10q10k10q10k.net

What changed in Revolution Medicines, Inc.'s 10-K — 2024 vs 2025

vs

Paragraph-level year-over-year comparison of Revolution Medicines, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+499 added−580 removedSource: 10-K (2026-02-25) vs 10-K (2025-02-26)

Top changes in Revolution Medicines, Inc.'s 2025 10-K

499 paragraphs added · 580 removed · 314 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

81 edited+58 added−125 removed177 unchanged
Biggest changeBased on tumor mutation frequencies from Foundation Medicine data, scaled to estimated patient numbers using cancer incidence from the American Cancer Society (ACS) Cancer Facts and Figures 2023, there are estimated to be more than 200,000 RAS-mutant cancer diagnoses each year in the United States, including approximately 60,000 NSCLC diagnoses (approximately 30% of NSCLC diagnoses), approximately 75,000 CRC diagnoses (approximately 50% of CRC diagnoses) and approximately 56,000 PDAC diagnoses (more than 90% of PDAC diagnoses). 6 Our Innovation Engine We have built an innovation engine that enables us to discover and develop novel targeted therapies for elusive high-value frontier cancer targets with a particular focus on a cohesive set of disease targets within notorious growth and survival pathways.
Biggest changeWe believe these goals are complementary and lead to a virtuous cycle of innovation driven by bench, bedside and commercial insights. 8 Our Innovation Engine We have built an innovation engine that enables us to discover and develop novel targeted therapies for elusive high-value frontier cancer targets with a particular focus on a cohesive set of disease targets within notorious growth and survival pathways.
Non-Clinical Studies and Clinical Trials Similar to the United States, the various phases of non-clinical and clinical research in the European Union, or EU, are subject to significant regulatory controls. Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances.
Non-Clinical Studies and Clinical Trials Similar to the United States, the various phases of non-clinical and clinical research in the European Union (EU) are subject to significant regulatory controls. Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances.
The EU laws that have been transposed into UK law through secondary legislation remain applicable in Great Britain (GB) (comprising England, Scotland and Wales), but new legislation such as the (EU) CTR is not applicable in GB. Since January 1, 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) has been the UK’s standalone medicines and medical devices regulator.
The EU laws that have been transposed into UK law through secondary legislation remain applicable in Great Britain (GB) (comprising England, Scotland and Wales), but new legislation such as the (EU) CTR is not applicable in the UK. Since January 1, 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) has been the UK’s standalone medicines and medical devices regulator.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls; • fines, warning or untitled letters or holds on clinical studies; 28 • refusal by the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals; • product seizure or detention, or refusal by the FDA to permit the import or export of products; • mandated modifications of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls; • fines, warning or untitled letters or holds on clinical studies; • refusal by the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals; • product seizure or detention, or refusal by the FDA to permit the import or export of products; • mandated modifications of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
Our principal executive offices are located at 700 Saginaw Drive, Redwood City, California 94063, and our telephone number is (650) 481-6801. 34 On November 9, 2023, we completed the announced acquisition of EQRx, Inc., a Delaware corporation (EQRx), pursuant to an Agreement and Plan of Merger, dated as of July 31, 2023. See “Item 7.
Our principal executive offices are located at 700 Saginaw Drive, Redwood City, California 94063, and our telephone number is (650) 481-6801. On November 9, 2023, we completed the announced acquisition of EQRx, Inc., a Delaware corporation (EQRx), pursuant to an Agreement and Plan of Merger, dated as of July 31, 2023. See “Item 7.
A fast track product candidate may also be eligible for rolling review, 26 where the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.
A fast track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.
However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical or biological entity, and products may not qualify for data exclusivity. Orphan Medicinal Products The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the United States.
However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical or biological entity, and products may not qualify for data exclusivity. 19 Orphan Medicinal Products The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the United States.
Significant uncertainty exists as to the coverage and reimbursement status of any newly approved product. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis. One third-party payor’s decision to cover a particular product does not ensure that other payors will also provide coverage for the product.
Significant uncertainty exists as to the coverage and reimbursement 21 status of any newly approved product. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis. One third-party payor’s decision to cover a particular product does not ensure that other payors will also provide coverage for the product.
We plan to seek any available patent term extension to any issued patents we may be granted in any jurisdiction where such extensions are available; however, there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and, if granted, the length of such extensions.
We plan to seek any available patent term extension to any issued patents we may be granted in any jurisdiction where such extensions are available; however, there is no 11 guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and, if granted, the length of such extensions.
The FDA and the sponsor must reach an agreement on the iPSP. A sponsor can submit amendments to an agreed-upon iPSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.
The FDA and the sponsor must reach an 16 agreement on the iPSP. A sponsor can submit amendments to an agreed-upon iPSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.
National Institutes of Health, ClinicalTrials.gov. Human clinical trials are typically divided into three or four phases. Although the phases are usually conducted sequentially, they may overlap or be combined. • Phase 1. The drug is initially introduced into healthy human subjects or into patients with the target disease or condition.
National Institutes of Health, ClinicalTrials.gov. 13 Human clinical trials are typically divided into three or four phases. Although the phases are usually conducted sequentially, they may overlap or be combined. • Phase 1. The drug is initially introduced into healthy human subjects or into patients with the target disease or condition.
If granted, the data exclusivity period prevents generic and biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU during a period of eight years from the date on which the reference product was first authorized in 30 the EU.
If granted, the data exclusivity period prevents generic and biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU during a period of eight years from the date on which the reference product was first authorized in the EU.
These doublets form a core part of our strategy to improve the standard of care for patients with RAS-addicted cancers, along with monotherapy and combination with standard of care therapies. This approach is based on our biological understanding of RAS addiction and leverages the unique nature of our pipeline.
These doublets form a core part of our strategy to improve the standard of care for patients with RAS-addicted cancers, along with monotherapy and combination with standard of care and novel therapies. This approach is based on our biological understanding of RAS addiction and leverages the unique nature of our pipeline.
We offer our employees career-specific training and resources and support development opportunities through company-sponsored programs, including learning, mentoring, and coaching opportunities. We host regular company-wide sessions where our employees discuss ideas related to corporate initiatives and scientific breakthroughs and recognize each other’s contributions.
We offer our employees career-specific training and resources and support development opportunities through company-sponsored programs, including learning, mentoring, and coaching opportunities. We host regular company-wide sessions where our employees discuss ideas related to corporate initiatives and scientific breakthroughs and recognize each other’s 23 contributions.
Clinical data, the indications and lines of therapy we pursue, the specific compounds from our pipeline we advance, our combination therapy and testing strategies, the size of the addressable patient populations, the commercial infrastructure and manufacturing needs and other factors, may all influence or alter our commercialization plans.
Clinical data, the indications and lines of therapy we pursue, the specific compounds from our pipeline we advance, our combination therapy and testing strategies, the size of the addressable patient populations, the commercialization infrastructure and manufacturing needs and other factors, may all influence or alter our commercialization plans.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. 14 Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured.
The purpose of such studies can include, among other things, assessments designed to evaluate a known serious risk or signals of serious risk related to the drug or to identify an unexpected serious risk when available data indicate the potential for a serious risk.
The purpose of such studies can include, among other things, assessments designed to evaluate a known serious risk or signals of serious risk related to the drug or to identify an unexpected serious risk when available data 17 indicate the potential for a serious risk.
Data can come from company-sponsored clinical studies intended to test the 25 safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators.
Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators.
The issued patents, and any patents 23 issuing from these patent applications, are expected to expire between 2035 and 2043, without accounting for potentially available patent term adjustments or extensions.
The issued patents, and any patents issuing from these patent applications, are expected to expire between 2035 and 2043, without accounting for potentially available patent term adjustments or extensions.
In such a case, the IND 24 may be placed on clinical hold, and the IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical studies can begin.
In such a case, the IND may be placed on clinical hold, and the IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical studies can begin.
The orphan exclusivity period may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for which it received orphan destination, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.
The orphan exclusivity period may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for which it received orphan designation, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023) and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023) and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).
The consistent finding from the first-generation mutant-selective RAS inhibitors is that the main resistance mechanism that curtails durable efficacy is through reactivation of RAS pathway, highlighting the oncogenic addiction in RAS-mutated cancers. We believe many of these resistance mechanisms may be amenable to inhibition with a RAS(ON) multi-selective inhibitor.
The consistent finding from the first-generation mutant-selective KRAS inhibitors is that the main resistance mechanism that curtails durable efficacy is through reactivation of the RAS pathway, highlighting the oncogenic addiction in RAS mutant cancers. We believe many of these resistance mechanisms may be amenable to inhibition with a RAS(ON) multi-selective inhibitor.
As a result of the Northern Ireland Protocol, different rules applied in Northern Ireland than in GB; broadly, Northern Ireland continued to follow the EU regulatory regime. However, on January 1, 2025, a new arrangement called the “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products.
As a result of the Northern Ireland Protocol, different rules applied in Northern Ireland than in GB; broadly, Northern Ireland continued to follow the EU regulatory regime. However, on January 1, 2025, an arrangement called the “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicinal products.
Our agreements with CMOs may obligate them to develop and qualify upstream and downstream processes, develop drug product process, validate (and, in some cases, develop) suitable analytical methods for test and release as well as stability testing, produce drug substance for preclinical testing, produce cGMP-compliant drug substance, or produce cGMP-compliant drug product.
Our agreements with CDMOs may obligate them to develop and qualify upstream and downstream processes, develop drug product process, validate (and, in some cases, develop) suitable analytical methods for test and release as well as stability testing, produce drug substance for preclinical testing, produce cGMP-compliant drug substance, or produce cGMP-compliant drug product.
The issued patents, and any patents issuing from these patent applications are expected to expire between 2031 (for patents originating from the Warp Drive Bio portfolio) and 2044 (for patents from our portfolio that did not originate from Warp Drive Bio), without accounting for potentially available patent term adjustments or extensions.
The issued patents, and any patents issuing from these patent applications are expected to expire between 2031 (for patents originating from the Warp Drive Bio portfolio) and 2045 (for patents from our portfolio that did not originate from Warp Drive Bio), without accounting for potentially available patent term adjustments or extensions.
We conduct audits of CMOs prior to initiation 21 of activities under these agreements and monitor operations to ensure compliance with the mutually agreed process descriptions and to cGMP regulations. Competition The biotechnology and pharmaceutical industries, and the oncology sector in particular, are characterized by rapid evolution of technologies, fierce competition and strong defense of intellectual property rights.
We conduct audits of CDMOs prior to initiation of activities under these agreements and monitor operations to ensure compliance with the mutually agreed process descriptions and with cGMP regulations. Competition The biotechnology and pharmaceutical industries, and the oncology sector in particular, are characterized by rapid evolution of technologies, fierce competition and strong defense of intellectual property rights.
We further believe that in some cases, it could be beneficial to combine daraxonrasib with a RAS(ON) mutant-selective inhibitor, with daraxonrasib functioning as the backbone of these RAS(ON) Inhibitor doublets. In addition, we believe that in some cases, combination of our RAS(ON) Inhibitors with standard of care therapies, including immunotherapies, may be optimal.
We further believe that in some cases, it could be beneficial to combine daraxonrasib with a RAS(ON) mutant-selective inhibitor, with daraxonrasib functioning as the backbone of these RAS(ON) Inhibitor doublets. In addition, we believe that in some cases, combination of our RAS(ON) Inhibitors with standard of care therapies, including immunotherapies, or other novel therapies, may be optimal.
Our outsourced approach to manufacturing relies on CMOs to first develop manufacturing processes that are compliant with current Good Manufacturing Practice (cGMP), then produce material for preclinical and clinical studies.
Our outsourced approach to manufacturing relies on CDMOs to first develop manufacturing processes that are compliant with current Good Manufacturing Practice (cGMP), then produce material for preclinical and clinical studies.
The CTA must include, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation.
The clinical trial application (CTA) must include, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation.
If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.
If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same approved use or indication within such disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.
The SEC maintains a site on the worldwide web that contains reports, proxy and information statements and other information regarding our filings at www.sec.gov. 35
The SEC maintains a site on the worldwide web that contains reports, proxy and information statements and other information regarding our filings at www.sec.gov. 24
Orphan drug exclusivity also could block the approval of a product for seven years if a competitor obtains approval of the “same drug” as defined by the FDA, or if a product candidate is determined to be contained within the approved product for the same disease or condition.
Orphan drug exclusivity also could block the approval of a product for seven years if a competitor obtains approval of the “same drug” as defined by the FDA, or if a product candidate is determined to be contained within the approved product for the same use or indication within the relevant rare disease or condition.
In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.
In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs relating to the approved use or indication of patients with the relevant rare disease or condition.
Our pipeline of RAS(ON) multi-selective and RAS(ON) mutant-selective inhibitors offer an opportunity for RAS(ON) doublet combinations designed to potentially maximize durable clinical benefit by effectively targeting the most common KRAS mutant variants in cancer.
Our pipeline of RAS(ON) multi-selective and RAS(ON) mutant-selective inhibitors offers an opportunity for RAS(ON) inhibitor doublet combinations designed to potentially maximize durable clinical benefit by effectively targeting the most common RAS mutant variants in cancer.
(licensed to Genfleet Therapeutics), InventisBio, Jacobio Pharmaceuticals Co. Ltd., Jiangsu Hansoh Pharmaceutical Group Co., Ltd., Merck, Sharpe & Dohme LLC, Roche, Shanghai Junshi Biosciences Co., Ltd., Shanghai YingLi Pharmaceutical, Shouyao Holdings (Beijing) Co. Ltd. and Suzhou Zelgen Biopharmaceuticals. BridgeBio Pharma, Inc. and Frontier Medicines each have a dual KRAS(ON/OFF) G12C program in the clinic.
(licensed to Shanghai Allist Pharmaceuticals), Jiangsu Hansoh Pharmaceutical Group Co., Ltd., Merck, Sharpe & Dohme LLC, Roche/Genentech, Shanghai Junshi Biosciences Co., Ltd., Shanghai YingLi Pharmaceutical, Shouyao Holdings (Beijing) Co. Ltd. and Suzhou Zelgen Biopharmaceuticals. BridgeBio Pharma, Inc. and Frontier Medicines each have a dual KRAS G12C (ON/OFF) program in the clinic.
Employees and Human Capital Resources As of December 31, 2024, we had 534 full-time employees. Within our workforce, as of December 31, 2024, 423 employees were engaged in research and development. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.
Employees and Human Capital Resources As of December 31, 2025, we had 883 full-time employees. Within our workforce, as of December 31, 2025, 673 employees were engaged in research and development. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.
CMS has published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and the list of the subsequent 15 drugs that will be subject to negotiation, although the Medicare drug price negotiation program is currently subject to legal challenges. For that and other reasons, it is currently unclear how the IRA will be effectuated.
CMS has published the negotiated prices for the initial ten drugs, which went into effect in 2026, and 22 the subsequent 15 drugs, which will first be effective in 2027, although the Medicare drug price negotiation program is currently subject to legal challenges. For that and other reasons, it is currently unclear how the IRA will be effectuated.
As of December 31, 2024, females represented 58% of our full-time employees, and 426 of our employees self-identified their race, of which 55% self-identified as an “underrepresented minority,” as that term is defined by Nasdaq rules. We are equally committed to the development of our employees and one of our corporate core values (Exceptional Together) captures this commitment.
