Caribou Biosciences, Inc. 10-Q

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations. You should read the following discussion and analysis of our financial condition and results of operations together with our unaudited condensed consolidated financial statements and the related notes included in Part I, Item 1, of this Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2024 (“Form 10-Q”) and with the audited consolidated financial statements and the related notes for the fiscal year ended December 31, 2023 included in our Annual Report on Form 10-K (“Form 10-K”) filed with the U.S. Securities and Exchange Commission (“SEC”) on March 11, 2024. Special Note Regarding Forward-Looking Statements This Form 10-Q contains “forward-looking” statements within the meaning of Section 27A of the Securities Act of 1933, as amended (“Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (“Exchange Act”). All statements, other than statements of historical facts, contained in this Form 10-Q are forward-looking statements, including statements regarding our business strategy, plans, and objectives; expectations regarding our clinical and preclinical development programs, including our expectations about the timing of such programs; the expected timing of disclosure of clinical data from such programs; the safety, efficacy, and potential advantages of our product candidates; future regulatory filings and interactions with regulatory authorities; our results of operations and financial position; and plans and objectives of management for future operations. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. As a result of many factors, including but not limited to risks related to our limited operating history, history of net operating losses, financial position and our ability to raise additional capital as needed to fund our operations and product candidate development; risks inherent in the development of cell therapy products; risks associated with the initiation, cost, timing, progress, and results of current and future research and development programs, preclinical studies, and clinical trials; the risk that initial, preliminary, or interim clinical trial data will not ultimately be predictive of the safety and efficacy of our product candidates or that clinical outcomes may differ as patient enrollment continues and as more clinical data becomes available or different conclusions or considerations are reached once additional data have been received and fully evaluated; the risk that preclinical study results will not be borne out in human patients; risks related to our ability to obtain and maintain regulatory approval for our product candidates; risks that our product candidates, if approved, may not gain market acceptance due to negative public opinion and increased regulatory scrutiny of cell therapies involving genome editing; risks related to our ability to meet future regulatory standards with respect to our products; risks related to our ability to establish and/or maintain intellectual property rights covering our product candidates and genome-editing technology; risks of third parties asserting that our product candidates infringe their patents; risks related to developments of our competitors and our industry; risks related to our reliance on third parties to conduct our clinical trials and manufacture our product candidates; risks caused by public health crises or geopolitical events on our business and operations; and other risks described in greater detail in the section of our Form 10-K titled “Risk Factors,” and in other filings we make with the SEC, the events and circumstances reflected in our forward-looking statements may not be achieved or may not occur, and actual results could differ materially from those described in or implied by the forward-looking statements. As a result of these risks, you should not place undue reliance on these forward-looking statements. We assume no obligation to revise or update any forward-looking statements for any reason, except as required by law. Overview We are a clinical-stage C lustered R egularly I nterspaced S hort P alindromic R epeats (“CRISPR”) genome-editing biopharmaceutical company dedicated to developing transformative therapies for patients with devastating diseases. Our genome-editing platform, including our novel chRDNA ( C RISPR h ybrid R NA- DNA , or “chRDNA,” pronounced “chardonnay”) technology, enables more precise genome editing to develop cell therapies that are armored to improve activity against diseases. We are advancing a pipeline of allogeneic, or off-the-shelf, cell therapies from our chimeric antigen receptor (“CAR”) T (“CAR-T”) cell platform as readily available therapeutic treatments for patients. We are currently focused on advancing our allogeneic cell therapies for the treatment of hematologic malignancies and autoimmune diseases. Our therapies are directed at established cell surface targets for which autologous CAR-T cell therapeutics have already demonstrated clinical proof of concept, including CD19 and B cell maturation antigen (“BCMA”), as well as other targets such as C-type lectin-like molecule-1 (“CLL-1,” also known as CD371). We use our 20 Table of Contents chRDNA technologies to armor our cell therapies through multiple genome-editing strategies, such as checkpoint disruption, immune cloaking, or a combination of these two strategies, to enhance activity against devastating diseases. Our lead product candidate, CB-010, is an allogeneic anti-CD19 CAR-T cell therapy that is being evaluated in patients with relapsed or refractory large B cell non-Hodgkin lymphoma (“r/r B-NHL”) in our ongoing ANTLER phase 1 clinical trial. To our knowledge, CB-010 is the first clinical-stage allogeneic anti-CD19 CAR-T cell therapy with programmed cell death protein 1 (“PD-1”) removed from the CAR-T cell surface by a genome-edited knockout of the PDCD1 gene. In our ANTLER phase 1 clinical trial, 16 patients with multiple subtypes of aggressive r/r B-NHL were enrolled in the dose escalation portion of the clinical trial, and three dose levels of CB-010 were evaluated: dose level 1 (40x10 6 viable CAR-T cells, n=8), dose level 2 (80x10 6 viable CAR-T cells, n=5), and dose level 3 (120x10 6 viable CAR-T cells, n=3). Following the conclusion of the dose escalation portion of our ANTLER clinical trial, we began enrolling second-line (“2L”) large B cell lymphoma (“LBCL”) patients in the dose expansion phase of our ANTLER clinical trial, which is still ongoing. Dose level 2 (80x10 6 viable CAR-T cells) was selected as the recommended phase 2 dose (“RP2D”). In early June 2024, we presented safety, efficacy, and translational data for the first 46 patients evaluated