs may be significantly delayed and BBOT may need to conduct additional studies or collect additional data independently. In either case, BBOT’s development costs would increase. BBOT is currently conducting Phase 1 clinical trials of BBO-8520, BBO-10203 and BBO-11818. An IND submission must become effective prior to initiating any clinical trials in the U.S. for any of BBOT’s future product candidates. BBOT could also encounter delays if a clinical trial is suspended or terminated by BBOT, by the independent institutional review board (“ IRB ”) or independent ethics committee (“ IEC ”) of the institutions in which such trials are being conducted, by a data safety monitoring board for such trial or by the FDA or foreign regulatory authorities. Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or BBOT’s clinical protocols, inspection of the clinical trial operations or trial site by the FDA or foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse events, failure to demonstrate a benefit from using a pharmaceutical, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. In addition, changes in regulatory requirements and policies may occur, and BBOT may need to amend clinical trial protocols to comply with these changes. Amendments may require BBOT to resubmit its clinical trial protocols to IRBs/IECs for reexamination, which may impact the costs, timing or successful completion of a clinical trial. Further, if BBOT is slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, BBOT’s development plans may be impacted. Certain of BBOT’s current or future scientific advisors or consultants who receive compensation from BBOT may become investigators for BBOT’s future clinical trials. Under certain circumstances, BBOT may be required to report some of these relationships to the FDA. Although BBOT expects any such relationships to be within the FDA’s guidelines, the FDA may conclude that a financial relationship between BBOT and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study. The FDA may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of BBOT’s marketing applications by the FDA and may ultimately lead to the denial of marketing approval of BBOT’s product candidates. If BBOT experiences delays in the completion of, or any termination or suspension of, any clinical trial of any product candidate, the commercial prospects of such product candidate will be harmed, and BBOT’s ability to generate product revenue will be delayed. Moreover, any delays in completing BBOT’s clinical trials will increase BBOT’s costs, slow down BBOT’s development and approval process and jeopardize BBOT’s ability to commence product sales and generate revenue, which may harm BBOT’s business, financial condition, results of operations and prospects significantly. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and the results of BBOT’s clinical trials may not satisfy the requirements of the FDA, EMA or other comparable foreign regulatory authorities. BBOT will be required to demonstrate with substantial evidence through well-controlled clinical trials that BBOT’s product candidates are safe and effective for use in the target population before BBOT can seek marketing approvals for their commercial sale. Preclinical and clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during the preclinical study and clinical trial processes; there is a high risk of failure and BBOT may never succeed in developing marketable products. The results of preclinical studies may not be predictive of the results of clinical trials of BBOT’s product candidates, and the results of early clinical trials may not be predictive of the results of later-stage clinical trials. Although product candidates may demonstrate promising results in preclinical studies and early clinical trials, they may not prove to be safe or effective in subsequent clinical trials. Favorable results from certain animal studies may not accurately predict the results of other animal studies or of human trials, due to the inherent biologic differences in species, the differences between testing conditions in animal studies and human trials, and the particular goals, purposes, and designs of the relevant studies and trials. Similarly, certain of BBOT’s hypotheses regarding the potential clinical and therapeutic benefits of its product candidates compared to other approved products and product candidates or molecules in development are based on observations from the preclinical studies and early clinical trials that BBOT has completed, and results from such preclinical studies and early clinical trials are not necessarily predictive of the results of later preclinical studies or clinical trials. There is typically an extremely high rate of attrition from the failure of product candidates proceeding through preclinical studies and clinical trials. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy profile despite having progressed through preclinical studies and initial clinical trials. Likewise, early, smaller-scale clinical trials may not be predictive 47 Table of Contents of eventual safety or effectiveness in large-scale pivotal clinical trials. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their drugs. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy, insufficient durability of efficacy or unacceptable safety issues, notwithstanding promising results in earlier trials. Most product candidates that commence preclinical studies and clinical trials are never approved as products. The development of BBOT’s product candidates and its stock price may also be impacted by inferences, whether correct or not, that are drawn between the success or failure of preclinical studies or clinical trials of BBOT’s competitors or other companies in the biopharmaceutical industry, in addition to BBOT’s own preclinical studies and clinical trials. In some instances, there can be significant variability in safety and efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial protocols, differences in size and type of the patient populations, differences in and adherence to the dose and dosing regimen and other trial protocols and the rate of dropout among clinical trial participants. Patients treated with BBOT’s product candidates may also be undergoing surgical, radiation and chemotherapy treatments and may be using other approved products or investigational new drugs, which can cause adverse events that are unrelated to BBOT’s product candidates. As a result, assessments of efficacy can vary widely for a particular patient, and from patient to patient and site to site within a clinical trial. This subjectivity can increase the uncertainty of, and adversely impact, BBOT’s clinical trial outcomes. Any preclinical studies or clinical trials that BBOT conducts may not demonstrate the safety and efficacy necessary to obtain regulatory approval to market BBOT’s product candidates. If the results of BBOT’s ongoing or future preclinical studies and clinical trials are inconclusive with respect to the safety and efficacy of BBOT’s product candidates, if BBOT does not meet the clinical endpoints with statistical and clinically meaningful significance, or if there are safety concerns associated with BBOT’s product candidates, BBOT may be prevented or delayed in obtaining marketing approval for such product candidates. BBOT does not know whether any clinical trials BBOT conducts will demonstrate consistent or adequate efficacy and safety sufficient to obtain approval to market any of BBOT’s product candidates. In addition to BBO-8520, BBO-10203 and BBO-11818, BBOT’s prospects depend in part upon discovering, developing and commercializing additional product candidates from BBOT’s discovery programs, which may fail in development or suffer delays that adversely affect their commercial viability. BBOT’s future operating results are dependent on its ability to successfully discover, develop, obtain regulatory approval for and commercialize BBO-8520, BBO-10203 and BBO-11818 and future product candidates from BBOT’s discovery programs. A research candidate can unexpectedly fail at any stage of development. The historical failure rate for research candidates is high due to risks relating to safety, efficacy, clinical execution, changing standards of medical care and other unpredictable variables. The results from preclinical testing or early clinical trials of a product candidate may not be predictive of the results that will be obtained in later stage clinical trials of the product candidate. The success of other research candidates that BBOT may develop will depend on many factors, including the following: • generating sufficient data to support the initiation or continuation of preclinical studies and clinical trials; • obtaining regulatory permission to initiate clinical trials; • contracting with the necessary parties to conduct clinical trials; • successful enrollment of patients in, and the completion of, clinical trials on a timely basis; • the timely manufacture of sufficient quantities of a product candidate for use in clinical trials; • adverse events in clinical trials; and • addressing any delays resulting from factors related to public health emergencies, natural disasters or geopolitical events. Even if BBOT successfully advances any research candidates into preclinical and clinical development, their success will be subject to all of the preclinical, clinical, regulatory and commercial risks described elsewhere in this “Risk Factors” section. Accordingly, there can be no assurance that BBOT will ever be able to discover, develop, obtain regulatory approval of, commercialize or generate significant revenue from any product candidates. 48 Table of Contents BBOT’s approach to the discovery and development of product candidates is unproven, and BBOT may not be successful in its efforts to use and expand its approach to build a pipeline of product candidates with commercial value. A key element of BBOT’s strategy, which is unproven, is to use and expand BBOT’s expertise in chemistry, structure-based drug design and patient-driven approach to build a pipeline of product candidates and progress these product candidates through clinical development. Although BBOT’s research and development efforts to date have resulted in the discovery of and initiation of clinical development of BBO-8520, BBO-10203 and BBO-11818, such product candidates and any other product candidates BBOT may develop may not be determined to be safe or effective as cancer therapeutics, and BBOT may not be able to develop any other product candidates. For example, the potential product candidates that BBOT has identified or identifies in the future may not generate acceptable clinical data, including as a result of being shown to have unacceptable toxicity or other characteristics that indicate that they are unlikely to be product candidates that will receive marketing approval from the FDA, EMA or other regulatory authorities or achieve market acceptance. If BBOT does not successfully develop and commercialize product candidates, BBOT will not be able to generate product revenue in the future, which would result in significant harm to BBOT’s financial position and adversely affect its business. The regulatory approval processes of the FDA, EMA and other comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable. If BBOT is ultimately unable to obtain regulatory approval of its product candidates, BBOT will be unable to generate product revenue and its business will be substantially harmed. Obtaining approval by the FDA, EMA and other comparable foreign regulatory authorities is unpredictable, typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the type, complexity and novelty of the product candidates involved. In addition, approval policies, regulations or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, which may cause delays in the approval or the decision not to approve an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that BBOT’s data are insufficient for approval and require additional preclinical, clinical or other data. In addition, the U.S. Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies and decisions may become subject to increasing legal challenges, delays, and/or changes. Even if BBOT eventually completes clinical testing and receives approval for its product candidates, the FDA, EMA and other comparable foreign regulatory authorities may approve BBOT’s product candidates for a more limited indication or a narrower patient population than BBOT originally requested or may impose other prescribing limitations or warnings that limit the product candidate’s commercial potential. Even if approved, BBOT may be required to conduct additional studies to or obtained, regulatory approval for any product candidate, and it is possible that none of BBOT’s product candidates will ever obtain regulatory approval. Further, development of BBOT’s product candidates and/or regulatory approval may be delayed for reasons beyond its control. Applications for BBOT’s product candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA, EMA or other comparable foreign regulatory authorities may disagree with the design, implementation or results of BBOT’s clinical trials; • the FDA, EMA or other comparable foreign regulatory authorities may determine that BBOT’s product candidates are not safe and effective, are only moderately effective or have undesirable or unintended adverse events, toxicities or other characteristics that preclude BBOT obtaining marketing approval or prevent or limit commercial use; • the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which BBOT seeks approval; • the FDA, EMA or other comparable foreign regulatory authorities may disagree with BBOT’s interpretation of data from preclinical studies or clinical trials; • the clinical data of the clinical trial may fail to meet the level of statistical significance required to obtain approval of BBOT’s product candidates by the FDA, EMA or other comparable foreign regulatory authorities; • BBOT may be unable to demonstrate to the FDA, EMA or other comparable foreign regulatory authorities that BBOT’s product candidates’ risk-benefit ratios for their proposed indications are acceptable; • the FDA, EMA or other comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications or facilities of third-party manufacturers with which BBOT contracts for clinical and commercial supplies; • the FDA, EMA or other comparable regulatory authorities may fail to approve companion diagnostic tests required for BBOT’s product candidates; 49 Table of Contents • BBOT may not obtain or maintain adequate funding to complete its clinical trials in a manner that is satisfactory to the FDA, EMA or other comparable foreign regulatory authorities; and • the approval policies or regulations of the FDA, EMA or other comparable foreign regulatory authorities may significantly change in a manner rendering BBOT’s clinical data insufficient for approval. This lengthy approval process, as well as the unpredictability of the results of clinical trials, may result in BBOT failing to obtain regulatory approval to market any of its product candidates, which would significantly harm BBOT’s business, results of operations and prospects. BBOT may not be able to submit INDs, CTAs or comparable applications to commence clinical trials on the timelines BBOT expects, and even if BBOT is able to, the FDA, EMA or any comparable foreign regulatory authority may not permit BBOT to proceed. BBOT’s research and development efforts to date have resulted in the initiation of clinical development of BBO-8520, BBO-10203 and BBO-11818. BBOT may not be able to submit INDs for any future product candidates it may identify on the timelines it expects, or such submissions may not take effect on the timeline that BBOT anticipates, or at all. For example, BBOT may experience manufacturing delays or other delays with IND-enabling studies. Moreover, BBOT cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that could cause BBOT or regulatory authorities to suspend or terminate clinical trials. Additionally, even if the FDA agrees with the design and implementation of the clinical trials set forth in an IND, BBOT cannot guarantee that the FDA will not change its requirements in the future. These considerations also apply to new clinical trials BBOT may submit as amendments to existing INDs or to a new IND. Any failure to submit INDs, CTAs or comparable applications on the timelines BBOT expects or to obtain regulatory approvals for BBOT’s planned clinical trials may prevent BBOT from initiating or completing its clinical trials or commercializing its product candidates on a timely basis, if at all. BBOT’s product candidates may cause significant adverse events, toxicities or other undesirable adverse events when used alone or in combination with other approved products or investigational new drugs that may result in a safety profile that could prevent regulatory approval, prevent market acceptance, limit their commercial potential or result in significant negative consequences. If BBOT’s product candidates are associated with undesirable adverse events or have unexpected characteristics in preclinical studies or clinical trials when used alone or in combination with other approved products or investigational new drugs, BBOT may need to interrupt, delay or abandon their development or limit development to more narrow uses or subpopulations in which the undesirable adverse events or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective. Treatment-related adverse events could also affect patient recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. Any of these occurrences may prevent BBOT from achieving or maintaining market acceptance of the affected product candidate and may harm BBOT’s business, financial condition and prospects significantly. There have been, and it is likely that there will be additional, adverse events associated with the use of BBOT’s product candidates as is typically the case with oncology drugs. Results of BBOT’s studies or trials could reveal a high and unacceptable severity and prevalence of these or other adverse events. In such an event, BBOT’s trials could be suspended or terminated and the FDA, EMA or comparable foreign regulatory authorities could order BBOT to cease further development of or deny approval of BBOT’s product candidates for any or all targeted indications. Drug-related adverse events could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harm BBOT’s business, financial condition and prospects significantly. In addition, BBOT’s product candidates may be used in populations for which safety concerns may be particularly scrutinized by regulatory authorities. BBOT’s product candidates may be studied in combination with other therapies, which may exacerbate adverse events associated with the therapy. Patients treated with BBOT’s product candidates may also be undergoing surgical, radiation and chemotherapy treatments, which can cause adverse events that are unrelated to BBOT’s product candidates but may still impact the success of BBOT’s clinical trials. The inclusion of critically ill patients in BBOT’s clinical trials may result in deaths or other adverse medical events due to other therapies or medications that such patients may be using or due to the gravity of such patients’ illnesses. If significant adverse events are observed in any of BBOT’s current or future clinical trials, BBOT may have difficulty recruiting patients to the clinical trials, patients may drop out of BBOT’s trials, or BBOT may be required to abandon the trials or its development efforts of that product candidate altogether. BBOT, the FDA, EMA, other comparable foreign regulatory authorities or an IRB may suspend clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse events. Some potential therapeutics developed in the biotechnology industry that initially showed therapeutic promise in early-stage trials have later been found to cause adverse events that prevented their further development. Even if the adverse events do not preclude the product candidate from obtaining or maintaining marketing approval, undesirable adverse events may inhibit market acceptance due to its tolerability versus other therapies. Any of these developments could materially harm BBOT’s business, financial condition and prospects. Further, if any of BBOT’s product candidates obtain marketing approval, toxicities associated with such product candidates previously not seen during clinical testing may also develop after such approval and lead to a requirement to conduct additional clinical safety trials, additional contraindications, warnings and precautions being added to the drug 50 Table of Contents label, significant restrictions on the use of the product or the withdrawal of the product from the market. BBOT cannot predict whether its product candidates will cause toxicities in humans that would preclude or lead to the revocation of regulatory approval based on preclinical studies or early-stage clinical trials. Interim, preliminary and topline data from BBOT’s preclinical studies and clinical trials that BBOT announces or publishes from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data. BBOT expects to publicly disclose interim, preliminary or topline data from its clinical trials in the future. These interim updates are anticipated to be based on preliminary analyses of then-available data, and the results and related findings and conclusions may be subject to change following a more comprehensive review of the data related to the particular study or trial. For example, BBOT may report responses in certain patients that are unconfirmed at the time and which do not ultimately result in confirmed responses to treatment after follow-up evaluations. BBOT