As of December 31, 2025, females represented 59% of our full-time employees, and 702 of our employees self-identified their race, of which 51% self-identified as an “underrepresented minority,” as that term is defined by Nasdaq rules. We are equally committed to the development of our employees and one of our corporate core values (Exceptional Together) captures this commitment.
Once the CTA is approved, clinical study development may proceed. The CTR transition period ended on January 31, 2025, and all clinical trials (and related applications) are now fully subject to the provisions of the CTR. Medicines used in clinical trials must be manufactured in accordance with cGMP. Other national and EU-wide regulatory requirements may also apply.
Once the CTA is approved, clinical study development may proceed. The CTR transition period ended on January 31, 2025, and all clinical trials (and related applications) are now fully subject to the provisions of the CTR. Medicines used in clinical trials must be manufactured in accordance with cGMP.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of KRAS G13C-bearing cancer cells and is engineered to covalently inactivate KRAS G13C for irreversible inhibition. Clinical development of RMC-8839 is subject to our continuing assessment of our portfolio priorities.
Clinical development of RMC-0708 is subject to our continuing assessment of portfolio priorities. RMC-8839 RMC-8839 is designed as a RAS(ON) oral G13C-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of KRAS G13C-bearing cancer cells and is engineered to covalently inactivate KRAS G13C for irreversible inhibition.
The process required by the FDA before product candidates may be marketed in the United States generally involves the following: • completion of certain extensive preclinical laboratory tests and animal studies, including safety and toxicity studies performed in accordance with applicable regulations, including the FDA’s Good Laboratory Practice (GLP) regulations; • manufacture of clinical drug supply in accordance with the FDA’s cGMP regulations for use in clinical studies; • submission to the FDA of an Investigational New Drug application (IND), which must become effective before human clinical studies may begin and must be updated annually or when certain changes or updates are made; • approval by an independent institutional review board (IRB) or ethics committee representing each clinical site before a clinical study may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice (GCP), regulations to establish the safety and efficacy of the product candidate for each proposed indication; • preparation of and submission to the FDA of a New Drug Application (NDA) after completion of all pivotal trials; • a determination by the FDA within 60 days of its receipt of an NDA to file the application for review; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility(ies) where the product is manufactured to assess compliance with cGMP regulations, and of potential inspection selected clinical investigation sites to assess compliance with GCP; • payment of user fees for FDA review of the NDA; and • FDA review and approval of an NDA to permit commercial marketing of the product for its particular labeled uses in the United States.
Failure to comply with applicable FDA or other requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA clinical holds, refusal to approve pending applications, withdrawal of an approval, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution. 12 The process required by the FDA before product candidates may be marketed in the United States generally involves the following: • completion of certain extensive preclinical laboratory tests and animal studies, including safety and toxicity studies performed in accordance with applicable regulations, including the FDA’s Good Laboratory Practice (GLP) regulations; • manufacture of clinical drug supply in accordance with the FDA’s cGMP regulations for use in clinical studies; • submission to the FDA of an Investigational New Drug application (IND), which must become effective before human clinical studies may begin and must be updated annually or when certain changes or updates are made; • approval by an independent institutional review board (IRB) or ethics committee representing each clinical site before a clinical study may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice (GCP) regulations to establish the safety and efficacy of the product candidate for each proposed indication; • preparation of and submission to the FDA of a New Drug Application (NDA) after completion of all pivotal trials; • a determination by the FDA within 60 days of its receipt of an NDA to file the application for review; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility(ies) where the product is manufactured to assess compliance with cGMP regulations, and of potential inspection of selected clinical investigation sites to assess compliance with GCP; • payment of user fees for FDA review of the NDA; and • FDA review and approval of an NDA to permit commercial marketing of the product for its particular labeled uses in the United States.
We have entered into contracts with CMOs for production of drug substance and drug product for our clinical trials and IND-enabling development studies, and plan to enter into additional contracts with these or other manufacturers for additional supply.
We have entered into contracts with CDMOs for production of drug substance and drug product for our clinical trials, IND-enabling development studies and commercial supply (if our product candidates receive marketing approval). We plan to enter into additional contracts with these or other manufacturers for additional supply.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions. Clinical development of RMC-0708 is subject to our continuing assessment of our portfolio priorities. RMC-8839 RMC-8839 is designed as a RAS(ON) oral G13C-selective inhibitor.
Other Development Opportunities RMC-0708 RMC-0708 is designed as a RAS(ON) oral Q61H-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions.
Supreme Court dismissed a judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. 33 Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers, which will remain in effect through 2032, with the exception of a temporary suspension that occurred from May 1, 2020 through March 31, 2022, absent additional congressional action.
Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers, which will remain in effect through 2032, with the exception of a temporary suspension that occurred from May 1, 2020 through March 31, 2022, absent additional congressional action.
Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.
Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same approved use or indication within the rare disease or condition, or the same drug for any use or indication within a different disease or condition.
Manufacturing We rely on and will continue to rely on contract manufacturing organizations (CMOs) for both drug substance and drug product. Currently, all of our manufacturing is outsourced to well-established third-party manufacturers.
Manufacturing We rely on and will continue to rely on contract development and manufacturing organizations (CDMOs) for all manufacturing activities. Currently, all of our manufacturing is outsourced to well-established third-party manufacturers.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS G12V-bearing cancer cells and is engineered for selective inhibition of RAS G12V over other RAS isoforms via non-covalent binding interactions.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS G12V-bearing cancer cells and is engineered for selective inhibition of RAS G12V over other RAS isoforms via non-covalent binding interactions. A first-in-human dose escalation clinical trial of RMC-5127 is ongoing.
Marketing Authorization In order to market our product candidates in the EU and many other foreign jurisdictions, we must obtain separate regulatory approvals. More concretely, in the EU, medicinal product candidates can only be commercialized after obtaining a marketing authorization (MA). To obtain regulatory approval of a product candidate under EU regulatory systems, we must submit a MA application (MAA).
Other national and EU-wide regulatory requirements may also apply. 18 Marketing Authorization In order to market our product candidates in the EU and many other foreign jurisdictions, we must obtain separate regulatory approvals. More concretely, in the EU, medicinal product candidates can only be commercialized after obtaining a marketing authorization (MA).
The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state.
The CTR provides for a centralized process and only requires the submission of a single application for multi-center trials. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state.
Pipeline Our pipeline is summarized below: RAS(ON) Inhibitor Data Daraxonrasib (RMC-6236) Daraxonrasib (RMC-6236), our RAS(ON) multi-selective inhibitor, is designed as a potent, oral, RAS-selective tri-complex inhibitor of multiple RAS(ON) variants including cancer drivers at all three of the major mutation hotspot positions, G12, G13, and Q61. 7 Daraxonrasib inhibits all three major RAS isoforms, suppressing the mutant cancer driver and cooperating wild-type RAS proteins.
Daraxonrasib Daraxonrasib, our RAS(ON) multi-selective inhibitor, is designed as an oral, RAS-selective tri-complex inhibitor of multiple RAS(ON) variants containing cancer driver mutations at all three of the major RAS mutation hotspot positions, G12, G13, and Q61. Daraxonrasib inhibits all three major RAS isoforms, suppressing the mutant cancer driver and cooperating wild-type RAS proteins. In October 2025, the U.S.
Additionally, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
Depending on whether a drug contains a new molecular entity, priority review designation means the FDA’s goal is to take an action on the marketing application within six months of the 60-day filing date, compared with 12 months under standard review. 15 Additionally, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
Since January 1, 2024, an international recognition procedure has been in place whereby the MHRA has been able to conduct targeted assessments of an MAA by recognizing approvals from trusted partner agencies such as the European Medicines Agency. 31 The UK regulatory framework in relation to clinical trials is derived from pre-existing EU legislation (as implemented into UK law, through secondary legislation).
Since January 1, 2024, an international recognition procedure has been in place whereby the MHRA has been able to conduct targeted assessments of an MAA by recognizing approvals from trusted partner agencies such as the European Medicines Agency.
Violation of any of such laws or any other government regulations that apply may result in penalties, including, without limitation, civil and criminal penalties, damages, fines, additional reporting obligations, the curtailment or restructuring of operations, exclusion from participation in government healthcare programs and individual imprisonment. 32 Data Privacy and Security We may be subject to numerous federal, state and foreign laws, regulations that govern the collection, use, disclosure and protection of health-related and other personal information.
Violation of any of such laws or any other government regulations that apply may result in penalties, including, without limitation, civil and criminal penalties, damages, fines, additional reporting obligations, the curtailment or restructuring of operations, exclusion from participation in government healthcare programs and individual imprisonment.
Since its enactment, there have been judicial, executive and congressional challenges to certain aspects of the ACA. In June 2021, the U.S.
Since its enactment, there have been judicial, executive and congressional challenges to certain aspects of the ACA. In June 2021, the U.S. Supreme Court dismissed a judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.
The KRAS G12C mutation has been clinically validated as a therapeutic target, and the evidence is strong that numerous other oncogenic mutations in the RAS family of proteins are likewise compelling cancer targets. Our collection of RAS(ON) Inhibitors is tailored to target RAS mutations that together comprise the driver mutations in the vast majority of RAS-addicted cancers.
RAS proteins drive a significant number of human cancers and are largely unserved by targeted therapeutics. The KRAS G12C mutation has been clinically validated as a therapeutic target, and the evidence is strong that numerous other oncogenic mutations in the RAS family of proteins are likewise compelling cancer targets.
These competitors also compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. 22 Intellectual Property Our success depends in part on our ability and the ability of our collaborators to obtain and maintain proprietary protection for our technology, programs and know-how related to our business, defend and enforce our intellectual property rights, in particular, our patent rights, preserve the confidentiality of our trade secrets, and operate without infringing valid and enforceable intellectual property rights of others.
Intellectual Property Our success depends in part on our ability and the ability of our collaborators to obtain and maintain proprietary protection for our technology, programs and know-how related to our business, defend and enforce our intellectual property rights, in particular, our patent rights, preserve the confidentiality of our trade secrets, and operate without infringing valid and enforceable intellectual property rights of others.
Among the other benefits of orphan drug designation are opportunities for grant funding towards clinical trial costs, tax credits for certain research and a waiver of the application user fee. 27 A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the disease or condition for which it received orphan designation.
Among the other benefits of orphan drug designation are opportunities for grant funding towards clinical trial costs, tax credits for certain research and a waiver of the application user fee.
Commercial Plan We intend to retain significant development and commercialization rights to our product candidates and, if marketing approval is obtained, to commercialize our product candidates on our own, or potentially with one or more collaborators, in the United States and other regions. We currently have limited sales, marketing and commercial product distribution capabilities.
Commercialization Plans We intend to retain significant development and commercialization rights to our product candidates and, if marketing approval is obtained, to commercialize our product candidates on our own in the U.S. and other regions.
We currently expect to substantially complete enrollment of the RASolute 302 study in 2025, to enable an expected clinical readout in 2026. 3 Having finalized the study protocol, we are now activating sites for a global, randomized Phase 3 registrational trial comparing daraxonrasib versus docetaxel in patients with locally advanced or metastatic RAS-mutated non-small cell lung cancer (NSCLC) who have been treated with immunotherapy and platinum-containing chemotherapy, which we call the RASolve 301 study.
Based on encouraging early-stage clinical results we are evaluating daraxonrasib in RASolve 301, a global, randomized Phase 3 registrational trial comparing daraxonrasib versus docetaxel in patients with locally advanced or metastatic RAS mutant NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. We currently expect to substantially complete enrollment in RASolve 301 in 2026.
Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement it into national law.
Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement it into national law. The CTR notably harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical Trials Information System, which contains a centralized EU portal and database.
We believe that in some cases, patients may experience maximal clinical benefit from the broad activity of our RAS(ON) multi-selective inhibitor, daraxonrasib (RMC-6236), if approved. In others, we believe treatment with a RAS(ON) mutant-selective inhibitor may be optimal.
In some cases, patients may experience maximal clinical benefit from the broad activity of a RAS(ON) multi-selective inhibitor, such as daraxonrasib (RMC-6236), which is designed to inhibit multiple oncogenic RAS variants. In other settings, treatment with a RAS(ON) mutant-selective inhibitor, designed to selectively target a specific RAS mutation, may be optimal.
Elironrasib is designed to be differentiated from first-generation KRAS(OFF) G12C inhibitors, which sequester the KRAS(OFF) G12C form, by its potential mechanism of directly inhibiting the RAS(ON) G12C form. We believe direct inhibition of the ON form offers important biological advantages, including more rapid termination of RAS signaling and more robust inhibition in the face of known resistance mechanisms.
Elironrasib is designed to be differentiated from first-generation KRAS(OFF) G12C inhibitors, which sequester the KRAS(OFF) G12C form, by its mechanism of directly inhibiting the RAS(ON) G12C form.
Our RAS(ON) Inhibitors are designed to be used as monotherapy, in combination with other RAS(ON) Inhibitors and/or in combination with RAS companion inhibitors or other therapeutic agents. RAS(ON) Inhibitors Our RAS(ON) Inhibitors are based on our proprietary tri-complex technology platform, which enables a highly differentiated approach to inhibiting the active, GTP-bound form of RAS, which we refer to as RAS(ON).
RAS(ON) Inhibitors Our RAS(ON) Inhibitors are based on our proprietary tri-complex technology platform, which enables a highly differentiated approach to inhibiting the active, GTP-bound form of RAS, which we refer to as RAS(ON). We are developing a portfolio of compounds that we believe were the first RAS(ON) Inhibitors to use this mechanism of action.
Guided by our understanding of genetic drivers and adaptive resistance mechanisms in cancer, we deploy precision medicine approaches to inform innovative monotherapy and combination regimens.
Guided by our understanding of genetic drivers and adaptive resistance mechanisms in cancer, we deploy precision medicine approaches to inform innovative monotherapy and combination regimens. Our research and development pipeline comprises inhibitors that bind directly to RAS variants (RAS(ON) Inhibitors) that are designed to be used as monotherapy, in combination with other RAS(ON) Inhibitors and/or other therapeutic agents.
If and when our products receive FDA approval, they could be subject to maximum fair price (MFP) negotiation and application by the Centers for Medicare & Medicaid Services (CMS) under terms of the Inflation Reduction Act of 2022 (the IRA), nine years after launch in the United States.
If and when our products receive FDA approval, they could be subject to (i) maximum fair price (MFP) negotiation and application by the Centers for Medicare & Medicaid Services (CMS) under terms of the Inflation Reduction Act of 2022 (the IRA), nine years after launch in the U.S or (ii) mandatory payment models under which manufacturers of eligible drugs would be required to pay rebates to the federal government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing.
Also on December 2, 2024, we disclosed initial clinical safety, tolerability and activity data as of a data cutoff date of October 28, 2024 from our clinical study of the combination of daraxonrasib with elironrasib, which we believe showed the combination was generally well tolerated and provide initial proof-of-mechanism for a RAS(ON) inhibitor doublet in patients with colorectal cancer (CRC) who were previously treated with KRAS(OFF) G12C inhibitors.
Clinical Data On December 2, 2024, we reported updated data from our Phase 1 study evaluating daraxonrasib in combination with elironrasib in patients with late line CRC who were previously treated with a KRAS(OFF) G12C inhibitor. We believe these data showed that the combination was generally well tolerated in these patients.
Other Healthcare Laws Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business.
The amendment, which will take full effect from April 2026, aims to provide a more flexible regime to make it easier to conduct clinical trials in the UK, increase the transparency of clinical trials conducted in the UK and make clinical trials more patient centered. 20 Other Healthcare Laws Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business.