in our ANTLER phase 1 clinical trial during a poster presentation at the 2024 American Society of Clinical Oncology (“ASCO”) Annual Meeting. CB-010 was generally well-tolerated with adverse events as expected for anti-CD19 CAR-T cell therapies. A retrospective analysis of the ANTLER clinical trial data showed that patients who received a dose of CB-010 manufactured from a healthy donor who shared four or more matching human leukocyte antigen (“HLA”) alleles with the patient (referred to as “partial HLA matching”) demonstrated the potential for improved efficacy. Based on these data, we have begun dosing a cohort of approximately 20 2L LBCL patients to prospectively evaluate whether partial HLA matching improves patient outcomes. In addition, we are enrolling approximately 10 patients who have relapsed following any prior CD19-targeted therapy in a proof-of-concept cohort, which will also incorporate partial HLA matching. We plan to report initial data from both cohorts in the first half of 2025. Upon confirmation of improved outcomes in 2L LBCL patients receiving a partially HLA matched dose of CB-010, we expect to initiate a pivotal phase 3 clinical trial in the second half of 2025, following agreement with the U.S. Food and Drug Administration (“FDA”) on a pivotal trial design. CB-010 received regenerative medicine advanced therapy (“RMAT”) designation for relapsed or refractory LBCL, fast track designation for r/r B-NHL, and orphan drug designation for follicular lymphoma (“FL”) from the FDA. We are expanding our clinical development of CB-010 to include autoimmune diseases, and we plan to evaluate CB-010 in our multicenter, open label, GALLOP phase 1 clinical trial in adult patients with lupus nephritis (“LN”) and extrarenal lupus (“ERL”), which will incorporate partial HLA matching. We expect to initiate our GALLOP clinical trial by year-end 2024. CB-010 received fast track designation for refractory systemic lupus erythematosus (“SLE”) from the FDA. Our second product candidate, CB-011, is an allogeneic CAR-T cell therapy that is, to our knowledge, the first anti-BCMA CAR-T cell therapy incorporating an immune cloaking approach that includes both the removal of the endogenous beta-2 microglobulin (“B2M”) protein and insertion of a beta-2-microglobulin–human-leukocyte-antigen-E–peptide transgene (“B2M–HLA-E”). This strategy is designed to reduce CAR-T cell rejection by both patient T cells and natural killer (“NK”) cells to potentially enable more durable antitumor activity. CB-011 is being evaluated in our CaMMouflage phase 1 clinical trial in adult patients with relapsed or refractory multiple myeloma (“r/r MM”), and we are currently enrolling patients in the dose escalation portion of the CaMMouflage trial. Recently, we implemented a lymphodepletion regimen that includes a higher dose of cyclophosphamide than was part of the original protocol, and we plan to present initial dose escalation data from our CaMMouflage phase 1 clinical trial in the first half of 2025. CB-011 received fast track and orphan drug designations for r/r MM from the FDA. The third product candidate from our CAR-T cell platform is CB-012, an allogeneic CAR-T cell therapy targeting CLL-1. CB-012 is, to our knowledge, the first allogeneic CAR-T cell therapy with both checkpoint disruption and immune cloaking strategies. We believe that CLL-1 is an attractive target for acute myeloid leukemia (“AML”) due to its expression on myeloid cancer cells, its enrichment on leukemic stem cells, and its absence on hematopoietic stem cells (“HSCs”). CB-012 is being evaluated in our AMpLify phase 1 clinical trial in adult patients with relapsed or refractory AML (“r/r AML”), and we are currently enrolling patients in the dose escalation portion of the AMpLify phase 1 trial. We plan to provide updates on dose escalation as our AMpLify phase 1 clinical trial advances. CB-012 received fast track and orphan drug designations for r/r AML from the FDA. Since our founding in 2011, we have devoted substantially all our resources to organizing and staffing, business planning, raising capital, expanding our genome-editing platform technologies, developing our product candidates and building our pipeline, creating and maintaining our intellectual property portfolio, and establishing arrangements with third parties for the manufacture, testing, and clinical trial evaluations of our product candidates. We do not have any products 21 Table of Contents approved for commercial sale and have not generated any revenue from product sales. We have incurred operating losses since commencement of our operations. To date, we have primarily funded our operations through proceeds from the sales of our capital stock, revenue from our license and collaboration agreements, and proceeds from the sale of shares of Intellia Therapeutics, Inc. (“Intellia”) common stock. Our net losses for the three months ended September 30, 2024, and 2023, were $34.7 million and $10.0 million, respectively. Our net losses for the nine months ended September 30, 2024, and 2023, were $113.6 million and $67.6 million, respectively. We had an accumulated deficit of $412.9 million as of September 30, 2024. Our net losses and operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of expenses associated with our clinical trials and nonclinical studies and our other research and development expenses. We anticipate that our expenses will increase substantially as we: • advance clinical trials for our CAR-T cell therapy product candidates; • continue our current research programs and our preclinical and clinical development of our current product candidates and any other product candidates we identify and choose to develop; • further develop our genome-editing technologies; • acquire or in-license new technologies; • expand, maintain, enforce, and defend our intellectual property portfolio; • seek regulatory and marketing approvals for any of our product candidates that successfully complete clinical trials, if any; • establish and expand manufacturing capabilities and supply chain capacity for our product candidates; • add operational, legal, financial, and management information systems to support growth initiatives; • hire additional personnel as we advance our product candidates; • experience any delays, challenges, or other issues associated with any of the above, including the failure of clinical trials meeting endpoints, the generation of unanticipated preclinical study results or clinical trial data subject to differing interpretations, or the occurrence of potential safety issues or other development or regulatory challenges; • make royalty, milestone, or other payments under current, and any future, in-license