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We are very early in our development efforts and are substantially dependent on our clinical-stage product candidates, BDTX-1535 and BDTX-4933.
−Removed: If we are unable to advance BDTX-1535, BDTX-189 or any of our other product candidates through clinical development, obtain regulatory approval and ultimately commercialize BDTX-1535 or BDTX-189 or any of our other product candidates, or experience significant delays in doing so, our business will be materially harmed.
+Added: If we are unable to advance BDTX-1535, BDTX-4933 or any of our other product candidates through clinical development, obtain regulatory approval and ultimately commercialize BDTX-1535, BDTX-4933 or any of our other product candidates, or experience significant delays in doing so, our business will be materially harmed.
We are very early in our development efforts.
−Removed: Most of our product candidates are still in preclinical development and have never been tested in human subjects.
+Added: We are currently evaluating BDTX-1535 in a Phase 1 clinical trial, and anticipate initiating a Phase 1 clinical trial for BDTX-4933 in the first-half of 2023.
+Added: Our other product candidates are still in preclinical development and have never been tested in human subjects.
Our ability to generate product revenues, which we do not expect will occur for many years, if ever, will depend heavily on the successful clinical development and eventual commercialization of BDTX-1535, BDTX-4933 and one or more of our other product candidates.
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• approval of INDs for our planned clinical trials or future clinical trials;
−Removed: • FDA acceptance of our tumor-agnostic development strategy;
+Added: • FDA acceptance of our clinical development strategy;
• successful initiation of clinical trials;
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the ongoing COVID-19 pandemic).
−Removed: There is no guarantee that the results obtained in current preclinical studies or our open-label clinical trial of BDTX-1535 or BDTX-189 will be sufficient to obtain regulatory approval or marketing authorization for such product candidates.
+Added: There is no guarantee that the results obtained in current preclinical studies, our ongoing clinical trial of BDTX-1535, or our planned clinical trial of BDTX-4933 will be sufficient to obtain regulatory approval or marketing authorization for such product candidates.
Negative results in the development of our lead product candidates may also impact our ability to obtain regulatory approval for our other product candidates, either at all or within anticipated timeframes because, although other product candidates may target different indications, the underlying technology platform, manufacturing process and development process is the same for all of our product candidates.
Accordingly, a failure in any one program may affect the ability to obtain regulatory approval to continue or conduct clinical programs for other product candidates.
−Removed: For example, although we believe based on our preclinical studies that the conformational change to the active site receptor is similar for all of the genetic mutations we are targeting and therefore the chemical structures of our lead product candidates will suffice to bind adequately to such receptor for all such mutations, this may not prove true in clinical testing for all or any of the targeted mutations.
−Removed: Moreover, anti-tumor activity may be different in each of the different tumor types we plan on evaluating in the clinical trial.
+Added: Moreover, anti-tumor activity may be different in each of the different tumor types and for the different genetic mutations we plan on evaluating in the clinical trial and may differ from the results seen in our preclinical studies.
Therefore, the tumor response may be low in patients with some cancers compared to others.
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Difficulty in enrolling patients could delay or prevent clinical trials of our product candidates.
−Removed: We may find it difficult to enroll patients in our Phase 1 clinical trial for BDTX-1535 or our open-label Phase 1/2 clinical trial for BDTX-189 with the genetic mutations these product candidates are designed to target.
+Added: We may find it difficult to enroll patients in our Phase 1 clinical trial for BDTX-1535 or our planned Phase 1 clinical trial for BDTX-4933 with the genetic mutations these product candidates are designed to target.
Identifying and qualifying patients to participate in clinical studies of our product candidates is critical to our success.
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• our ability to obtain and maintain patient consents;
−Removed: • impacts of the ongoing COVID-19 pandemic on clinical trial site activation;
+Added: • impacts of the ongoing COVID-19 pandemic on clinical trial site activation and patient enrollment;
• reporting of the preliminary results of any of our clinical trials;
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We have limited experience as a company in conducting clinical trials.
−Removed: In part because of this limited experience, we cannot be certain that our ongoing preclinical studies will be completed on time or if the planned preclinical studies and clinical trials will begin or be completed on time, if at all.
+Added: In part because of this limited experience, we cannot be certain that our ongoing preclinical studies and clinical trials will be completed on time or if the planned preclinical studies and clinical trials will begin or be completed on time, if at all.
Large-scale clinical trials would require significant additional financial and management resources and reliance on third-party clinical investigators, contract research organizations, or CROs, and consultants.
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We may not be able to file INDs or IND amendments to commence additional clinical trials on the timelines we expect, and even if we are able to, the FDA may not permit us to proceed.
−Removed: We submitted an IND for BDTX-189 in November 2019, which was allowed by the FDA on December 13, 2019.
−Removed: Further, we submitted an IND for BDTX-1535 in December 2021, which was allowed by the FDA on January 6, 2022.
+Added: We submitted an IND for BDTX-1535 in December 2021, which was allowed by the FDA in the first quarter of 2022 and submitted an IND for BDTX-4933 in December 2022, which was allowed by the FDA in the first quarter of 2023.
However, we may not be able to file INDs for our other product candidates on the timelines we expect.
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Any delay or failure by us or third- party collaborators to develop or obtain regulatory approval of a companion diagnostic could delay or prevent approval of our related product candidates.
−Removed: Since the number of patients that we plan to dose in our Phase 1 clinical trial of BDTX-1535 and our Phase 1/2 clinical trial of BDTX-189 is small, the results from such clinical trials, once completed, may be less reliable than results achieved in larger clinical trials, which may hinder our efforts to obtain regulatory approval for our product candidates.
+Added: Since the number of patients that we plan to dose in our Phase 1 clinical trial of BDTX-1535 and our planned Phase 1 clinical trial of BDTX-4933 is smaller than the number of patients that would be enrolled in a registration trial, the results from such clinical trials, once completed, may be less reliable than results achieved in larger clinical trials, which may hinder our efforts to obtain regulatory approval for our product candidates.
The number of patients that we plan to dose in our initial clinical trials is small.
−Removed: The preliminary results of clinical trials with smaller sample sizes can be disproportionately influenced by various biases associated with the conduct of small clinical trials, such as the potential failure of the smaller sample size to accurately depict the features of the broader patient population, which limits the ability to generalize the results across a broader community, thus making
−Removed: the clinical trial results less reliable than clinical trials with a larger number of patients.
+Added: The preliminary results of clinical trials with smaller sample sizes can be disproportionately influenced by various biases associated with the conduct of small clinical trials, such as the potential failure of the smaller sample size to accurately depict the features of the broader patient population, which limits the ability to generalize the results across a broader community, thus making the clinical trial results less reliable than clinical trials with a larger number of patients.
As a result, there may be less certainty that such product candidates would achieve a statistically significant effect in any future clinical trials.
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In addition, open-label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received treatment and may interpret the information of the treated group more favorably given this knowledge.
−Removed: Given that our Phase 1 clinical trial of BDTX-1535 and our Phase 1/2 clinical trial of BDTX-189 include an open-label dosing design, the results from these clinical trials may not be predictive of future clinical trial results with these or other product candidates for which we conduct an open-label clinical trial when studied in a controlled environment with a placebo or active control.
+Added: Given that our Phase 1 clinical trial of BDTX-1535 and planned Phase 1 clinical trial of BDTX-4933 include an open-label dosing design, the results from these clinical trials may not be predictive of future clinical trial results with these or other product candidates for which we conduct an open-label clinical trial when studied in a controlled environment with a placebo or active control.
We may experience delays in obtaining the FDA’s authorization to initiate clinical trials under future INDs, completing ongoing preclinical studies of our other product candidates, and initiating our planned preclinical studies and clinical trials.