Other clinical programs directed at mutant RAS, including pan-RAS inhibitors and Plk1 inhibitors, are being conducted, including those by Alaunos Therapeutics, Inc., BeiGene, Boehringer Ingelheim, Cardiff Oncology, Chugai Pharmaceutical Co., Ltd., Eli Lilly, Elicio Therapeutics, Gritstone bio, Inc., Moderna, Inc., Pfizer, Inc., Quanta Therapeutics, RasCal Therapeutics, Shanghai YingLi Pharmaceutical, Silenseed Ltd., Silexion Therapeutics and Targovax ASA.
Other clinical programs directed at mutant RAS, including pan-RAS and pan-KRAS inhibitors and Plk1 inhibitors, are being conducted, including those by Adlai Nortye Ltd., Alterome Therapeutics, Amgen, Astellas Pharma Inc., Auricula Biosciences, BeOne Medicines (formerly BeiGene), Betta Pharmaceuticals Co., Ltd., Boehringer Ingelheim, BridgeBio Oncology Therapeutics Inc., Cardiff Oncology, Chugai Pharmaceutical Co., Ltd., Circio Holding (formerly Targovax), Eli Lilly, Elicio Therapeutics, Erasca Inc., GenFleet Therapeutics, Guangzhou Jiayue Pharmaceutical Technology Co.
The process for doing this depends, among other things, on the nature of the medicinal product.
To obtain regulatory approval of a product candidate under EU regulatory systems, we must submit a MA application (MAA). The process for doing this depends, among other things, on the nature of the medicinal product.
Food and Drug Administration (FDA) approval (KRAS G12C inhibitors sotorasib and adagrasib), which interact exclusively with the OFF form.
This differentiated mechanism of action offers potential improvements over that of the first RAS inhibitors to gain FDA approval (KRAS G12C inhibitors sotorasib and adagrasib), which interact exclusively with the OFF form.
We are developing a portfolio of compounds that we believe were the first RAS(ON) Inhibitors to use this mechanism of action. We believe that direct inhibitors of RAS(ON) suppress cell growth and survival and are less susceptible to adaptive resistance mechanisms recognized for RAS(OFF) inhibitors.
We believe that direct inhibitors of RAS(ON) suppress cell growth and survival and are less susceptible to adaptive resistance mechanisms recognized for RAS inhibitors that target the inactive, GDP-bound form of RAS, which we refer to as RAS(OFF) inhibitors. We believe tailored RAS(ON) Inhibitors will be useful to serve the diverse landscape of RAS-addicted cancers optimally.
Our RAS(ON) Inhibitors are unique in that they are the first RAS inhibitors in clinical development to specifically target the activated, or ON, form of oncogenic RAS proteins. This differentiated mechanism of action offers potential improvements over that of the first RAS inhibitors to gain U.S.
Our collection of RAS(ON) Inhibitors is tailored to target RAS mutations that together comprise the driver mutations in the vast majority of RAS-addicted cancers. Our RAS(ON) Inhibitors are the first RAS inhibitors in clinical development to specifically target the activated, or ON, form of oncogenic RAS proteins.
There are also several clinical programs directed at KRAS G12D, including those being conducted by Astellas Pharma Inc., AstraZeneca, Eli Lilly, Genentech, Incyte Corporation, Jiangsu Hengrui Pharmaceuticals Company Ltd, Quanta Therapeutics, Tyligand Bioscience and Zelgen Biopharmaceuticals. In addition, there are a few clinical programs directed at KRAS G12V, including those being conducted by Affini-T Therapeutics and Yingkai Saiwei (Beijing) Biotechnology.
There are also several clinical programs directed at KRAS G12D, including those being conducted by Anocca, Arvinas, Astellas Pharma Inc., AstraZeneca, Beijing DCTY Biotech Co. Ltd., D3 BIO, Inc., Eli Lilly, Elicio Therapeutics, GenFleet Therapeutics (licensed to Verastem Oncology), Hyperway Pharmaceutical Co. Ltd., Incyte Corporation, Jiangsu Hansoh Pharmaceutical Group Co., Jiangsu Hengrui Pharmaceuticals Co.
There are several programs in clinical development targeting KRAS G12C, including programs directed at KRAS(OFF) G12C being conducted by Amgen Inc., Betta Pharmaceuticals Co., Ltd., Bristol Myers Squibb Company, Chengdu Huajian Future Technology Co. Ltd., D3 BIO, Inc., Eli Lilly, GenEros Biopharma Ltd., Genhouse Bio Co. Ltd., Guangzhou BeBetter Medicine Technology Co., Ltd., HUYA Bioscience, Innovent Biologics, Inc.
These treatments consist of small molecule drug products, biologics, cell-based therapies and traditional chemotherapy. There are several programs in clinical development targeting KRAS G12C, including programs directed at KRAS(OFF) G12C being conducted by Amgen, Betta Pharmaceuticals Co., Ltd., BMS, Chengdu Huajian Future Technology Co.
We are advancing a deep pipeline of RAS(ON) Inhibitors, including daraxonrasib (RMC-6236), our RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), our G12C-selective inhibitor; and zoldonrasib (RMC-9805), our G12D-selective inhibitor. Together, we consider these three clinical-stage candidates as the first wave of RAS(ON) inhibitors that we are advancing through clinical development. We also currently plan to advance RMC-5127 (G12V) into clinical development.
We are advancing a deep pipeline of RAS(ON) Inhibitors, including daraxonrasib, our multi-selective inhibitor, z oldonrasib (RMC-9805), our G12D-selective inhibitor, elironrasib (RMC-6291), our G12C-selective inhibitor, and RMC-5127, our G12V-selective inhibitor. We also have other preclinical-stage RAS(ON) Inhibitor clinical development opportunities, including the RAS(ON) mutant-selective inhibitors RMC-0708 (Q61H) and RMC-8839 (G13C) and additional novel targeted approaches for patients with RAS-addicted cancers.
Our Strategy Overview Our goal is to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative, targeted medicines. RAS proteins drive a significant number of human cancers, and are largely unserved by targeted therapeutics.
With a data cutoff of October 28, 2024, we observed an ORR of 25%, which compared favorably to the observed ORR of either compound as monotherapy, and a DCR of 92%. Our Strategy Our goal is to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative, targeted medicines.
We believe these observations support continued evaluation of the combination of daraxonrasib with pembrolizumab in NSCLC patients in the 1L setting.
We believe these data showed that the combination of daraxonrasib with pembrolizumab, with or without chemotherapy, demonstrated acceptable tolerability in these patients.
We currently expect to initiate a global, randomized Phase 3 daraxonrasib monotherapy study in patients with first-line (1L) metastatic PDAC in the second half of 2025. We also currently expect to initiate a global, randomized Phase 3 monotherapy study of daraxonrasib as adjuvant treatment for patients with resectable PDAC in the second half of 2025.
We also currently expect to initiate RASolve 308, a global, randomized placebo-controlled Phase 3 registrational trial evaluating zoldonrasib in combination with standard of care in patients with 1L metastatic RAS G12D NSCLC in the first half of 2026. We currently expect to provide an update on our plans for advancing daraxonrasib combination therapy in 1L NSCLC in 2026.
We also reported clinical activity data as of a September 30, 2024 data cutoff date for daraxonrasib from the RMC-6236-001 study in patients with NSCLC with tumors harboring RAS G12X mutations who had received one or two prior lines of therapy which must have included prior immunotherapy and platinum chemotherapy administered either concurrently or sequentially, but not docetaxel, a study population matching the planned RASolve 301 enrollees.
On December 2, 2024, we reported data from our Phase 1 study evaluating daraxonrasib monotherapy in patients with previously treated NSCLC with tumors harboring RAS G12 mutations, which must have included prior immunotherapy and platinum chemotherapy administered either concurrently or sequentially, but did not include docetaxel. We believe these data showed that daraxonrasib was generally well tolerated in these patients.

… 184 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

173 edited+83 added−56 removed546 unchanged
Biggest changeOur future relationships with customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, transparency, and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.
Biggest changeOur current and anticipated future dependence upon others for the manufacture of our product candidates (or the key starting and intermediate materials for such product candidates) may adversely affect our future profit margins and our ability to develop product candidates and commercialize any products that receive marketing approval on a timely and competitive basis. 54 Our future relationships with customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, transparency, and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.
Our current and future product candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA, the EMA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA, the EMA or comparable foreign regulatory authorities that a product candidate is safe or effective for its proposed indication or indications; • the results of clinical trials may not meet the level of statistical significance required by the FDA, the EMA or comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA, the EMA or comparable foreign regulatory authorities may disagree with our interpretation of data from clinical trials or preclinical studies; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA to the FDA or other submission or to obtain regulatory approval in the United States, the European Union (EU) or elsewhere; • the FDA, the EMA or comparable foreign regulatory authorities may find deficiencies with or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA, the EMA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our current and future product candidates could fail to receive regulatory approval for many reasons, including the following: • the FDA, the EMA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA, the EMA or comparable foreign regulatory authorities that a product candidate is safe or effective for its proposed indication or indications; • the results of clinical trials may not meet the level of statistical significance required by the FDA, the EMA or comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA, the EMA or comparable foreign regulatory authorities may disagree with our interpretation of data from clinical trials or preclinical studies; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA to the FDA or other submission or to obtain regulatory approval in the United States, the European Union (EU) or elsewhere; • the FDA or comparable foreign regulatory authorities may find deficiencies with or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA, the EMA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our business and operations, or those of our CROs or other third parties, may suffer in the event of information technology system failures, cyberattacks or deficiencies in our cybersecurity, which could materially affect our business, results of operations and financial condition.
Our business and operations, or those of our CROs or other third parties, may suffer in the event of information technology system failures, cyberattacks or deficiencies in our cybersecurity, which could materially affect our business, financial condition and results of operations.
We may be subject to a third-party pre-issuance submission of prior art to the United States Patent and Trademark Office (the USPTO) or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others, or other proceedings in the USPTO or applicable foreign offices that challenge priority of invention or other features of patentability.
We may be subject to a third-party pre-issuance submission of prior art to the United States Patent and Trademark Office (the USPTO) or applicable foreign offices or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others, or other proceedings in the USPTO or applicable foreign offices that challenge priority of invention or other features of patentability.
Such provision is intended to benefit and may be enforced by us, our officers and directors, the underwriters to any offering giving rise to such complaint and any other professional or entity whose profession gives authority to a statement made by that person or entity and who has prepared or certified any part of the documents underlying the offering.
Such provision is intended to benefit and may be enforced by us, our officers and directors, by the underwriters to any offering giving rise to such complaint and any other professional or entity whose profession gives authority to a statement made by that person or entity and who has prepared or certified any part of the documents underlying the offering.
Collaborations involving our current and future product candidates may pose the following risks to us: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations and may have incentives that are different than ours; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates; • collaborators with marketing, manufacturing or distribution rights to one or more products may not commit sufficient resources to or otherwise not perform satisfactorily in carrying out these activities as it relates to our product candidates or products; • collaborators may not properly prosecute, maintain, enforce or defend our intellectual property rights or may use our proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation, or other intellectual property proceedings; • collaborators may own or co-own intellectual property covering products that result from our collaboration with them, and in such cases, we may not have the exclusive right to develop, license or commercialize this intellectual property; • disputes may arise with respect to ownership of any intellectual property developed pursuant to our collaborations; • disputes may arise between a collaborator and us that cause the delay or termination of the research, development or commercialization of the product candidate, or that result in costly litigation or arbitration that diverts management attention and resources; and • if a current or future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under our collaboration could be delayed, diminished or terminated, including if the partner in such a business combination has products that compete with ours.
Collaborations involving our current and future product candidates may pose the following risks to us: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations and may have incentives that are different than ours; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates; • collaborators with marketing, manufacturing or distribution rights to one or more products may not commit sufficient resources to or otherwise not perform satisfactorily in carrying out these activities as it relates to our product candidates or products; • collaborators may not properly prosecute, maintain, enforce or defend our intellectual property rights or may use our proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation, or other intellectual property proceedings; 50 • collaborators may own or co-own intellectual property covering products that result from our collaboration with them, and in such cases, we may not have the exclusive right to develop, license or commercialize this intellectual property; • disputes may arise with respect to ownership of any intellectual property developed pursuant to our collaborations; • disputes may arise between a collaborator and us that cause the delay or termination of the research, development or commercialization of the product candidate, or that result in costly litigation or arbitration that diverts management attention and resources; and • if a current or future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under our collaboration could be delayed, diminished or terminated, including if the partner in such a business combination has products that compete with ours.
Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statutes or specific intent to violate them; • the Physician Payments Sunshine Act, created under the ACA, and its implementing regulations, which requires manufacturers of drugs, devices, biologics 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 CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (defined to include physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse midwives), 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; and 65 • analogous or related foreign, state or local laws and regulations, including anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-government third-party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; and state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures.
Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statutes or specific intent to violate them; • the Physician Payments Sunshine Act, created under the ACA, and its implementing regulations, which requires manufacturers of drugs, devices, biologics 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 CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (defined to include physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse midwives), 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; and • analogous or related foreign, state or local laws and regulations, including anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-government third-party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; and state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures.
For example: • others may be able to make products that are similar to our current or future product candidates or utilize similar technology but that are not covered by the claims of our patents or the patents that we license or may own in the future; • we, or our current or future collaborators might not have been the first to make the inventions covered by an issued patent or pending patent application that we license or may own in the future; • we or our current or future collaborators might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; 74 • generative AI technologies are a relatively novel development with evolving regulatory regimes that may not offer intellectual property protections; • our pending owned or licensed patent applications or those that we may own or license in the future may not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: • others may be able to make products that are similar to our current or future product candidates or utilize similar technology but that are not covered by the claims of our patents or the patents that we license or may own in the future; • we, or our current or future collaborators might not have been the first to make the inventions covered by an issued patent or pending patent application that we license or may own in the future; • we or our current or future collaborators might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • generative AI Technologies are a relatively novel development with evolving regulatory regimes that may not offer intellectual property protections; • our pending owned or licensed patent applications or those that we may own or license in the future may not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
Orphan medicinal product designation is intended to promote the development of medicines (1) that are intended for the diagnosis, prevention or treatment of 55 life-threatening or chronically debilitating conditions where (2) either (a) such conditions affect no more than 5 in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the investment needed for its development; and (3) for which no satisfactory method of diagnosis, prevention, or treatment has been authorized (or if such method exists, the product would be a significant benefit to those affected).
Orphan medicinal product designation is intended to promote the development of medicines (1) that are intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions where (2) either (a) such conditions affect no more than 5 in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the investment needed for its development; and (3) for which no satisfactory method of diagnosis, prevention, or treatment has been authorized (or if such method exists, the product would be a significant benefit to those affected).
The success of our current and future product candidates will depend on several factors, including the following: • successful completion of clinical trials and preclinical studies; • sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials; • allowance to proceed with clinical trials under Investigational New Drug applications (INDs) by the FDA or under comparable applications by comparable regulatory authorities for our planned clinical trials or future clinical trials; • successful enrollment and completion of clinical trials, particularly where competitors may also be recruiting patients; • data from our clinical programs that supports an acceptable risk-benefit profile of our product candidates in the intended populations; • receipt and maintenance of marketing approvals from applicable regulatory authorities; • establishing agreements with third-party manufacturers for clinical supply for our clinical trials and commercial manufacturing, if one of our product candidates is approved; 39 • entry into collaborations to further the development of our product candidates; • obtaining and maintaining our portfolio of intellectual property rights, including patents, trade secrets and know-how; • enforcing and defending intellectual property rights and claims; • obtaining and maintaining regulatory exclusivity for our product candidates; • successfully launching commercial sales of our product candidates, if approved; • acceptance of the product candidate’s benefits and uses, if approved, by patients, the medical community and third-party payors; • the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates prior to or following any approval; • effectively competing with other therapies; and • obtaining and maintaining healthcare coverage and adequate reimbursement from third-party payors.