also makes assumptions, estimations, calculations and conclusions as part of its analyses of data, and BBOT may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the interim, preliminary or topline results that BBOT reports may differ from future results of the same studies or trials, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Interim, preliminary and topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the interim, preliminary or topline data previously published. As a result, interim, preliminary and topline data should be viewed with caution until the final data are available. In addition, BBOT may report interim analyses of only certain endpoints rather than all endpoints. Interim, preliminary and topline data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Adverse changes between interim, preliminary or topline data and final data could significantly harm BBOT’s business and prospects. Further, additional disclosure of interim, preliminary or topline data by BBOT or by its competitors in the future could result in volatility in the price of BBOT’s common stock. In addition, the information BBOT chooses to publicly disclose regarding a particular study or trial is typically selected from a more extensive amount of available information. Investors may not agree with what BBOT determines is the material or otherwise appropriate information to include in its public disclosures, and any information BBOT determines not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or BBOT’s business. If the interim, preliminary or topline data that BBOT reports differs from late, final or actual results, or if others, including regulatory authorities, disagree with the conclusions reached, BBOT’s ability to obtain approval for, and commercialize, any of its product candidates may be harmed, which could harm BBOT’s business, financial condition, results of operations and prospects. If BBOT experiences delays or difficulties in the enrollment or maintenance of patients in clinical trials, BBOT’s regulatory submissions or receipt of necessary marketing approvals could be delayed or prevented. BBOT may not be able to initiate or continue clinical trials for its product candidates if BBOT is unable to locate and enroll a sufficient number of eligible patients to participate in these trials to such trial’s conclusion as required by the FDA, EMA or other comparable foreign regulatory authorities. Patient enrollment is a significant factor in the timing of clinical trials. BBOT’s ability to enroll eligible patients may be limited or may result in slower enrollment than anticipated. BBOT utilizes profiling of patients’ tumors to identify suitable patients for recruitment into its clinical trials. For these clinical trials, BBOT seeks patients who carry specific gene mutation or amplification that its product candidates are designed to precisely target. BBOT cannot be certain (i) how many patients will have the requisite mutation or amplification that qualify for inclusion in its clinical trials, (ii) that the number of patients enrolled in each program will suffice for regulatory approval or (iii) if regulatory approval is obtained, whether each specific mutation or amplification will be included in the approved drug label. Additionally, BBOT faces competition, including from large pharmaceutical companies with significantly more resources than BBOT, for enrollment of BBOT’s targeted patient populations, which may impact BBOT’s ability to successfully recruit patients for its clinical trials. If BBOT’s strategies for patient identification and enrollment prove unsuccessful, BBOT may have difficulty enrolling or maintaining patients appropriate for its product candidates. Patient enrollment may be affected if BBOT’s competitors have ongoing clinical trials for programs that are under development for the same indications as BBOT’s product candidates, and patients who would otherwise be eligible for BBOT’s clinical trials instead enroll in clinical trials of its competitors’ programs. Patient enrollment for BBOT’s current or future clinical trials may be affected by other factors, including: • size and nature of the patient population; • severity of the disease under investigation; • availability and efficacy of approved drugs for the disease under investigation; • patient eligibility criteria for the trial in question as defined in the protocol, including biomarker-driven identification and/or certain highly-specific criteria related to stage of disease progression, which may limit the patient populations eligible for 51 Table of Contents BBOT’s clinical trials to a greater extent than competing clinical trials for the same indication that do not have a biomarker-driven patient eligibility criteria; • perceived risks and benefits of the product candidate under study; • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or other product candidates being investigated for the indications BBOT is investigating; • clinicians’ willingness to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in BBOT’s clinical trials; • patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • proximity and availability of clinical trial sites for prospective patients; and • the risk that patients enrolled in clinical trials will drop out of the trials before completion or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials. BBOT’s inability to enroll a sufficient number of patients for its clinical trials would result in significant delays or may require BBOT to abandon one or more clinical trials altogether. Enrollment delays in BBOT’s clinical trials may result in increased development costs for its product candidates and jeopardize its ability to obtain marketing approval for the sale of its product candidates. Furthermore, even if BBOT is able to enroll a sufficient number of patients for its clinical trials, BBOT may have difficulty maintaining participation in its clinical trials through treatment and any follow-up periods. BBOT has limited resources and is currently focusing its efforts on the development of BBO-8520, BBO-10203 and BBO-11818 in particular indications and advancing its discovery programs. As a result, BBOT may fail to capitalize on other indications or product candidates that may ultimately have proven to be more profitable. BBOT is currently focusing its resources and efforts on its lead product candidates, BBO-8520 a KRAS inhibitor for KRASG12C NSCLC, BBO-10203 a PI3Kα:RAS breaker for PIK3CAmut BC, HER2amp BC, KRASmut NSCLC, KRASmut PDAC, and KRASmut CRC, and BBO-11818 a Pan-KRAS inhibitor for KRASG12X NSCLC, KRASG12X PDAC, KRASG12X CRC, and on advancing BBOT’s discovery programs. As a result, because BBOT has limited resources, BBOT may forgo or delay pursuit of opportunities for other indications or with other product candidates that may have greater commercial potential. BBOT’s resource allocation decisions may cause BBOT to fail to capitalize on viable commercial products or profitable market opportunities. BBOT’s spending on current and future research and development activities for BBO-8520, BBO-10203 and BBO-11818 and BBOT’s discovery programs may not yield any commercially viable products. If BBOT does not accurately evaluate the commercial potential or target markets for BBO-8520, BBO-10203 and BBO-11818 or any future product candidates identified through BBOT’s discovery programs, BBOT may enter into collaboration, licensing or other strategic arrangements with the effect of relinquishing valuable rights in cases in which it would have been more advantageous for BBOT to retain sole development and commercialization rights. In addition, given the similar approaches being utilized by BBOT’s lead product candidates, negative developments for one candidate in the pipeline may have negative implications for other candidates in the pipeline. BBOT currently relies on third parties to supply and manufacture preclinical and clinical drug supplies, and BBOT intends to rely on third parties to produce commercial supplies of any approved product, which increases the risk that BBOT will not have sufficient quantities of these product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair BBOT’s development or commercialization efforts. BBOT does not own or operate manufacturing facilities for the production of preclinical, clinical or commercial supplies of the product candidates that BBOT is developing or evaluating in its drug development programs. BBOT has limited personnel with experience in drug manufacturing and lacks the resources and the capabilities to manufacture any of BBOT’s product candidates on a preclinical, clinical or commercial scale. BBOT relies on third parties for supply of its preclinical and clinical drug supplies (including key active pharmaceutical ingredients, or API, drug product, and starting and intermediate materials), and BBOT’s strategy is to outsource to third parties all manufacturing of BBOT’s product candidates and products from preclinical development through clinical trials and commercialization, if any product candidates are approved. In order to conduct clinical trials of product candidates, BBOT will need to have them manufactured in potentially large quantities, particularly for later-stage trials. BBOT’s third-party manufacturers may be unable to successfully increase the manufacturing capacity for any of its clinical drug supplies (including API, drug product, and key starting and intermediate materials) in a timely or cost-effective manner, or at all. In addition, quality issues may arise during scale-up activities and at any other time. If these third-party 52 Table of Contents manufacturers are unable to successfully scale up the manufacture of BBOT’s product candidates in sufficient quality and quantity, the development, testing and clinical trials of that product candidate may be delayed or infeasible, and regulatory approval or commercial launch of that product candidate may be delayed or not obtained. In addition, some of BBOT’s third-party suppliers (including suppliers of key active pharmaceutical ingredients, or API, drug product, and starting and intermediate materials) are currently BBOT’s sole source of supplies and, as a result, an issue with one of these suppliers may more significantly impact or delay BBOT’s development or commercial plans, as discussed further under the risk factor titled, “Some of the third parties upon whom BBOT currently relies for the supply of the active pharmaceutical ingredients, drug product and starting materials used in BBOT’s product candidates are BBOT’s sole source of supply, and the loss of any of these suppliers could delay BBOT’s development efforts and harm BBOT’s business.” BBOT’s use of new third-party manufacturers or suppliers also increases the risk of delays in production or insufficient supplies of BBOT’s product candidates (and the key API, drug product, and starting and intermediate materials for such product candidates) as BBOT transfers its manufacturing technology to these manufacturers or suppliers and as they gain experience manufacturing or producing BBOT’s product candidates (and the key API, drug product, and starting and intermediate materials for these product candidates). Even after a third-party manufacturer has gained significant experience in manufacturing BBOT’s product candidates (or the key API, drug product, and starting and intermediate materials for such product candidates), or even if BBOT believes it has succeeded in optimizing the manufacturing process, there can be no assurance that such manufacturer will supply or produce sufficient quantities of BBOT’s product candidates (or the key API, drug product, and starting and intermediate materials for such product candidates) in a timely manner or continuously over time, or at all. BBOT may be delayed if BBOT needs to change the manufacturing process used by a third party. Further, if BBOT changes an approved manufacturing process, then BBOT may be delayed if the FDA or a comparable foreign authority needs to review the new manufacturing process before it may be used. Reliance on third-party manufacturers for preclinical, clinical and commercial supplies entails risks, including: • reliance on the third party for regulatory compliance and quality assurance; • the possible breach of the manufacturing or master services agreement by the third party; • the possible misappropriation of BBOT’s proprietary information, including trade secrets and know-how; and • the possible termination or non-renewal of the agreement by the third party at a time that is costly or inconvenient for BBOT. While BBOT has entered into master services agreements with its current suppliers under which work is performed on an as-needed basis pursuant to quotations or proposals, BBOT does not currently have any agreements with third-party manufacturers for long-term commercial supply. In the future, BBOT may be unable to enter into agreements with third-party manufacturers for commercial supplies of any of BBOT’s product candidates, or may be unable to do so on acceptable terms. Even if BBOT is able to establish and maintain arrangements with third-party manufacturers for commercial supply, reliance on third-party manufacturers entails risks, including those described above. Third-party manufacturers may not be able to comply with cGMP requirements or similar regulatory requirements outside the United States. BBOT’s failure, or the failure of its third-party manufacturers, to comply with applicable requirements could result in sanctions being imposed on BBOT, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and/or criminal prosecutions, any of which could significantly and adversely affect supplies of BBOT’s product candidates. BBOT’s future product candidates and any products that BBOT may develop may compete with other product candidates and products for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP requirements particularly that use chromatography or purification technology necessary for the manufacture of BBO-10203, and that might be capable of manufacturing for BBOT. BBOT is also unable to predict how changing regulatory requirements, global economic conditions or ongoing geopolitical conflicts, trade policy, and related global economic sanctions, or potential global health concerns will affect BBOT’s third-party suppliers and manufacturers. Any negative impact of such matters on BBOT’s third-party suppliers and manufacturers may also have an adverse impact on BBOT’s results of operations or financial condition. For example, in 2024, there was Congressional activity related to interactions with Chinese biopharmaceutical companies, including the introduction of the BIOSECURE Act. Although the BIOSECURE Act has not been passed by Congress, if this bill is re-introduced and is passed, or if similar laws are passed in the future, they would have the potential to restrict the ability of U.S. biopharmaceutical companies like BBOT to purchase services or products from, or otherwise collaborate with, certain Chinese biotechnology companies “of concern” without losing the ability to contract with, or otherwise receive funding from, the U.S. government. Some of BBOT’s sole source suppliers are companies in China, including some named in these bills, and it is possible some of BBOT’s contractual counterparties could be impacted by the legislation described above. 53 Table of Contents If the third parties that BBOT engages to supply any materials or manufacture product for its preclinical tests and clinical trials should cease to continue to do so for any reason, BBOT likely would experience delays in advancing these tests and trials while BBOT identifies and qualifies replacement suppliers or manufacturers, and BBOT may be unable to obtain replacement supplies on terms that are favorable to BBOT or at all. In addition, if BBOT is not able to obtain adequate supplies of its product candidates or the substances used to manufacture them, it will be more difficult for BBOT to develop its product candidates and compete effectively. BBOT’s current and anticipated future dependence upon others for the manufacture of BBOT’s product candidates (or the key API, drug product, and starting and intermediate materials for such product candidates) may adversely affect BBOT’s future profit margins and ability to develop product candidates and commercialize any products that receive marketing approval on a timely and competitive basis. BBOT faces substantial competition which may result in others discovering, developing or commercializing products before or more successfully than BBOT does. The pharmaceutical and biotechnology industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary and novel products and product candidates. BBOT’s competitors have developed, are developing or may develop products, product candidates and processes competitive with BBOT’s product candidates. Any product candidates that BBOT successfully develops and commercializes will compete with existing therapies and new therapies that may become available in the future. BBOT believes that a significant number of product candidates are currently under development, and may become commercially available in the future, for the treatment of conditions for which BBOT is currently attempting and may in the future attempt to develop product candidates. In addition, BBOT’s product candidates may need to compete with drugs physicians use off-label to treat the indications for which BBOT seeks approval. This may make it difficult for BBOT to replace existing therapies with BBOT’s product candidates. In particular, there is intense competition in the field of oncology. BBOT has competitors both in the U.S. and internationally, including major multinational pharmaceutical companies, established biotechnology companies, specialty pharmaceutical companies, emerging and start-up companies, universities and other research institutions. BBOT also competes with these organizations to recruit and retain qualified scientific and management personnel, which could negatively affect BBOT’s level of expertise and BBOT’s ability to execute its business plan. BBOT will also face competition in establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, BBOT’s programs. For BBO-8520, there are currently two KRASG12C inhibitors approved by the FDA for use in KRASG12C mutant advanced or metastatic NSCLC. For BBO-10203, there is one PI3Kα inhibitor approved by the FDA for the treatment of HR+ / HER2- advanced or metastatic PIK3CAmut breast cancer. For BBO-11818, there are no pan-KRAS inhibitors approved by the FDA for the treatment of KRASG12X mutant lung, colorectal, or pancreatic cancers. Many of BBOT’s competitors, either alone or with their collaborators, have significantly greater financial resources, established presence in the market, and expertise in research and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals and reimbursement and marketing approved products than BBOT. Large pharmaceutical and biotechnology companies, in particular, have extensive experience in clinical testing, obtaining regulatory approvals, recruiting patients and manufacturing biotechnology product candidates. These companies also have significantly greater research and marketing capabilities than BBOT and may also have product candidates that have been approved or are in late stages of development, and collaborative arrangements in BBOT’s target markets with leading companies and research institutions. Established pharmaceutical and biotechnology companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that BBOT develops obsolete. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies, as well as in acquiring technologies complementary to, or necessary for, BBOT’s programs. As a result of all of these factors, BBOT’s competitors may succeed in obtaining approval from the FDA, EMA or other comparable foreign regulatory authorities or in discovering, developing and commercializing product candidates in BBOT’s field before BBOT does. BBOT’s potential commercial opportunity could be reduced or eliminated if competitors develop and commercialize products that are safer, more effective, have fewer or less severe adverse events, are more convenient, have a broader label, are marketed more effectively, are more widely reimbursed or are less expensive than any products that BBOT may develop. Physicians may be more willing to prescribe competitors’ products for various reasons, and may rely on guidelines related to treatment of patients issued by medical societies, industry groups or other organizations, which may not include, and may never include, BBOT’s products. BBOT’s competitors also may obtain marketing approval from the FDA, EMA or other comparable foreign regulatory authorities for their products more rapidly than BBOT may obtain approval for its product candidates, which could result in competitors establishing a strong 54 Table of Contents market position before BBOT is able to enter the market, or make BBOT’s development and marketing more complicated. Even if the product candidates BBOT develops achieve marketing approval, they may be priced at a significant premium over competitive products if any have been approved by then, resulting in reduced competitiveness. Technological advances or products developed by BBOT’s competitors may render BBOT’s technologies or product candidates obsolete, less competitive or not economical. If BBOT is unable to compete effectively, BBOT’s opportunity to generate revenue from the sale of products BBOT may develop, if approved, could be adversely affected. BBOT’s product candidates may not achieve adequate market acceptance among physicians, patients, healthcare payors and others in the medical community necessary for commercial success. Even if BBOT’s product candidates receive regulatory approval, they may not gain adequate market acceptance among physicians, patients, third-party payors and others in the medical community. The degree of market acceptance of any of BBOT’s approved product candidates will depend on a number of factors, including: • the efficacy and safety profile as demonstrated in clinical trials compared to alternative treatments; • the timing of market introduction of the product candidate as well as competitive products; • the clinical indications for which a product candidate is approved; • restrictions on the use of product candidates in the labeling approved by regulatory authorities, such as boxed warnings or contraindications in labeling, or a REMS, if any, which may not be required of alternative treatments and competitor products; • the potential and perceived advantages of BBOT’s product candidates over alternative treatments; • the cost of treatment in relation to alternative treatments; • the availability of coverage and adequate reimbursement by third-party payors, including government authorities; • willingness of physicians to use BBOT’s product candidates, if approved, in lieu of (or in conjunction with) other approved therapies; • the availability of an approved product candidate for use as a combination therapy; • relative convenience and ease of administration; • the willingness of the target patient population to try new therapies and undergo required diagnostic screening to determine treatment eligibility and of physicians to prescribe these therapies and diagnostic tests; • the effectiveness of sales and marketing efforts; • unfavorable publicity relating to BBOT’s product candidates; and • the approval of other new therapies for the same indications. If any of BBOT’s product candidates are approved but do not achieve an adequate level of acceptance by physicians, hospitals, healthcare payors and patients, BBOT may not generate or derive sufficient revenue from that product candidate and BBOT’s financial results could be negatively impacted. The market opportunities for any product candidates BBOT develops, if approved, may be limited to certain smaller patient subsets and may be smaller than BBOT estimates them to be. When cancer is detected early (referred to as localized disease), conventional treatments, which include chemotherapy, hormone therapy, surgery and radiation therapy and/or selected targeted therapies, may be adequate to cure the patient in many cases. However, once cancer has spread to other areas (advanced or metastatic disease), cancer treatments may not be sufficient to provide a cure but often can significantly prolong life without curing the cancer. First-line therapies designate treatments that are initially administered to patients with advanced or metastatic disease, while second and third-line therapies are administered to patients when the prior therapies lose their effectiveness. The FDA, EMA and other regulatory bodies often approve cancer therapies for a particular line of treatment. Typically, drug approvals are initially granted for use in later lines of treatment, but with additional evidence of significant efficacy from clinical trials, biopharmaceutical companies can successfully seek and gain approval for use in earlier lines of treatment. In most instances, BBOT plans to initially seek approval of BBO-8520, BBO-10203 and BBO-11818 and any other future product candidates for previously treated patients with advanced or metastatic cancer where at least one prior therapy has limited clinical benefit or where tumors have developed resistance to such therapy. For those product candidates that prove to be sufficiently safe and effective, 55 Table of Contents if any, BBOT would potentially expect to seek approval ultimately as a first line therapy. There is no guarantee that BBOT’s product candidates, even if approved for previously treated patients, would be approved for an earlier line of therapy, and prior to any such approvals BBOT may have to conduct additional clinical trials that may be costly, time-consuming and subject to risk. BBOT’s projections of both the number of people who have the cancers BBOT is targeting, as well as the subset of people with these cancers in a position to receive a particular line of therapy and who have the potential to benefit from treatment with BBOT’s product candidates, are based on BBOT’s beliefs and estimates. These estimates have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect. Further, new data and studies may change the estimated incidence or prevalence of the cancers that BBOT is targeting, especially if new therapies that are approved while BBOT advances its product candidates affect the treatment paradigm and/or the size of the target population. The potentially addressable patient population for BBOT’s product candidates may be limited or may not be amenable to treatment with BBOT’s product candidates. Consequently, even if BBOT’s product candidates are approved, the number of patients that may be eligible for treatment with BBOT’s product candidates may turn out to be much lower than expected. In addition, BBOT has not yet conducted market research to determine how treating physicians would expect to prescribe a product that is approved for multiple tumor types if there are different lines of approved therapies for each such tumor type. Even if BBOT obtains significant market share for its products, if approved, if the potential target populations are small, BBOT may never achieve profitability without obtaining regulatory approval for additional indications. Any product candidates BBOT develops may become subject to unfavorable third-party coverage and reimbursement practices, as well as pricing regulations. Patients rely on insurance coverage by third-party payors (third-party payors include Medicare and Medicaid (government payors) and commercial insurance companies such as Blue Cross Blue Shield, Humana, Cigna, etc.), to pay for products. The availability and extent of coverage and adequate reimbursement by third-party payors, including government health administration authorities, private health coverage insurers, managed care organizations and other third-party payors is essential for most patients to be able to afford expensive treatments. Sales of any of BBOT’s product candidates that receive marketing approval will depend substantially, both in the U.S. and internationally, on the extent to which the costs of such product candidates will be covered and reimbursed by third-party payors. No uniform policy exists for coverage and reimbursement in the U.S. If reimbursement is not available, or is available only to limited levels, BBOT may not be able to successfully commercialize its product candidates. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow BBOT to establish or maintain pricing sufficient to realize an adequate return on BBOT’s investment. Further, it is possible that a third-party payor may consider BBOT’s product candidates as substitutable with competitor products and offer to reimburse patients only for the less expensive competitor product. Coverage and reimbursement may impact the demand for, or the price of, any product candidate for which BBOT obtains marketing approval. If coverage and reimbursement are not available or reimbursement is available only to limited levels, BBOT may not successfully commercialize any product candidate for which BBOT obtains marketing approval. There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products. In the U.S., for example, principal decisions about reimbursement for new products are typically made by the Center for Medicare & Medicaid Services (“ CMS ”), an agency within the U.S. Department of Health and Human Services (“ HHS ”). CMS decides whether and to what extent a new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding coverage and reimbursement to a substantial degree. However, one third-party payor’s determination to provide coverage for a product candidate does not assure that other payors will also provide coverage for the product candidate. As a result, the coverage determination process is often time-consuming and costly. Factors payors consider in determining reimbursement are based on whether the product is: (i) a covered benefit under its health plan; (ii) safe, effective and medically necessary; (iii) appropriate for the specific patient; (iv) cost-effective; and (v) neither experimental nor investigational. This process will require BBOT to provide scientific and clinical support for the use of BBOT’s products to each third-party payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. As federal and state governments implement additional health care cost containment measures, including measures to lower prescription drug pricing, BBOT cannot be sure that its products, if approved, will be covered by private or public payors, and if covered, whether the reimbursement will be adequate or competitive with other marketed products. Such other actions by federal and state governments and health plans may put additional downward pressure on pharmaceutical pricing and health care costs, which could negatively impact coverage and reimbursement for BBOT’s products if approved, BBOT’s revenue, and its ability to compete with other marketed products and to recoup the costs of its research and development. For further discussion, see “- Current and future legislation may increase the difficulty and cost for BBOT to obtain reimbursement for its product candidates;” and “- The prices of prescription pharmaceuticals in the U.S. and foreign jurisdictions are the subject of considerable legislative and executive actions and could impact the prices BBOT obtains for its products, if and when licensed for marketing.” 56 Table of Contents Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Further, such payors are increasingly challenging the price, examining the medical necessity and reviewing the cost effectiveness of medical product candidates. There may be especially significant delays in obtaining coverage and reimbursement for newly approved drugs. Third-party payors may limit coverage to specific product candidates on an approved list, known as a formulary, which might not include all FDA-approved drugs for a particular indication. BBOT may need to conduct expensive pharmaco-economic studies to demonstrate the medical necessity and cost effectiveness of its products. Nonetheless, BBOT’s product candidates may not be considered medically necessary or cost effective. BBOT cannot be sure that coverage and reimbursement will be available for any product that BBOT commercializes and, if reimbursement is available, what the level of reimbursement will be. In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or products, will apply to companion diagnostics. Additionally, if any companion diagnostic provider is unable to obtain reimbursement or is inadequately reimbursed, that may limit the availability of such companion diagnostic, which would negatively impact prescriptions for BBOT’s product candidates, if approved. Outside the U.S., the commercialization of therapeutics is generally subject to extensive governmental price controls and other market regulations, and BBOT believes the increasing emphasis on cost containment initiatives in Europe, Canada and other countries has and will continue to put pressure on the pricing and usage of therapeutics such as BBOT’s product candidates. In many countries, particularly the countries of the EU, medical product prices are subject to varying price control mechanisms as part of national health systems. In these countries, pricing negotiations with governmental authorities can take considerable time after a product receives marketing approval. To obtain reimbursement or pricing approval in some countries, BBOT may be required to conduct a clinical trial that compares the cost-effectiveness of BBOT’s product candidate to other available therapies. In general, product prices under such systems are substantially lower than in the U.S. Other countries allow companies to fix their own prices for products but monitor and control company profits. Additional foreign price controls or other changes in pricing regulation could restrict the amount that BBOT is able to charge for its product candidates. Accordingly, in markets outside the U.S., the reimbursement for BBOT’s products may be reduced compared with the U.S. and may be insufficient to generate commercially reasonable revenue and profits. If BBOT is unable to establish or sustain coverage and adequate reimbursement for any product candidates from third-party payors, the adoption of those products and sales revenue will be adversely affected, which, in turn, could adversely affect the ability to market or sell those product candidates, if approved. Coverage policies and third-party payor reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which BBOT receives regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. BBOT’s business entails a significant risk of product liability and if BBOT is unable to obtain sufficient insurance coverage such inability could have an adverse effect on BBOT’s business and financial condition. BBOT’s business exposes BBOT to significant product liability and other risks inherent in the development, testing, manufacturing and marketing of therapeutic treatments. Product liability and other claims or incidents, such as cyber incidents and breaches, could delay or prevent completion of BBOT’s development programs. If BBOT succeeds in marketing products, such claims could result in an FDA, EMA or other regulatory authority investigation of the safety and effectiveness of BBOT’s products, manufacturing processes and facilities or BBOT’s marketing programs. FDA, EMA or other regulatory authority investigations could potentially lead to a recall of BBOT’s products or more serious enforcement action, limitations on the approved indications for which they may be used or suspension or withdrawal of approvals. Regardless of the merits or eventual outcome, liability claims may also result in decreased demand for BBOT’s products, injury to BBOT’s reputation, costs to defend the related litigation, a diversion of management’s time and BBOT’s resources and substantial monetary awards to trial participants or patients. BBOT currently has product liability and other insurance that BBOT believes is appropriate for its stage of development and may need to obtain higher levels prior to advancing BBOT’s product candidates into later stages of development or marketing any of BBOT’s product candidates, if approved. Any insurance BBOT has or may obtain may not provide sufficient coverage against potential liabilities. Furthermore, clinical trial, product liability, and other types of insurance (such as cyber insurance) are becoming increasingly expensive and difficult to obtain. As a result, BBOT may be unable to obtain sufficient insurance at a reasonable cost to protect BBOT against losses caused by product liability or other claims or incidents, including data breach and incidents, that could have an adverse effect on BBOT’s business and financial condition. Certain of BBOT’s product candidates are novel, complex and difficult to manufacture. BBOT could experience manufacturing problems that result in delays in BBOT’s development or commercialization or otherwise harm BBOT’s business. The manufacturing processes BBOT’s third-party contract manufacturing organizations (“ CMOs ”) use to produce its product candidates are complex, novel and have not been validated for commercial use. Several factors have caused and may cause future production interruptions, including restrictions on certain manufacturing operations and shortages in on-site personnel at BBOT’s CMOs’ manufacturing facilities, equipment malfunctions, facility contamination, raw material shortages or contamination, natural 57 Table of Contents disasters, disruption in utility services, human error or disruptions in the operations of BBOT’s suppliers, including historical disruptions, which could reoccur in connection with any future global pandemic or health emergency. Several of BBOT’s small molecule product candidates are particularly complex and difficult to manufacture, in some cases due to the number of steps required, the process complexity and the toxicity of end or intermediate-stage products. BBOT’s product candidates require processing steps that are more complex than those required for most small molecule drugs. As a result, assays of the finished product may not be sufficient to ensure that the product is consistent from lot-to-lot or will perform in the intended manner. Accordingly, BBOT’s CMOs must employ multiple steps to control the manufacturing process to assure that the process is reproducible and the product candidate is made strictly and consistently in compliance with the process. Problems with the manufacturing process, even minor deviations from the normal process, could result in product defects or manufacturing failures that result in lot failures, product recalls, product liability claims or insufficient inventory to conduct clinical trials or supply commercial markets. BBOT may encounter problems achieving adequate quantities and quality of clinical-grade materials that meet the FDA, the EMA or other applicable standards or specifications with consistent and acceptable production yields and costs. In addition, the FDA, the EMA and other foreign regulatory authorities may require BBOT to submit samples of any lot of any approved product together with the protocols showing the results of applicable tests at any time. Under some circumstances, the FDA, the EMA or other foreign regulatory authorities may require that BBOT not distribute a lot until the agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause BBOT to delay clinical trials, which could be costly to BBOT and otherwise harm BBOT’s business, financial condition, results of operations and prospects. BBOT’s CMOs also may encounter problems hiring and retaining the experienced scientific, quality assurance, quality-control and manufacturing personnel needed to operate BBOT’s manufacturing processes, which could result in delays in production or difficulties in maintaining compliance with applicable regulatory requirements. Any problems in BBOT’s CMOs’ manufacturing process or facilities could result in delays in planned clinical trials and increased costs, and could make BBOT a less attractive collaborator for potential partners, including larger biotechnology companies and academic research institutions, which could limit access to additional attractive development programs. Problems in BBOT’s manufacturing process could also restrict BBOT’s ability to meet potential future market demand for any products that may be approved. Certain of BBOT’s product candidates are under development for the treatment of patient populations with significant comorbidities that may result in deaths or serious adverse or unacceptable side effects and require BBOT to abandon or limit its clinical development activities. Patients in certain of BBOT’s ongoing and planned clinical trials of product candidates in genetically driven cancers, as well as patients who may undergo treatment with other product candidates that BBOT may develop, may also receive chemotherapy, radiation, and/or other high dose or myeloablative treatments in the course of treatment of their disease, and may therefore experience side effects or AEs, including death, that are unrelated to BBOT’s product candidates. While these side effects or AEs may be unrelated to BBOT’s product candidates, they may still affect the success of BBOT’s clinical trials. The inclusion of critically ill patients in BBOT’s clinical trials may also result in deaths or other adverse medical events due to underlying disease or to other therapies or medications that such patients may receive. Any of these events could prevent BBOT from advancing its product candidates through clinical development, and from obtaining regulatory approval, and would impair BBOT’s ability to commercialize its product candidates. Any inability to advance BBOT’s product candidates through clinical development may harm BBOT’s business, financial condition, results of operations and prospects. Risks Related to Regulatory Approval and Other Legal Compliance Matters BBOT may be unable to obtain U.S. or foreign regulatory approval and, as a result, may be unable to commercialize its product candidates. BBOT’s product candidates are and will continue to be subject to extensive governmental regulations relating to, among other things, research, testing, development, manufacturing, safety, efficacy, approval, recordkeeping, reporting, labeling, storage, packaging, advertising and promotion, pricing, marketing and distribution of drugs. Rigorous preclinical testing and clinical trials and an extensive regulatory approval process must be successfully completed in the U.S. and in many foreign jurisdictions before a new drug can be approved for marketing. Satisfaction of these and other regulatory requirements is costly, time consuming, uncertain and subject to unanticipated delays. BBOT cannot provide any assurance that any product candidate BBOT may develop will progress through required clinical testing and obtain the regulatory approvals necessary for BBOT to begin selling them. 58 Table of Contents BBOT does not have experience conducting, managing or completing large-scale or pivotal clinical trials nor managing the regulatory approval process with the FDA, EMA or any other regulatory authority. The time required to obtain approvals from the FDA, EMA and other regulatory authorities is unpredictable and requires successful completion of extensive clinical trials which typically