Additionally, we cannot be certain that preclinical studies or clinical trials for our product candidates will begin on time, not require redesign, enroll an adequate number of subjects on time, or be completed on schedule, if at all.
−Removed: For example, at a meeting with the FDA in March 2021, the FDA notified us that, because the then planned Phase 2 portion of our ongoing clinical trial of BDTX-189 would be potentially registrational and support a new drug application, we could only enroll up to 50 patients in Phase 2 before results of routine three-month good laboratory practice, or GLP, toxicology studies have been submitted and accepted by the FDA.
−Removed: This partial clinical hold on Phase 2 enrollment was not based on any safety findings from the MasterKey-01 trial and has no impact on completion of our Phase 1 study (including the currently enrolling safety expansion cohort).
−Removed: We have completed the three-month GLP toxicology studies and submitted the reports to the FDA who accepted the findings and lifted the partial clinical hold in January 2022.
Clinical trials can be delayed or terminated for a variety of reasons, including delays or failures related to:
• the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical trials;
−Removed: • the FDA or comparable foreign regulatory authorities disagreeing with our tumor-agnostic development strategy;
+Added: • the FDA or comparable foreign regulatory authorities disagreeing with our clinical development strategy;
• delays in obtaining regulatory approval to commence a clinical trial;
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If one or more of our product candidates generally prove to be ineffective, unsafe or commercially unviable, our entire pipeline and MAP drug discovery engine could have little, if any, value, which would have a material and adverse effect on our business, financial condition, results of operations and prospects.
−Removed: We may conduct clinical trials for product candidates outside the United States, and the FDA and comparable foreign regulatory authorities may not accept data from such trials.
−Removed: We may choose to conduct one or more clinical trials outside the United States, including in Europe.
+Added: We are conducting clinical trials for product candidates outside the United States, and the FDA and comparable foreign regulatory authorities may not accept data from such trials.
+Added: We are conducting clinical trials for our product candidates outside the United States.
The acceptance of study data from clinical trials conducted outside the United States or another jurisdiction by the FDA or comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all.
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Although we believe, based on our preclinical work, that the mutations targeted by our programs are oncogenic drivers, clinical results may not confirm this hypothesis or may only confirm it for certain mutations or certain tumor types.
−Removed: The patient populations for our product candidates are limited to those with specific target mutations and may not be completely defined but are substantially smaller than the general treated
−Removed: cancer population, and we will need to screen and identify these patients with the targeted mutations.
+Added: The patient populations for our product candidates are limited to those with specific target mutations and may not be completely defined but are substantially smaller than the general treated cancer population, and we will need to screen and identify these patients with the targeted mutations.
Successful identification of patients is dependent on several factors, including achieving certainty as to how specific genetic alterations respond to our product candidates and developing companion diagnostics to identify such genetic alterations.
Furthermore, even if we are successful in identifying patients, we cannot be certain that the resulting patient populations for each mutation will be large enough to allow us to successfully obtain approval for each mutation type and commercialize our products and achieve profitability.
−Removed: In addition, even if our approach is successful in showing clinical benefit for tumors harboring the targeted mutations affecting the ErbB proteins EGFR and HER2, we may never successfully identify additional oncogenic mutations for other receptor tyrosine kinases.
+Added: In addition, even if our approach is successful in showing clinical benefit for tumors harboring the targeted mutations targeted in our current clinical trials, we may never successfully identify additional oncogenic mutations for other receptor tyrosine kinases.
Therefore, we do not know if our approach of treating patients with genetically defined cancers will be successful, and if our approach is unsuccessful, our business will suffer.
−Removed: In addition, we are pursuing a tumor-agnostic development strategy (i.e., pursuing approval based on a biomarker rather than a specific cancer indication).
−Removed: There is currently a limited number of approved tumor-agnostic therapies.
−Removed: We may not receive approval for a tumor-agnostic indication or may be delayed in receiving tumor-agnostic approval.
Our approach to the discovery and development of product candidates is unproven, and we may not be successful in our efforts to use and expand our MAP drug discovery engine to build a pipeline of product candidates with commercial value.
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Although our research and development efforts to date have resulted in our discovery and development of BDTX-1535 and BDTX-4933, these clinical-stage candidates may not be safe or effective as cancer treatments, and we may not be able to develop any other product candidates.
−Removed: Our MAP drug discovery engine is evolving and may not reach a state at which building a pipeline of product candidates is possible.
+Added: Our MAP drug discovery engine is evolving and may not in the future support the continued expansion of our pipeline of product candidates.
For example, we may not be successful in identifying additional genetic mutations which are oncogenic and which can be “basketed” into a group that is large enough to present a sufficient commercial opportunity or that is druggable with one chemical compound.
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In addition, we have 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.
−Removed: Risks related to the ongoing COVID-19 pandemic
−Removed: Business or economic disruptions or global health concerns could seriously harm our development efforts and increase our costs and expenses.
−Removed: Broad-based business or economic disruptions could adversely affect our ongoing or planned research and development activities.
−Removed: The ongoing COVID-19 pandemic is evolving, and to date has led to the implementation of various responses, including government-imposed quarantines, travel restrictions and other public health safety measures.
−Removed: The continued spread of COVID-19 or other global health matters, has impacted and may continue to impact our target patient populations as well as the hospitals and clinical sites in which we conduct any of our clinical trials, which could lead to delays in completing enrollment of our clinical trials.
−Removed: For instance, the COVID-19 outbreak may continue to impair our ability to recruit and retain patients and engage principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19 if an outbreak occurs in their geography or due to prioritization of hospital resources toward the outbreak and restrictions on travel.
−Removed: Furthermore, some patients may be unwilling to enroll in our trials or be unable to comply with clinical trial protocols if quarantines or travel restrictions impede patient movement or interrupt healthcare services.
−Removed: COVID-19 already has affected and may further negatively affect the operations of third party contract research organizations that we rely upon to carry out our discovery work, clinical trials or the operations of our third party manufacturers, which could result in delays or disruptions in the supply of our product candidates and the conduct of experiments and studies.
−Removed: Any negative impact COVID-19 has to patient enrollment or treatment or the timing and execution of our preclinical studies or clinical trials could cause costly delays to our development programs, which could adversely affect our ability to obtain regulatory approval for and to commercialize our product candidates, increase our operating expenses and have a material adverse effect on our business and financial results.
−Removed: COVID-19 has also caused, and may continue to cause for an extended period, volatility in the global financial markets and threatened a slowdown in the global economy, which would reduce our ability to access capital and could negatively affect our liquidity.
−Removed: While our lab-based employees have returned to our labs with enhanced safety measures, our office-based employees continue to work primarily from home and we expect this to continue for an extended period.
−Removed: Furthermore, there has been a resurgence of COVID-19 cases, which could prompt a reinstatement of “shelter-in-place” orders and restrictions at the state and local levels impacting our reentry to the workplace and causing hospital and clinical sites to suspend our clinical trials or could deter patients from continuing to participate in our trials.
−Removed: Since the beginning of the COVID-19 pandemic, three vaccines for COVID-19 have received Emergency Use Authorization by the FDA and two of those later received marketing approval.
−Removed: Additional vaccines may be authorized or approved in the future.
−Removed: The resultant demand for vaccines and potential for manufacturing facilities and materials to be commandeered under the Defense Production Act of 1950, or equivalent foreign legislation, may make it more difficult to obtain materials or manufacturing slots for the products needed for our clinical trials, which could lead to delays in these trials.
−Removed: The global outbreak of COVID-19 continues to rapidly evolve.
−Removed: The extent to which COVID-19 impacts our business, results of operations and financial condition will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration of the outbreak, new information that may emerge concerning the severity of COVID-19, new strains of the virus, including the Delta and Omicron variants and any future variants that may emerge, which may impact rates of infection and vaccination efforts, developments or perceptions regarding the safety of vaccines, or the extent and effectiveness of actions taken in the United States and other countries to contain COVID-19 or treat its impact, including vaccination campaigns and lockdown measures, among others.