The success of our current and future product candidates will depend on several factors, including the following: • successful completion of clinical trials and preclinical studies; • sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials; • allowance to proceed with clinical trials under Investigational New Drug applications (INDs) by the FDA or under comparable applications by comparable regulatory authorities for our planned clinical trials or future clinical trials; • successful enrollment and completion of clinical trials, particularly where competitors may also be recruiting patients; • data from our clinical programs that supports an acceptable risk-benefit profile of our product candidates in the intended populations; • receipt and maintenance of marketing approvals from applicable regulatory authorities; • establishing agreements with third-party manufacturers for clinical supply for our clinical trials and commercial manufacturing, if one of our product candidates is approved; • entry into collaborations to further the development of our product candidates; • obtaining and maintaining our portfolio of intellectual property rights, including patents, trade secrets and know-how; • enforcing and defending intellectual property rights and claims; • obtaining and maintaining regulatory exclusivity for our product candidates; 29 • successfully launching commercial sales of our product candidates, if approved; • acceptance of the product candidate’s benefits and uses, if approved, by patients, the medical community and third-party payors; • the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates prior to or following any approval; • effectively competing with other therapies; and • obtaining and maintaining healthcare coverage and adequate reimbursement from third-party payors.
If we or our vendors fail to comply with the GDPR and the applicable national data protection laws of the EEA member states, or if regulators assert we have failed to comply with these laws, it may lead to regulatory enforcement actions, which can result in, among other things, monetary penalties of up to €20,000,000 or up to 4% of the total worldwide annual turnover of the noncompliant undertaking for the preceding financial year, whichever is higher, and other administrative penalties.
If we or our vendors fail to comply with the GDPR and the applicable national data protection laws of the EEA member states, or if 47 regulators assert we have failed to comply with these laws, it may lead to regulatory enforcement actions, which can result in, among other things, monetary penalties of up to €20,000,000 or up to 4% of the total worldwide annual turnover of the noncompliant undertaking for the preceding financial year, whichever is higher, and other administrative penalties.
Delaware law provides that a corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to our best interests and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful; • we may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law; 80 • we are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such directors or officers shall undertake to repay such advances if it is ultimately determined that such person is not entitled to indemnification; • we are not obligated pursuant to our amended and restated bylaws to indemnify a person with respect to proceedings initiated by that person against us or our other indemnitees, except with respect to proceedings authorized by our board of directors or brought to enforce a right to indemnification; • the rights conferred in our amended and restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons; and • we may not retroactively amend our amended and restated bylaws to reduce our indemnification obligations to our directors, officers, employees and agents.
Delaware law provides that a corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to our best interests and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful; • we may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law; • we are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such directors or officers shall undertake to repay such advances if it is ultimately determined that such person is not entitled to indemnification; 70 • we are not obligated pursuant to our amended and restated bylaws to indemnify a person with respect to proceedings initiated by that person against us or our other indemnitees, except with respect to proceedings authorized by our board of directors or brought to enforce a right to indemnification; • the rights conferred in our amended and restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons; and • we may not retroactively amend our amended and restated bylaws to reduce our indemnification obligations to our directors, officers, employees and agents.
Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the 43 United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
Therefore, our pending and future patent applications may not result in patents being issued in relevant jurisdictions that protect our product candidates, in whole or in part, or which effectively prevent others from commercializing competitive product candidates, and, even if our patent applications issue as patents in relevant jurisdictions, they may not issue in a form that will provide us with any meaningful protection for our product candidates or technology, prevent competitors from competing with us or otherwise provide us with any competitive advantage.
Therefore, our 56 pending and future patent applications may not result in patents being issued in relevant jurisdictions that protect our product candidates, in whole or in part, or which effectively prevent others from commercializing competitive product candidates, and, even if our patent applications issue as patents in relevant jurisdictions, they may not issue in a form that will provide us with any meaningful protection for our product candidates or technology, prevent competitors from competing with us or otherwise provide us with any competitive advantage.
The terms of the private warrants are substantially the same as the public warrants; provided, that, except as described above in the discussion of the redemption of public warrants when the price per share of our common stock equals or exceeds $89.93, the private warrants are exercisable on a cashless basis and are non-redeemable for cash so long as they are held by the initial purchasers or their permitted transferees.
The terms of the private warrants are substantially the same as to the public warrants; provided, that, except as described above in the discussion of the redemption of public warrants when the price per share of our common stock equals or exceeds $89.93, the private warrants are exercisable on a cashless basis and are non-redeemable for cash so long as they are held by the initial purchasers or their permitted transferees.
Further, we may not be aware of all third-party intellectual property rights 66 potentially relating to our product candidates. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until approximately 18 months after filing or, in some cases, not at all.
Further, we may not be aware of all third-party intellectual property rights potentially relating to our product candidates. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until approximately 18 months after filing or, in some cases, not at all.
If securities analysts or investors perceive those results to be negative, it could cause the price of shares of our common stock to decline. 72 Third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could negatively impact the success of our business.
If securities analysts or investors perceive those results to be negative, it could cause the price of shares of our common stock to decline. Third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could negatively impact the success of our business.
After March 2013, under the Leahy-Smith America Invents Act (the Leahy-Smith Act) enacted in September 2011, the United States transitioned to a first inventor to file system in which, assuming that other requirements for patentability are met, the first inventor to file a patent application will be entitled to the patent on an invention regardless of whether a third party was the first to invent the claimed invention.
After March 2013, under the Leahy-Smith America Invents Act (the Leahy-Smith Act) enacted in September 2011, the United States transitioned to a first inventor to file system in which, assuming that other requirements for patentability are met, the first 60 inventor to file a patent application will be entitled to the patent on an invention regardless of whether a third party was the first to invent the claimed invention.
This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. 70 Changes in patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. Changes in patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology or product.
However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology or 62 product.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by 75 consultants is compromised for any reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain marketing approval of any current or future product candidates or otherwise advance our business.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by consultants is compromised for any reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain marketing approval of any current or future product candidates or otherwise advance our business.
If we raise additional capital through marketing and distribution 81 arrangements or other collaborations, strategic alliances or licensing arrangements with third parties, 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.
If we raise additional capital through marketing and distribution arrangements or other collaborations, strategic alliances or licensing arrangements with third parties, 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.
If we raise additional funds by issuing equity securities, our stockholders may suffer dilution and the terms of any financing may adversely affect the rights of our stockholders. For example, the EQRx Acquisition, an all-stock transaction pursuant to which we issued shares of our common stock according to a blended formula, resulted in substantial dilution to our stockholders.
If we raise additional funds by issuing equity securities, our stockholders may suffer dilution and the terms of any financing may adversely affect the rights of our stockholders. For example, the EQRx Acquisition, an all-stock 71 transaction pursuant to which we issued shares of our common stock according to a blended formula, resulted in substantial dilution to our stockholders.
In addition, as a public company, we are required to file accurate and timely quarterly and annual reports with the SEC under the Exchange Act. In order to report our results of operations and financial statements on an accurate and timely basis, we will depend on third-party vendors to provide timely and accurate notice of their costs to us.
In addition, as a 73 public company, we are required to file accurate and timely quarterly and annual reports with the SEC under the Exchange Act. In order to report our results of operations and financial statements on an accurate and timely basis, we will depend on third-party vendors to provide timely and accurate notice of their costs to us.
Our product candidates will require substantial additional development time and resources before we will be able to apply for or receive regulatory approvals and, if approved, begin generating revenue from product sales. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We have never generated revenue from product sales and may never be profitable.
Our product candidates will require additional development time and resources before we will be able to apply for or receive regulatory approvals and, if approved, begin generating revenue from product sales. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We have never generated revenue from product sales and may never be profitable.
If any of our product candidates receives marketing approval and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw their approval of the product; • we may be required to recall a product or change the way such product is administered to patients; • additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any component thereof; • regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication; 48 • we may be required to implement a risk evaluation and mitigation strategy (REMS) or create a medication guide outlining the risks of such side effects for distribution to patients; • we could be sued and held liable for harm caused to patients; • the product may become less competitive; and • our reputation may suffer.
If any of our product candidates receives marketing approval and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw their approval of the product; • we may be required to recall a product or change the way such product is administered to patients; • additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any component thereof; • regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication; • we may be required to implement a risk evaluation and mitigation strategy (REMS) or create a medication guide outlining the risks of such side effects for distribution to patients; • we could be sued and held liable for harm caused to patients; • the product may become less competitive; and 36 • our reputation may suffer.
We face significant competition in seeking appropriate strategic partners, and the negotiation process is time-consuming and complex. Whether we reach a definitive agreement for other collaborations will depend, among other things, upon our assessment of the 61 collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors.
We face significant competition in seeking appropriate strategic partners, and the negotiation process is time-consuming and complex. Whether we reach a definitive agreement for other collaborations will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors.
If we do not have sufficient funds, we may not be able to further develop our product candidates or bring them to market and generate product revenue. If conflicts arise between us and our collaborators or strategic partners, these parties may act in a manner adverse to us and could limit our ability to implement our strategies.
If we do not have sufficient funds, we may not be able to further develop our product candidates or bring them to market and generate product revenue. 51 If conflicts arise between us and our collaborators or strategic partners, these parties may act in a manner adverse to us and could limit our ability to implement our strategies.
Such a stock price decline could occur even when we have met any previously publicly stated revenue or operating guidance we may provide. Risks related to product development and regulatory process Our business is dependent on the successful development of our current and future product candidates.
Such a stock price decline could occur even when we have met any previously publicly stated revenue or operating guidance we may provide. 28 Risks related to product development and regulatory process Our business is dependent on the successful development of our current and future product candidates.
In each case, this interim data included a limited number of patients and time of exposure to the study drug. Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes 47 may materially change as patient enrollment continues and more data on existing patients become available.
In each case, this interim data included a limited number of patients and time of exposure to the study drug. Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more data on existing patients become available.
Third parties may: • have staffing difficulties; • fail to comply with contractual obligations; • experience regulatory compliance issues; • have incentives that are different than ours; • undergo changes in priorities or become financially distressed; or • form relationships with other entities, some of which may be our competitors.
Third parties may: • have staffing difficulties; • fail to comply with contractual obligations; • experience regulatory compliance issues; • have incentives that are different than ours; 52 • undergo changes in priorities or become financially distressed; or • form relationships with other entities, some of which may be our competitors.
We rely on third parties for supply of our preclinical and clinical drug supplies (including key starting and intermediate materials), and our strategy is to outsource all manufacturing of our product candidates and products to third parties. 63 In order to conduct clinical trials of product candidates, we will need to have them manufactured in potentially large quantities.
We rely on third parties for supply of our preclinical and clinical drug supplies (including key starting and intermediate materials), and our strategy is to outsource all manufacturing of our product candidates and products to third parties. In order to conduct clinical trials of product candidates, we will need to have them manufactured in potentially large quantities.
Later discovery of previously unknown problems with any 50 approved candidate, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or product recalls; • restrictions on product distribution or use, or requirements to conduct post-marketing studies or clinical trials; • fines, untitled and warning letters, or holds on clinical trials; • refusal by the FDA or comparable foreign authorities to approve pending applications or supplements to approved applications or suspension or revocation of approvals; • product seizure or detention, or refusal to permit the import or export of the product; and • injunctions or the imposition of civil or criminal penalties.
Later discovery of previously unknown problems with any 38 approved candidate, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or product recalls; • restrictions on product distribution or use, or requirements to conduct post-marketing studies or clinical trials; • fines, untitled and warning letters, or holds on clinical trials; • refusal by the FDA or comparable foreign authorities to approve pending applications or supplements to approved applications or suspension or revocation of approvals; • product seizure or detention, or refusal to permit the import or export of the product; and • injunctions or the imposition of civil or criminal penalties.
These studies may not produce results that are consistent with expectations or that are predicted by our earlier clinical observations for these compounds. Our plans for these and future planned registrational trials are, and will be based on our observations from the results of early-stage clinical trials using the same product candidates.
These studies may not produce results that are consistent with expectations or that are predicted by our earlier clinical 30 observations for these compounds. Our plans for these and future planned registrational trials are, and will be based on our observations from the results of early-stage clinical trials using the same product candidates.
Any failure or perceived failure by us to comply with federal, state or foreign laws or regulations, our internal policies and procedures or our contracts governing our processing of personal information could result in negative publicity, government investigations and enforcement actions, claims by third parties and damage to our reputation.
Any failure or perceived failure by us to comply with federal, state or foreign laws or regulations, our internal policies and procedures or our contracts governing our 46 processing of personal information could result in negative publicity, government investigations and enforcement actions, claims by third parties and damage to our reputation.
If we were to initiate legal proceedings against a third party to enforce a patent directed to our product candidates, or one of our future product candidates, the defendant could counterclaim that our patent is invalid or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are commonplace.
If we were to initiate legal proceedings against a third party to enforce a patent directed to our product candidates, or one of our future product candidates, the defendant could counterclaim that our patent is invalid or unenforceable. In patent litigation in the United 61 States, defendant counterclaims alleging invalidity or unenforceability are commonplace.
We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, including decisions to initiate pivotal clinical trials based on then-available data, and we may not have received or had the opportunity to fully and carefully evaluate all data.
We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, including decisions to initiate pivotal clinical trials based on then-available data, and we may not have 35 received or had the opportunity to fully and carefully evaluate all data.
In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third-party intellectual 68 property rights on terms that would allow us to make an appropriate return on our investment or at all.
In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third-party intellectual property rights on terms that would allow us to make an appropriate return on our investment or at all.
These fluctuations may occur due to a variety of factors, many of which are outside of our control and may be difficult to predict, including: • the timing and cost of, and level of investment in, research, development and commercialization activities, which may change from time to time; • the timing and status of enrollment for our clinical trials; • the timing of regulatory approvals, if any, in the United States and internationally; • the timing of expanding our operational, financial and management systems and personnel, including personnel to support our clinical development, quality control, manufacturing and commercialization efforts and our operations as a public company; • the cost of manufacturing, as well as building out our supply chain, which may vary depending on the quantity of productions, and the terms of any agreements we enter into with third-party suppliers; • the timing and amount of any milestone, royalty or other payments due under any current or future collaboration or license agreements; • coverage and reimbursement policies with respect to any future approved products, and potential future drugs that compete with our products; • the timing and costs to establish sales, marketing, medical affairs and distribution infrastructure to commercialize any products for which we may obtain marketing approval and intend to commercialize on our own or jointly with one or more collaborators; • expenditures that we may incur to acquire, develop or commercialize additional products and technologies; • the level of demand for any future approved products, which may vary significantly over time; • future accounting pronouncements or changes in our accounting policies; and • the timing and success or failure of preclinical studies and clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, including consolidation among our competitors or collaboration partners.