or assignment agreements; • establish a sales, marketing, and distribution infrastructure to commercialize any product candidates for which we obtain regulatory approval; and • continue to operate as a public company. We do not own or operate any manufacturing facilities. We use multiple contract manufacturing organizations (“CMOs”) to individually manufacture, under current good manufacturing processes, our chRDNA guides, Cas9 and Cas12a proteins, plasmids, and adeno-associated virus serotype 6 (“AAV6”) vectors used in the manufacture of our cell therapy product candidates as well as the CAR-T cell therapy product candidates themselves. We expect to continue to rely on CMOs for the manufacturing of our preclinical study and clinical trial materials, and most of our current CMOs have capabilities for commercial manufacturing. Additionally, we may decide to bring certain manufacturing functions in house and/or build our own manufacturing facility in the future to provide greater flexibility and control over our clinical and commercial manufacturing needs. Because of the numerous risks and uncertainties associated with therapeutic product development, we may never achieve profitability and, unless and until we are able to develop and commercialize our product candidates, we will need to continue to raise additional capital. Until we can generate significant revenue from product sales, if ever, we expect to finance our operations through equity offerings (including our at-the-market equity offering program), debt financings, collaborations and strategic alliances, licensing arrangements, or other sources. There are no assurances that we will be successful in obtaining an adequate level of financing to support our business plans as needed on acceptable terms, or at all. If we raise additional funds through collaborations, strategic alliances, or licensing arrangements with third parties, we may have to relinquish valuable rights to our intellectual property, future revenue streams, research programs, or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise capital as and when needed 22 Table of Contents or on attractive terms, we may have to significantly delay, reduce, or discontinue the development and commercialization of our product candidates or scale back or terminate our pursuit of new in-licenses and acquisitions. On July 16, 2024, we announced that we had discontinued preclinical research activities associated with our allogeneic CAR-NK platform and had reduced our workforce by 21 positions, or approximately 12%. This workforce reduction, together with other cost containment measures, is expected to extend our cash runway by at least six months into the second half of 2026, which will enable us to focus resources on our allogeneic CAR-T cell therapy platform and on rapidly advancing our four oncology and autoimmune disease clinical programs through certain milestones expected in 2025. In connection with the workforce reduction, we recorded a total of $0.6 million in non-recurring restructuring charges during the three months ended September 30, 2024, consisting primarily of cash severance costs, continuation of benefits, and transition support services for impacted employees. Components of Results of Operations Licensing and Collaboration Revenue We have not generated any revenue from product sales to date and do not expect to generate any revenue from the sale of products in the foreseeable future. If our development efforts for our product candidates are successful and result in regulatory approval and commercialization, we may generate revenue in the future from product sales. We cannot predict if, when, or to what extent we will generate revenue from the commercialization and sale of our product candidates if we succeed in obtaining regulatory approval for these product candidates. To date, all our revenue consists of licensing and collaboration revenue earned from collaboration and/or licensing agreements entered into with third parties, including related parties. Under these agreements, we license rights to certain intellectual property controlled by us. The terms of these arrangements typically include payments to us of one or more of the following: nonrefundable, upfront license fees or exclusivity fees; annual maintenance fees; regulatory and/or commercial milestone payments; research and development payments; and royalties on the net sales of products and/or services. Each of these payments results in licensing and collaboration revenue. Revenue under such licensing and collaboration agreements was $2.0 million and $23.7 million for the three months ended September 30, 2024, and 2023, respectively, and $7.9 million and $30.9 million for the nine months ended September 30, 2024, and 2023, respectively. See Notes 4, 5, and 7 to our unaudited condensed consolidated financial statements included elsewhere in this Form 10-Q for additional information. For additional information about our revenue recognition policy related to our licensing and collaboration agreements, see Note 2 to the consolidated financial statements included in our Form 10-K. For the foreseeable future, we expect substantially all our revenue will be generated from licensing and collaboration agreements. Operating Expenses Research and Development Expenses Our research and development expenses consist of internal and external expenses incurred in connection with the development of our product candidates and our platform technologies, and our in-licensing, assignment, and other third-party agreements. External costs include: • costs associated with acquiring technology and intellectual property licenses that have no alternative future uses, sublicensing revenues, and milestones; • costs incurred in connection with the preclinical and clinical development and manufacturing of our product candidates, including under agreements with CMOs, suppliers, clinical research organizations (“CROs”), and clinical sites; and • other research and development costs, including laboratory materials and supplies, and consulting services. Internal costs include: • personnel-related costs, including salaries, benefits, and share-based compensation expense, for our research and development personnel; and 23 Table of Contents • allocated facilities and other overhead expenses, including expenses for rent, facilities maintenance, and depreciation. We expense research and development costs as incurred. Costs of certain activities are recognized based on an evaluation of the progress to completion of specific tasks. However, payments made prior to the receipt of goods or services that will be used or rendered for future research and development activities are deferred and capitalized as prepaid expenses and other current assets on our unaudited condensed consolidated balance sheets. The capitalized amounts are recognized as expenses as the goods are delivered or as related services are performed. We separately track certain external costs on a program-by-program basis; however, we do not track costs that are deployed across multiple programs. Research and development activities are central to our business strategy. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect that our research and development expenses will increase substantially for the foreseeable future as we continue to implement our business strategy; advance our product candidates through clinical trials and later stages of development; conduct preclinical studies and clinical trials for our other product candidates; seek regulatory approvals for any product candidates that successfully complete clinical trials; and seek to identify, in-license, acquire, and/or develop additional product candidates. The successful development of our CAR-T cell therapy product candidates, as well as other potential future product candidates, is highly uncertain. Accordingly, we cannot reasonably estimate or know the nature, timing, and costs of the efforts that will be necessary to complete the development of our product candidates. We are also unable to predict when, if ever, we will generate revenue and material net cash inflows from the commercialization and sale of any of our product candidates for which we may obtain regulatory approval. We may never succeed in achieving regulatory approval for any of our product candidates. The duration, costs, and timing of preclinical studies, clinical trials, and development of our product candidates will depend on a variety of factors, including: • sufficiency of our financial and other resources; • acceptance of our CRISPR chRDNA genome-editing technology and other new technologies we may develop or in-license; • the ability to develop differentiating features so that our products have a competitive edge; • establishment, maintenance, enforcement, and defense of our patents and other intellectual property rights; • the ability to not infringe, misappropriate, or otherwise violate third-party intellectual property rights; • clearance of IND applications to initiate clinical trials on new product candidates; • successful enrollment in, and completion of, our clinical trials on our product candidates; • generation of data from our clinical trials that support an acceptable risk-benefit profile of our product candidates for the intended patient populations and that demonstrate safety and efficacy; • entry into collaborations to further the development of our product candidates or for the development of new product candidates; • successful development of our internal process development and transfer to CMOs; • maintenance of, and compliance with, our agreements with CMOs and suppliers for clinical and commercial supplies and scaling up manufacturing processes and capabilities to support our clinical trials; • receipt of marketing approvals from applicable regulatory authorities; • grant of regulatory exclusivity for our product candidates; • establishment of sales, marketing, and distribution capabilities necessary for commercialization of our product candidates if and when approved by the applicable regulatory authorities, whether by us or in collaboration with third parties; • maintenance of a continued acceptable safety profile of our products post-approval; • acceptance of our product candidates, if and when approved by the applicable regulatory authorities, by patients, the medical community, and third-party payors; 24 Table of Contents • ability of our products to compete with other therapies and treatment options; • establishment and maintenance of healthcare coverage and adequate reimbursement; and • expanded indications and patient populations for our products. The following table summarizes our research and development expenses for the periods indicated: Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 (in thousands) (in thousands) External costs: Expenses related to licenses, sublicensing revenue, and milestones $ 375 $ 968 $ 4,429 $ 2,141 Services provided by CROs, CMOs, and third parties that conduct preclinical studies and clinical trials on our behalf 13,060 11,928 37,215 32,345 Other research and development expenses 3,655 3,352 18,065 12,181 Total external costs 17,090 16,248 59,709 46,667 Internal costs: Personnel-related expenses 9,869 8,836 30,344 25,702 Facilities and other allocated expenses 3,462 3,500 9,636 8,427 Total internal costs 13,331 12,336 39,980 34,129 Total research and development expenses $ 30,421 $ 28,584 $ 99,689 $ 80,796 General and Administrative Expenses Our general and administrative expenses consist primarily of personnel-related costs, intellectual property costs, consulting costs, and allocated overhead, including rent, equipment depreciation, and utilities. Personnel-related costs consist of salaries, benefits, and stock-based compensation for our general and administrative personnel. Intellectual property costs include expenses for filing, prosecuting, and maintaining patents and patent applications, including certain patents and patent applications that we license from third parties. We are entitled to receive reimbursement from third parties of a portion of the costs for filing, prosecuting, and maintaining certain patents and patent applications. We accrue for these reimbursements as the respective expenses are incurred and classify such reimbursements as a reduction of general and administrative expenses. During the three months ended September 30, 2024, and 2023, we recorded $0.4 million and $0.2 million, respectively, of patent cost reimbursements as a reduction to general and administrative expense. During the nine months ended September 30, 2024, and 2023, we recorded $0.9 million and $1.3 million, respectively, of patent cost reimbursements as a reduction to general and administrative expense. We expect that our general and administrative expenses will increase in the future as a result of expanding our operations, including preparing for potential commercialization of our product candidates, and additional facility occupancy costs, as well as other expenses necessary to support the growth and operations of a clinical-stage public company. Other Income Other income consists primarily of interest income earned on cash and marketable securities and the change in fair value of the Memorial Sloan Kettering Cancer Center (“MSKCC”) success payments liability under our Exclusive License Agreement, dated November 13, 2020, with MSKCC (“MSKCC Agreement”). 