−Removed: In addition, recurrences or additional waves of COVID-19 cases could cause other widespread or more severe impacts depending on where infection rates are highest.
−Removed: We cannot presently predict the scope and severity of any potential business shutdowns or disruptions, but if we or any of the third parties with whom we engage, including the suppliers, clinical trial sites, service providers, regulators and other third parties with whom we conduct business, were to experience prolonged business shutdowns or other business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively impacted.
+Added: Risks related to global events
+Added: Business, economic or geopolitical disruptions or global health concerns could seriously harm our development efforts and increase our costs and expenses.
+Added: Broad-based business, economic or geopolitical disruptions or global health concerns could adversely affect our ongoing or planned research and development activities.
+Added: Any such disruptions or concerns may impact a broad range of stakeholders, including our target patient populations, the hospitals and clinical sites in which we conduct any of our clinical trials, third parties with whom we engage, including our CROs, suppliers and regulators, and our lab-based employees.
+Added: Such impacts could materially negatively affect our ability to conduct our business in the manner or on the timelines presently planned by causing delays in the enrollment of our clinical trials, the manufacture and supply of our product candidates, the conduct of experiments and studies and other interruptions and potential limitations on the quality, completeness and interpretability of data we are able to collect.
+Added: For example, if the operations of our third-party manufacturers of drug substances and drug products in China were to be negatively affected, it could result in delays or disruptions in the supply of our product candidates and the conduct of experiments and studies.
+Added: Any negative impact to patient enrollment or treatment or the timing and execution of our preclinical studies or clinical trials could cause costly delays to our development programs, which could adversely affect our ability to obtain regulatory approval for and to commercialize our product candidates, increase our operating expenses and have a material adverse effect on our business and financial results.
+Added: Due to the COVID-19 pandemic, our lab-based employees continue to work from our labs with enhanced safety measures, and we continue to support hybrid work arrangements for our office-based employees;
+Added: however, the extent to which future COVID-19 developments may impact our business, results of operations and financial condition are uncertain and cannot be predicted with confidence.
+Added: Uncertainties include the duration of the outbreak, new information that may emerge concerning the severity of COVID-19, new strains of the virus, including the existing variants and any future variants that may emerge, which may impact rates of infection and vaccination efforts, developments or perceptions regarding the safety of vaccines, or the extent and effectiveness of any additional preventative and protective actions taken to contain the pandemic or treat its impact, among others.
+Added: In addition, recurrences or additional waves of COVID-19 cases could cause other widespread, severe impacts depending on where infection rates are highest.
+Added: COVID-19 has also caused, and may continue to cause for an extended period, volatility in the global financial markets and a slowdown in the global economy, which would reduce our ability to access capital and could negatively affect our liquidity.
We or third parties upon whom we depend may be adversely affected by natural disasters and/or global health pandemics, and our business, financial condition and results of operations could be adversely affected.
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Our contract manufacturers may incorporate their own proprietary processes into our product candidate manufacturing processes.
−Removed: We have limited control and oversight of a third party’s contract manufacturer’s proprietary process, and a third party contract manufacturer may elect to modify its process without our consent or knowledge.
+Added: We have limited control and oversight of a thirdparty’s contract manufacturer’s proprietary process, and a third-party contract manufacturer may elect to modify its process without our consent or knowledge.
These modifications could negatively impact our manufacturing, including product loss or failure that requires additional manufacturing runs or a change in manufacturer, both of which could significantly increase the cost of and significantly delay the manufacture of our product candidates.
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We will also need to verify, such as through a manufacturing comparability study, that any new manufacturing process will produce our product candidate according to the specifications previously submitted to the FDA or another regulatory authority.
+Added: We may be unsuccessful in demonstrating the comparability of clinical supplies which could require the conduct of additional clinical trials.
The delays associated with the verification of a new contract manufacturer could negatively affect our ability to develop product candidates or commercialize our products in a timely manner or within budget.
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and epitinib, which is under development by Hutchison MediPharma Ltd.
−Removed: Specifically for BDTX-189, we expect competition primarily in the EGFR and HER2 exon 20 insertion NSCLC patient populations, including:
−Removed: mobocertinib (TAK-788), which is marketed by Takeda Pharmaceutical Company Ltd;
−Removed: amivantamab (JNJ-61186372), which is marketed by Janssen Research & Development, LLC;
−Removed: trastuzumab deruxtecan (DS-8201), marketed by Daiichi Sankyo Company Ltd.
−Removed: and AstraZeneca plc under the trade name Enhertu, which is currently approved for HER2+ breast cancer, but under development for HER2 mutant solid tumors;
−Removed: poziotinib, which is under development by Spectrum Pharmaceuticals, Inc;
−Removed: CLN-081 (formerly TAS6417), which is under development by Cullinan Oncology, LLC;
−Removed: and DZD9008, which is under development by Dizal Pharmaceutical Co., Ltd.
−Removed: In addition, there are other small molecule and precision oncology-focused companies with whom we may eventually compete, including Loxo Oncology, Inc.
−Removed: (recently acquired by Eli Lilly and Company), SpringWorks Therapeutics, Inc., Centessa Pharmaceuticals, Theseus Pharmaceuticals, Inc., Voronoi, Deciphera Pharmaceuticals, Inc., Turning Point Therapeutics, Inc., and Mirati Therapeutics, Inc, and Kinnate Biopharma, Inc.
If our drug candidates, including BDTX-1535 and BDTX-4933, are approved for the indications for which we are currently planning clinical trials, they will likely compete with the competitor drugs mentioned above and with other drugs that are currently in development.
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We are still in the early stages of development of our product candidates.
−Removed: Our most advanced product candidates, BDTX-1535 and BDTX-189, are currently only in Phase 1 clinical studies.
+Added: Our most advanced product candidate, BDTX-1535, is currently only in a Phase 1 clinical trial.
We have no products approved for commercial sale and have not generated any revenue from product sales to date, and we continue to incur significant research and development and other expenses related to our ongoing operations.
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We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase substantially if and as we:
−Removed: • continue our research and development efforts and submit INDs for our lead product candidates;
−Removed: • conduct preclinical studies and clinical trials for our current and future product candidates based on our Mutation—Allostery—Pharmacology, or MAP, platform;
+Added: • continue our research and development efforts and submit INDs for our product candidates;
+Added: • conduct preclinical studies and clinical trials for our current and future product candidates based on our Mutation—Allostery—Pharmacology, or MAP, drug discovery engine;
• seek marketing approvals for any product candidates that successfully complete clinical trials;
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Most of our product candidates are in early clinical or preclinical stages of development and will require additional preclinical studies, clinical development, regulatory review and approval, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales.
−Removed: Our most advanced product candidates, BDTX-1535 and BDTX-189, are currently only in Phase 1 clinical studies.
+Added: Our most advanced product candidate, BDTX-1535, is currently only in a Phase 1 clinical trial.
Our other product candidates are in various stages of preclinical development.
3 unchanged sentences
• our ability to complete IND-enabling studies and successfully submit INDs or comparable applications;
−Removed: • whether we are required by the U.S.
−Removed: Food and Drug Administration, or the FDA, or similar foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates;
−Removed: • our ability to demonstrate to the satisfaction of the FDA and similar foreign regulatory authorities the safety, potency, purity, efficacy and acceptable risk to benefit profile of our product candidates or any future product candidates and such regulatory authorities’ acceptance of our tumor-agnostic development strategy (i.e., our pursuit of approval based on a biomarker rather than a specific cancer indication);
+Added: • whether we are required by the FDA or similar foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates;
+Added: • our ability to demonstrate to the satisfaction of the FDA and similar foreign regulatory authorities the safety, potency, purity, efficacy and acceptable risk to benefit profile of our product candidates or any future product candidates and such regulatory authorities’ acceptance of our clinical development strategy (i.e., our pursuit of approval based on a biomarker rather than a specific cancer indication);
• the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any;
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If we are unable to raise capital when needed, we would be compelled to delay, reduce or eliminate our product development programs or commercialization efforts.