These fluctuations may occur due to a variety of factors, many of which are outside of our control and may be difficult to predict, including: • the timing and cost of, and level of investment in, research, development and commercialization activities, which may change from time to time; • the timing and status of enrollment for our clinical trials; • the timing of regulatory approvals, if any, in the United States and internationally; • the timing of expanding our operational, financial and management systems and personnel, including personnel to support our clinical development, quality control, manufacturing and commercialization efforts and our operations as a public company; • the cost of manufacturing, as well as building out our supply chain, which may vary depending on the quantity of productions, the terms of any agreements we enter into with third-party suppliers and tariffs that may apply; • the timing and amount of any milestone, royalty or other payments due under any current or future collaboration or license agreements; • the timing and level of royalty payments under the Royalty Purchase Agreement; • coverage and reimbursement policies with respect to any future approved products, and potential future drugs that compete with our products; • the timing and costs to establish sales, marketing, medical affairs and distribution infrastructure to commercialize any products for which we may obtain marketing approval and intend to commercialize on our own or jointly with one or more collaborators; • expenditures that we may incur to acquire, develop or commercialize additional products and technologies; • the level of demand for any future approved products, which may vary significantly over time; • future accounting pronouncements or changes in our accounting policies; and • the timing and success or failure of preclinical studies and clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, including consolidation among our competitors or collaboration partners.
The enrollment of patients depends on many factors, including: • the patient eligibility criteria defined in the protocol; • our ability to enroll a sufficient number of patients with mutations in the signaling pathways that our therapies are designed to target; • the size of the patient population required for analysis of the trial’s primary endpoints; • the proximity of patients to study sites; • the design of the trial; • the ability to recruit clinical trial investigators with the appropriate competencies and experience; • clinicians’ and patients’ perceptions as to the potential advantages of our product candidate being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • the ability to obtain and maintain patient consents for participation in our clinical trials and, where appropriate, biopsies for future patient enrichment efforts; • the risk that patients enrolled in clinical trials will not remain on the trial through the completion of evaluation; and 41 • the ability of clinical trial investigators to enroll patients in cases of outbreak of disease, geopolitical or other conflicts or natural disasters, including as a result of the ongoing war between Russia and Ukraine or escalation of conflicts in the Middle East.
The enrollment of patients depends on many factors, including: • the patient eligibility criteria defined in the protocol; • our ability to enroll a sufficient number of patients with mutations in the signaling pathways that our therapies are designed to target; • the size of the patient population required for analysis of the trial’s primary endpoints; • the proximity of patients to study sites; • the design of the trial; • the ability to recruit clinical trial investigators with the appropriate competencies and experience; • clinicians’ and patients’ perceptions as to the potential advantages of our product candidate being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • the ability to obtain and maintain patient consents for participation in our clinical trials and, where appropriate, biopsies for future patient enrichment efforts; • the risk that patients enrolled in clinical trials will not remain on the trial through the completion of evaluation; and • the ability of clinical trial investigators to enroll patients in cases of outbreak of disease, geopolitical or other conflicts or natural disasters, including as a result of the ongoing conflicts between Russia and Ukraine or in the Middle East.
Furthermore, escalation of geopolitical tensions, including as a result of the ongoing war between Russia and Ukraine or escalation of conflicts in the Middle East, could impact our current or planned clinical operations and our business partners and suppliers, which could adversely affect our business, partners, suppliers or the economy as a whole.
Furthermore, escalation of geopolitical tensions, including as a result of the ongoing conflicts between Russia and Ukraine or in the Middle East, could impact our current or planned clinical operations and our business partners and suppliers, which could adversely affect our business, partners, suppliers or the economy as a whole.
If these additional shares of common stock are sold, or if it is perceived that they will be sold, in the public market, the market price of our common stock could decline. There is no guarantee that our public and private warrants will ever be in the money, and they may expire worthless.
If these additional shares of common stock are sold, or if it is perceived that they will be sold, in the public market, the market price of our common stock could decline. There is no guarantee that the warrants will ever be in the money, and they may expire worthless.
These regulations are enforced by the FDA, the competent authorities of the EU member states and comparable foreign regulatory authorities for any drugs in clinical development. The FDA and comparable foreign regulatory authorities enforce GCP requirements through periodic inspections of clinical trial sponsors, principal investigators 62 and trial sites.
These regulations are enforced by the FDA, the competent authorities of the EU member states and comparable foreign regulatory authorities for any drugs in clinical development. The FDA and comparable foreign regulatory authorities enforce GCP requirements through periodic inspections of clinical trial sponsors, principal investigators and trial sites.
The loss of the services of any of them may adversely impact the achievement of our objectives. Any of our executive officers could leave our employment at any time, as all of our employees are “at-will” employees. We currently do not have “key person” insurance on any of our employees.
The loss of the services of any of them may adversely impact the achievement of our objectives. Any of our executive officers could leave our employment at any time, as all of our employees are 64 “at-will” employees. We currently do not have “key person” insurance on any of our employees.
These companies also have significantly greater research and marketing capabilities than we do and may also have products that have been approved or are in late stages of development, and collaborative arrangements in our 42 target markets with leading companies and research institutions.
These companies also have significantly greater research and marketing capabilities than we do and may also have products that have been approved or are in late stages of development, and collaborative arrangements in our target markets with leading companies and research institutions.
If we 73 or our licensors fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, intellectual property that is important to our product candidates.
If we or our licensors fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, intellectual property that is important to our product candidates.
The time required to obtain approval by the FDA, the EMA and comparable foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.
The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.
Even if we believe the data collected from future clinical trials of our product candidates are promising, this data may not be sufficient to support approval by the FDA, the EMA or any other regulatory authority.
Even if we believe the data collected from future clinical trials of our product candidates are promising, this data may not be sufficient to support approval by the FDA or any other regulatory authority.
In addition, if any of the research resulting in certain of our owned and/or in-licensed patent rights and technology were funded in part by the U.S. federal or state governments, the government would have certain rights, including march-in rights, to such patent rights and technology.
If any of the research resulting in certain of our owned and/or in-licensed patent rights and technology were funded in part by the U.S. federal or state governments, the government would have certain rights, including march-in rights, to such patent rights and technology.
If and when these warrants become redeemable by us, we may exercise our redemption right even if we are unable to register or qualify the underlying securities for sale under all applicable state securities laws.
If and when the warrants become redeemable by us, we may exercise our redemption right even if we are unable to register or qualify the underlying securities for sale under all applicable state securities laws.
We receive, generate and store significant and increasing volumes of sensitive information, such as health-related information, clinical trial data, proprietary business information and the personal information of our employees and contractors (collectively, Confidential 59 Information).
We receive, generate and store significant and increasing volumes of sensitive information, such as health-related information, clinical trial data, proprietary business information and the personal information of our employees and contractors (collectively, Confidential Information).
In many countries, the pricing review period begins after marketing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing government control even after initial approval is granted.
In many countries, the pricing review period 39 begins after marketing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing government control even after initial approval is granted.
Redemption of the outstanding public and private warrants could force the warrant holders: (i) to exercise their warrants and pay the exercise price therefor at a time when it may be disadvantageous for them to do so; (ii) to sell their warrants at the then-current market price when they might otherwise wish to hold their warrants; or (iii) to accept the nominal redemption price which, at the time the outstanding warrants are called for redemption, is likely to be substantially less than the market value of their warrants.
Redemption of the outstanding warrants could force the warrant holders: (i) to exercise their warrants and pay the exercise price therefor at a time when it may be disadvantageous for them to do so; (ii) to sell their warrants at the then-current market price when they might otherwise wish to hold their warrants; or (iii) to accept the nominal redemption price which, at the time the outstanding warrants are called for redemption, is likely to be substantially less than the market value of their warrants.
We may be unsuccessful in entering into or maintaining collaborations for the development of companion diagnostics for use with our current or future product candidates in our markets of interest. 53 Complementary diagnostics and companion diagnostics are subject to regulation by the FDA and similar regulatory authorities outside the United States as medical devices and require separate regulatory approval, clearance or certification prior to commercialization.
We may be unsuccessful in entering into or maintaining collaborations for the development of companion diagnostics for use with our current or future product candidates in our markets of interest. 41 Complementary diagnostics and companion diagnostics are subject to regulation by the FDA and similar regulatory authorities outside the United States as medical devices and require separate regulatory approval, clearance or certification prior to commercialization.
In addition, the laws and enforcement practices of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. The current conflict between Russia and Ukraine may also make it difficult or impossible to continue to prosecute patent applications or maintain patents in those countries or other affected territories.
In addition, the laws and enforcement practices of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. The ongoing conflict between Russia and Ukraine may also make it difficult or impossible to continue to prosecute patent applications or maintain patents in those countries or other affected territories.
Use of our federal and state net 79 operating loss carryforwards has been limited as a result of ownership changes and could be further limited if we experience additional ownership changes. Provisions in our charter documents and under Delaware law could discourage a takeover that stockholders may consider favorable and may lead to entrenchment of management.
Use of our federal and state net operating loss carryforwards has been limited as a result of ownership changes and could be further limited if we experience additional ownership changes. 69 Provisions in our charter documents and under Delaware law could discourage a takeover that stockholders may consider favorable and may lead to entrenchment of management.
If we or potential future collaboration partners experience delays in obtaining approval or if we fail to obtain approval of any of our current or future product candidates, the commercial prospects for those product candidates may be harmed. 49 Obtaining and maintaining marketing approval of our current and future product candidates in one jurisdiction does not mean that we or our potential future collaboration partners will be successful in obtaining marketing approval of our current and future product candidates in other jurisdictions.
If we or potential future collaboration partners experience delays in obtaining approval or if we fail to obtain approval of any of our current or future product candidates, the commercial prospects for those product candidates may be harmed. 37 Obtaining and maintaining marketing approval of our current and future product candidates in one jurisdiction does not mean that we or our potential future collaboration partners will be successful in obtaining marketing approval of our current and future product candidates in other jurisdictions.
These warrants entitle registered holders to purchase 0.1112 shares of our common stock at an exercise price of $11.50 per such fractional 78 share of common stock. There is no guarantee that the warrants will ever be in the money prior to their expiration, and as such, the warrants could expire worthless.
The warrants entitle registered holders to purchase 0.1112 shares of our common stock at an exercise price of $11.50 per such fractional share of common stock. There is no guarantee that the warrants will ever be in the money prior to their expiration, and as such, the warrants could expire worthless.
In addition, our clinical trials will compete with approved therapies, including sotorasib and adagrasib, as well as other clinical trials for product candidates that are in the same therapeutic areas (and that seek to evaluate patients with cancer cells having the same mutations), particularly for patients having KRAS G12C or KRAS G12D mutations, as our current and potential future product candidates.
In addition, our clinical trials will compete with approved therapies, including sotorasib and adagrasib, as well as other clinical trials for product candidates that are in the same therapeutic areas (and that seek to evaluate patients with cancer cells having the same mutations), particularly for patients having KRAS G12C, KRAS G12D, KRAS G12V mutations, as our current and potential future product candidates.
To the extent that any disruption or security breach were to result in a loss of or damage to data or applications, or inappropriate disclosure of Confidential Information, the costs associated with the investigation, remediation and potential notification of the breach to counterparties and data subjects could be material, we could incur liability due to delays in the development and commercialization of our product candidates or other business activities, and we may be exposed to reputational harm, litigation, regulatory investigations and enforcement, fines and penalties, or increased costs of compliance and system remediation.
To the extent that any disruption or security breach were to result in a loss of or damage to data or applications, or inappropriate disclosure of Confidential Information, the costs associated with the investigation, remediation and potential notification of the breach to counterparties and data subjects could be material, we could incur liability due to delays in the development and commercialization of our product candidates or other business activities, and we may be exposed to reputational harm, litigation (including class actions), regulatory investigations and enforcement, fines and penalties, or increased costs of compliance and system remediation.
These risks include the failure of enrolled subjects in foreign 46 countries to adhere to clinical protocols as a result of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, and political and economic risks, including war, relevant to these foreign countries.
These risks include the failure of enrolled subjects in foreign 34 countries to adhere to clinical protocols as a result of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, and political and economic risks, including war, relevant to these foreign countries.
Our ability to generate future revenue from product sales depends heavily on our, and any potential future collaborators’, success in: • completing clinical and preclinical development of product candidates and programs and identifying and developing new product candidates; • seeking and obtaining marketing approvals for our product candidates; • launching and commercializing product candidates for which we obtain marketing approval by establishing a sales force, marketing, medical affairs and distribution infrastructure or, alternatively, collaborating with a commercialization partner; • achieving adequate coverage and reimbursement by third-party payors for our product candidates; • establishing and maintaining supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and the market demand for our product candidates, if approved; • obtaining market acceptance of our product candidates as viable treatment options, if approved; 36 • addressing any competing technological and market developments; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter and performing our obligations under such collaborations; • maintaining, protecting, enforcing and expanding our portfolio of intellectual property rights, including patents, trademarks, trade secrets and know-how; • defending against third-party interference, infringement or other intellectual property-related claims, if any; and • attracting, hiring and retaining qualified personnel.
We have never generated revenue from product sales and our ability to generate future revenue from product sales and achieve profitability depends heavily on our, and any potential future collaborators’, success in: • completing clinical and preclinical development of product candidates and programs and identifying and developing new product candidates; • seeking and obtaining marketing approvals for our product candidates; • launching and commercializing product candidates for which we obtain marketing approval by establishing a sales force, marketing, medical affairs and distribution infrastructure or, alternatively, collaborating with a commercialization partner; • achieving adequate coverage and reimbursement by third-party payors for our product candidates; • establishing and maintaining supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and the market demand for our product candidates, if approved; • obtaining market acceptance of our product candidates as viable treatment options, if approved; • addressing any competing technological and market developments; 25 • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter and performing our obligations under such collaborations; • maintaining, protecting, enforcing and expanding our portfolio of intellectual property rights, including patents, trademarks, trade secrets and know-how; • defending against third-party interference, infringement or other intellectual property-related claims, if any; and • attracting, hiring and retaining qualified personnel.
Further, our product candidates may not receive regulatory approval even if they are successful in clinical trials. If we do not receive regulatory approvals for our product candidates, we may not be able to continue our operations. 45 Clinical product development involves a lengthy and expensive process, with uncertain outcomes.
Further, our product candidates may not receive regulatory approval even if they are successful in clinical trials. If we do not receive regulatory approvals for our product candidates, we may not be able to continue our operations. 33 Clinical product development involves a lengthy and expensive process, with uncertain outcomes.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and 45 replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).
Our competitors also may obtain FDA, EMA or other marketing approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.
Our competitors also may obtain FDA or other marketing 32 approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.
A redemption in accordance with (B) above may result in public warrant holders having to exercise the public warrants at a time when they are out-of-the-money or receive nominal consideration from us for them.
A redemption in accordance with (B) above may result in public warrant holders having to exercise the public warrants at a time when they are out-of-the-money or receive nominal consideration from the Company for them.