takes many years, depending upon the type, complexity and novelty of the product candidate. The standards that the FDA and its foreign counterparts use when evaluating clinical trial data can change during drug development, which makes it difficult to predict with any certainty how such standards will be applied. BBOT may also encounter unexpected delays or increased costs due to new government regulations, including future legislation or administrative action, changes in applicable FDA, EMA or other regulatory policy during the period of drug development, clinical trials and regulatory review, or significant changes to FDA personnel during the regulatory review. Applications for BBOT’s product candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA, EMA or other comparable foreign regulatory authorities may disagree with the design, implementation or results of BBOT’s clinical trials; • the FDA, EMA or other comparable foreign regulatory authorities may determine that BBOT’s product candidates are not safe and effective or have undesirable or unintended adverse events, toxicities or other characteristics that preclude BBOT obtaining marketing approval or prevent or limit commercial use; • the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which BBOT seeks approval; • the FDA, EMA or other comparable foreign regulatory authorities may disagree with BBOT’s interpretation of data from preclinical studies or clinical trials; • BBOT may be unable to demonstrate to the FDA, EMA or other comparable foreign regulatory authorities that BBOT’s product candidates’ risk-benefit ratios for their proposed indications are acceptable; • the FDA, EMA or other comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications or facilities of third-party manufacturers with which BBOT contracts for clinical and commercial supplies; and • the approval policies or regulations of the FDA, EMA or other comparable foreign regulatory authorities may significantly change in a manner rendering BBOT’s clinical data insufficient for approval. Any delay or failure in seeking or obtaining required approvals would have a material and adverse effect on BBOT’s ability to generate revenue from any particular product candidates BBOT is developing and for which BBOT is seeking approval. Furthermore, any regulatory approval to market a drug may be subject to significant limitations on the approved uses or indications for which BBOT may market, promote and advertise the drug or the labeling or other restrictions. In addition, the FDA has the authority to require a REMS plan as part of approving a New Drug Application (“ NDA ”), or after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug. These requirements or restrictions might include limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria, distribution through controlled distribution channels, and requiring treated patients to enroll in a registry. These limitations and restrictions may significantly limit the size of the market for the drug and affect reimbursement by third-party payors. BBOT is also subject to numerous foreign regulatory requirements governing, among other things, the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party reimbursement. The foreign regulatory approval process varies among countries, and generally includes all of the risks associated with FDA approval described above as well as risks attributable to the satisfaction of local regulations in foreign jurisdictions. Moreover, the time required to obtain approval may differ from that required to obtain FDA approval. BBOT plans to develop certain of its current product candidates and potentially future product candidates in combination with other therapies, which would expose BBOT to additional risks. BBOT plans to develop certain of its current product candidates in combination with one or more currently approved cancer therapies or therapies in development and may pursue a similar strategy for future product candidates. For example, the ongoing Phase 1 trial of BBO-8520 is evaluating BBO-8520 both as a monotherapy and in combination with pembrolizumab. On January 7, 2026, BBOT reported positive preliminary safety and antitumor data across its three orally bioavailable, differentiated small molecule RAS and PI3Ka programs. The data updates included BBO-8520, a direct inhibitor targeting both the ON and OFF states of KRASG12C; BBO-11818, a panKRAS inhibitor targeting mutant KRAS in both the ON and OFF states, and BBO-10203, a RAS-PI3Ka breaker with a novel mechanism of action designed to inhibit the physical interaction between RAS and PI3Ka. Even if any of BBOT’s current or future product candidates were to receive marketing approval or be commercialized for use in combination with other existing therapies, BBOT would continue to be subject to the risks that the FDA, EMA or other comparable foreign regulatory authorities could revoke 59 Table of Contents approval of the therapy used in combination with any of BBOT’s product candidates, or safety, efficacy, manufacturing or supply issues could arise with these existing therapies. In addition, it is possible that existing therapies with which BBOT’s product candidates are approved for use could themselves fall out of favor or be relegated to later lines of treatment. This could result in the need to identify other combination therapies for BBOT’s product candidates or BBOT’s own products being removed from the market or being less successful commercially. BBOT may also evaluate its current or future product candidates in combination with one or more other cancer therapies that have not yet been approved for marketing by the FDA, EMA or comparable foreign regulatory authorities. For example, none of BBOT’s product candidates have obtained approval for marketing from any regulatory authority, and BBOT plans to evaluate certain of its product candidates in combination with each other. BBOT will not be able to market and sell any product candidate in combination with any such unapproved cancer therapies that do not ultimately obtain marketing approval. If the FDA, EMA or other comparable foreign regulatory authorities do not approve or withdraw their approval of these other therapies, or if safety, efficacy, commercial adoption, manufacturing or supply issues arise with the therapies BBOT chooses to evaluate in combination with any of its current or future product candidates, BBOT may be unable to obtain approval of or successfully market any one or all of the current or future product candidates BBOT develops. Additionally, if the third-party providers of therapies or therapies in development used in combination with BBOT’s current or future product candidates are unable to produce sufficient quantities for clinical trials or for commercialization of BBOT’s current or future product candidates, or if the cost of combination therapies are prohibitive, BBOT’s development and commercialization efforts would be impaired, which would have an adverse effect on BBOT’s business, financial condition, results of operations and growth prospects. BBOT has conducted and intends to continue conducting certain of its clinical trials globally. However, the FDA and other foreign equivalents may not accept data from such trials, in which case BBOT’s development plans may be delayed, which could materially harm BBOT’s business. BBOT has conducted and intends to continue conducting certain of its clinical trials globally. The acceptance by the FDA or other regulatory authorities of study data from clinical trials conducted outside of their respective jurisdictions may be subject to certain conditions or may not be accepted at all. In cases where data from foreign clinical trials are intended to serve as the sole basis for marketing approval in the U.S., the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the U.S. population and U.S. medical practice; (ii) the trials were performed by clinical investigators of recognized competence and pursuant to good clinical practice (“ GCP ”) regulations; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. In addition, even where the foreign study data are not intended to serve as the sole basis for approval, the FDA will not accept the data as support for an application for marketing approval unless the study is well-designed and well-conducted in accordance with GCP requirements, and the FDA is able to validate the data from the study through an onsite inspection if deemed necessary. Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the U.S. or the applicable jurisdiction and FDA has discussed proposals to increase user fees for marketing applications containing certain foreign clinical data. If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of BBOT’s business plan, and which may result in BBOT’s product candidates not receiving approval or clearance for commercialization in the applicable jurisdiction. Conducting clinical trials outside the U.S. also exposes BBOT to additional risks, including risks associated with: • additional foreign regulatory requirements; • foreign exchange fluctuations; • compliance with foreign manufacturing, customs, shipment and storage requirements; • cultural differences in medical practice and clinical research; • diminished protection of intellectual property in some countries; and • interruptions or delays in BBOT’s trials resulting from geopolitical events, including civil or political unrest or military conflicts. 60 Table of Contents Obtaining and maintaining regulatory approval of BBOT’s product candidates in one jurisdiction does not mean that BBOT will be successful in obtaining regulatory approval of its product candidates in other jurisdictions. Obtaining and maintaining regulatory approval of BBOT’s product candidates in one jurisdiction does not guarantee that BBOT will be able to obtain or maintain regulatory approval in any other jurisdiction. For example, even if the FDA grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the marketing of the product candidate in those countries. However, a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the U.S., including additional preclinical studies or clinical trials as clinical trials conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the U.S., a product candidate must obtain pricing and/or reimbursement determinations before it can achieve broad commercial access. In some cases, the price that BBOT intends to charge for its products is also subject to approval. Obtaining foreign regulatory approvals and establishing and maintaining compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for BBOT and could delay or prevent the introduction of BBOT’s products in certain countries. If BBOT or any future collaborator fails to comply with the regulatory requirements in international markets or fails to receive applicable marketing approvals, BBOT’s target market will be reduced and BBOT’s ability to realize the full market potential of BBOT’s product candidates will be harmed. Further, BBOT could face heightened risks with respect to obtaining marketing authorization in the United Kingdom (“ U.K. ”) as a result of the withdrawal of the U.K. from the EU, commonly referred to as Brexit. Following the end of the Brexit transition period on January 1, 2021 and the implementation of the Windsor Framework on January 1, 2025, the U.K. is not generally subject to EU laws in respect of medicines. The EU laws that have been transposed into U.K. law through secondary legislation remain applicable in the U.K., however, new legislation such as the EU Clinical Trials Regulation is not applicable in the U.K.. As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency, (“ MHRA ”), is the UK's standalone medicines and medical devices regulator. From January 1, 2025, under the Windsor Framework, the MHRA regulates medicines through UK-wide marketing authorizations, including for Northern Ireland. As a result, BBOT will be required to obtain separate authorizations in order to market its product candidates in the U.K. and EU. In addition, foreign regulatory authorities may change their approval policies and new regulations may be enacted. For instance, the EU pharmaceutical legislation is currently undergoing a complete review and reform process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission’s proposal for the revision of several legislative instruments related to medicinal products (potentially reducing the duration of regulatory data protection, revising the eligibility for expedited pathways, etc.) was published on April 26, 2023. In April 2024, the European Parliament adopted its position on the legislative proposals and, in June 2025, the Council of the European Union adopted its position. A provisional political agreement on the reform was reached and a common position on the text was agreed upon on December 11, 2025, in the context of subsequent inter-institutional trilogue negotiations. The revised legislation must still be formally adopted by the European Parliament and the Council of the European Union and the final text may be further refined before formal adoption and publication. The proposed revisions are not expected to become applicable before 2028. The revisions may however have a significant impact on the pharmaceutical industry and BBOT’s business in the long term. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, may force BBOT to restrict or delay efforts to seek regulatory approval in the U.K. for its product candidates, which could significantly and materially harm BBOT’s business. Further, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries. Also, regulatory approval for BBOT’s product candidates may be withdrawn. If BBOT fails to comply with the applicable regulatory requirements, BBOT’s target market will be reduced, BBOT’s ability to realize the full market potential of its product candidates will be harmed, and BBOT’s business, financial condition, results of operations and prospects could be harmed. Even if BBOT’s product candidates receive regulatory approval, they will be subject to significant post-marketing regulatory requirements and oversight. Any regulatory approvals that BBOT may receive for its product candidates will require the submission of reports to regulatory authorities and ongoing surveillance to monitor the safety and efficacy of the product candidate, may contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, and may include burdensome post-approval study or risk management requirements and regulatory inspection. For example, the FDA may require a REMS in order to approve BBOT’s product candidates, which could entail requirements for a medication guide, physician training and communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA, EMA or foreign regulatory authorities approve BBOT’s product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for BBOT’s 61 Table of Contents product candidates will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as ongoing compliance with cGMP and GCP for any clinical trials that BBOT conducts post-approval. In addition, manufacturers of drug products and their facilities are subject to continual review and periodic, unannounced inspections by the FDA, EMA and other regulatory authorities for compliance with cGMP regulations and standards. If BBOT or a regulatory authority discover previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facilities where the product is manufactured, a regulatory authority may impose restrictions on that product, the manufacturing facility or BBOT, including requiring recall or withdrawal of the product from the market or suspension of manufacturing. In addition, failure to comply with FDA, EMA and other comparable foreign regulatory requirements may subject BBOT to administrative or judicially imposed sanctions, including: • delays in or the rejection of product approvals; • restrictions on BBOT’s ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials; • restrictions on the products, manufacturers or manufacturing process; • warning or untitled letters; • civil and criminal penalties; • injunctions; • suspension or withdrawal of regulatory approvals; • product seizures, detentions or import bans; • voluntary or mandatory product recalls and publicity requirements; • total or partial suspension of production; • imposition of restrictions on operations, including costly new manufacturing requirements; • revisions to the labeling, including limitation on approved uses or the addition of additional warnings, contraindications or other safety information, including boxed warnings; • imposition of a REMS, which may include distribution or use restrictions; and • requirements to conduct additional post-market clinical trials to assess the safety of the product. The FDA, EMA and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of BBOT’s product candidates. BBOT cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the U.S. or abroad. If BBOT is slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if BBOT is not able to maintain regulatory compliance, BBOT may lose any marketing approval that BBOT may have obtained and BBOT may not achieve or sustain profitability. The FDA, EMA and other regulatory authorities actively enforce the laws and regulations prohibiting the promotion of off-label uses. If any of BBOT’s product candidates are approved and BBOT is found to have improperly promoted off-label uses of those products, BBOT may become subject to significant liability. The FDA, competent authorities of the EU Member States and other regulatory authorities strictly regulate the promotional claims that may be made about prescription products, such as BBOT’s product candidates, if approved. In particular, a product may not be promoted in the U.S. for uses that are not approved by the FDA as reflected in the product’s approved labeling, or in other jurisdictions for uses that differ from the labeling or uses approved by the applicable regulatory authorities. While physicians may prescribe products for off-label uses, the FDA, competent authorities of the EU Member States and other regulatory authorities actively enforce laws and regulations that prohibit the promotion of off-label uses by companies, including promotional communications made by companies’ sales forces with respect to off-label uses that are not consistent with the approved labeling, and a company that is found to have improperly promoted off-label uses may be subject to significant civil, criminal and administrative penalties. If BBOT is found to have promoted such off-label uses, BBOT may become subject to significant liability. The U.S. federal government has levied large civil and criminal fines against companies for alleged improper promotion of off-label use and has enjoined several companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If BBOT cannot successfully manage the promotion of its product candidates, if approved, BBOT could become subject to significant liability, which would materially adversely affect BBOT’s business and financial condition. 