−Removed: We expect our expenses to increase in parallel with our ongoing activities, particularly as we continue our discovery and preclinical development activities to identify new product candidates and initiate clinical trials of, and seek marketing approval for, our product candidates.
+Added: We expect our expenses to increase in parallel with our ongoing activities, particularly as we continue our clinical, discovery and preclinical development activities to identify new product candidates and initiate clinical trials of, and seek marketing approval for, our product candidates.
In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution.
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Our net proceeds from our initial public offering were $212.1 million, based the initial public offering price of $19.00 per share, after deducting underwriting discounts and commissions and offering expenses payable by us.
−Removed: We believe that, based upon our current operating plan, our existing capital resources, including net proceeds from our initial public offering will be sufficient to fund our anticipated operations into 2024, including the Phase 1 trial of BDTX-1535 and the Phase 1 safety expansion cohort of the clinical trial of BDTX-189 and IND-enabling studies for our BRAF program, with additional resources for continued development of our MAP drug discovery engine.
+Added: We believe that, based upon our current operating plan, our existing capital resources, including net proceeds from our initial public offering will be sufficient to fund our anticipated operations into the third quarter of 2024, including the Phase 1 trial of BDTX-1535, the initiation of a Phase 1 trial for BDTX-4933, with additional resources for continued development of our early research programs and the MAP drug discovery engine.
Our future capital requirements will depend on many factors, including:
22 unchanged sentences
• approval of INDs for our planned clinical trials or future clinical trials;
−Removed: • FDA acceptance of our tumor-agnostic development strategy;
−Removed: • successful enrollment in future clinical trials;
−Removed: • positive results from future clinical trials that are supportive of safety and efficacy in the intended patient populations;
+Added: • FDA acceptance of our clinical development strategy;
+Added: • successful enrollment in current and future clinical trials;
+Added: • positive results from current or future clinical trials that are supportive of safety and efficacy in the intended patient populations;
• successful development of companion diagnostics for use with certain of our product candidates;
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Before we can commercialize any of our product candidates, we must obtain marketing approval.
−Removed: Our most advanced product candidates, BDTX-1535 and BDTX-189, are currently only in Phase 1 clinical studies.
+Added: Our most advanced product candidate, BDTX-1535, is currently only in Phase 1 clinical studies and we plan to initiate a Phase 1 clinical trial for BDTX-4933 in the first half of 2023.
Whether the results from our current and future clinical trials will suffice to obtain approval will be a review issue and the FDA may not grant approval and may require that we conduct one or more controlled, randomized Phase 3 clinical trials to obtain approval.
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Our product candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following:
−Removed: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials, including our Phase 1 clinical trial design for BDTX-1535 and our Phase 1/2 clinical trial design for BDTX-189;
−Removed: • the FDA or comparable foreign regulatory authorities may disagree with our tumor-agnostic development strategy;
+Added: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials, including our Phase 1 clinical trial design for BDTX-1535 and our planned Phase 1 clinical trial design for BDTX-4933;
+Added: • the FDA or comparable foreign regulatory authorities may disagree with our clinical development strategy;
• we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a drug candidate is safe and effective for its proposed indication or a related companion diagnostic is suitable to identify appropriate patient populations;
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• the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
−Removed: Additionally, as of May 26, 2021, the FDA noted it is continuing to ensure timely reviews of applications for medical products during the ongoing COVID-19 pandemic in line with its user fee performance goals.
−Removed: However, the FDA may not be able to continue its current pace and approval timelines could be extended, including where a pre-approval inspection or an inspection of clinical sites is required and due to the ongoing COVID-19 pandemic and travel restrictions FDA is unable to complete such required inspections during the review period.
−Removed: During the COVID-19 public health emergency, a number of companies announced receipt of complete response letters due to the FDA's inability to complete required inspections for their applications.
Of the large number of drugs in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized.
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Even if the trials are successfully completed, clinical data are often susceptible to varying interpretations and analyses, and we cannot guarantee that the FDA, the EMA, or other comparable foreign regulatory authorities will interpret the results as we do, and more trials could be required before we submit our product candidates for approval.
−Removed: We cannot guarantee that the FDA, the EMA or other comparable foreign regulatory authorities will view our product candidates as having sufficient efficacy to support a tumor-agnostic indication even if positive results are observed in clinical trials.
+Added: We cannot guarantee that the FDA, the EMA or other comparable foreign regulatory authorities will view our product candidates as having sufficient efficacy to support a targeted indication even if positive results are observed in clinical trials.
To the extent that the results of the trials are not satisfactory to the FDA, the EMA or other comparable foreign regulatory authorities for support of a marketing application, approval of our product candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates.
−Removed: Additionally, any safety or efficacy concerns observed in any tumor-specific subgroup of our clinical trials could limit the prospects for regulatory approval of our product candidates for a tumor-agnostic indication, which could have a material adverse effect on our business, financial condition and results of operations.
+Added: Additionally, any safety or efficacy concerns observed in any tumor-specific subgroup of our clinical trials could limit the prospects for regulatory approval of our product candidates for a targeted indication, which could have a material adverse effect on our business, financial condition and results of operations.
We may in the future seek orphan drug status for BDTX-1535, BDTX-4933 and some of our other future product candidates, but we may be unable to obtain such designations or to maintain the benefits associated with orphan drug status, including market exclusivity, which may cause our revenue, if any, to be reduced.
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In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that the product no longer meets the conditions for qualification.
−Removed: Thus, even though we intend to seek Breakthrough Therapy designation for BDTX-1535, BDTX-189 and some or all of our future product candidates for the treatment of various cancers, there can be no assurance that we will receive breakthrough therapy designation.
+Added: Thus, even though we may seek Breakthrough Therapy designation for BDTX-1535, BDTX-4933 and some or all of our future product candidates for the treatment of various cancers, there can be no assurance that we will receive breakthrough therapy designation.
A Fast Track designation by the FDA may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval.
If a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates the potential to address unmet medical needs for this condition, the drug sponsor may apply for FDA Fast Track designation for a particular indication.
−Removed: We have been granted Fast Track designation for BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric human epidermal growth factor receptor 2 (HER2) mutation or an epidermal growth factor receptor (EGFR) or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options.
−Removed: We may seek Fast Track designation for other indications or for BDTX-1535 or certain of our future product candidates, but there is no assurance that the FDA will grant this status to any of our other proposed product candidates.
+Added: We may seek Fast Track designation for BDTX-1535, BDTX-4933 or certain of our future product candidates, but there is no assurance that the FDA will grant this status to any of our other proposed product candidates.
Marketing applications filed by sponsors of products in Fast Track development may qualify for priority review under the policies and procedures offered by the FDA, but the Fast Track designation does not assure any such qualification or ultimate marketing approval by the FDA.
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In addition, the FDA may withdraw any Fast Track designation at any time.
−Removed: Accelerated approval by the FDA, even if granted for any of our product candidates, may not lead to a faster development or regulatory review or approval process and it does not increase the likelihood that our product candidates will receive marketing approval.
+Added: We may seek approval of our product candidates, where applicable, under the FDA’s accelerated approval pathway.
+Added: This pathway may not lead to a faster development, regulatory review or approval process and it does not increase the likelihood that our product candidates will receive marketing approval.
We may seek approval of product candidates using the FDA’s accelerated approval pathway.
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These confirmatory trials must be completed with due diligence.