We have the ability to redeem our outstanding public warrants at any time prior to their expiration (A) at a price of $0.01 per public warrant; provided that the last reported sales price of our common stock equals or exceeds $161.87 per share (as adjusted for stock splits, stock dividends, reorganizations, recapitalizations and the like) for any 20 trading days within a 30 trading-day period ending on the third trading day prior to the date on which we give notice of such redemption to the public warrant holders and provided certain other conditions are met, and (B) at a price of $0.10 per public warrant; provided that (i) holders will be able to exercise their public warrants on a cashless basis prior to redemption and receive that number of shares determined by reference to an agreed table based on the redemption date and the “fair market value” of the common stock, (ii) if the last reported sales price of Common Stock equals or exceeds $89.93 per share (as adjusted for adjustments to the number of shares issuable upon exercise or the exercise price of a public warrant as described in the “Description of Securities” filed as Exhibit 4.3 to this Annual Report on Form 10-K under the heading “Public warrants — Anti-dilution Adjustments”) for any 20 trading days within the 30-trading day period ending three trading days before we send the notice of redemption to the public warrant holders, (iii) if the closing price of our common stock for any 20 trading days within a 30-trading day period ending three trading days before we send the notice of redemption to the public warrant holders is less than $161.87 per share (as adjusted), the private warrants must also be concurrently called for redemption on the same terms as the outstanding public warrants and (iv) provided certain other conditions are met.
We have the ability to redeem our outstanding public warrants at any time prior to their expiration in December 2026 (A) at a price of $0.01 per public warrant; provided that the last reported sales price of our common stock equals or exceeds $161.87 per share (as adjusted for stock splits, stock dividends, reorganizations, recapitalizations and the like) for any 20 trading days within a 30 trading-day period ending on the third trading day prior to the date on which we give notice of such redemption to the public warrant holders and provided certain other conditions are met, and (B) at a price of $0.10 per public warrant; provided that (i) holders will be able to exercise their public warrants on a cashless basis prior to redemption and receive that number of shares determined by reference to an agreed table based on the redemption date and the “fair market value” of the common stock, (ii) if the last reported sales price of Common Stock equals or exceeds $89.93 per share (as adjusted for adjustments to the number of shares issuable upon exercise or the exercise price of a public warrant as described in the “Description of Securities” filed as Exhibit 4.3 hereto under the heading “Public warrants — Anti-dilution Adjustments”) for any 20 trading days within the 30-trading day period ending three trading days before we send the notice of redemption to the public warrant holders, (iii) if the closing price of our common stock for any 20 trading days within a 30-trading day period ending three trading days before we send the notice of redemption to the public warrant holders is less than $161.87 per share (as adjusted), the private warrants must also be concurrently called for redemption on the same terms as the outstanding public warrants and (iv) provided certain other conditions are met.
Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time. Patents have a limited lifespan. In the United States, if all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date.
Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time. Patents have a limited lifespan. If all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date.
Insurance coverage is increasingly expensive. We may not be able to maintain insurance at a reasonable cost or in an amount adequate to satisfy any liability that may arise, if at all. Our insurance policy contains various exclusions, and we may be subject to a product liability claim for which we have no coverage.
We may not be able to maintain insurance at a reasonable cost or in an amount adequate to satisfy any liability that may arise, if at all. Our insurance policy contains various exclusions, and we may be subject to a product liability claim for which we have no coverage.
Furthermore, because the technologies used to obtain unauthorized access to, or to sabotage or disrupt, systems change frequently and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures. We may also experience security breaches that may remain undetected for an extended period.
Furthermore, because technologies (such as AI) that are used to obtain unauthorized access to, or to sabotage or disrupt, systems change frequently and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures. We may also experience security breaches that may remain undetected for an extended period.
Since our inception, we have invested a significant portion of our efforts and financial resources in research and development activities for our initial preclinical and clinical product candidates. Preclinical studies, clinical trials and additional research and development activities will require substantial funds to complete. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $2.3 billion.
Since our inception, we have invested a significant portion of our efforts and financial resources in research and development activities for our initial preclinical and clinical product candidates. Preclinical studies, clinical trials and additional research and development activities will require substantial funds to complete. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $2.0 billion.
Generally, if a drug with an orphan drug designation subsequently receives the first marketing approval for the disease or condition for which it has such designation, the drug is entitled to a period of marketing exclusivity, which precludes the FDA or foreign authorities from approving another marketing application for the same drug for the same disease or condition for that time period, except in limited circumstances.
Generally, if a drug with an orphan drug designation subsequently receives the first marketing approval for the disease or condition for which it has such designation, the drug is entitled to a period of marketing exclusivity, which precludes the FDA or foreign authorities from approving another marketing application for the same drug for the same approved use or indication within such disease or condition for that time period, except in limited circumstances.
Further, although we have implemented policies regarding limited permitted use of generative artificial intelligence (AI) by our employees, Confidential Information could be leaked, disclosed or revealed as a result of or in connection with our employees’ use of generative AI technologies.
Although we have implemented policies regarding limited permitted use of generative AI by our employees, Confidential Information could be leaked, disclosed or revealed as a result of or in connection with our employees’ use of generative AI Technologies.
Even after an orphan drug is approved, the FDA or comparable foreign authorities can subsequently approve the same drug for the same disease or condition if the FDA or comparable foreign authorities conclude that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.
Even after an orphan drug is approved, the FDA or comparable foreign authorities can subsequently approve the same drug for the same approved use or indication within the relevant disease or condition if the FDA or comparable foreign authorities conclude that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.
The Warrant Agreement provides that the terms of our public and private warrants may be amended without the consent of any holder to cure any ambiguity or correct any defective provision, but requires the approval by the holders of at least 50% of the then-outstanding warrants to make any change that adversely affects the interests of the registered holders.
The Warrant Agreement provides that the terms of the warrants may be amended without the consent of any holder to cure any ambiguity or correct any defective provision, but requires the approval by the holders of at least 50% of the then-outstanding warrants to make any change that adversely affects the interests of the registered holders.
Our decisions to allocate our research and development, management and financial resources toward particular development candidates or therapeutic areas, including the RASolute 302 study, the RASolve 301 study and other pivotal trials, may not lead to the development of viable commercial products and may divert resources from better opportunities.
Our decisions to allocate our research and development, management and financial resources toward particular development candidates or therapeutic areas, including RASolute 302, RASolute 303, RASolute 304, RASolute 305, RASolve 301 and other pivotal trials, may not lead to the development of viable commercial products and may divert resources from better opportunities.
Moreover, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition.
Moreover, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs relating to the approved use or indication of patients with the relevant rare disease or condition.
If one of our product candidates is approved and a patent covering that product candidate is not listed in the Orange Book, a manufacturer of generic drugs would not have to provide advance notice to us of any abbreviated NDA filed with the FDA to obtain permission to sell a generic version of such product candidate.
If one of our product candidates is approved and a patent covering that product candidate is not listed in the Orange Book or foreign equivalent, a manufacturer of generic drugs would not have to provide advance notice to us of any abbreviated NDA filed with the FDA or relevant foreign regulatory authority to obtain permission to sell a generic version of such product candidate.
We currently have a limited commercial organization. If we are unable to establish sufficient sales and marketing capabilities on our own or through third parties, we may not be able to market and sell any products effectively, if approved, or generate product revenue. We currently have a limited commercial organization.
We are currently building out our commercial organization. If we are unable to establish sufficient sales and marketing capabilities on our own or through third parties, we may not be able to market and sell any products effectively, if approved, or generate product revenue. We are currently building out our commercial organization.
The timing and amount of our future funding requirements depends on many factors, including: • the scope, progress, results and costs of researching and developing our product candidates and programs, and of conducting preclinical studies and clinical trials; • the cost of manufacturing our current and future product candidates for clinical trials in preparation for marketing approval and in preparation for commercialization; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates if clinical trials are successful; • the cost of commercialization activities for any of our product candidates, whether alone or in collaboration, including marketing, sales and distribution costs if any product candidate is approved for sale; • our ability to establish and maintain strategic licenses or other arrangements and the financial terms of such agreements; • the costs involved in preparing, filing, prosecuting, maintaining, expanding, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; • the timing, receipt and amount of sales of, profit share or royalties on, our future products, if any; • the emergence of competing cancer therapies or other adverse market developments; and • any plans to acquire or in-license other programs or technologies. 37 We will require substantial additional financing for our development efforts for our current and future programs and to prepare for their potential commercialization.
The timing and amount of our future funding requirements depends on many factors, including: • the scope, progress, results and costs of researching and developing our product candidates and programs, and of conducting preclinical studies and clinical trials; • the cost of manufacturing our current and future product candidates for clinical trials in preparation for marketing approval and in preparation for commercialization; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates if clinical trials are successful; • the cost of commercialization activities for our product candidates, whether alone or in collaboration, including marketing, sales and distribution costs if any product candidate is approved for sale; • our ability to establish and maintain strategic licenses or other arrangements and the financial terms of such agreements; • the costs involved in preparing, filing, prosecuting, maintaining, expanding, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; • the timing, receipt and amount of sales of, profit share or royalties on, our product candidates, if approved; • the emergence of competing cancer therapies or other adverse market developments; and 26 • any plans to acquire or in-license other programs or technologies.

… 232 more changes not shown on this page.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

4 edited+1 added−0 removed10 unchanged
Biggest changeKey elements of our cybersecurity risk management program include but are not limited to the following: • risk assessments designed to help identify material risks from cybersecurity threats to our critical systems and information; • a security team principally responsible for managing (1) our cybersecurity risk assessment processes, (2) our security controls and (3) our response to cybersecurity incidents; 84 • the use of external service providers, where appropriate, to assess, test or otherwise assist with aspects of our security processes; • cybersecurity awareness training that is provided to our employees and contractors, including those who are involved in incident response; • a cybersecurity incident response plan that includes procedures for responding to cybersecurity incidents; and • assessment of cybersecurity risks posed by third parties, including current and potential collaborators, service providers, suppliers, vendors and other contractual counterparties, in each case, to the extent they have access to our critical systems or information.
Biggest changeKey elements of our cybersecurity risk management program include but are not limited to the following: • risk assessments designed to help identify material risks from cybersecurity threats to our critical systems and information; • a security team principally responsible for managing (1) our cybersecurity risk assessment processes, (2) our security controls and (3) our response to cybersecurity incidents; • the use of external service providers, where appropriate, to assess, test or otherwise assist with aspects of our security processes; • cybersecurity awareness training that is provided to our employees and contractors, including those who are involved in incident response; • a cybersecurity incident response plan that includes procedures for responding to cybersecurity incidents; and • assessment of cybersecurity risks posed by third parties, including current and potential collaborators, as well as key service providers (based on our assessment of their criticality to our operations and respective risk profile) .
For more information, see the section titled “Risk Factor— Risks related to product development and regulatory process— Our business and operations, or those of our CROs or other third parties, may suffer in the event of information technology system failures, cyberattacks or deficiencies in our cybersecurity, which could materially affect our business, results of operations and financial condition.”.
For more information, see the section titled “Risk Factor— Risks related to product development and regulatory process— Our business and operations, or those of our CROs or other third parties, may suffer in the event of 74 information technology system failures, cyberattacks or deficiencies in our cybersecurity, which could materially affect our business, results of operations and financial condition.”.
Our full board of directors also receives briefings from management where it deems appropriate regarding cybersecurity. Our management team—including our Chief Information Officer and our Vice President, Information Security, Risk and Compliance—is responsible for assessing and managing our material risks from cybersecurity threats.
The Audit Committee reports to the full Board regarding its activities, including those related to cybersecurity. Our full board of directors also receives briefings from management where it deems appropriate regarding cybersecurity. Our management team—including our Chief Information Officer and our Vice President, Information Security, Risk and Compliance—is responsible for assessing and managing our material risks from cybersecurity threats.
The Audit Committee receives scheduled annual reports from management on our cybersecurity risks, our cybersecurity risk management program and other cybersecurity-related educational topics. In addition, management updates the Audit Committee as necessary, regarding other cybersecurity incidents, including any material cybersecurity incidents. The Audit Committee reports to the full Board regarding its activities, including those related to cybersecurity.
The Audit Committee receives scheduled semi-annual reports from management on our cybersecurity risks, our cybersecurity risk management program and other cybersecurity-related educational topics. In addition, management updates the Audit Committee as necessary, regarding other cybersecurity incidents it considers to be significant or potentially significant .
Added
In 2025, we achieved ISO/IEC 27001 certification for our cybersecurity systems and processes, which, along with other recognized frameworks, informs our approach to identifying, assessing, and managing cybersecurity risks.

Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−1 removed1 unchanged
Biggest changeItem 2. Pro perties. Our corporate headquarters is located in Redwood City, California, where we lease and occupy approximately 233,065 square feet of office and laboratory space. The term of our Redwood City lease expires in December 2035.
Biggest changeItem 2. Pro perties. Our corporate headquarters is located in Redwood City, California, where we lease and occupy approximately 293,906 square feet of office and laboratory space. The term of our Redwood City lease expires in December 2035. We believe our existing facilities are sufficient for our needs for the foreseeable future.
Removed
Our lease of approximately 22,000 square feet of office and laboratory space in Cambridge, Massachusetts, which was subleased to Casma Therapeutics, Inc. expired in February 2023. We believe our existing facilities are sufficient for our needs for the foreseeable future.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

3 edited+1 added−1 removed3 unchanged
Biggest changeWe intend to defend vigorously against the Complaint. Item 4. Mine Safe ty Disclosures. Not applicable. 86 PART II
Biggest changeMine Safe ty Disclosures. Not applicable. 75 PART II
The results of any current or future litigation cannot be predicted with certainty, and regardless of the outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources, and other factors. 85 On December 9, 2024, Nemeth v. Casdin, et al. , Case No. 2024-1268-KSJM (Del.
The results of any current or future litigation cannot be predicted with certainty, and regardless of the outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources, and other factors. On December 9, 2024, Nemeth v. Casdin, et al., Case No. 2024-1268-KSJM (Del.
The Complaint also brings claims for aiding and abetting breaches of fiduciary duties against certain investment firms involved with the merger process, the Company, solely as successor-in-interest to EQRx, and Legacy EQRx’s former Executive Chairman and CEO, Alexis Borisy, who is also on our board of directors. Defendants’ response to the Complaint is due on February 28, 2025.
The Complaint also brings claims for aiding and abetting breaches of fiduciary duties against certain investment firms involved with the merger process, the Company, solely as successor-in-interest to EQRx, and Legacy EQRx’s former Executive Chairman and CEO, Alexis Borisy, who is also on the Company’s board of directors. Defendants moved to dismiss the Complaint in February 2025.
Removed
At this juncture, we do not believe this action will have a material adverse impact on our operations or financial position. Although we believe a loss relating to the Complaint is reasonably possible, given the early stage of the case (i.e., before any motion to dismiss rulings or discovery), we cannot make an estimate regarding the range of loss.
Added
The parties reached an agreement to resolve the matter, which was filed with the court on January 6, 2026, and remains subject to court approval. We have recorded an accrual of $5.0 million in accrued and other current liabilities as of December 31, 2025, based on its expected contribution under the agreement and anticipated insurance recoveries. Item 4.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

4 edited+1 added−0 removed7 unchanged
Biggest changeThe stockholder returns shown on the graph below are based on historical results and are not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns. 87 Recent sales of unregistered securities None. Issuer Purchases of Equity Securities None. Item 6. [R e served.] 88
Biggest changeThe stockholder returns shown on the graph below are based on historical results and are not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns. Recent sales of unregistered securities None. 76 Issuer Purchases of Equity Securities None. Item 6. [R e served.] 77
The following graph compares the cumulative total return to stockholder return on our common stock relative to the cumulative total returns of the NASDAQ Composite Index and the NASDAQ Biotechnology Index.
The following graph compares the cumulative total stockholder return on our common stock relative to the cumulative total returns of the NASDAQ Composite Index and the NASDAQ Biotechnology Index.
An investment of $100 is assumed to have been made in our common stock and each index on February 13, 2020 (the first day of trading of our common stock) and its relative performance is tracked through December 31, 2024.