62 Table of Contents If BBOT is required by the FDA, EMA or comparable regulatory authority to obtain clearance or approval of a companion diagnostic test in connection with approval of any of BBOT’s product candidates or a group of therapeutic products, and BBOT does not obtain or BBOT faces delays in obtaining clearance or approval of a diagnostic test, BBOT may not be able to commercialize the product candidate and BBOT’s ability to generate revenue may be materially impaired. If BBOT is required by the FDA, EMA or a comparable regulatory authority to obtain clearance or approval of a companion diagnostic test in connection with approval of any of BBOT’s product candidates, such companion diagnostic test would be used during BBOT’s more advanced phase clinical trials as well as in connection with the commercialization of BBOT’s product candidates. To be successful in developing and commercializing product candidates in combination with these companion diagnostics, BBOT or its collaborators will need to address a number of scientific, technical, regulatory and logistical challenges. According to FDA guidance, if the FDA determines that a companion diagnostic device is essential to ensuring the safe and effective use of a novel therapeutic product or new indication, the FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic is not also approved or cleared. In certain circumstances (for example, when a therapeutic product is intended to treat a serious or life-threatening condition for which no satisfactory available therapy exists or when the labeling of an approved product needs to be revised to address a serious safety issue), however, the FDA may approve a therapeutic product without the prior or contemporaneous marketing authorization of a companion diagnostic. In this case, approval of a companion diagnostic may be a post-marketing requirement or commitment. Co-development of companion diagnostics and therapeutic products is critical to the advancement of precision medicine. Whether initiated at the outset of development or at a later point, co-development should generally be conducted in a way that will facilitate obtaining contemporaneous marketing authorizations for the therapeutic product and the associated companion diagnostic. If a companion diagnostic is required to identify patients who are most likely to benefit from receiving the product, to be at increased risk for serious adverse events as a result of treatment with a particular therapeutic product, or to monitor response to treatment with a particular therapeutic product for the purpose of adjusting treatment to achieve improved safety or effectiveness, then the FDA has required marketing approval of all companion diagnostic tests essential for the safe and effective use of a therapeutic product for cancer therapies. Various foreign regulatory authorities also regulate in vitro companion diagnostics as medical devices and, under those regulatory frameworks, will likely require the conduct of clinical trials to demonstrate the safety and effectiveness of any future diagnostics BBOT may develop, which BBOT expects will require separate regulatory clearance or approval prior to commercialization in those countries. The approval of a companion diagnostic as part of the therapeutic product’s labeling limits the use of the therapeutic product to only those patients who express the specific genomic alteration or mutation alteration that the companion diagnostic was developed to detect. If the FDA, EMA or a comparable regulatory authority requires clearance or approval of a companion diagnostic for any of BBOT’s product candidates, whether before, concurrently with approval, or post-approval of the product candidate, BBOT and/or future collaborators, may encounter difficulties in developing and obtaining clearance or approval for these companion diagnostics. The process of obtaining or creating such diagnostic is time consuming and costly. The FDA previously has required in vitro companion diagnostics intended to select the patients who will respond to a product candidate to obtain pre-market approval (“ PMA ”), simultaneously with approval of the therapeutic candidate. The PMA process, including the gathering of preclinical and clinical data and the submission and review by the FDA, can take several years or longer. It involves a rigorous pre-market review during which the sponsor must prepare and provide FDA with reasonable assurance of the device’s safety and effectiveness and information about the device and its components regarding, among other things, device design, manufacturing, and labeling. After a device is placed on the market, it remains subject to significant regulatory requirements, including requirements governing development, testing, manufacturing, distribution, marketing, promotion, labeling, import, export, record-keeping, and adverse event reporting. Any delay or failure by BBOT or third-party collaborators to develop or obtain regulatory clearance or approval of a companion diagnostic could delay or prevent approval or continued marketing of BBOT’s related product candidates. Changes in policy or approach to regulation by the FDA, EMA and other regulatory authorities may impact BBOT’s development of a companion diagnostic for BBOT’s product candidates and could result in delays in regulatory clearance or approval or a change in the determination for whether or not a companion diagnostic is still required for BBOT’s product candidates. BBOT may be required to conduct additional studies to support a broader claim or more narrowed claim for a subset population. Also, to the extent other approved diagnostics are able to broaden their labeling claims to include any of BBOT’s future approved product candidates’ covered indications, BBOT may no longer need to continue its companion diagnostic development plans or BBOT needs to alter those companion diagnostic development strategies, which could adversely impact BBOT’s ability to generate revenue from the sale of BBOT’s companion diagnostic test. Additionally, BBOT may rely on third parties for the design, development and manufacture of companion diagnostic tests for BBOT’s product candidates. If BBOT enters into such collaborative agreements, BBOT will be dependent on the sustained cooperation and effort of its future collaborators in developing and obtaining clearance or approval for these companion diagnostics. It may be necessary to resolve issues such as selectivity/ specificity, analytical validation, reproducibility, or clinical validation of companion diagnostics during the development and regulatory clearance or approval processes. Moreover, even if data from preclinical studies and early clinical trials appear to support development of a companion diagnostic for a product candidate, data generated in later clinical 63 Table of Contents trials may fail to support the analytical and clinical validation of the companion diagnostic. BBOT and its future collaborators may encounter difficulties in developing, obtaining regulatory clearance or approval for, manufacturing and commercializing companion diagnostics similar to those BBOT faces with respect to its product candidates themselves, including issues with achieving regulatory clearance or approval, production of sufficient quantities at commercial scale and with appropriate quality standards, and in gaining market acceptance. If BBOT is unable to successfully develop companion diagnostics for its product candidates, or experiences delays in doing so, the development of BBOT’s product candidates may be adversely affected, BBOT’s product candidates may not obtain marketing approval, and BBOT may not realize the full commercial potential of any of its product candidates that obtain marketing approval. As a result, BBOT’s business, results of operations and financial condition could be materially harmed. In addition, a diagnostic company with whom BBOT contracts may decide to discontinue selling or manufacturing the companion diagnostic test that BBOT anticipates using in connection with development and commercialization of product candidates or BBOT’s relationship with such diagnostic company may otherwise terminate. BBOT may not be able to enter into arrangements with another diagnostic company to obtain supplies of an alternative diagnostic test for use in connection with the development and commercialization of BBOT’s product candidates or do so on commercially reasonable terms, which could adversely affect and/or delay the co-development or commercialization of BBOT’s companion diagnostic and therapeutic product candidates. Where appropriate, BBOT plans to pursue approval from the FDA, EMA or comparable foreign regulatory authorities through the use of accelerated approval pathways. If BBOT is unable to obtain such approval, BBOT may be required to conduct additional preclinical studies or clinical trials beyond those that BBOT contemplates, which could increase the expense of obtaining, and delay the receipt of, necessary marketing approvals. Even if BBOT receives accelerated approval from the FDA, EMA or comparable regulatory authorities, if BBOT’s confirmatory trials do not verify clinical benefit, or if BBOT does not comply with rigorous post-marketing requirements, the FDA, EMA or such other regulatory authorities may seek to withdraw accelerated approval. Where appropriate, BBOT plans to pursue accelerated development strategies in areas of medical need. BBOT may seek an accelerated approval pathway for one or more of its product candidates from the FDA, EMA or comparable foreign regulatory authorities. Under the accelerated approval provisions in the Federal Food, Drug, and Cosmetic Act, and the FDA’s implementing regulations, the FDA may grant accelerated approval to a product candidate designed to treat a serious or life-threatening condition that provides meaningful therapeutic benefit over available therapies upon a determination that the product candidate has an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit. The FDA considers a clinical benefit to be a positive therapeutic effect that is clinically meaningful in the context of a given disease, such as irreversible morbidity or mortality. For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. An intermediate clinical endpoint is a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. The accelerated approval pathway may be used in cases in which the advantage of a new drug over available therapy may not be a direct therapeutic advantage, but is a clinically important improvement from a patient and public health perspective. As a condition of approval, the FDA may require that a sponsor of a product receiving accelerated approval perform adequate and well-controlled post-marketing confirmatory clinical trials. These confirmatory trials must be completed with due diligence. Under FDORA, the FDA is permitted to require, as appropriate, that a post-approval confirmatory trial or trials be underway prior to approval or within a specified time period after the date accelerated approval was granted. FDORA also requires sponsors to send updates to the FDA every 180 days on the status of such studies, including progress toward enrollment targets, and the FDA must promptly post this information publicly. Furthermore, under FDORA, the FDA is empowered to take action, such as issuing fines, against companies that fail to conduct with due diligence any post-approval confirmatory trial or submit timely reports to the agency on their progress. In the Consolidated Appropriations Act, Congress provided FDA with additional authorities to help prevent such delays, including that FDA may, when appropriate, require a confirmatory study or studies to be underway prior to approval. In addition, for products under consideration for accelerated approval, the FDA currently requires, unless otherwise requested by the agency, pre-approval of promotional materials prior to dissemination or publication, which could adversely impact the timing of the commercial launch of the product. In the EU, a “conditional” marketing authorization may be granted in cases where all the required safety and efficacy data are not yet available but where the medicinal product meets certain other criteria, including that the medicine fulfils an unmet medical need and the benefit of the medicine's immediate availability to patients is greater than the risk inherent in the fact that additional data are still required. A conditional marketing authorization is subject to conditions to be fulfilled for generating missing data or ensuring increased safety measures. A conditional marketing authorization is valid for one year and has to be renewed annually until fulfillment of all relevant conditions. Once the applicable pending studies are provided, a conditional marketing authorization can become a “standard” marketing authorization. However, if the conditions are not fulfilled within the timeframe set by the EMA, the marketing authorization will cease to be renewed. Prior to seeking accelerated approval, BBOT will seek feedback from the FDA, EMA or comparable foreign regulatory authorities and will otherwise evaluate BBOT’s ability to seek and receive such accelerated approval. There can be no assurance that after BBOT’s evaluation of the feedback and other factors BBOT will decide to pursue or submit an NDA for accelerated approval or any other form 64 Table of Contents of expedited development, review or approval. Similarly, there can be no assurance that after subsequent feedback from the FDA, EMA or comparable foreign regulatory authorities, BBOT will continue to pursue or apply for accelerated approval or any other form of expedited development, review or approval, even if BBOT initially decides to do so. Furthermore, if BBOT decides to submit an application for accelerated approval or any other form of expedited development, review or approval, there can be no assurance that such submission or application will be accepted or that any expedited development, review or approval will be granted on a timely basis, or at all. The FDA, EMA or other comparable foreign regulatory authorities could also require BBOT to conduct further studies prior to considering BBOT’s application or granting approval of any type. A failure to obtain accelerated approval or any other form of expedited development, review or approval for BBOT’s product candidate would result in a longer time period to commercialization of such product candidate, could increase the cost of development of such product candidate and could harm BBOT’s competitive position in the marketplace. BBOT may seek certain designations for its product candidates, including Breakthrough Therapy, Fast Track and Priority Review in the U.S., and PRIME (priority medicines) in the EU, but BBOT might not receive such designations, and even if BBOT does, such designations may not lead to a faster development or regulatory review or approval process. BBOT may seek certain designations for BBO-8520, BBO-10203 and BBO-11818 or future product candidates that could expedite review and approval by the FDA, such as Breakthrough Therapy or Fast Track designation for its product candidates, or priority review for its marketing applications for its candidates. A Breakthrough Therapy product is defined as a product that is intended, alone or in combination with one or more other products, to treat a serious condition, and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For products that have been designated as Breakthrough Therapies, early and frequent interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development. Sponsors may also have greater interactions with the FDA and the FDA may initiate review of sections of the NDA of a product candidate with Breakthrough Therapy designation before the application is complete. This rolling review may be available if the FDA determines, after preliminary evaluation of data submitted by the sponsor, that a product with Breakthrough Therapy designation may be effective. BBOT may also seek Fast Track designation for one or more of its product candidates. The FDA may designate a product for Fast Track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition. Like with Breakthrough Therapy designation, sponsors with Fast Track products may have greater FDA interactions and the FDA may initiate review of sections of a Fast Track product’s NDA before the application is complete if it determines, after its preliminary data evaluation, that the product may be effective. BBOT may also seek a priority review designation for one or more of its product candidates. If the FDA determines that a product candidate intended to treat a serious condition and, if approved, offers a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation shortens the goal for the FDA to review an application within six months, rather than the standard review period of ten months. These designations require a sponsor to submit an application for review and approval by the FDA. Accordingly, even if BBOT believes that one of its product candidates meets the criteria for these designations, the FDA may disagree and instead determine not to make such designation. Further, even if BBOT receives a designation, such as the Fast Track designation BBOT has received for BBO-8520 for the treatment of adult patients with previously treated, KRASG12C-mutated metastatic non-small cell lung cancer, the receipt of such designation for a product candidate may not result in a faster development or regulatory review or approval process compared to products considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if BBOT’s product candidates qualify for these designations, the FDA may later decide that the product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. In the EU, BBOT may seek support under the EMA’s PRIME scheme for some of its product candidates in the future. PRIME is a voluntary program launched by the EMA that is aimed at enhancing the scientific and regulatory support for the development and accelerated assessment of new product candidates that target an unmet medical need. PRIME aims to offer early and proactive support to sponsors to optimize the generation of robust data on the product’s benefits and risks and enable accelerated regulatory assessment of new marketing authorization applications. To be eligible for PRIME, a product candidate must meet the eligibility criteria with respect to its potential to offer a major therapeutic advantage over existing treatments, or benefit patients who do not have any treatment options. The benefits of PRIME include the appointment of a rapporteur from CHMP to provide continued support and help to build knowledge ahead of a marketing authorization application, early dialogue and scientific advice at key development milestones, and the potential to qualify products for accelerated review, meaning reduction in the review time for an opinion on approvability to be issued earlier in the application process. PRIME enables an applicant to request parallel EMA scientific advice and health technology assessment advice to facilitate timely market access. BBOT may apply for support under the PRIME scheme for some of its product candidates and it may 65 Table of Contents not be granted. Even if BBOT receives PRIME designation for any of its product candidates, the designation may not result in a materially faster development process, review or approval compared to conventional EMA procedures. Further, obtaining PRIME designation does not assure or increase the likelihood of EMA’s grant of a marketing authorization. BBOT may not be able to obtain orphan drug designation or obtain or maintain orphan drug exclusivity for its product candidates and, even if BBOT does, that exclusivity may not prevent the FDA, EMA or other comparable foreign regulatory authorities, from approving competing products. Regulatory authorities in some jurisdictions, including the U.S. and the EU, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product candidate as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the U.S., or a patient population greater than 200,000 in the U.S. where there is no reasonable expectation that the cost of researching and developing the drug will be recovered from sales in the U.S. BBOT’s target indications may include diseases with large patient populations or may include orphan indications. There can be no assurances that BBOT will be able to obtain orphan designation for its current product candidates or candidates BBOT may discover and develop in the future. In the U.S., orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. In addition, if a product candidate that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product candidate is entitled to orphan drug exclusivity. Orphan drug exclusivity in the U.S. provides that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same indication for seven years, except in limited circumstances. The applicable exclusivity period is 10 years in the EU. The EU exclusivity period can be reduced to six years if, at the end of the fifth year, it is determined that a drug no longer meets the criteria for orphan drug designation or if the drug is sufficiently profitable so that market exclusivity is no longer justified. Even if BBOT obtains orphan drug designation for a product candidate, BBOT may not be able to obtain or maintain orphan drug exclusivity for that product candidate. BBOT may not be the first to obtain marketing approval of any product candidate for which BBOT has obtained orphan drug designation, if applicable, for the orphan-designated indication due to the uncertainties associated with developing pharmaceutical products. In addition, exclusive marketing rights in the U.S. may be limited if BBOT seeks approval for an indication broader than the orphan-designated indication or may be lost if the FDA later determines that the request for designation was materially defective or if BBOT is unable to ensure that BBOT will be able to manufacture sufficient quantities of the product to meet the needs of patients with the rare disease or condition. Further, even if BBOT obtains orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs with different active moieties may be approved for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the same drug with the same active moiety for the same condition if the FDA concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care or the manufacturer of the product with orphan exclusivity is unable to maintain sufficient product quantity. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the product candidate any advantage in the regulatory review or approval process or entitles the product candidate to Priority Review. The FDA and Congress may further reevaluate the Orphan Drug Act and its regulations and policies. This may be particularly true in light of a decision from the Court of Appeals for the 11th Circuit in September 2021 finding that, for the purpose of determining the scope of exclusivity, the term “same disease or condition” means the designated “rare disease or condition” and could not be interpreted by the FDA to mean the “indication or use.” Thus, the court concluded, orphan drug exclusivity applies to the entire designated disease or condition rather than the “indication or use” for which a product is approved. On January 23, 2023, the FDA announced that, in matters beyond the scope of that court’s order, the FDA would continue to apply its existing regulations tying orphan drug exclusivity to the uses or indications for which the orphan drug was approved. BBOT does not know if, when, or how the FDA or Congress may change the orphan drug regulations and policies in the future, and it is uncertain how any changes might affect BBOT’s business. Depending on what changes the FDA may make to its orphan drug regulations and policies, BBOT’s business could be adversely impacted. Current and future legislative and regulatory reform measures and cost containment initiatives may increase the difficulty and cost for BBOT to obtain adequate reimbursement for its product candidates and may adversely affect the prices we may set. Current and future legislation and regulations may increase the difficulty and cost for us to commercialize our drugs, if approved, and affect the prices we may obtain, including changes in coverage and reimbursement policies in certain market segments for our product candidates, which could make it difficult for us to sell our product candidates, if approved, profitably. If any such changes were to be imposed, they could adversely affect the operation of our business. Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, including MFN proposals such as GLOBE, GUARD, and GENEROUS, bundled payment models, or other drug pricing reforms. In addition, recently there has been heightened governmental scrutiny over the manner 66 Table of Contents in which manufacturers set prices for their commercial products, which has resulted in several Congressional inquiries and proposed and enacted state and federal legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products. Congress has indicated that it will continue to seek new legislative measures to control drug costs. In the U.S. and some foreign jurisdictions, there have been and continue to be a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of BBOT’s product candidates, restrict or regulate post-approval activities and affect BBOT’s ability to profitably sell any products for which BBOT obtains marketing approval. BBOT expects that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that BBOT may receive for any approved products. If reimbursement of BBOT’s products is unavailable or limited in scope, BBOT’s business could be materially harmed. These laws and other healthcare reform measures may result in additional reductions in Medicare and other healthcare funding and otherwise affect the reimbursement BBOT may obtain for any of its product candidates for which BBOT may obtain regulatory approval or the frequency with which any such product is prescribed or used. BBOT expects that the PPACA, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in coverage and payments from private payors. Accordingly, the implementation of cost containment measures or other healthcare reforms may prevent BBOT from being able to generate revenue, attain profitability or commercialize its product candidates. At the U.S. state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription product and other health care programs. These measures could reduce the ultimate demand for BBOT’s products, once approved, or put pressure on product pricing. In addition, in some countries, including member states of the EU, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take a significant amount of time after the receipt of marketing approval for a product. In addition, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices, and in certain instances render commercialization in certain markets infeasible or disadvantageous from a financial perspective. In some countries, BBOT or its collaborators may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of BBOT’s products to other available products in order to obtain or maintain reimbursement or pricing approval. Publication of discounts by third party payors or government authorities may lead to further pressure on the prices or reimbursement levels. If reimbursement of BBOT’s products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, the commercial launch of BBOT’s products could be delayed, possibly for lengthy periods of time, BBOT or its collaborators may not launch at all in a particular country, BBOT may not be able to recoup its investment in one or more products, and there could be a material adverse effect on BBOT’s business. BBOT is or may become subject to stringent privacy laws, information security laws, regulations, policies and contractual obligations related to data privacy and security and changes in such laws, regulations, policies, contractual obligations and failure to comply with such requirements could subject BBOT to significant fines and penalties, which may have a material adverse effect on BBOT’s business, financial condition or results of operations. There are multiple privacy and data security laws that may impact BBOT’s business activities in the U.S. and in other countries where BBOT conducts trials or where BBOT may do business in the future. These laws are evolving and may increase both BBOT’s obligations and its regulatory risks in the future. In the health care industry generally, for example, under the Health Insurance Portability and Accountability Act of 1996 (HIPAA), HHS has issued regulations to protect the privacy and security of protected health information (PHI) used or disclosed by specific covered entities including certain healthcare providers, health plans and healthcare clearinghouses. BBOT is not currently classified as a covered entity or business associate under HIPAA. Thus, BBOT is not directly subject to HIPAA’s requirements or penalties. The healthcare providers, including certain research institutions from which BBOT may obtain patient or subject health information, may be subject to privacy, security, and breach notification requirements under HIPAA. Additionally, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles. Consequently, depending on the facts and circumstances, BBOT could face criminal penalties if BBOT knowingly receives individually identifiable health information from a HIPAA covered entity, business associate or subcontractor that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information. In addition, BBOT may maintain sensitive personally 67 Table of Contents identifiable information, including health and genetic information, that BBOT receives throughout the clinical trial process, in the course of BBOT’s research collaborations, and directly from individuals (or their healthcare providers) who may enroll in patient assistance programs if BBOT chooses to implement such programs. As such, in addition to risks and obligations related to HIPAA, BBOT also may be subject to various state and federal laws regulating the use or disclosure of this information or requiring notification of affected individuals and state regulators in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA. Refer to “Other U.S. Regulatory Matters” for more information on these state and federal laws. Data breach notification laws, consumer protection laws and genetic information laws may also apply directly to BBOT’s operations and/or those of BBOT’s collaborators and may impose restrictions on BBOT’s collection, use and dissemination of individuals’ health information. Individuals from whom BBOT or its collaborators may obtain health information, as well as the healthcare providers who may share this information with BBOT, may have statutory or contractual rights that limit the ability to use and disclose the information. BBOT may be required to expend significant capital and other resources to ensure ongoing compliance with applicable privacy and data security laws. Claims that BBOT has violated individuals’ privacy rights or breached its contractual obligations, even if BBOT is not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm BBOT’s business. Additionally, the collection, use, disclosure, transfer or other processing of personal data regarding individuals in the European Economic Area or EEA and the UK, including data concerning health, is subject to the EU General Data Protection Regulation, or EU GDPR, with respect to the EEA, and the UK General Data Protection Regulation, or UK GDPR, with respect to the UK, and collectively with the EU GDPR referred to as the “GDPR” in this report unless specified otherwise. The GDPR applies to companies established in the EEA/UK, as well as to any company established outside the EEA/UK, if they collect and use personal data in connection with the offering of goods or services to individuals in the EEA/UK or the monitoring of their behavior in the EEA/ Switzerland/UK. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, having legal bases and/or conditions for processing personal data, providing details to those individuals regarding the processing of their personal data, implementing safeguards to protect the security and confidentiality of personal data, having data processing agreements with third parties who process personal data, responding to individuals’ requests to exercise their rights in respect of their personal data, ensuring appropriate technical and organisational measures are in place and reporting security breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments, ensuring certain accountability measures are in place and record keeping. The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million (£17.5 million under the UK GDPR) or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. Brexit may adversely impact BBOT’s ability to obtain regulatory approvals for its product candidates in the EU, result in restrictions or imposition of taxes and duties for importing BBOT’s product candidates into the EU, and may require BBOT to incur additional expenses in order to develop, manufacture and commercialize BBOT’s product candidates in the EU. Disruptions at the FDA, the SEC and other government agencies or comparable regulatory authorities caused by funding shortages or global health concerns, in addition to continued uncertainty regarding the U.S. presidential administration’s initiatives and staffing cuts and how these might impact the FDA, its implementation of laws, regulations, policies and guidance, and its personnel, could hinder government agencies’ ability to hire and retain key leadership and other personnel, or otherwise prevent new products and services from being developed or commercialized in a timely manner, or otherwise prevent those agencies from performing normal business functions on which BBOT’s business operations rely, including timely reviews, which could negatively impact BBOT’s business. The ability of the FDA or comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes that may otherwise affect the FDA’s or comparable foreign regulatory authorities’ ability to perform routine functions. In addition, government funding of the SEC and other government agencies or comparable foreign regulatory authorities on which BBOT’s operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other agencies, including substantial leadership departures, personnel cuts, and policy changes, may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would harm BBOT’s business. Changes and cuts in FDA staffing could result in delays in the FDA’s responsiveness or in its ability to review IND submissions or applications, issue regulations or guidance, or implement or enforce regulatory requirements in a timely fashion or at all. 68 Table of Contents Similar consequences would also result in the event of another significant shutdown of the federal government. For example, over the last several years, the U.S. federal government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop critical activities. If a prolonged government shutdown occurs, or if geopolitical or global health concerns prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA to timely review and process BBOT’s regulatory submissions, which could materially adversely affect BBOT’s business, financial condition, results of operations and prospects. Such changes could significantly impact the ability of the FDA to timely review and take action on BBOT’s regulatory submissions, which could have a material adverse effect on BBOT’s business, including INDs placed on clinical holds or delayed new drug approvals. Further, in BBOT’s operations as a public company, future government shutdowns or substantial leadership, personnel, and policy changes could impact BBOT’s ability to access the public markets and obtain necessary capital in order to properly capitalize and continue BBOT’s operations. If the FDA is constrained in its ability to engage in oversight and implementation activities in the normal course, BBOT’s business may be negatively impacted. With the change in the U.S. presidential administration in 2025, there continues to be substantial uncertainty as to whether and how the administration will seek to modify or revise the requirements and policies of the FDA and other regulatory agencies with jurisdiction over BBOT’s product candidates and any products for which BBOT obtains approval. This uncertainty could present new challenges and/or opportunities as BBOT navigates development and approval of BBOT’s product candidates. Some of these efforts have manifested to date in the form of personnel cuts and measures that could impact the FDA’s ability to hire and retain key personnel, which could result in delays or limitations on BBOT’s ability to obtain guidance from the FDA on BBOT’s product candidates in development and obtain the requisite regulatory approvals in the future. There remains general uncertainty regarding future activities. The current administration could issue or promulgate executive orders, regulations, policies or guidance that adversely affect BBOT or create a more challenging or costly environment to pursue the development of new therapeutic products. Alternatively, state governments may attempt to address or react to changes at the federal level with changes to their own regulatory frameworks in a manner that is adverse to BBOT’s operations. If BBOT becomes negatively impacted by future governmental orders, regulations, policies or guidance as a result of the new administration, there could be a material adverse effect on BBOT and its business. If BBOT’s product candidates are licensed for marketing and receive federal healthcare reimbursement, any relationships BBOT may have with healthcare providers will be subject to applicable healthcare fraud and abuse laws and regulations, which could expose BBOT to criminal and civil penalties and exclusion from participation in government healthcare programs. Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of any products for which BBOT is able to obtain marketing approval. Any arrangements BBOT has with healthcare providers, third-party payors and customers will subject BBOT to broadly applicable fraud and abuse and other healthcare laws and regulations. The laws and regulations may constrain the business or financial arrangements and relationships through which BBOT conducts clinical research, markets, sells and distributes any products for which BBOT obtains marketing approval. These include the laws and regulations described in the section titled “Other U.S. Regulatory Matters” included elsewhere in this Form 10-K. The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the EU. Infringement of these laws could result in substantial fines and imprisonment. Payments made to physicians in certain EU Member States must be publicly disclosed. Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual EU Member States. These requirements are provided in the national laws, industry codes or professional codes of conduct applicable in the EU Member States. BBOT’s failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment. Efforts to ensure that any business arrangements BBOT has with third parties and BBOT’s business generally will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that BBOT’s business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If BBOT’s operations are found to be in violation of any of these laws or any other governmental regulations that may apply to BBOT, BBOT may be subject to significant civil, criminal and administrative penalties, damages, fines, individual imprisonment, additional reporting requirements and oversight if BBOT becomes subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, disgorgement, contractual damages, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of BBOT’s operations. Defending against any such actions in connection with these laws can be costly and time-consuming and may require significant financial and personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired. Further, if any of the physicians or other healthcare providers or entities with whom we expect to do business are found not to be in compliance with applicable laws or regulations, they may be subject to significant criminal, civil, or administrative sanctions, including exclusions from government-funded healthcare programs. If any of the above occur, our ability to operate our business and our results of operations could be adversely affected. 69 Table of Contents BBOT’s employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, suppliers and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements. BBOT is exposed to the risk that its employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, suppliers and vendors may engage or may have engaged in fraud, misconduct or other improper activities. Misconduct by these parties could include failures to comply with FDA, EMA or comparable foreign regulatory authority regulations, provide accurate information to the FDA, EMA or comparable foreign regulatory authorities, comply with federal and state health care fraud and abuse laws and regulations, accurately report financial information or data or disclose unauthorized activities to BBOT. In particular, research, sales, marketing and business arrangements in the health care industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Misconduct by these parties could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to BBOT’s reputation. BBOT has adopted a code of conduct and engages contractors that agree to undertake certain measures with respect to their employees, but it is not always possible to identify and deter misconduct by these parties, and the precautions BBOT takes to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting BBOT from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. If any such actions are instituted against BBOT, and BBOT is not successful in defending itself or asserting its rights, those actions could have a significant impact on BBOT’s business, including the imposition of significant penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings and the curtailment or restructuring of BBOT’s operations. BBOT’s business activities may be subject to the U.S. Foreign Corrupt Practices Act (FCPA) and similar anti-bribery and anti-corruption laws of other countries in which BBOT operates, as well as U.S. and certain foreign export controls, economic sanctions, import, and trade and national security laws and regulations. Compliance with these legal requirements could limit BBOT’s ability to compete in foreign markets and subject BBOT to liability if BBOT violates them. BBOT’s business activities may be subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which BBOT operates. The FCPA generally prohibits companies and their employees and third-party intermediaries from offering, promising, giving or authorizing others to give anything of value, either directly or indirectly, to a non-U.S. government official in order to influence official action or otherwise obtain or retain business. The FCPA also requires public companies to make and keep books and records that accurately and fairly reflect the transactions of the corporation and to devise and maintain an adequate system of internal accounting controls. BBOT’s business is heavily regulated and therefore involves significant interaction with public officials, including officials of non-U.S. governments. Additionally, in many other countries, hospitals are owned and operated by the government, and doctors and other hospital employees would be considered foreign officials under the FCPA. The biotechnology and pharmaceutical industries have historically presented a heightened risk profile for FCPA enforcement. There is no certainty that all of BBOT’s employees, agents or contractors, or those of BBOT’s affiliates, will comply with all applicable laws and regulations, particularly given the high level of complexity of these laws. Violations of these laws and regulations could result in fines, criminal sanctions against BBOT, its officers or employees, disgorgement, and other sanctions and remedial measures, and prohibitions on the conduct of BBOT’s business. Any such violations could include prohibitions on BBOT’s ability to offer its products in one or more countries and could materially damage BBOT’s reputation, brand, international activities, ability to attract and retain employees and business, prospects, operating results and financial condition. In addition, BBOT’s business activities (including conduct of clinical trials) and products may be subject to U.S. and foreign export controls, economic sanctions, import and trade and national security laws and regulations. Governmental regulation of the import or export of BBOT’s products, or BBOT’s failure to obtain any required import or export authorization for its products, when applicable, could harm BBOT’s international or domestic sales and adversely affect revenue. Compliance with applicable regulatory requirements regarding the conduct of clinical trials and export of BBOT’s products may create delays in the introduction of BBOT’s products in international markets or, in some cases, prevent the export of BBOT’s products to some countries altogether. Furthermore, U.S. export control laws and economic sanctions prohibit certain transactions and the shipment of certain products and services to countries, governments, and persons targeted by U.S. sanctions. If BBOT fails to comply with export and import regulations and such economic sanctions, penalties could be imposed, including fines and/or denial of certain export privileges and reputational harm. Moreover, any new export controls, import restrictions, economic sanctions, national security policy, new legislation or shifting approaches in the enforcement or scope of existing regulations, or in the countries, persons, or products targeted by such regulations, could result in decreased use of BBOT’s products by, or in BBOT’s decreased ability to export its products to, existing or potential customers with international operations, in addition to adversely affecting cross-border operations and transactions. Any