+Added: Under FDORA, the FDA is permitted to require, as appropriate, that a post-approval confirmatory study or studies be underway prior to approval or within a specified time period after the date of accelerated approval was granted.
+Added: 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.
+Added: FDORA also gives the FDA increased authority to withdraw approval of a drug or biologic granted accelerated approval on an expedited basis if the sponsor fails to conduct such studies in a timely manner, send the necessary updates to the FDA, or if such post-approval studies fail to verify the drug’s predicted clinical benefit.
+Added: 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 study or submit timely reports to the agency on their progress.
In addition, the FDA currently requires, unless otherwise informed by the agency, pre-approval of promotional materials for products receiving accelerated approval, which could adversely impact the timing of the commercial launch of the product.
−Removed: Even if we do receive accelerated approval, we may not experience a faster development or regulatory review or approval process, and receiving accelerated approval does not provide assurance of ultimate full FDA approval.
+Added: Thus, even if we seek to utilize the accelerated approval pathway, we may not be able to obtain accelerated approval and, even if we do receive accelerated approval, we may not experience a faster development or regulatory review or approval process, and receiving accelerated approval does not provide assurance of ultimate full FDA approval.
If we are unable to successfully validate, develop and obtain regulatory approval for companion diagnostic tests for our drug candidates that are required or experience significant delays in doing so, we may not realize the full commercial potential of these drug candidates.
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• injunctions or the imposition of civil or criminal penalties.
+Added: Additionally, under FDORA, sponsors of approved drugs and biologics must provide 6 months’ notice to the FDA of any changes in marketing status, such as the withdrawal of a drug, and failure to do so could result in the FDA placing the product on a list of discontinued products, which would revoke the product’s ability to be marketed.
The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates.
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Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent.
−Removed: Reimbursement rates may vary
−Removed: according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services.
+Added: Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services.
Our inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for any approved products we may develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize product candidates, and our overall financial condition.
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We cannot predict what affect further changes to the ACA would have on our business, especially given the new administration.
−Removed: Members of the U.S.
−Removed: Congress and the Trump administration expressed an intent to pass legislation or adopt executive orders to fundamentally change or repeal parts of the ACA.
−Removed: While Congress has not passed repeal legislation to date, the Tax Cuts and Jobs Act of 2017, or TCJA, repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” On December 14, 2018, a federal district court in Texas ruled the individual mandate is a critical and inseverable feature of the ACA, and therefore, because it was repealed as part of the TCJA, the remaining provisions of the ACA are invalid as well.
−Removed: The Trump Administration and CMS both stated that the ruling will have no immediate effect, and on December 18, 2019, the Fifth Circuit U.S.
−Removed: Court of Appeals held that the individual mandate is unconstitutional, and remanded the case to the lower court to reconsider its earlier invalidation of the full ACA.
−Removed: Pending review, the ACA remains in effect, but it is unclear at this time what effect the latest ruling will have on the status of the ACA.
+Added: There have been legislative and executive efforts to fundamentally change or repeal parts of the ACA.
+Added: While Congress has not passed repeal legislation to date, the Tax Cuts and Jobs Act of 2017, or TCJA, repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” On June 17, 2021, the U.S.
+Added: Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.
Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results.
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The effects of this gap in reimbursement on third-party payors, the viability of the ACA marketplace, providers, and potentially our business, are not yet known.
−Removed: On December 20, 2019, President Trump signed into law the Further Consolidated Appropriations Act (H.R.
−Removed: 1865), which repealed the so called “Cadillac” tax on certain high cost employer-sponsored insurance plans, the annual fee imposed on certain health insurance providers based on market share, and the medical devise excise tax on non-exempt medical devises.
+Added: On December 20, 2019, the Further Consolidated Appropriations Act (H.R.
+Added: 1865) was signed into law and repealed the so called “Cadillac” tax on certain high cost employer-sponsored insurance plans, the annual fee imposed on certain health insurance providers based on market share, and the medical devise excise tax on non-exempt medical devises.
It is impossible to determine whether similar taxes could be instated in the future.
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Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.
−Removed: In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.
−Removed: A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.
−Removed: This includes aggregate reductions of Medicare payments to providers up to 2% per fiscal year, and, due to subsequent legislative amendments, will remain in effect through 2030 unless additional Congressional action is taken.
−Removed: Pursuant to the Coronavirus Aid, Relief, and Economic Security Act, also known as the CARES Act, as well as subsequent legislation, these reductions have been suspended from May 1, 2020 through March 31, 2021 due to the COVID-19 pandemic.
−Removed: Proposed legislation, if passed, would extend this suspension until the end of the pandemic.
+Added: In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress including resulting in aggregate reductions of Medicare payments to providers up to 2% per fiscal year, and, due to subsequent legislative amendments, will remain in effect through 2030 unless additional Congressional action is taken.
In January 2013, the American Taxpayer Relief Act of 2012, or ATRA, was signed into law, which, among other things, reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
+Added: In addition, the Inflation Reduction Act of 2022, or IRA, includes several provisions that may impact our business to varying degrees, including provisions that reduce the out-of-pocket cap for Medicare Part D beneficiaries to $2,000 starting in 2025;
+Added: impose new manufacturer financial liability on certain drugs under Medicare Part D, allow the U.S.
+Added: government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition, which can include small molecule drugs;
+Added: and require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation, also including small molecule drugs.
There has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.
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Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.
−Removed: Since March 2020, when foreign and domestic inspections were largely placed on hold, the FDA has been working to resume routine surveillance, bioresearch monitoring and pre-approval inspections on a prioritized basis.
−Removed: Since April 2021, the FDA has conducted limited inspections and employed remote interactive evaluations and risk management methods to meet user fee commitments and goal dates.
−Removed: Ongoing travel restrictions and other uncertainties continue to impact oversight operations both domestic and abroad and it is unclear when standard operational levels will resume.
−Removed: The FDA is continuing to complete mission-critical work, prioritize other higher-tiered inspectional needs (e.g., for-cause inspections), and carry out surveillance inspections using risk-based approaches for evaluating public health.
+Added: Since March 2020, when foreign and domestic inspections were largely placed on hold, the FDA has been working to resume pre-pandemic levels of inspection activities, including routine surveillance, bioresearch monitoring and pre-approval inspections.
Should the FDA determine that an inspection is necessary for approval and an inspection cannot be completed during the review cycle due to restrictions on travel, and the FDA does not determine a remote interactive evaluation to be adequate, the FDA has stated that it generally intends to issue, depending on the circumstances, a complete response letter or defer action on the application until an inspection can be completed.
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In particular, the promotion, sales and marketing of healthcare items and services, as well as certain business arrangements in the healthcare industry, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices.
−Removed: These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion,
−Removed: structuring and commission(s), certain customer incentive programs and other business arrangements generally.
+Added: These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally.
Activities subject to these laws also involve the improper use of information obtained in the course of patient recruitment for clinical trials.
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HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions;
−Removed: • the federal Physician Payment Sunshine Act, created under the ACA and its implementing regulations, which require manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to HHS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
−Removed: Effective January 1, 2022, these reporting obligations will extend to include transfers of value made to certain non-physician providers such as physician assistants and nurse practitioners;
+Added: • the federal Physician Payment Sunshine Act, created under the ACA and its implementing regulations, which require manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to HHS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other licensed health care professionals, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;
• federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;
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Risks related to protecting our intellectual property
−Removed: If we are unable to obtain and maintain patent and other intellectual property protection for BDTX-1535, BDTX-189, our MAP drug discovery engine and our other product candidates and technology, or any other product candidates or technology we may develop, or if the scope of intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize products and technology similar or identical to ours, and our ability to commercialize BDTX-1535, BDTX-189, or any other product candidates or technology may be adversely affected.