25 Table of Contents Results of Operations Comparison of the Three Months Ended September 30, 2024, and 2023 The following table summarizes our results of operations for the periods indicated: Three Months Ended September 30, 2024 2023 Change (in thousands) Licensing and collaboration revenue $ 2,024 $ 23,662 $ (21,638) Operating expenses: Research and development 30,421 28,584 1,837 General and administrative 9,841 9,711 130 Total operating expenses 40,262 38,295 1,967 Loss from operations (38,238) (14,633) (23,605) Other income: Change in fair value of equity securities (14) (4) (10) Change in fair value of the MSKCC success payments liability (164) (139) (25) Other income, net 3,732 4,774 (1,042) Total other income 3,554 4,631 (1,077) Net loss $ (34,684) $ (10,002) $ (24,682) Licensing and Collaboration Revenue Licensing and collaboration revenue decreased by $21.6 million to $2.0 million for the three months ended September 30, 2024, from $23.7 million for the three months ended September 30, 2023. This decrease was primarily related to a decrease of $21.5 million of revenue recognized under the now-terminated Collaboration and License Agreement, dated February 9, 2021 (as amended, “AbbVie Agreement”) with AbbVie Manufacturing Management Unlimited Company (“AbbVie”). The following table summarizes our revenue by licensee for the periods indicated: Three Months Ended September 30, 2024 2023 Change (in thousands) AbbVie $ — $ 21,476 $ (21,476) Pfizer, related party 622 622 — Other licensees 1,402 1,564 (162) Total licensing and collaboration revenue $ 2,024 $ 23,662 $ (21,638) Research and Development Expenses Research and development expenses increased by $1.8 million to $30.4 million for the three months ended September 30, 2024, from $28.6 million for the three months ended September 30, 2023. This increase was primarily related to (i) a net increase of $1.1 million in external CMO and CRO activities for our clinical CAR-T cell therapy product candidates, driven by (a) an increase of $1.4 million in CRO activities for clinical trials; partially offset by (b) a decrease of $0.3 million due to timing of CMO activities; (ii) an increase of $1.0 million in personnel-related expenses, including stock-based compensation, primarily due to severance and other related expenses recorded as a result of the July 2024 workforce reduction; and (iii) an increase of $0.3 million in other research and development expenses to advance preclinical and clinical research for our programs, as well as other consulting services related to research and development; partially offset by a decrease of $0.6 million in expenses related to licenses, sublicensing revenue, and milestones. General and Administrative Expenses 26 Table of Contents General and administrative expenses increased by $0.1 million to $9.8 million for the three months ended September 30, 2024, from $9.7 million for the three months ended September 30, 2023. This increase was primarily related to increases of $0.4 million in patent prosecution and maintenance costs; partially offset by a decrease of $0.3 million in legal and other service-related expenses. Total Other Income Total other income decreased by $1.1 million for three months ended September 30, 2024, as compared to the three months ended September 30, 2023. We recognized a loss related to the change in the fair value of the MSKCC success payments liability in the amount of $0.2 million and $0.1 million, for the three months ended September 30, 2024, and 2023, respectively. Other income, net decreased by $1.0 million during the three months ended September 30, 2024, compared to September 30, 2023. This decrease was primarily related to a $1.0 million decrease in interest income earned from marketable securities. Comparison of the Nine Months Ended September 30, 2024, and 2023 The following table summarizes our results of operations for the periods indicated: Nine Months Ended September 30, 2024 2023 Change (in thousands) Licensing and collaboration revenue $ 7,917 $ 30,919 $ (23,002) Operating expenses: Research and development 99,689 80,796 18,893 General and administrative 35,969 28,740 7,229 Total operating expenses 135,658 109,536 26,122 Loss from operations (127,741) (78,617) (49,124) Other income: Change in fair value of equity securities (116) 3 (119) Change in fair value of the MSKCC success payments liability 1,934 395 1,539 Other income, net 12,308 10,654 1,654 Total other income 14,126 11,052 3,074 Net loss $ (113,615) $ (67,565) $ (46,050) Licensing and Collaboration Revenue Licensing and collaboration revenue decreased by $23.0 million to $7.9 million for the nine months ended September 30, 2024, from $30.9 million for the nine months ended September 30, 2023. This decrease was primarily related to a decrease of $24.5 million in revenue recognized under the now-terminated AbbVie Agreement; partially offset by (i) an increase of $1.2 million in revenue recognized under our Information Rights Agreement with Pfizer, dated June 29, 2023; and (ii) a net increase of $0.5 million in revenue recognized under our agreements with Edge, driven by (a) an increase of $1.6 million related to the Edge chRDNA License Agreement; partially offset by (b) a decrease of $1.2 million related to the Edge Cas9 License Agreement. 27 Table of Contents The following table summarizes our revenue by licensee for the periods indicated: Nine Months Ended September 30, 2024 2023 Change (in thousands) AbbVie $ — $ 24,458 $ (24,458) Edge Animal Health, related party 1,623 1,150 473 Pfizer, related party 1,865 622 1,243 Other licensees 4,429 4,689 (260) Total licensing and collaboration revenue $ 7,917 $ 30,919 $ (23,002) Research and Development Expenses Research and development expenses increased by $18.9 million to $99.7 million for the nine months ended September 30, 2024, from $80.8 million for the nine months ended September 30, 2023. This increase was primarily related to (i) an increase of $5.9 million in other research and development expenses to advance preclinical and clinical research for our programs, as well as other consulting services related to research and development; (ii) a net increase of $4.9 million in external CMO and CRO activities for our clinical CAR-T cell therapy product candidates, driven by (a) an increase of $10.5 million in CRO activities for clinical trials; partially offset by (b) a decrease of $5.6 million due to timing of CMO activities; (iii) an increase of $4.6 million in personnel-related expenses, including stock-based compensation, due to headcount increases; (iv) an increase of $2.3 million in expenses related to licenses, sublicensing revenue, and milestones; and (v) an increase of $1.2 million in other