decreased use of BBOT’s products or limitation on BBOT’s ability to export or sell its products, or import materials for its products, would likely adversely affect BBOT’s business. For instance, the U.S. Department of Justice’s Bulk Data Rule, which went into effect April 8, 2025 70 Table of Contents prohibits certain covered data transactions (including for human ‘omic and personal health data) and establishing data security requirements for restricted transactions involving China, Russia, and other countries of concern on national security grounds. The regulations also restrict certain investment agreements, employment agreements and vendor agreements involving such data and countries of concern, absent specified cybersecurity controls. Actual or alleged violations of these regulations may be punishable by criminal and/or civil sanctions, and may result in exclusion from participation in federal and state programs. More recently, tariffs have been proposed on products from Canada, China, Mexico and potentially other countries, which could have the effect of disrupting, and increasing costs associated with, BBOT’s supply chain of materials and other imports needed for its operations and business in the United States. The course of trade relations between the United States and other countries is difficult to predict, including how operations, transactions, products, and services may be impacted by the respective trade policies of the United States and other countries (including those in retaliation). If BBOT is unable to conduct transactions, obtain or use services, or export or sell products or services to third parties, including vendors, customers, and partners in other countries, BBOT’s business, liquidity, financial condition, or operations would be materially and adversely affected. If BBOT fails to comply with applicable environmental, health and safety laws and regulations, BBOT could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of BBOT’s business. BBOT is subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures, and the handling, use, storage, treatment and disposal of hazardous materials and wastes. BBOT’s operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials. BBOT’s operations also produce hazardous waste products. BBOT generally contracts with third parties for the disposal of these materials and wastes. BBOT cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from BBOT’s use of hazardous materials, BBOT could be held liable for any resulting damages, and any liability could exceed BBOT’s resources. BBOT also could incur significant costs associated with civil or criminal fines and penalties. Although BBOT maintains workers’ compensation insurance to cover BBOT for costs and expenses BBOT may incur due to injuries to its employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. BBOT does not maintain insurance for environmental liability or toxic tort claims that may be asserted against BBOT in connection with BBOT’s storage or disposal of biological, hazardous or radioactive materials. Compliance with applicable environmental, health and safety laws and regulations is expensive, and current or future environmental regulations may impair BBOT’s business, prospects, financial condition or results of operations. Risks Related to BBOT’s Business BBOT’s success is highly dependent on BBOT’s ability to attract, hire and retain highly skilled executive officers and employees, and BBOT may experience difficulties in managing the future growth of BBOT’s organization. BBOT currently has a small team focused on research and development of RAS-pathway targeted small molecules. To succeed, BBOT must recruit, hire, retain, manage and motivate qualified clinical, scientific, technical, financial and management personnel, and BBOT faces significant competition for experienced personnel. Personnel with the required skills and experience may be scarce or may not be available at all. In addition, competition for these skilled personnel is intense and recruiting and retaining skilled employees is difficult, particularly for a development-stage company such as BBOT. Even if BBOT is successful in identifying, attracting, hiring and retaining qualified employees, recent market changes, including labor shortages, and rising inflation have increased employee-related costs substantially, which may negatively affect BBOT’s operating results. BBOT is highly dependent on the principal members of its management and scientific and medical staff. If BBOT does not succeed in attracting and retaining qualified personnel in these positions, it could adversely affect BBOT’s ability to execute its business plan and harm its operating results. In particular, the loss of one or more of BBOT’s executive officers could be detrimental if BBOT cannot recruit suitable replacements in a timely manner. Many of the other biotechnology companies that BBOT competes against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than BBOT does. They also may provide higher compensation, more diverse opportunities and better prospects for career advancement. Some of these characteristics may be more appealing to high-quality candidates than what BBOT has to offer. If BBOT is unable to continue to attract and retain high-quality personnel, the rate and success at which BBOT can discover, develop and commercialize its product candidates will be limited and the potential for successfully growing BBOT’s business will be harmed. Additionally, BBOT relies on its clinical advisory board and other scientific and clinical advisors and consultants to assist BBOT in formulating its research, development and clinical strategies. Most of these advisors and consultants are not BBOT’s employees and may have commitments to, or consulting or advisory contracts with, other entities that may limit their availability. In addition, these advisors and consultants typically will not enter into non-compete agreements with BBOT. If a conflict of interest arises between their 71 Table of Contents work for BBOT and their work for another entity, BBOT may lose their services. Furthermore, BBOT’s advisors may have arrangements with other companies to assist those companies in developing products or technologies that may compete with BBOT’s. In particular, if BBOT is unable to maintain consulting or employment relationships with other scientific and clinical advisors, or if they provide services to BBOT’s competitors, BBOT’s development and commercialization efforts will be impaired and BBOT’s business will be significantly harmed. For example, if BBOT is no longer able to access its network of physician-scientists, BBOT’s ability to define and characterize patients’ needs for future product candidate development may be negatively affected. In order to successfully implement BBOT’s development and commercialization plans and strategies, and as BBOT grows as a public company, BBOT expects to need significant additional managerial, operational, financial, sales, marketing and other personnel. Future growth will impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining, retaining and motivating BBOT’s current and additional employees; • managing BBOT’s internal development efforts effectively, including the preclinical, clinical, FDA, EMA and other comparable foreign regulatory authorities’ review process for BBO-8520, BBO-10203 and BBO-11818 and BBOT’s discovery programs, while complying with any contractual obligations to contractors and other third parties; • managing increasing operational and managerial complexity; and • improving BBOT’s operational, financial and management controls, reporting systems and procedures. BBOT currently relies, and for the foreseeable future will continue to rely, in substantial part on certain independent organizations, advisors and consultants to provide certain services, including key aspects of research, clinical development and manufacturing. There can be no assurance that the services of independent organizations, advisors and consultants will continue to be available to BBOT on a timely basis when needed, or that BBOT can find qualified replacements. In addition, if BBOT is unable to effectively manage its outsourced activities or if the quality or accuracy of the services provided by third-party service providers is compromised for any reason, BBOT’s preclinical studies and clinical trials may be extended, delayed or terminated, and BBOT may not be able to obtain marketing approval for any of its product candidates or otherwise advance its business. There can be no assurance that BBOT will be able to manage its existing third-party service providers or find other competent outside contractors and consultants on economically reasonable terms, or at all. If BBOT is not able to effectively expand its organization by hiring new employees and/or engaging additional third-party service providers, BBOT may not be able to successfully implement the tasks necessary to further develop and commercialize BBO-8520, BBO-10203 and BBO-11818 or any future product candidate from BBOT’s discovery programs and, accordingly, may not achieve its research, development and commercialization goals. BBOT’s reliance on a limited number of employees who provide various administrative, research and development, and other services across BBOT’s organization presents operational challenges that may adversely affect BBOT’s business. As of December 31, 2025, BBOT had 92 full-time employees, upon whom BBOT relies for various administrative, research and development, and other services. The small size of BBOT’s team may limit BBOT’s ability to devote adequate personnel, time, and resources to support BBOT’s operations or research and development activities, and the management of financial, accounting, and reporting matters. If BBOT’s team fails to provide adequate administrative, research and development, or other services across BBOT’s organization, its business, financial condition, and results of operations could be harmed. 72 Table of Contents BBOT’s internal computer systems, or those of any of BBOT’s CROs, manufacturers, other contractors or consultants or potential future collaborators, may fail or suffer actual or suspected security incidents, data breaches or other unauthorized or improper access to, use of, or destruction of BBOT’s proprietary or confidential data, employee data, or personal data. Such security incidents, data breaches, and other unauthorized activities could result in additional costs, loss of revenue, significant liabilities, harm to BBOT’s brand, material disruption of BBOT’s operations, and potentially significant delays in BBOT’s delivery to market. Despite the implementation of security measures, BBOT’s systems and the systems of BBOT’s third-party CROs, other contractors (including sites performing BBOT’s clinical trials) and consultants may be vulnerable to breakdown or other damage or interruption from service interruptions, system malfunction, natural disasters, terrorism, war and telecommunication and electrical failures, as well as security incidents or data breaches. BBOT and the third parties upon which BBOT relies face a variety of evolving threats, including from inadvertent or intentional actions by BBOT’s employees, contractors, consultants, business partners, and/or other third parties as well as from cyber-attacks by malicious third parties (including the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering (including phishing attacks) and other means to affect service reliability and threaten the confidentiality, integrity and availability of information). Security incidents, data breaches and other adverse activity may compromise BBOT’s system infrastructure or lead to the loss, destruction, alteration or dissemination of, or damage to, BBOT’s data. These attacks and activity are also being facilitated or enhanced by evolving technologies, including artificial intelligence. The risk of a security incident, data breach or other disruption through cyber-attacks has generally increased as the number, intensity and sophistication of attempted attacks from around the world have increased. Attempts to disrupt or gain unauthorized access to BBOT’s and BBOT’s third-party vendors’ information systems from malicious third parties or insider threats may incorporate widely varying and frequently changing tactics, which may be enhanced or facilitated by artificial intelligence. Also, many of BBOT’s employees are working remotely. As a result, BBOT may have increased cybersecurity and data security risks, due to increased use of home wi-fi networks and virtual private networks, as well as increased disbursement of physical machines. While BBOT implements IT controls to reduce the risk of a security incident or data breach, there is no guarantee that these measures will be adequate to safeguard all systems. Like other companies in the industry, BBOT, and BBOT’s third party vendors, have experienced threats and security incidents relating to their information technology systems and infrastructure. To the extent that any disruption, security incident, or data breach were to result in a loss, destruction, unavailability, alteration or dissemination of, or damage to, BBOT’s data (including confidential information and personal data) or applications, or for it to be believed or reported that any of these occurred, BBOT could incur liability and reputational damage. Further, in such an event, the development and commercialization of BBOT’s product candidates could be delayed. There can be no assurance that BBOT’s data protection efforts, or the efforts or investments of CROs, consultants or other third parties, will prevent significant breakdowns, data breaches or other security incidents that cause loss, destruction, unavailability, alteration or dissemination of, or damage to, BBOT’s data. Such events could have a material adverse effect upon BBOT’s reputation, business, operations or financial condition. For example, if such an event were to occur and cause interruptions in BBOT’s operations, it could result in a material disruption of BBOT’s programs and the development of BBOT’s product candidates could be delayed. In addition, the loss of clinical trial data for BBOT’s product candidates could result in delays in BBOT’s marketing approval efforts and significantly increase BBOT’s costs to recover or reproduce the data, as well as claims or investigations from regulators or other third parties. Furthermore, significant disruptions of BBOT’s internal information technology systems, security incidents or data breaches could result in the loss, misappropriation, and/or unauthorized access, use, or disclosure of, or the prevention of access to, data (including trade secrets or other confidential information, intellectual property, proprietary business information, and personal data), which could result in financial, legal, business, and reputational harm to BBOT. Such harm may include significant expenses, remediation costs, litigation, disputes, claims by third parties and regulatory actions or investigations. For example, any such event that leads to unauthorized access, use, or disclosure of personal data, including personal data regarding BBOT’s clinical trial subjects or employees, could harm BBOT’s reputation directly, compel BBOT to comply with federal and/or state breach notification laws and foreign law equivalents, subject BBOT to financial exposure related to the investigation of the security incident or data breach (including cost of forensic examinations), subject BBOT to mandatory corrective action, and otherwise subject BBOT to liability under laws and regulations that protect the privacy and security of data, which could result in significant legal and financial exposure and reputational damages that could potentially have a material adverse effect on BBOT’s business. Notifications, follow-up actions, claims and investigations related to a security incident or data breach could impact BBOT’s reputation and cause BBOT to incur significant costs, including legal expenses and remediation costs. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in BBOT’s regulatory approval efforts and significantly increase BBOT’s costs to recover or reproduce the lost data. BBOT expects to incur significant costs in an effort to detect and prevent security incidents and data breaches, and BBOT may face increased costs and requirements to expend substantial resources in the event of an actual or perceived security incident or data breach. BBOT also relies on third parties to manufacture its product candidates, and similar events relating to their computer systems could also have a material adverse effect on BBOT’s business. To the extent that any disruption, data breach or security incident were to result in a loss, destruction or alteration of, or damage to, BBOT’s data (including personal data), or inappropriate disclosure of confidential or proprietary information, BBOT could be exposed to litigation and governmental investigations. Moreover, the further development and commercialization of BBOT’s product candidates could be delayed, and BBOT could be subject to significant fines or penalties for any noncompliance with state, federal and/or international privacy and security laws. 73 Table of Contents BBOT’s contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in those contracts are sufficient to protect BBOT from liabilities, damages, or claims related to its privacy and data security obligations. BBOT’s insurance policies may not be adequate to compensate BBOT for the potential losses arising from any such disruption in, or failure, security incident, or data breach of, BBOT’s systems or third-party systems where information important to BBOT’s business operations or commercial development is stored. In addition, such insurance may not be available to BBOT in the future on economically reasonable terms, or at all. Further, BBOT’s insurance may not cover all claims made against BBOT and could have high deductibles in any event, and defending a suit, regardless of its merit, could be costly and divert management attention. BBOT’s use of new and evolving technologies, such as artificial intelligence, may present risks and challenges that can impact BBOT’s business, including by posing cybersecurity and other risks to BBOT’s confidential and/or proprietary information, including personal information, and as a result BBOT may be exposed to reputational harm and liability. BBOT may use and integrate artificial intelligence into BBOT’s business processes, and this innovation presents risks and challenges that could affect its adoption, and therefore BBOT’s business. Use of this technology could pose cybersecurity, data privacy, IT, intellectual property, regulatory, legal, operational, competitive, reputational and other risks and challenges that could affect BBOT’s business. The rapid evolution of artificial intelligence will require the application of significant resources to design, develop, test and maintain BBOT products and services to help ensure that artificial intelligence is implemented in accordance with applicable law and regulation and in a socially responsible manner and to minimize any real or perceived unintended harmful impacts. The development of artificial intelligence models requires resources for design, development, testing and maintenance. If BBOT enables or uses models that contain actual or perceived biases, or otherwise draws controversy due to perceived or actual negative societal impact, BBOT may experience brand or reputational harm, competitive harm or legal liability. In addition, the use of artificial intelligence technologies can give rise to intellectual property risks, including the disclosure or compromise of BBOT’s confidential information or other proprietary intellectual property through the use of generative AI tools, or the ability to assert or defend ownership rights in intellectual property created with the use of generative artificial intelligence tools. Further, BBOT expects to see increasing government and supranational regulation related to artificial intelligence use and ethics, which may also significantly increase the burden and cost of research, development and compliance in this area. For example, the EU’s Artificial Intelligence Act (“ AI Act ”) originally entered into force on August 1, 2024, and is expected to undergo amendments as introduced in the EU’s November 2025 Digital Omnibus on AI. As enacted, the AI Act imposes significant obligations on providers and deployers of high-risk artificial intelligence systems, and encourages providers and deployers of artificial intelligence systems to account for EU ethical principles in their development and use of these systems. The scope of requirements depends on judicial interpretations and forthcoming legislative amendments, and non-compliance can lead to significant fines. Likewise, in the U.S., the regulatory environment is complex and uncertain. President Trump's Executive Order "Ensuring a National Policy Framework for Artificial Intelligence," effective December 11, 2025, directed federal agency reviews of state AI laws and coordination between White House advisors and Congress to reach a legislative proposal for a uniform federal AI policy framework. At the same time, several states, including Colorado and California, passed laws that regulate various facets of AI, some of which have taken effect and will continue to take effect through 2026 and beyond. These laws address a wide range of AI-related topics, including consequential decisions, transparency, training data, among others, and it remains unclear which requirements, if any, will be superseded by the Executive Order. So far, these efforts have not been successful in curtailing state action on AI