+Added: If we are unable to obtain and maintain patent and other intellectual property protection for BDTX-1535, BDTX-4933 and our other product candidates and technology, or any other product candidates or technology we may develop, or if the scope of intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize products and technology similar or identical to ours, and our ability to commercialize BDTX-1535, BDTX-4933, or any other product candidates or technology may be adversely affected.
Our success depends in large part on our ability to obtain and maintain patent and other intellectual property protection in the United States and other countries with respect to our product candidates, including BDTX-1535, BDTX-4933, their respective components, formulations, combination therapies, methods used to manufacture them and methods of treatment and development that are important to our business, as well as successfully defending these patents against third-party challenges.
−Removed: If we do not adequately protect our intellectual property rights, competitors
−Removed: may be able to erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.
+Added: If we do not adequately protect our intellectual property rights, competitors may be able to erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.
We intend to rely upon a combination of patent applications, confidentiality agreements, trade secret protection and license agreements to protect the intellectual property related to our product candidates and technologies.
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Therefore, we may miss potential opportunities to establish our patent position.
−Removed: To protect our proprietary position, we plan to file patent applications in the United States and abroad relating to our product candidates and MAP drug discovery engine that are important to our business;
+Added: To protect our proprietary position, we plan to file patent applications in the United States and abroad relating to our product candidates that are important to our business;
we may in the future also license or purchase patents or patent applications owned by others.
Our ability to stop unauthorized third parties from making, using, selling, offering to sell or importing our product candidates is dependent upon the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities.
−Removed: If we are unable to secure or maintain patent protection with respect to BDTX-1535, BDTX-189, our MAP drug discovery engine or any other proprietary products and technology we develop, our business, financial condition, results of operations, and prospects would be materially harmed.
+Added: If we are unable to secure or maintain patent protection with respect to BDTX-1535, BDTX-4933, or any other proprietary products and technology we develop, our business, financial condition, results of operations, and prospects would be materially harmed.
provisional patent applications, the U.S.
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however, the life of a patent, and the protection it affords, is limited.
−Removed: Given the amount
−Removed: of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
+Added: Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
Even if they are unchallenged, our patent applications, if issued, and any patents we may own or in-license in the future, may not provide us with any meaningful protection or prevent competitors from designing around our patent claims to circumvent any patents we may own or in-license in the future by developing similar or alternative technologies or therapeutics in a non-infringing manner.
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Moreover, some of our intellectual property, including any patents we may own or in-license in the future, may be co-owned with third parties.
−Removed: If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such intellectual property, including patents or patent applications, such co-owners may be able to license their rights to other third parties, including our competitors, and our competitors could market competing products and
+Added: If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such intellectual property, including patents or patent applications, such co-owners may be able to license their rights to other third parties, including our competitors, and our competitors could market competing products and technology.
In addition, we or our future licensors may need the cooperation of any such co-owners of our owned and in-licensed intellectual property, including patents and patent applications, in order to enforce such intellectual property against third parties, and such cooperation may not be provided to us or our future licensors.
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In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace, and there are numerous grounds upon which a third-party can assert invalidity or unenforceability of a patent.
−Removed: Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of patentable subject matter, lack of
−Removed: written description, lack of novelty, obviousness, or non-enablement.
+Added: Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of patentable subject matter, lack of written description, lack of novelty, obviousness, or non-enablement.
Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution.
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We have limited foreign intellectual property rights and may not be able to protect our intellectual property rights throughout the world.
−Removed: We may not be able to pursue generic coverage of our product candidates or MAP drug discovery engine outside of the United States.
+Added: We may not be able to pursue generic coverage of our product candidates outside of the United States.
Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and intellectual property rights in some countries outside the United States can be less extensive than those in the United States.
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Moreover, the applicable time period or the scope of patent protection afforded could be less than we request.
−Removed: If we are unable to
−Removed: obtain patent term extension or the term of any such extension is shorter than what we request, our competitors may obtain approval of competing products following expiration of any patents that issue from our patent applications, and our business, financial condition, results of operations, and prospects could be materially harmed.
+Added: If we are unable to obtain patent term extension or the term of any such extension is shorter than what we request, our competitors may obtain approval of competing products following expiration of any patents that issue from our patent applications, and our business, financial condition, results of operations, and prospects could be materially harmed.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our marks of interest and our business may be adversely affected.
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Even if we obtain a license, it may be nonexclusive, thereby giving our competitors access to the same technologies licensed to us.
−Removed: In addition, if the breadth or strength of protection provided by our patent applications or any patents we may own or in-license in the future is threatened, it
−Removed: could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.
+Added: In addition, if the breadth or strength of protection provided by our patent applications or any patents we may own or in-license in the future is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.
Parties making claims against us may seek and obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize our product candidates.
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In addition, our clinical trials must be conducted with pharmaceutical product produced under cGMP regulations and will require a large number of test patients.
−Removed: Our failure or any failure by these third parties to comply with these regulations or to recruit a sufficient number of patients may require us to
−Removed: repeat clinical trials, which would delay the regulatory approval process.
+Added: Our failure or any failure by these third parties to comply with these regulations or to recruit a sufficient number of patients may require us to repeat clinical trials, which would delay the regulatory approval process.
Moreover, our business may be implicated if any of these third parties violates federal or state fraud and abuse or false claims laws and regulations or healthcare privacy and security laws.
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Our ability to compete in the highly competitive biotechnology and pharmaceutical industries depends upon our ability to attract and retain highly qualified managerial, scientific and medical personnel.
−Removed: We are highly dependent on our management, scientific and medical personnel, including our President and Chief Executive Officer, our Chief Business Officer & Interim Chief Financial Officer, Chief Scientific Officer, and Interim Chief Medical Officer.
−Removed: Our Interim Chief Medical Officer, Karsten Witt, M.D., is not our employee and provides services under a consulting agreement.
+Added: We are highly dependent on our management, scientific and medical personnel, including our President and Chief Executive Officer, our Chief Business Officer & Chief Financial Officer, Chief Scientific Officer, and Chief Medical Officer.
We face a variety of risks and uncertainties relating to management transition, including diversion of management attention from business concerns, failure to retain other key personnel or loss of institutional knowledge.
In addition, the loss of the services of any of our executive officers, other key employees and other scientific and medical advisors, and an inability to find suitable replacements could result in delays in product development and harm our business.
−Removed: We conduct our operations at our facilities in Cambridge, MA, New York, NY, and Stony Brook, NY.
+Added: We conduct our operations at our facilities in Cambridge, MA and New York, NY.
The Massachusetts region is headquarters to many other biopharmaceutical companies and many academic and research institutions.
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Even if our agreements with any future corporate collaborators entitle us to indemnification against losses, such indemnification may not be available or adequate should any claim arise.
+Added: We may fail to realize some or all of the anticipated benefits of the contribution of assets and license to Launchpad Therapeutics, Inc.
+Added: The anticipated financial, strategic and other benefits of our contribution to Launchpad Therapeutics, Inc., or Launchpad, of certain early discovery-stage antibody programs and license to our MAP Drug Discovery engine for certain large molecule therapies may not be achieved.
Risks related to tax
Our ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.
−Removed: Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or IRC, if a corporation undergoes an “ownership change” (generally defined as a greater than 50% change (by value) in its equity ownership by 5% stockholders over a three-year period), the corporation’s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes to offset its post-change taxable income may be limited.
+Added: Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (IRC), if a corporation undergoes an “ownership change” (generally defined as a greater than 50% change (by value) in its equity ownership by 5% stockholders over a three-year period), the corporation’s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes to offset its post-change taxable income may be limited.
As a result of our most recent private placements and other transactions that have occurred over the past three years, we may have experienced, and may experience, an “ownership change.” We may also experience ownership changes in the future as a result of subsequent shifts in our stock ownership.
As of December 31, 2022, we had U.S.