facilities and allocated expenses. General and Administrative Expenses General and administrative expenses increased by $7.2 million to $36.0 million for the nine months ended September 30, 2024, from $28.7 million for the nine months ended September 30, 2023. This increase was primarily related to increases of $5.4 million in legal, and other service-related expenses, including $3.9 million of accrued costs for the securities litigation settlement and $2.7 million in personnel-related expenses, including stock-based compensation, due to headcount increases; partially offset by a decrease of $0.7 million in patent prosecution and maintenance costs. Total Other Income Total other income increased by $3.1 million for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023. We recognized a gain related to the change in the fair value of the MSKCC success payments liability in the amount of $1.9 million and $0.4 million, for the nine months ended September 30, 2024, and 2023, respectively. Other income, net increased by $1.7 million during the nine months ended September 30, 2024, compared to September 30, 2023. This increase was primarily related to a $1.7 million increase in interest income earned from marketable securities. Liquidity, Capital Resources, and Capital Requirements Sources of Liquidity Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations. We have funded our operations through sales of our capital stock, including sales of our convertible preferred stock, which generated approximately $150.1 million in aggregate net proceeds through 2021; from our initial public offering (“IPO”) in 2021, which generated approximately $321.0 million in net proceeds; and from our underwritten follow-on public offering in 2023, which generated approximately $134.4 million in net proceeds. We have also received approximately $88.4 million in net proceeds from the sale of Intellia common stock through 2020. Additionally, we received a $25.0 million equity investment from Pfizer through a private placement transaction in June 2023. Through September 30, 2024, we received approximately $99.8 million from licensing agreements, licensing and collaboration agreements, a service agreement, patent assignments, and government grants, including $36.7 million that we received from AbbVie under the now-terminated AbbVie Agreement. 28 Table of Contents On August 9, 2022, we filed a universal shelf registration statement on Form S-3 (“Shelf Registration Statement”) with the SEC, which allows us to, from time to time, sell up to $400.0 million of common stock, preferred stock, debt securities, warrants, rights, or units comprised of any combination thereof (including the $100.0 million of common stock reserved for our at-the-market equity offering program). The Shelf Registration Statement was declared effective by the SEC on August 16, 2022. On August 9, 2022, we entered into an at-the-market Open Market Sale Agreement SM (“ATM Sales Agreement”) with Jefferies LLC (“Jefferies”), pursuant to which, upon the terms and subject to the conditions and limitations set forth in the ATM Sales Agreement, we may, from time to time, in our sole discretion, issue and sell, through Jefferies, acting as sales agent, up to $100.0 million of our shares of common stock under the Shelf Registration Statement, by any method permitted by law deemed to be an “at the market offering” as defined in Rule 415(a)(4) of the Securities Act. Jefferies uses commercially reasonable efforts consistent with its normal sales and trading practices to sell shares from time to time, based upon our instructions (including any price or size limits or other customary parameters or conditions we may impose). We pay Jefferies a commission equal to 3.0% of the aggregate gross proceeds of any shares sold through Jefferies pursuant to the ATM Sales Agreement. As of September 30, 2024, we have sold 1,762,806 shares of our common stock under the ATM Sales Agreement, at an average price per share of $7.32 for aggregate gross proceeds of $12.9 million ($12.3 million net of offering expenses). In July and August 2023, we issued and sold a total of 22,115,384 shares of our common stock in an underwritten follow-on public offering at a price to the public of $6.50 per share, which included the full exercise of the underwriters’ right to purchase 2,884,615 additional shares of our common stock. The total gross proceeds from the offering were approximately $143.7 million ($134.4 million net of underwriting discounts and commissions and offering expenses). The shares were sold under the Shelf Registration Statement. As of September 30, 2024, we had cash, cash equivalents, and marketable securities of $281.0 million. We will continue to be dependent upon equity financing, debt financing, collaboration and licensing arrangements, and/or other forms of capital raises at least until we are able to generate significant positive cash flows from our operations. We have no current ongoing material contractual commitments that are expected to affect our liquidity over the next five years, except for our lease commitments and payments under certain of our agreements with CMOs, suppliers, CROs, clinical trial sites, licensors, assignors, and the like. On April 22, 2024, we reached an agreement in principle with plaintiffs in the securities litigation to settle the case for $3.9 million and, on October 15, 2024, the court issued an order preliminarily approving the settlement pending a final settlement approval hearing. For information regarding our material contractual obligations and commitments and other contingencies, refer to Notes 4, 8, and 9 to our unaudited condensed consolidated financial statements included elsewhere in this Form 10-Q. Based on our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operations for at least the next 12 months from the date of this Form 10-Q. We have based these estimates on our current assumptions, which may require future adjustments based on our ongoing business decisions. Strategic Investment On June 29, 2023, we entered into a Securities Purchase Agreement with Pfizer Inc. (“Pfizer”) pursuant to which we issued and sold to Pfizer 4,690,431 shares of our common stock, par value $0.0001 per share, at a purchase price of $5.33 per share, for aggregate gross proceeds of approximately $25.0 million in a private placement transaction (“Pfizer Investment”). The issuance and sale of the shares to Pfizer closed on June 30, 2023. We granted certain registration rights to Pfizer under the Securities Purchase Agreement covering the resale of the shares. Unless otherwise agreed by Pfizer, we have agreed to use the proceeds from the Pfizer Investment solely in connection with (i) the