An investment of $100 is assumed to have been made in our common stock and each index on February 13, 2020 (the first day of trading of our common stock) and its relative performance is tracked through December 31, 2025.
As of February 21, 2025, there were 64 holders of record of our common stock and 5 holders of record of our public warrants.
As of February 20, 2026, there were 46 holders of record of our common stock and 5 holders of record of our public warrants.
Added
Additionally, the terms of our Loan Agreement restrict our ability to pay dividends, except for certain customary exceptions.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

45 edited+41 added−83 removed27 unchanged
Biggest changeResults of operations Comparison of the years ended December 31, 2024 and 2023 Years Ended December 31, 2024 2023 Increase/ (decrease) (in thousands) Revenue: Collaboration revenue $ — $ 11,580 $ (11,580 ) Total revenue — 11,580 (11,580 ) Operating expenses: Research and development 592,225 423,144 169,081 General and administrative 97,299 75,621 21,678 Total operating expenses 689,524 498,765 190,759 Loss from operations (689,524 ) (487,185 ) (202,339 ) Other income (expense), net: Interest income 86,883 47,482 39,401 Other expense (2,528 ) (303 ) (2,225 ) Change in fair value of warrant liability and contingent earn-out shares 4,323 115 4,208 Total other income, net 88,678 47,294 41,384 Loss before income taxes (600,846 ) (439,891 ) (160,955 ) Benefit from income taxes 753 3,524 (2,771 ) Net loss $ (600,093 ) $ (436,367 ) $ (163,726 ) 93 Collaboration revenue Collaboration revenue in 2023 consisted of revenue under the Sanofi Agreement, which was terminated in June 2023.
Biggest changeResults of operations Comparison of the years ended December 31, 2025 and 2024 Years Ended December 31, 2025 2024 Increase/ (decrease) (in thousands) Operating expenses: Research and development 987,332 592,225 395,107 General and administrative 195,037 97,299 97,738 Total operating expenses 1,182,369 689,524 492,845 Loss from operations (1,182,369 ) (689,524 ) (492,845 ) Non-operating income (expense), net: Interest income 90,694 86,883 3,811 Interest expense (24,231 ) — (24,231 ) Change in fair value of warrant liability and contingent earn-out shares (15,358 ) 4,323 (19,681 ) Other expense, net (37 ) (2,528 ) 2,491 Total non-operating income, net 51,068 88,678 (37,610 ) Loss before income taxes (1,131,301 ) (600,846 ) (530,455 ) Benefit from income taxes — 753 (753 ) Net loss $ (1,131,301 ) $ (600,093 ) $ (531,208 ) Research and development expenses Our research and development efforts during the year ended December 31, 2025 were focused on our clinical development programs and our preclinical programs.
Research and development expenses consist primarily of costs incurred for the development of our product candidates and costs associated with identifying compounds through our discovery platform, which include: • external costs incurred under agreements with third-party contract organizations, investigative clinical trial sites that conduct research and development activities on our behalf and consultants; • costs related to the production of preclinical, clinical and pre-launch materials, including fees paid to contract manufacturers; • laboratory and vendor expenses related to the execution of discovery programs, preclinical and clinical trials; • employee-related expenses, which include salaries, benefits and stock-based compensation; and 92 • facilities and other expenses, which include allocated expenses for rent and maintenance of facilities, depreciation and amortization expense, information technology and other supplies.
Research and development expenses consist primarily of costs incurred for the development of our product candidates and costs associated with identifying compounds through our discovery platform, which include: • external costs incurred under agreements with third-party contract organizations, investigative clinical trial sites that conduct research and development activities on our behalf and consultants; • costs related to the production of preclinical, clinical and pre-launch materials, including fees paid to contract manufacturers; • laboratory and vendor expenses related to the execution of discovery programs, preclinical and clinical trials; • employee-related expenses, which include salaries, benefits and stock-based compensation; and • facilities and other expenses, which include allocated expenses for rent and maintenance of facilities, depreciation and amortization expense, information technology and other supplies.
As a result, we believe the fair value of these agreements is minimal. Critical Accounting Policies, Significant Judgments and Use of Estimates Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with United States generally accepted accounting principles (U.S. 98 GAAP).
As a result, we believe the fair value of these agreements is minimal. Critical Accounting Policies, Significant Judgments and Use of Estimates Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with United States generally accepted accounting principles (U.S. GAAP).
The timing and amount of our future funding requirements depends on many factors, including: • the scope, progress, results and costs of researching and developing our product candidates and programs, and of conducting preclinical studies and clinical trials; • the cost of manufacturing our current and future product candidates for clinical trials in preparation for marketing approval and in preparation for commercialization; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates if clinical trials are successful; • the cost of commercialization activities for any of our product candidates, whether alone or in collaboration, including marketing, sales and distribution costs if any product candidate is approved for sale; • our ability to establish and maintain strategic licenses or other arrangements and the financial terms of such agreements; • the costs involved in preparing, filing, prosecuting, maintaining, expanding, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; 96 • the timing, receipt and amount of sales of, profit share or royalties on, our future products, if any; • the emergence of competing cancer therapies or other adverse market developments; and • any plans to acquire or in-license other programs or technologies.
The timing and amount of our future funding requirements depends on many factors, including: • the scope, progress, results and costs of researching and developing our product candidates and programs, and of conducting preclinical studies and clinical trials; • the cost of manufacturing our current and future product candidates for clinical trials in preparation for marketing approval and in preparation for commercialization; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates if clinical trials are successful; • the cost of commercialization activities for our product candidates, whether alone or in collaboration, including marketing, sales and distribution costs if any product candidate is approved for sale; • our ability to establish and maintain strategic licenses or other arrangements and the financial terms of such agreements; • the costs involved in preparing, filing, prosecuting, maintaining, expanding, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; • the timing, receipt and amount of sales of, profit share or royalties on, our product candidates, if approved; • the emergence of competing cancer therapies or other adverse market developments; and • any plans to acquire or in-license other programs or technologies.
Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.
Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making 86 judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.
In August 2024, we terminated the 2021 ATM and entered into a new sales agreement with TD Cowen to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $500 million, through an at-the-market equity offering program (the 2024 ATM).
In August 2024, we terminated the 2021 ATM and entered into a new sales agreement with TD Cowen to sell shares of our common stock, from time 83 to time, with aggregate gross proceeds of up to $500 million, through an at-the-market equity offering program (the 2024 ATM).
Contractual Obligations and Commitments We have contractual obligations related to our office and laboratory space lease in Redwood City, California, described in “Note 7. Commitments and contingencies” in the “Notes to Consolidated Financial Statements” contained in Part II, Item 8 of this Annual Report on Form 10-K.
Contractual Obligations and Commitments We have contractual obligations related to our office and laboratory space lease in Redwood City, California, described in “Note 8. Commitments and contingencies” in the “Notes to Consolidated Financial Statements” contained in Part II, Item 8 of this Annual Report on Form 10-K.
Elironrasib is designed to be differentiated from 90 first-generation KRAS(OFF) G12C inhibitors, which sequester the KRAS(OFF) G12C form, by its mechanism of directly inhibiting the RAS(ON) G12C form.
Elironrasib is designed to be differentiated from first-generation KRAS(OFF) G12C inhibitors, which sequester the KRAS(OFF) G12C form, by its mechanism of directly inhibiting the RAS(ON) G12C form.
We expect our expenses to continue to increase in connection with our ongoing activities, particularly as we continue to advance our product candidates into later stages of development, which includes conducting larger clinical trials, and increase our efforts of preparing to become a commercial-stage company.
We expect our expenses to continue to increase in connection with our ongoing activities, particularly as we continue to advance our product candidates into later stages of development, which includes conducting larger clinical trials, and increasing our efforts to prepare to become a commercial-stage company.
In March 2023, we issued 15,681,818 shares of our common stock in an underwritten public offering at a price to the public of $22.00 per share, for net proceeds of $323.7 million, after deducting underwriting discounts and commissions of $20.7 million and expenses of $0.6 million.
In March 2023, we issued 15,681,818 shares of our common stock in an underwritten public offering at a price to the public of $22.00 per share, for net proceeds of $323.7 million, after deducting underwriting discounts and commissions of $20.7 million and expenses of $0.6 million. In November 2023, we completed the acquisition (the EQRx Acquisition) of EQRx Inc.
Facilities costs consist of rent, utilities and maintenance of facilities. We expect our general and administrative expenses to increase for the foreseeable future due to anticipated increases in operating and commercial preparation activities, which may result in increases in personnel-related costs associated with increased headcount, other administrative and professional services, and related overhead needed to support these efforts.
We expect our general and administrative expenses to increase for the foreseeable future due to anticipated increases in operating and commercial preparation activities, which may result in increases in personnel-related costs associated with increased headcount, other administrative and professional services, and related overhead needed to support these efforts.
In November 2023, we completed the EQRx Acquisition and issued 54,786,528 shares of common stock in the transaction in which we received approximately $1.1 billion in net cash, cash equivalents and marketable securities after deducting EQRx wind-down and transition costs.
(EQRx) and issued 54,786,528 shares of common stock in the transaction in which we received $1.1 billion in net cash, cash equivalents and marketable securities after deducting EQRx wind-down and transition costs.
We will require substantial additional financing for our development efforts for our current and future programs and to prepare for their potential commercialization.
We will require additional funds for our development efforts for our current and future programs and to prepare for their potential commercialization.
The grant date fair value of an RSU award is based on our stock price on the date of grant. For options, we estimate the grant date fair value, and the resulting stock-based compensation, using the Black-Scholes option-pricing model, and we use the straight-line method for expense attribution.
The grant date fair value of an RSU award is based on our stock price on the date of grant. For options, we estimate the grant date fair value, and the resulting stock-based compensation, using the Black-Scholes option-pricing model, and we use the straight-line method for expense attribution. For additional information about measurements of stock-based compensation see “Note 13.
The change in operating assets and liabilities was primarily due to a $9.7 million increase in prepaid expenses and other current assets, a $5.9 million increase in other noncurrent assets, a $6.5 million decrease in accounts payable, offset by a $22.0 million increase in accrued expenses and other current liabilities primarily related to clinical trial and clinical supply manufacturing expenses and increased personnel related expenses due to increased headcount and a $1.3 million decrease in accounts receivable.
The change in operating assets and liabilities was primarily due to a $112.3 million increase in accrued expenses and other current liabilities primarily related to clinical trial and clinical supply manufacturing expenses and increased personnel related expenses due to increased headcount and a $9.5 million increase in accounts payable, offset by a $9.7 million increase in prepaid expenses and other current assets, a $12.9 million increase in other noncurrent assets, a $12.0 million increase in long-term deposits and a $1.0 million decrease in operating lease liability.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of KRAS G13C-bearing cancer cells and is engineered to covalently inactivate KRAS G13C for irreversible inhibition. Clinical development of RMC-8839 is subject to our continuing assessment of our portfolio priorities.
Clinical development of RMC-0708 is subject to our continuing assessment of portfolio priorities. RMC-8839 RMC-8839 is designed as a RAS(ON) oral G13C-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of KRAS G13C-bearing cancer cells and is engineered to covalently inactivate KRAS G13C for irreversible inhibition.
Recent Accounting Pronouncements For a description of the expected impact of recent accounting pronouncements, see “Note 2. Summary of significant accounting policies” in the “Notes to Consolidated Financial Statements” contained in Part II, Item 8 of this Annual Report on Form 10-K.
Stock-based compensation” in the “Notes to the Consolidated Financial Statements contained in Part II, Item 8 of this Annual Report on Form 10-K. Recent Accounting Pronouncements For a description of the expected impact of recent accounting pronouncements, see “Note 2.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions. Clinical development of RMC-0708 is subject to our continuing assessment of our portfolio priorities. RMC-8839 RMC-8839 is designed as a RAS(ON) oral G13C-selective inhibitor.
Other Development Opportunities RMC-0708 RMC-0708 is designed as a RAS(ON) oral Q61H-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions.
(Aethon) pursuant to which Aethon is conducting research related to use of novel bispecific antibodies to mount an immune attack directed at the cancer cells targeted by our RAS(ON) Inhibitors (the Aethon Collaboration Agreement).
Aethon Collaboration In March 2024, we entered into a collaboration agreement with Aethon Therapeutics, Inc. (Aethon) pursuant to which Aethon is conducting research related to use of novel bispecific antibodies to mount an immune attack directed at the cancer cells targeted by our RAS(ON) Inhibitors (the Aethon Collaboration Agreement).
General and administrative expenses General and administrative expenses increased by $21.7 million, or 29%, during the year ended December 31, 2024 compared to 2023.
General and administrative expenses General and administrative expenses increased by $97.7 million, or 100%, during the year ended December 31, 2025 compared to 2024.
Each pre-funded warrant will be exercisable from the date of issuance until fully exercised, subject to an ownership limitation. Total net proceeds from the offering were $823.0 million, after deducting underwriting discounts and commissions of $38.8 million and expenses of $0.6 million.
Each pre-funded warrant is exercisable from the date of issuance until fully exercised, subject to an ownership limitation. Total net proceeds from the offering were $823.0 million, after deducting underwriting discounts and commissions of $38.8 million and expenses of $0.6 million. As of December 31, 2025, all of the pre-funded warrants have been converted to equity.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS G12V-bearing cancer cells and is engineered for selective inhibition of RAS G12V over other RAS isoforms via non-covalent binding interactions.
It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS G12V-bearing cancer cells and is engineered for selective inhibition of RAS G12V over other RAS isoforms via non-covalent binding interactions. A first-in-human dose escalation clinical trial of RMC-5127 is ongoing.
During the year ended December 31, 2023, cash used in investing activities of $342.6 million was primarily comprised of purchases of marketable securities of $1.1 billion and purchases of property and equipment of $7.7 million, offset by cash provided by maturities of marketable securities of $724.0 million.
Cash provided by (used in) investing activities During the year ended December 31, 2025, cash provided by investing activities of $118.1 million was primarily comprised of cash provided by maturities of marketable securities of $1.9 billion and sale of marketable securities of $6.4 million, offset by purchases of marketable securities of $1.8 billion and purchases of property and equipment of $16.0 million.
From November 2021 to August 2024, we sold an aggregate of 6,502,078 shares of our common stock under the 2021 ATM, resulting in gross proceeds to us of $186.0 million. During the year ended December 31, 2024, we sold an aggregate of 1,294,050 shares of common stock under the 2021 ATM, resulting in gross proceeds of $60.8 million.
During the year ended December 31, 2024, we sold an aggregate of 1,294,050 shares of common stock under the 2021 ATM, resulting in gross proceeds of $60.8 million.
Through December 31, 2024, we have sold an aggregate of 1,147,893 shares of common stock under the 2024 ATM, resulting in gross proceeds of $60.4 million.
During the year ended December 31, 2024, we sold an aggregate of 1,147,893 shares of common stock under the 2024 ATM, resulting in gross proceeds of $60.4 million. During the year ended December 31, 2025, we sold an aggregate of 6,163,501 shares of common stock under the 2024 ATM, resulting in gross proceeds of $353.4 million.
The non-cash charges primarily consisted of stock-based compensation expense of $79.2 million, depreciation and amortization of $7.6 million, amortization of operating lease right-of-use asset of $4.2 million, offset by net amortization of premium on marketable securities of $44.6 million and change in the fair value of warrant liability and contingent earn-out shares of $4.3 million.