−Removed: federal and state net operating loss carryforwards of $209,607 and U.S.
−Removed: federal research and development tax credit carryforwards of $5,439, each of which will begin to expire at various dates through 2039 and which could be limited if we experience an “ownership change.”
−Removed: Beginning in 2022, the TCJA eliminates the option to deduct research and development expenditures currently and requires taxpayers to amortize them over five years pursuant to IRC Section 174.
+Added: federal and state net operating loss carryforwards of $241 million and U.S.
+Added: federal research and development tax credit carryforwards of $8 million, each of which will begin to expire at various dates through 2039 and which could be limited if we experience an “ownership change.”
+Added: Beginning in 2022, the TCJA eliminates the option to deduct research and development expenditures and requires taxpayers to capitalize and amortize them over five years for U.S.
+Added: incurred expenditures or 15 years for non-U.S.
+Added: incurred expenditures, pursuant to IRC Section 174.
Although Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified.
−Removed: Therefore, based on current assumptions, this could potentially increase the effective tax rate and decrease the Company's cash from operations beginning in 2022.
+Added: We have followed the current legislation to capitalize Section 174 expenditures in our financial statements, however we do not anticipate a material change to our effective tax rate or a material impact to our cash from operations if repeal or modification of the legislation is enacted retroactively to 2022.
Risks related to ownership of our common stock
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Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
−Removed: We may seek additional capital through a combination of public and private equity offerings, debt financings, strategic partnerships and alliances and licensing arrangements.
+Added: We will seek additional capital through a combination of public and private equity offerings, debt financings, strategic partnerships and alliances and licensing arrangements.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms may include liquidation or other preferences that adversely affect your rights as a stockholder.
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Our principal stockholders and management own a significant percentage of our stock and will be able to exert significant influence over matters subject to stockholder approval.
−Removed: Based upon our common stock outstanding as of December 31, 2021, our executive officers, directors, and their affiliates beneficially owned over a majority of our outstanding voting stock.
+Added: Based upon our common stock outstanding as of December 31, 2022, our executive officers, directors, and their affiliates beneficially owned a significant percentage of our outstanding voting stock.
These stockholders, acting together, are able to significantly influence all matters requiring stockholder approval.
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Compliance with public company requirements will increase costs and make certain activities more time-consuming.
−Removed: A number of those requirements mandate us to carry out
−Removed: activities we have not done previously.
+Added: A number of those requirements mandate us to carry out activities we have not done previously.
In addition, additional expenses associated with SEC reporting requirements are being incurred.
−Removed: Furthermore, if any issues in complying with those requirements are identified (for example, if our auditors identify a material weakness or significant deficiency in the internal control over financial reporting), we could incur additional costs rectifying those issues, and the existence of those issues could adversely affect our reputation or investor perceptions of it.
+Added: Furthermore, if any issues in complying with those requirements are identified (for example, if management identifies a material weakness or significant deficiency in the internal control over financial reporting), we could incur additional costs rectifying those issues, and the existence of those issues could adversely affect our reputation or investor perceptions of it.
It is also more expensive to obtain and maintain director and officer liability insurance as a public company.
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Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price.
−Removed: The global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability.
+Added: As widely reported, the global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, high inflation, increases in interest rates, increases in unemployment rates and uncertainty about economic stability.
+Added: For example, inflation generally affects us by increasing our employee-related costs and clinical trial expenses, as well as other operating expenses.
+Added: There can be no assurance that further deterioration in credit and financial markets and in global economic and political conditions will not occur.
We believe that the state of global economic conditions are particularly volatile and uncertain, not only in light of the ongoing COVID-19 pandemic and the potential global recession resulting therefrom, but also due to recent and expected shifts in political, legislative and regulatory conditions concerning, among other matters, international trade and taxation, and that an uneven recovery or a renewed global downturn may negatively impact our ability to conduct clinical trials on the scale and timelines anticipated.
−Removed: There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur.
+Added: Increases in interest rates, especially if coupled with reduced government spending and volatility in financial markets, may have the effect of further increasing economic uncertainty and heightening these risks.
Our general business strategy may be adversely affected by any such economic downturn, volatile business or political environment or continued unpredictable and unstable market conditions.
−Removed: If the current equity and credit markets deteriorate, it may make obtaining any necessary debt or equity financing more difficult, more costly and more dilutive.
+Added: For instance, the current military conflict between Russia and Ukraine could disrupt or otherwise adversely impact our operations and those of third parties upon which we rely or may rely in the future.
+Added: Related sanctions, export controls or other actions may be initiated by nations including the U.S., the European Union or Russia (e.g., potential cyberattacks, disruption of energy flows, etc.), which could adversely affect our business and/or our supply chain, our CROs, CMOs and other third parties with which we conduct or in the future may conduct business.
+Added: Further, state-sponsored cyberattacks could expand as part of the conflict, which would adversely affect our and our suppliers' ability to maintain or enhance key cybersecurity and data protection measures.
+Added: Our financial condition and results of operations may also be impacted by other factors we may not be able to control, such as global supply chain disruptions, global trade disputes or political instability.
+Added: If the current equity and credit markets deteriorate, or do not improve, it may make obtaining any necessary debt or equity financing more difficult, more costly and more dilutive.
Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growth strategy, financial performance and stock price and could require us to delay or abandon clinical development plans.
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This exclusive forum provision will not apply to any causes of action arising under the Securities Act or the Exchange Act.
−Removed: In addition, our amended and restated bylaws will provide that any person or entity purchasing or otherwise acquiring any interest in shares of our common stock is deemed to have notice of and consented to the
−Removed: foregoing provisions.
+Added: In addition, our amended and restated bylaws will provide that any person or entity purchasing or otherwise acquiring any interest in shares of our common stock is deemed to have notice of and consented to the foregoing provisions.
We recognize that the forum selection clause in our bylaws may impose additional litigation costs on stockholders in pursuing any such claims, particularly if the stockholders do not reside in or near the State of Delaware.
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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, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.
−Removed: 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 or 4% of annual global revenues, whichever is greater.
+Added: The GDPR permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million 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.
The GDPR increased our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, including as implemented by individual countries.
−Removed: Compliance with the GDPR will be a rigorous and time-intensive process that
−Removed: may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities.
−Removed: In addition, further to the UK’s exit from the EU on January 31, 2020, the GDPR ceased to apply in the UK at the end of the transition period on December 31, 2020.
−Removed: However, as of January 1, 2021, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.
−Removed: The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but aligned to the EU’s data protection regime.
+Added: Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities.
+Added: The GDPR provides that EEA Member States may make their own further laws and regulations in relation to the processing of genetic, biometric or health data, which could result in differences between Member States, limit our ability to use and share personal data or could cause our costs to increase, and harm our business and financial condition.
+Added: The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA, including the United States.
+Added: We are subject to evolving and strict rules on the transfer of personal data out of the EEA to third countries such as the United States.
+Added: Unless the destination country is an adequate country (as recognized by the European Commission), we will be required to incorporate a GDPR transfer mechanism (such as the European Commission approved standard contractual clauses ("SCCs”)) into our agreements with third parties to govern transfers of personal data outside the EEA.
+Added: The new SCCs may also impact our business as companies based in the EEA may be reluctant to utilize the new clauses to legitimize transfers of personal data to third countries given the burdensome requirements of transfer impact assessments and the substantial obligations that the new SCCs impose upon exporters.
+Added: In addition, further to the UK’s exit from the EU on January 31, 2020, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR into UK law, referred to as the UK GDPR.
+Added: The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but currently still aligned to the EU’s data protection regime.
Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.
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Like the EU GDPR, the UK GDPR restricts personal data transfers outside the UK to countries not regarded by the UK as providing adequate protection.
+Added: The transfer of personal data outside of the UK is not subject to the new forms of SCCs but the UK has issued its own transfer mechanism – the UK international data transfer agreement – which, like the SCCs, requires exporters to carry out a transfer impact assessment.