development program for our allogeneic anti-BCMA CAR-T cell therapy known as CB-011 product candidate that is being evaluated in our CaMMouflage clinical trial and/or (ii) any other single-targeted anti-BCMA CAR-T cell therapy using an anti-BCMA single-chain variable fragment owned or controlled by us (collectively, cell therapies described in clauses (i) and (ii) are referred to as a “BCMA Product Candidate”), for 36 months beginning on June 29, 2023. On June 29, 2023, in connection with the Pfizer Investment, we and Pfizer also entered into an Information Rights Agreement, having a 36-month term. Under the Information Rights Agreement, we granted Pfizer a 30 calendar day right of first negotiation if we commence or engage with any third party with respect to a potential grant of rights to develop and/or commercialize a BCMA Product Candidate, including, without limitation, a license agreement, a co-promotion/co-commercialization agreement, a profit share agreement, a joint venture agreement, or an asset sale agreement (a “Grant of Program Rights”). If we and Pfizer do not reach an agreement with respect to a Grant of Program Rights within the 30-day period, then we may pursue negotiations and enter into an agreement with any third party. If we and such third party do not 29 Table of Contents reach agreement on the Grant of Program Rights within a specified time period, Pfizer’s right of first negotiation will be reinstated. Under the Information Rights Agreement, we also granted Pfizer the right to designate one representative to serve on our scientific advisory board. Through an information sharing committee, we provide calendar quarter updates to Pfizer regarding the development program for a BCMA Product Candidate. Additionally, we provide Pfizer access to any preclinical or interim or final clinical data (including raw data) and results generated as part of the development program for a BCMA Product Candidate at the same time that we provide such data to a third party (other than to our service providers or the FDA or other regulatory authorities), subject to certain confidentiality exceptions. Funding Requirements Our primary use of cash is to fund operating expenses and research and development expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable, accrued expenses, and prepaid expenses. Our future funding requirements will depend on many factors, including the following: • the initiation, progress, timing, costs, and results of preclinical studies and clinical trials for our product candidates; • the clinical development plans we establish for our product candidates; • the number and characteristics of the new product candidates that we develop; • the outcome, timing, and cost of meeting regulatory requirements established by the FDA and other comparable foreign regulatory authorities; • whether we enter into any collaboration agreements and the terms of any such agreements; • the cost of filing and prosecuting our patent applications, and maintaining and enforcing our patents and other intellectual property rights; • the extent to which we acquire or in-license other product candidates and/or new technologies; • the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against our products after we receive regulatory approval; • the effect of competing technological and market developments; • the cost and timing of completion of commercial-scale outsourced manufacturing activities; • the cost and timing of completion of clinical-scale and commercial-scale internal manufacturing activities, if we elect to conduct these activities ourselves; • increases in the number of our employees and expansion of our physical facilities to support growth initiatives; • the cost of establishing sales, marketing, and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products without a partner; • the amount of revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive regulatory approval; • the achievement of milestones or occurrence of other developments that trigger payments by or to third parties; • our implementation of various computerized informational systems and efforts to enhance operational systems; • the impact of public health crises or geopolitical events on our clinical development or operations; • the impact of inflationary pressures on the cost of our operations; and • the costs associated with being a public company. Furthermore, our operating plans may change, and we expect to need additional funds to meet operational needs and capital requirements for clinical trials and other research and development expenditures. 30 Table of Contents Because of the numerous risks and uncertainties associated with the development of human therapeutics, we may never achieve profitability and, unless and until we are able to develop and commercialize our product candidates, we will need to continue to raise additional capital; however, funding may not be available to us on acceptable terms, or at all. If we are unable to obtain adequate financing when needed, we may have to delay, reduce the scope of, or suspend one or more of our preclinical studies, clinical trials, research and development programs, and/or commercialization efforts. We may seek to raise any necessary additional capital through a combination of equity offerings (including our at-the-market equity offering program), debt financings, collaborations and strategic alliances, licensing arrangements, or other sources. If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends. If we raise additional capital through the sale of equity or convertible debt securities, the issuance of these securities could result in dilution to our stockholders. If we raise additional capital through marketing and distribution arrangements or other collaborations, strategic alliances, or licensing arrangements with third parties or other sources, we may have to relinquish certain valuable rights to our product candidates, technologies, future revenue streams, or research programs or grant licenses on terms that may not be favorable to us. Cash Flows Comparison of the Nine Months Ended September 30, 2024, and 2023 The following table summarizes our cash flows for the periods indicated: Nine Months Ended September 30, 2024 2023 Change (in thousands) Cash used in operating activities $ (102,730) $ (71,912) $ (30,818) Cash provided by (used in) investing activities 70,677 (36,709) 107,386 Cash provided by financing activities 12,861 154,341 (141,480) Net (decrease) increase in cash, and cash equivalents, and restricted cash $ (19,192) $ 45,720 $ (64,912) Cash Used in Operating Activities Net cash used in operating activities was $102.7 million and $71.9 million for the nine months ended