regulation, contributing to a complicated legislative patchwork, which may be litigated in state and federal courts. Various federal and state regulators have also issued guidance and focused enforcement efforts on the use of AI in regulated sectors. The FDA, for example, issued guidance on the use of artificial intelligence in medical devices, requiring detailed risk management and review processes to obtain approvals. If BBOT develops or uses AI systems that are governed by the these laws or regulations, BBOT will need to meet higher standards of data quality, transparency, and human oversight, and BBOT would need to adhere to specific and potentially burdensome and costly ethical, accountability, and administrative requirements. BBOT may also be subject to significant enforcement or litigation in the event of any perceived non-compliance. BBOT’s vendors may in turn incorporate AI tools into their offerings, and the providers of these AI tools may not meet existing or rapidly evolving regulatory or industry standards, including with respect to privacy and data security. Further, bad actors around the world use increasingly sophisticated methods, including the use of artificial intelligence, to engage in illegal activities involving the theft and misuse of personal information, confidential information and intellectual property. In addition, the use of generative AI models in BBOT’s internal or third-party systems may create new attack surfaces or methods for adversaries, which could impact BBOT and its vendors. The integration of AI systems, by BBOT or by its vendors, may increase cybersecurity risk. Any of these effects could 74 Table of Contents damage BBOT’s reputation, result in the loss of valuable property and information, cause BBOT to breach applicable laws and regulations, and adversely impact BBOT’s business. BBOT’s operations are vulnerable to interruption by flood, fire, earthquakes, power loss, telecommunications failure, terrorist activity, pandemics and other events beyond BBOT’s control, which could harm BBOT’s business. BBOT’s corporate headquarters are located in South San Francisco, California. BBOT has not undertaken a systematic analysis of the potential consequences to its business and financial results from a major flood, fire, earthquake, power loss, telecommunications failure, terrorist activity, pandemic or other disasters and BBOT does not have a recovery plan for such disasters. In addition, BBOT does not carry sufficient insurance to compensate for actual losses from interruption of BBOT’s business that may occur, and any losses or damages incurred by BBOT could harm BBOT’s operations and financial condition and increase costs and expenses. BBOT has never commercialized a product candidate as a company before. If BBOT is unable to establish sales or marketing capabilities or enter into agreements with third parties to sell or market BBOT’s product candidates, BBOT may not be able to successfully sell or market its product candidates that obtain regulatory approval. BBOT has never commercialized a product and currently does not have and has never had a significant marketing or sales team. In order to commercialize any product candidates, if approved, BBOT must build marketing, sales, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these services for each of the territories in which BBOT may have approval to sell or market its product candidates. BBOT may not be successful in accomplishing these required tasks. Establishing an internal sales or marketing team with technical expertise and supporting distribution capabilities to commercialize BBOT’s product candidates will be expensive and time-consuming and will require significant attention of BBOT’s executive officers to manage. Any failure or delay in the development of BBOT’s internal sales, marketing and distribution capabilities could adversely impact the commercialization of any of BBOT’s product candidates that BBOT obtains approval to market if BBOT does not have arrangements in place with third parties to provide such services on its behalf. Alternatively, if BBOT chooses to collaborate, either globally or on a territory-by-territory basis, with third parties that have direct sales forces and established distribution systems, either to augment BBOT’s own sales force and distribution systems or in lieu of BBOT’s own sales force and distribution systems, BBOT will be required to negotiate and enter into arrangements with such third parties relating to the proposed collaboration and such arrangements may prove to be less profitable than commercializing the product on BBOT’s own. If BBOT is unable to enter into such arrangements when needed, on acceptable terms or at all, BBOT may not be able to successfully commercialize any of its product candidates that receive regulatory approval, or any such commercialization may experience delays or limitations. If BBOT is unable to successfully commercialize its approved product candidates, either on its own or through collaborations with one or more third parties, BBOT’s future product revenue will suffer, and BBOT may incur significant additional losses. A variety of risks associated with marketing BBOT’s product candidates internationally could materially adversely affect BBOT’s business. BBOT may seek regulatory approval of its product candidates outside of the U.S. and, accordingly, BBOT expects that it will be subject to additional risks related to operating in foreign countries if BBOT obtains the necessary approvals, including: • differing regulatory requirements and reimbursement regimes in foreign countries, such as the lack of pathways for accelerated drug approval, may result in foreign regulatory approvals taking longer and being more costly than obtaining approval in the U.S.; • foreign regulatory authorities may disagree with the design, implementation or results of BBOT’s clinical trials or BBOT’s interpretation of data from preclinical studies or clinical trials; • approval policies or regulations of foreign regulatory authorities may significantly change in a manner rendering BBOT’s clinical data insufficient for approval; • the impact of pandemics or other public health emergencies, natural disasters and geopolitical events on BBOT’s ability to produce its product candidates and conduct clinical trials in foreign countries; • unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with legal requirements applicable to privacy, data protection, information security and other matters; 75 Table of Contents • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign taxes, including withholding of payroll taxes; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • difficulties staffing and managing foreign operations; • complexities associated with managing multiple payor reimbursement regimes and government payors in foreign countries; • workforce uncertainty in countries where labor unrest is more common than in the U.S.; • potential liability under the FCPA or comparable foreign regulations; • challenges enforcing BBOT’s contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the U.S.; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • business interruptions resulting from geopolitical events, including war and terrorism, trade policies, treaties and tariffs. These and other risks associated with international operations may materially adversely affect BBOT’s ability to attain or maintain profitable operations. Changes in tax law could adversely affect BBOT’s business and financial condition. The rules dealing with U.S. federal, state, and local income taxation are constantly under review by persons involved in the legislative process and by the Internal Revenue Service, the U.S. Treasury Department and other applicable tax authorities. Changes to tax laws (which changes may have retroactive application) could adversely affect BBOT or holders of BBOT common stock. In recent years, many such changes have been made and changes are likely to continue to occur in the future. Future changes in tax laws could have a material adverse effect on BBOT’s business, cash flow, financial condition or results of operations. BBOT’s ability to utilize its net operating loss carryforwards and certain other tax attributes to offset future taxable income may be limited. BBOT’s federal net operating loss (“ NOL ”) carryforwards may be unavailable to offset future taxable income because of restrictions under U.S. tax law. Under the Tax Cut and Jobs Act, as amended by the Coronavirus Aid, Relief, and Economic Security Act, BBOT’s federal NOLs may be carried forward indefinitely, but for taxable years beginning after December 31, 2020, the deductibility of federal NOL carryforwards generated in tax years beginning after December 31, 2017 is limited to 80% of BBOT’s current year taxable income. As of December 31, 2025, BBOT had available federal NOL carryforwards of approximately $148.8 million and available state NOL carryforwards of approximately $129.8 million. In addition, under Section 382 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change” (generally defined as a cumulative change in the corporation’s ownership by “5-percent shareholders” that exceeds 50 percentage points (by value) over a rolling three-year period), the corporation’s ability to use its pre-change NOL carryforwards and certain other pre-change tax attributes to offset its post-change taxable income may be limited. Similar rules may apply under state tax laws. BBOT may have experienced such ownership changes in the past, and BBOT may experience ownership changes in the future as a result of shifts in BBOT’s stock ownership, some of which are outside BBOT’s control. There is also a risk that due to regulatory changes, such as suspensions on the use of NOL carryforwards, or other unforeseen reasons, BBOT’s existing NOL carryforwards could expire or otherwise be unavailable to offset future income tax liabilities. BBOT’s ability to utilize BBOT’s NOL carryforwards could have a material adverse effect on BBOT’s cash flows and results of operations. If BBOT engages in future acquisitions or strategic partnerships, this may increase BBOT’s capital requirements, dilute BBOT’s stockholders, cause BBOT to incur debt or assume contingent liabilities, and subject BBOT to other risks. From time to time, BBOT evaluates various acquisition opportunities and strategic partnerships, including licensing or acquiring complementary products, product candidates, intellectual property rights, technologies or businesses. Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption of additional indebtedness or contingent liabilities; 76 Table of Contents • the issuance of BBOT’s equity securities; • assimilation of operations, intellectual property, products and product candidates of an acquired company, including difficulties associated with integrating new personnel; • the diversion of BBOT’s management’s attention from its existing programs and initiatives in pursuing such a strategic merger or acquisition; • retention of key employees, the loss of key personnel and uncertainties in BBOT’s ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products, product candidates and marketing approvals; and • BBOT’s inability to generate revenue from acquired technology and/or products sufficient to meet BBOT’s objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs. In addition, if BBOT undertakes acquisitions or pursues partnerships in the future, BBOT may issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expense. Adverse events in the field of oncology or the biopharmaceutical industry could damage public perception of BBOT’s current or future product candidates and negatively affect BBOT’s business. The commercial success of BBOT’s products, if approved, will depend in part on public acceptance of the use of targeted cancer therapies. While a number of targeted cancer therapies have received regulatory approval and are being commercialized, BBOT’s approach to targeting cancer cells carrying tumor causing mutations, including oncogenic RAS pathway mutations, is novel and unproven. Adverse events in clinical trials of BBOT’s product candidates, or post-marketing activities, or in clinical trials of others developing similar products or that are related to approved targeted therapies, particularly those targeting oncogenic RAS pathway mutations, including sotorasib and adagrasib and the resulting publicity, as well as any other adverse events in the field of oncology that may occur in the future, could result in a decrease in demand for any product that BBOT may develop. If public perception is influenced by claims that the use of cancer therapies is unsafe, whether related to BBOT therapies or those of BBOT’s competitors, BBOT’s product candidates or products, if approved, may not be accepted by the general public or the medical community. Future adverse events in oncology or the biopharmaceutical industry could also result in greater government regulation, stricter labeling requirements and potential regulatory delays in the testing or approvals of BBOT’s products. Any increased scrutiny could delay or increase the costs of obtaining marketing approval for BBOT’s current or future product candidates. Risks Related to BBOT’s Intellectual Property Derivation proceedings may be necessary to determine priority of inventions, and an unfavorable outcome may require BBOT to cease using the related technology or to attempt to license rights from the prevailing party. Derivation proceedings provoked by third parties or brought by BBOT or declared by the U.S. Patent and Trademark Office (“ USPTO ”) may be necessary to determine the priority of inventions with respect to one or more of BBOT’s patents or patent applications or those of BBOT’s future licensors. An unfavorable outcome may require BBOT to cease using the related technology or to attempt to license rights to it from the prevailing party. BBOT’s business could be adversely affected if the prevailing party does not offer BBOT a license on commercially reasonable terms. BBOT’s defense of derivation proceedings may fail and, even if successful, may result in substantial costs and distract BBOT’s management and other employees. In addition, the uncertainties associated with such proceedings could have a material adverse effect on BBOT’s ability to raise the funds necessary to continue BBOT’s clinical trials and development programs, license necessary technology from third parties or enter into development or manufacturing partnerships that would help BBOT bring its product candidates to market. If BBOT is unable to obtain, maintain and enforce patent protection for its technology and product candidates, or if the scope of the patent protection obtained is not sufficiently broad, BBOT’s competitors could develop and commercialize technology and products similar or identical to BBOT’s, and BBOT’s ability to successfully develop and commercialize its technology and product candidates may be adversely affected. BBOT’s success depends in large part on its ability to obtain and maintain protection of the intellectual property rights BBOT owns (either solely and jointly with others), or may in the future license from third parties (in particular, worldwide patents relating to any proprietary technology and product candidates BBOT develops). BBOT seeks to protect its proprietary position by filing patent 77 Table of Contents applications in the U.S. and select other countries related to its technologies and product candidates that are important to its business and by in-licensing intellectual property related to such technologies and product candidates. BBOT does not yet have issued patents for all of its most advanced product candidates in all markets in which BBOT may commercialize them, but BBOT continues to actively pursue patent protection for its technology and product candidates in certain jurisdictions around the world. However, BBOT cannot guarantee that patents will be granted with respect to any of its pending patent applications or with respect to any patent applications BBOT may file in the future, nor can BBOT be sure that any patents that may be granted to BBOT in the future will be commercially useful in protecting BBOT’s products, or the methods of use or manufacture of those products. If BBOT is unable to obtain and maintain meaningful patent protection in jurisdictions important to BBOT’s business for its product candidates, their respective components, formulations, combination therapies, methods used to manufacture them and methods of treatment, or other proprietary technologies, BBOT’s business, financial condition, results of operations and prospects could be adversely affected. The patent prosecution process is expensive, time-consuming and complex, and BBOT may not be able to file, prosecute, maintain or defend all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that BBOT will fail to identify patentable aspects of its research and development output before it is too late to obtain patent protection. Moreover, in some circumstances involving technology that BBOT may license from third parties, BBOT may not have the sole right to control the preparation, filing and prosecution of patent applications or to maintain, enforce and defend the in-licensed patents. Therefore, any in-licensed patents and applications may not be prepared, filed, prosecuted, maintained, defended and enforced in a manner consistent with the best interests of BBOT’s business. The patent rights of pharmaceutical and biotechnology companies, like BBOT, generally are highly uncertain, involve complex legal and factual questions and have been the subject of much litigation in recent years. No consistent policy regarding the breadth of claims allowed in biotechnology and pharmaceutical patents, particularly those related to oncology, has emerged in the U.S. The relevant patent laws and their interpretation outside of the U.S. are also uncertain. Various courts, including the U.S. Supreme Court, have rendered decisions that affect the scope of patent eligibility of certain inventions or discoveries relating to biotechnology. These decisions conclude, among other things, that abstract ideas, natural phenomena and laws of nature are not themselves patent eligible subject matter. Precisely what constitutes a law of nature or abstract idea is uncertain, and certain aspects of BBOT’s technology could be considered ineligible for patenting under applicable law. In addition, the scope of patent protection outside the U.S. is uncertain, and laws of foreign countries may not protect BBOT’s rights to the same extent as the laws of the U.S. or vice versa. For example, European patent law precludes the patentability of methods of treatment of the human body by surgery or therapy. BBOT cannot predict whether the patent applications BBOT is currently pursuing will issue as patents that protect BBOT’s technology and product candidates, in whole or in part, in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors. Changes in either the patent laws or interpretation of the patent laws in the U.S. or other countries may diminish the value of BBOT’s patents and its ability to obtain, protect, maintain, defend and enforce BBOT’s patent rights, narrow the scope of BBOT’s patent protection and, more generally, affect the value or narrow the scope of BBOT’s patent rights. Further, third parties may have intellectual property rights relating to BBOT’s product candidates of which BBOT is unaware. For example, third parties may have blocking patents that could be used to prevent BBOT from commercializing its product candidates and practicing its proprietary technology. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are typically not published until 18 months after filing, or in some cases are not published at all. Therefore, neither BBOT nor its future licensors can know with certainty whether either BBOT or its future licensors were the first to make the inventions claimed in the patent applications BBOT owns or any patents or patent applications BBOT may own or in-license in the future, or that either BBOT or any of its future licensors were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of BBOT’s owned and future in-licensed patent rights are uncertain. For example, currently unpublished patent applications may later publish and limit BBOT’s ability to obtain valid and enforceable patents. Moreover, any issued patents BBOT does obtain or in-license may be challenged, invalidated, or circumvented. BBOT or its future licensors may be subject to a third-party pre-issuance submission of prior art to the USPTO, or to a foreign patent office, or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging BBOT’s patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, BBOT’s patent rights, allow third parties to commercialize BBOT’s technology or product candidates and compete directly with BBOT, without payment to BBOT, or result in BBOT’s inability to manufacture or commercialize its products without infringing third-party patent rights. If the breadth or strength of protection provided by any patents BBOT obtains and patent applications is threatened, regardless of the outcome, it could dissuade companies from collaborating with BBOT to license, develop or commercialize current or future product candidates. Moreover, BBOT’s competitors may independently develop similar technologies that are outside the scope of the rights granted under any issued patents BBOT may obtain. For these reasons and others, BBOT may face competition with respect to its product candidates. Additionally, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance. Even if BBOT’s owned and any future in-licensed patent applications issue as patents, they may not 78 Table of Contents issue in a form that will pr