The UK government has confirmed that personal data transfers from the UK to the EEA remain free flowing.
+Added: The UK Government has also now introduced a Data Protection and Digital Information Bill (or the UK Bill) into the UK legislative process with the intention for this bill to reform the UK’s data protection regime following Brexit.
+Added: If passed, the final version of the UK Bill may have the effect of further altering the similarities between the UK and EU data protection regime and threaten the UK Adequacy Decision from the EU Commission.
+Added: This may lead to additional compliance costs and could increase our overall risk.
In addition, certain state laws govern the privacy and security of health information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
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Some observers have noted that the CCPA could mark the beginning of a trend toward more stringent privacy legislation in the United States, which could increase our potential liability and adversely affect our business.
−Removed: Further, a new California privacy law, the California Privacy Rights Act (CPRA), was passed by California voters on November 3, 2020.
−Removed: The CPRA will create additional obligations with respect to processing and storing personal information that are scheduled to take effect on January 1, 2023 (with certain provisions having retroactive effect to January 1, 2022).
−Removed: Additionally, some observers have noted that the CCPA and CPRA could mark the beginning of a trend toward more stringent privacy legislation in the U.S., which could increase our potential liability and adversely affect our business.
−Removed: Already, in the United States, we have witnessed significant developments at the state level.
−Removed: For example, on March 2, 2021, Virginia enacted the Consumer Data Protection Act (CDPA) and, on July 8, 2021, Colorado’s governor signed the Colorado Privacy Act (CPA), into law.
−Removed: The CDPA and the CPA will both become effective January 1, 2023.
−Removed: While the CDPA and CPA incorporate many similar concepts of the CCPA and CPRA, there are also several key differences in the scope, application, and enforcement of the law that will change the operational practices of regulated businesses.
−Removed: The new laws will, among other things, impact how regulated businesses collect and process personal sensitive data, conduct data protection assessments, transfer personal data to affiliates, and respond to consumer rights requests.
−Removed: A number of other states have proposed new privacy laws, some of which are similar to the above discussed recently passed laws.
+Added: Further, a new California privacy law, the California Privacy Rights Act (CPRA), was passed by California voters on November 3, 2020 and entered into force on January 1, 2023.
+Added: The CPRA, which amended the CCPA, creates additional obligations with respect to processing and storing personal information.
+Added: Similar laws have been passed in Connecticut, Colorado, Utah and Virginia and a number of other states have proposed new privacy laws, some of which are similar to the above discussed recently passed laws.
Such proposed legislation, if enacted, may add additional complexity, variation in requirements, restrictions and potential legal risk, require additional investment of resources in compliance programs, impact strategies and the availability of previously useful data and could result in increased compliance costs and/or changes in business practices and policies.
The existence of comprehensive privacy laws in different states in the country would make our compliance obligations more complex and costly and may increase the likelihood that we may be subject to enforcement actions or otherwise incur liability for noncompliance.
−Removed: In addition, many jurisdictions outside of Europe are also considering and/or enacting comprehensive data protection legislation.
−Removed: For example, as of August 2020, the Brazilian General Data Protection Law imposes stringent requirements similar to GDPR with respect to personal information collected from individuals in Brazil.
In China, there have also been recent significant developments concerning privacy and data security.
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We may be required to make further significant adjustments to our business practices to comply with the personal information protection laws and regulations in China including the Personal Information Protection Law.
+Added: Furthermore, as we have begun to conduct trials in Korea, we are also subject to local Korean laws and regulations relating to privacy and use of confidential information of trial subjects, including, the Personal Information Protection Act and related legislation, regulations and orders (the “PIPA”).
+Added: PIPA requires consent by the individuals with respect to the use of his or her data and requires the persons responsible for management of personal data to take the necessary technological and managerial measures to prevent data breaches and, among other duties, to notify the Personal Information Protection Commission of any data breach incidents within 24 hours.
+Added: Failure to comply with PIPA in any manner may subject these persons responsible to personal liability for not obtaining such consent in an appropriate manner or for such breaches, including even negligent breaches, and violators face varying penalties ranging from monetary penalties to imprisonment.
+Added: We strive to take the necessary technological and managerial measures to comply with PIPA, however despite these efforts to comply with PIPA, these rules are complex and evolving, subject to interpretation by government regulators which may change over time and therefore we are subject to the risk of claims by regulators of failure to comply with PIPA.
+Added: Any failure, or perceived failure, by us to comply with such policies, laws, regulations, and other legal obligations and regulatory guidance could adversely affect our reputation, brand, and business, and may result in claims, proceedings, or actions, including criminal proceedings, against us and certain of our executive officers by governmental entities or others or other liabilities.
+Added: Any such claim, proceeding, or action, could hurt our reputation, brand, and business, force us to incur significant expenses in defense of such proceedings, distract our management, increase our costs of doing business, result in a loss of customers and merchants, and could have an adverse effect on our business, financial condition, and results of operations.
Compliance with U.S.
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These include provisions that affect the way patent applications are prosecuted, redefine prior art, may affect patent litigation, establish a new post-grant review system and switch the U.S.
−Removed: system from a “first-to-invent” system to a “first-to-file” system.
+Added: patent system from a “first-to-invent” system to a “first-to-file” system.
Under a “first-to-file” system, assuming the other requirements for patentability are met, the first inventor to file a patent application generally will be entitled to a patent on the invention regardless of whether another inventor had made the invention earlier.
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Although we devote resources to protect our information systems, we realize that cyberattacks are a threat, and there can be no assurance that our efforts will prevent information security breaches that would result in business, legal, financial or reputational harm to us, or would have a material adverse effect on our results of operations and financial condition.
−Removed: Any failure to prevent
−Removed: or mitigate security breaches or improper access to, use of, or disclosure of our clinical data or patients’ personal data could result in significant liability under state (e.g., state breach notification laws), federal (e.g., HIPAA, as amended by HITECH), and international law (e.g., the GDPR) and may cause a material adverse impact to our reputation, affect our ability to conduct new studies and potentially disrupt our business.
+Added: Any failure to prevent or mitigate security breaches or improper access to, use of, or disclosure of our clinical data or patients’ personal data could result in significant liability under state (e.g., state breach notification laws), federal (e.g., HIPAA, as amended by HITECH), and international law (e.g., the GDPR) and may cause a material adverse impact to our reputation, affect our ability to conduct new studies and potentially disrupt our business.
Some cyber security incidents may be very difficult to prevent.
−Removed: For example, supply chain incidents involving previously unknown vulnerabilities in widely-used software are becoming increasingly common, of which the recent SolarWinds and Log4j incidents are examples.
−Removed: While we are not currently aware of any impact from supply chain vulnerabilities including but not necessarily limited to SolarWinds and Log4j, these are recent events, and the full scope of the attacks are not yet known.
−Removed: Therefore, there is residual risk that we may experience a security breach arising from the SolarWinds, Log4j, and other supply chain vulnerabilities.
+Added: For example, supply chain incidents involving previously unknown vulnerabilities in widely-used software are becoming increasingly common, of which the Log4j incident is an example.
+Added: While we are not currently aware of any impact from supply chain vulnerabilities including but not necessarily limited to Log4j, these are recent events, and the full scope of the attacks are not yet known.
+Added: Therefore, there is residual risk that we may experience a security breach arising from Log4j, and other supply chain vulnerabilities.
Further, while we maintain insurance coverage, we cannot assure that such coverage will be adequate or otherwise protect us from or adequately mitigate liabilities or damages with respect to claims, costs, expenses, litigation, fines, penalties, business loss, data loss, regulatory actions or material adverse effects arising out of our privacy and security practices, or that such coverage will continue to be available on acceptable terms or at all.
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.