September 30, 2024, and 2023, respectively. Cash used in operating activities for the nine months ended September 30, 2024, was primarily due to our net loss of $113.6 million, adjusted by non-cash charges of $11.7 million and net changes in our operating assets and liabilities of $0.8 million. Our non-cash charges were primarily comprised of (i) $12.8 million of stock-based compensation, (ii) $2.7 million of depreciation and amortization expense, (iii) $1.7 million of non-cash lease expense, and (iv) $1.6 million of acquired in-process research and development; which were partially offset by (i) accretion of discounts on our marketable securities investments of $3.7 million, (ii) change in the fair value of the MSKCC success payments liability of $1.9 million, and (iii) non-cash consideration for licensing and collaboration revenue of $1.6 million. The changes in our operating assets and liabilities were primarily due to (i) increases of $3.2 million in other assets and $0.4 million in prepaid expenses and other current assets, and (ii) decreases of $2.2 million in deferred revenue, current and long-term and $0.5 million in operating lease liabilities; partially offset by (i) decreases of $0.6 million in other receivables and $0.6 million in contract assets, and (ii) an increase of $4.3 million in accrued expenses and other current liabilities. Cash used in operating activities for the nine months ended September 30, 2023, was primarily due to our net loss of $67.6 million, adjusted by non-cash charges of $8.0 million and net changes in our operating assets and liabilities of $12.3 million. Our non-cash charges were primarily comprised of (i) $10.2 million of stock-based compensation, (ii) $2.8 million of depreciation and amortization expense, and (iii) non-cash lease expense of $1.6 million; which were partially offset by (i) accretion of discounts on investments of $6.0 million, and (ii) change in the fair value of the MSKCC success payments liability of $0.4 million. The changes in our operating assets and liabilities were primarily due to an increase in accounts receivable of $0.9 million and decreases of $16.3 million in deferred revenue, current and long-term, and $0.3 million in operating lease liabilities; partially offset by (i) decreases in prepaid expenses and other current assets of $0.9 million, contract assets of $0.6 million, and (ii) increases of $2.8 million in accrued expenses and other current liabilities, and $1.1 million in accounts payable. 31 Table of Contents Cash Provided by Investing Activities During the nine months ended September 30, 2024, cash provided by investing activities was $70.7 million, and during the nine months ended September 30, 2023, cash used in investing activities was $36.7 million. Cash provided by investing activities for the nine months ended September 30, 2024, was primarily due to proceeds from the maturities of marketable securities of $325.6 million; partially offset by purchases of marketable securities of $248.9 million, property and equipment of $4.4 million, and in-process research and development of $1.6 million. Cash used in investing activities for the nine months ended September 30, 2023, was primarily due to purchases of marketable securities of $310.6 million and property and equipment of $9.3 million; partially offset by proceeds from the sales and maturities of marketable securities of $283.2 million. Cash Provided by Financing Activities During the nine months ended September 30, 2024, and 2023, cash provided by financing activities was $12.9 million and $154.3 million, respectively. Cash provided by financing activities for the nine months ended September 30, 2024, was primarily due to net proceeds from our at-the-market equity offering program of $11.3 million, the issuances of common stock under the 2021 Employee Stock Purchase Plan (“ESPP”) of $0.9 million, and the exercises of stock options of $0.6 million. Cash provided by financing activities for the nine months ended September 30, 2023, was primarily due to $134.5 million of net proceeds from our underwritten follow-on public offering, $17.3 million of net proceeds allocated to the issuances of common stock in a private placement transaction with Pfizer, net proceeds from our at-the-market equity offering program of $1.0 million, and the exercises of stock options and the issuances of common stock under the ESPP of $1.5 million. Critical Accounting Policies and Significant Judgments and Estimates Our critical accounting policies are disclosed in our audited consolidated financial statements for the year ended December 31, 2023, and the related notes included in our Form 10-K. Since the date of such financial statements, there have been no material changes to our significant accounting policies. There have been no material changes to our critical accounting estimates as compared to those disclosed in our Form 10-K. Recently Issued Accounting Pronouncements See Note 2 to our unaudited condensed consolidated financial statements included elsewhere in this Form 10-Q for more information regarding recently issued accounting pronouncements. Emerging Growth Company and Smaller Reporting Company Status We are an emerging growth company, as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”). Under the JOBS Act, emerging growth companies can delay adopting new or revised accounting standards issued subsequent to the enactment of the JOBS Act until such time as those standards apply to private companies. We have elected to use this extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that we (a) are no longer an emerging growth company or (b) affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act. As a result, our unaudited condensed consolidated financial statements may not be comparable to those of companies that comply with the new or revised accounting pronouncements as of public company effective dates. We expect to use the extended transition period for any other new or revised accounting standards during the period in which we remain an emerging growth company. We are also a “smaller reporting company.” If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies. Specifically, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited consolidated financial statements in our Form 10-K and, similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive compensation. 32 Table of Contents Item 3. Quantitative and Qualitative Disclosures about Market Risk. There have been no material changes to our market risk during the nine months ended September 30, 2024. For a discussion of our exposure to market risk, refer to the section titled “Quantitative and Qualitative Disclosures About Market Risk” in our Form 10-K.