The non-cash charges primarily consisted of stock-based compensation expense of $118.4 million, a $24.2 million non-cash interest expense on liability related to sale of future royalties, change in the fair value of warrant liability and contingent earn-out shares of $15.4 million, depreciation and amortization of $8.7 million, and amortization of operating lease right-of-use asset of $7.9 million, offset by net amortization of premium on marketable securities of $27.8 million.
We do not have any committed external source of funds or other support for these activities, and we expect to finance our cash needs through a combination of public or private equity offerings, debt financings, credit or loan facilities, acquisitions, collaborations, strategic alliances, licensing arrangements and other marketing or distribution arrangements.
Other than the Royalty Purchase Agreement and the Term Loan Facility (which provide for additional funding subject to certain terms and conditions and trigger events), we do not have any committed external source of funds or other support for these activities, and we may finance our cash needs through additional funding under the Royalty Purchase Agreement, the Term Loan Facility and/or a combination of public or private equity offerings, debt financings, other credit or loan facilities, acquisitions, collaborations, strategic alliances, licensing arrangements and other marketing or distribution arrangements.
As of December 31, 2024, we had an accumulated deficit of $1.7 billion. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures related to our product candidates and our pre-clinical research portfolio, and to a lesser extent, general and administrative expenditures.
Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures related to our product candidates and our pre-clinical research portfolio, and to a lesser extent, general and administrative and commercial preparation expenditures.
We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates. Revenue recognition We recognize revenue in accordance with Accounting Standards Codification Topic 606, Revenue from Contracts with Customers (ASC 606).
We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.
Interest income Interest income increased by $38.3 million for the year ended December 31, 2023, compared to 2022 due to a larger cash, cash equivalents and marketable securities balance and higher interest rates. 95 Liquidity and Capital Resources In November 2021, we entered into a sales agreement with Cowen and Company, LLC, an affiliate of TD Securities (USA) LLC (TD Cowen), as amended in March 2024, to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $250 million, through an at-the-market equity offering program (the 2021 ATM).
Liquidity and Capital Resources In November 2021, we entered into a sales agreement with TD Securities (USA) LLC (f/k/a Cowen and Company LLC) (TD Cowen), as amended in March 2024, to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $250 million, through an at-the-market equity offering program (the 2021 ATM).
Interest income Interest income primarily consists of interest earned on and accretion of our cash equivalents and marketable securities.
Interest income Interest income primarily consists of interest earned on and accretion of our cash equivalents and marketable securities. Interest expense Interest expense consists of non-cash interest expense associated with the sale of future royalties.
During the year ended December 31, 2022, cash provided by financing activities of $301.4 million was comprised of $248.1 million in net proceeds from the July 2022 underwritten public offering, $49.9 million in net proceeds from the issuance of common stock under the 2021 ATM, $1.9 million in proceeds from the issuance of common stock under the employee stock purchase plan and $1.5 million in proceeds from the issuance of common stock upon the exercise of stock options.
Cash provided by financing activities During the year ended December 31, 2025, cash provided by financing activities of $621.5 million was primarily comprised of $347.9 million in net proceeds from the issuance of common stock under the 2024 ATM, $244.2 million in net proceeds from the sale of future royalties, $21.1 million in proceeds from the issuance of common stock upon the exercise of stock options and $8.0 million in proceeds from the issuance of common stock under the employee stock purchase plan.
The increase in general and administrative expenses during the year ended December 31, 2023 was primarily due to a $14.6 million increase in stock-based compensation expense including $7.5 million in connection with the EQRx Acquisition; a $7.1 million increase in salaries and other employee-related expenses due to increased headcount; a $6.1 million increase in employee-related expenses in connection with the EQRx Acquisition; a $3.2 million increase in facilities and other allocated expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; a $2.3 million increase in legal and accounting fees; and a $1.6 million increase in pre-commercial development expenses.
The increase was primarily due to a $34.4 million increase in commercial preparation expenses; a $28.6 million increase in salaries and other employee-related expenses due to increased headcount; a $11.8 million increase in stock-based compensation expense; a $10.2 million increase in legal and accounting fees; a $8.2 million increase in facilities and other allocated expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; and a $2.9 million increase in other professional expenses.
Cash Flows The following table summarizes our consolidated cash flows for the periods indicated: Year Ended December 31, 2024 2023 2022 (in thousands) Net cash provided by (used in): Operating activities $ (557,436 ) $ (350,572 ) $ (224,401 ) Investing activities (554,394 ) (342,598 ) (24,116 ) Financing activities 959,413 1,229,200 301,432 Net change in cash and cash equivalents $ (152,417 ) $ 536,030 $ 52,915 Cash used in operating activities During the year ended December 31, 2024, cash used in operating activities of $557.4 million was attributable to a net loss of $600.1 million, partially offset by $42.3 million in non-cash charges and by a net change of $0.4 million in our operating assets and liabilities.
Cash Flows The following table summarizes our consolidated cash flows for the periods indicated: Year Ended December 31, 2025 2024 (in thousands) Net cash provided by (used in): Operating activities $ (897,741 ) $ (557,436 ) Investing activities 118,058 (554,394 ) Financing activities 621,524 959,413 Net change in cash and cash equivalents $ (158,159 ) $ (152,417 ) 85 Cash used in operating activities During the year ended December 31, 2025, cash used in operating activities of $897.7 million was attributable to a net loss of $1.1 billion, partially offset by $146.7 million in non-cash charges and by a net change of $86.8 million in our operating assets and liabilities.
We are advancing a deep pipeline of RAS(ON) Inhibitors, including daraxonrasib (RMC-6236), our RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), our G12C-selective inhibitor; and zoldonrasib (RMC-9805), our G12D-selective inhibitor. Together, we consider these three clinical-stage candidates as the first wave of RAS(ON) inhibitors that we are advancing through clinical development. We also currently plan to advance RMC-5127 (G12V) into clinical development.
RAS(ON) Inhibitors We are advancing a deep pipeline of RAS(ON) Inhibitors, including daraxonrasib (RMC-6236), our multi-selective inhibitor, zoldonrasib (RMC-9805), our G12D-selective inhibitor, elironrasib (RMC-6291), our G12C-selective inhibitor, and RMC-5127, our G12V-selective inhibitor.
The cumulative effect of revisions to estimated costs to fulfill our performance obligations will be recorded in the period in which changes are identified and amounts can be reasonably estimated. Accrued research and development expenses We accrue for estimated costs of research and development activities performed by third-party service providers, which include pre-clinical studies, clinical trials and contract manufacturing activities.
Accrued research and development expenses We accrue for estimated costs of research and development activities performed by third-party service providers, which include pre-clinical studies, clinical trials and contract manufacturing activities.
In addition, we have other preclinical-stage RAS(ON) inhibitor clinical development opportunities, including the RAS(ON) mutant-selective inhibitors RMC-0708 (Q61H) and RMC-8839 (G13C). Daraxonrasib (RMC-6236) Daraxonrasib (RMC-6236), our RAS(ON) multi-selective inhibitor, is designed as an oral, RAS-selective tri-complex inhibitor of multiple RAS(ON) variants containing cancer driver mutations at all three of the major RAS mutation hotspot positions (G12, G13 and Q61).
Daraxonrasib Daraxonrasib, our RAS(ON) multi-selective inhibitor, is designed as an oral, RAS-selective tri-complex inhibitor of multiple RAS(ON) variants containing cancer driver mutations at all three of the major RAS mutation hotspot positions, G12, G13, and Q61. Daraxonrasib inhibits all three major RAS isoforms, suppressing the mutant cancer driver and cooperating wild-type RAS proteins. In October 2025, the U.S.
The increase in research and development expenses during the year ended December 31, 2024 was primarily due to a $61.0 million increase in daraxonrasib expenses, primarily attributable to higher clinical trial expenses; a $31.8 million increase in salaries and other employee-related expenses due to increased headcount to support our research and development programs; a $23.5 million increase in zoldonrasib expenses, primarily attributable to higher clinical trial expenses; a $22.4 million increase in elironrasib expenses, primarily attributable to higher clinical trial expenses; a $16.8 million increase in stock-based compensation; a $14.9 million increase in other research and development expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; and a $7.9 million increase in preclinical research portfolio expenses; partially offset by a $9.3 million decrease in other RAS companion inhibitor program expenses.
The increase was primarily due to higher clinical trial and manufacturing expenses, including a $162.1 million increase related to daraxonrasib expenses, a $56.1 million increase related to zoldonrasib expenses and a $18.6 million increase related to elironrasib expenses; a $75.6 million increase in salaries and other employee-related expenses due to increased headcount to support our research and development programs; a $29.1 million increase in other research and development expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; a $27.4 million increase in stock-based compensation; and a $19.8 million increase in preclinical research portfolio expenses.
Acquisition” in the “Notes to Consolidated Financial Statements” contained in Part II, Item 8 of this Annual Report on Form 10-K. Aethon Collaboration In March 2024, we entered into a collaboration agreement with Aethon Therapeutics, Inc.
Summary of significant accounting policies” in the “Notes to Consolidated Financial Statements” contained in Part II, Item 8 of this Annual Report on Form 10-K.
Guided by our understanding of genetic drivers and adaptive resistance mechanisms in cancer, we deploy precision medicine approaches to inform innovative monotherapy and combination regimens.
Guided by our understanding of genetic drivers and adaptive resistance mechanisms in cancer, we deploy precision medicine approaches to inform innovative monotherapy and combination regimens. Our research and development pipeline comprises inhibitors that bind directly to RAS variants (RAS(ON) Inhibitors) that are designed to be used as monotherapy, in combination with other RAS(ON) Inhibitors and/or other therapeutic agents.
As a result, we are unable to determine the duration and completion costs of our research and development projects or clinical trials or if and to what extent we will generate revenue from the commercialization and sale of any of our product candidates, if approved.
As a result, we are unable to determine the duration and completion costs of our research and development projects or clinical trials or if and to what extent we will generate revenue from the commercialization and sale of any of our product candidates, if approved. 81 General and administrative expenses General and administrative expenses consist primarily of personnel-related costs, consultants and professional services expenses, including legal, audit, accounting and human resources services, insurance, commercial preparation activities, allocated facilities and information technology costs, and other general operating expenses not otherwise classified as research and development expenses.
The following table sets forth the components of our research and development expenses for the periods indicated: Years Ended December 31, 2024 2023 Increase/ (decrease) (in thousands) Third-party research and development expenses: Clinical Development Programs: Daraxonrasib (RMC-6236) $ 168,911 $ 107,947 $ 60,964 Elironrasib (RMC-6291) 55,034 32,593 22,441 Zoldonrasib (RMC-9805) 64,112 40,657 23,455 RAS companion inhibitors 6,955 16,252 (9,297 ) Preclinical programs 73,089 65,156 7,933 Total third-party research and development expenses 368,101 262,605 105,496 Salaries and other employee-related expenses 113,475 81,658 31,817 Stock-based compensation expense 50,973 34,126 16,847 Amortization of intangible assets 1,069 1,068 1 Other research and development costs 58,607 43,687 14,920 Total research and development expense $ 592,225 $ 423,144 $ 169,081 Research and development expenses increased by $169.1 million, or 40%, during the year ended December 31, 2024 compared to 2023.
The following table sets forth the components of our research and development expenses for the periods indicated: 82 Years Ended December 31, 2025 2024 Increase/ (decrease) (in thousands) Third-party research and development expenses: Clinical Development Programs: Daraxonrasib (RMC-6236) $ 330,982 $ 168,911 $ 162,071 Zoldonrasib (RMC-9805) 120,193 64,112 56,081 Elironrasib (RMC-6291) 73,671 55,034 18,637 RMC-5127 12,824 — 12,824 RAS companion inhibitors 746 6,955 (6,209 ) Preclinical programs 92,875 73,089 19,786 Total third-party research and development expenses 631,291 368,101 263,190 Salaries and other employee-related expenses 189,064 113,475 75,589 Stock-based compensation expense 78,356 50,973 27,383 Amortization of intangible assets 870 1,069 (199 ) Other research and development costs 87,751 58,607 29,144 Total research and development expense $ 987,332 $ 592,225 $ 395,107 Research and development expenses increased by $395.1 million, or 67%, during the year ended December 31, 2025 compared to 2024.
Having finalized the study protocol, we are now activating sites for a global, randomized Phase 3 registrational trial comparing daraxonrasib versus docetaxel in patients with locally advanced or metastatic RAS-mutated non-small cell lung cancer (NSCLC) who have been treated with immunotherapy and platinum-containing chemotherapy, which we call the RASolve 301 study.
Based on encouraging early-stage clinical results we are evaluating daraxonrasib in RASolve 301, a global, randomized Phase 3 registrational trial comparing daraxonrasib versus docetaxel in patients with locally advanced or metastatic RAS mutant NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. We currently expect to substantially complete enrollment in RASolve 301 in 2026.
Our operations have been financed primarily by our public offerings of common stock, the EQRx Acquisition and $188.7 million received under the Sanofi Agreement from June 2018 through June 2023 for upfront payments and for research and development cost reimbursement. As of December 31, 2024, we had $2.3 billion in cash, cash equivalents and marketable securities.
To date, our operations have been financed primarily by our public offerings of common stock, the EQRx Acquisition and the sale of future royalties. As of December 31, 2025, we had $2.0 billion in cash, cash equivalents and marketable securities. 84 As of December 31, 2025, we had an accumulated deficit of $2.9 billion.
We currently expect to initiate a global, randomized Phase 3 daraxonrasib monotherapy study in patients with first-line (1L) metastatic PDAC in the second half of 2025. We also currently expect to initiate a global, randomized Phase 3 monotherapy study of daraxonrasib as adjuvant treatment for patients with resectable PDAC in the second half of 2025.
We also currently expect to initiate RASolve 308, a global, randomized placebo-controlled Phase 3 registrational trial evaluating zoldonrasib in combination with standard of care in patients with 1L metastatic RAS G12D NSCLC in the first half of 2026. We currently expect to provide an update on our plans for advancing daraxonrasib combination therapy in 1L NSCLC in 2026.
Removed
Our research and development pipeline comprises RAS(ON) inhibitors that bind directly to RAS variants, which we refer to as RAS(ON) Inhibitors, and RAS companion inhibitors that target key nodes in the RAS pathway or associated pathways.
Added
Information pertaining to fiscal year 2024 was included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024 under Part II, Item 7, “Management’s Discussion and Analysis of Financial Position and Results of Operations,” which was filed with the Securities and Exchange Commission (the “SEC”) on February 26, 2025.
Removed
Our RAS(ON) Inhibitors are designed to be used as monotherapy, in combination with other RAS(ON) Inhibitors and/or in combination with RAS companion inhibitors or other therapeutic agents. RAS(ON) Inhibitors Our RAS(ON) Inhibitors are based on our proprietary tri-complex technology platform, which enables a highly differentiated approach to inhibiting the active, GTP-bound form of RAS, which we refer to as RAS(ON).
Added
We also have other preclinical-stage RAS(ON) Inhibitor clinical development opportunities, including the RAS(ON) mutant-selective inhibitors RMC-0708 (Q61H) and RMC-8839 (G13C) and additional novel targeted approaches for patients with RAS-addicted cancers.
Removed
We are developing a portfolio of compounds that we believe were the first RAS(ON) Inhibitors to use this mechanism of action. We believe that direct inhibitors of RAS(ON) suppress cell growth and survival and are less susceptible to adaptive resistance mechanisms recognized for RAS(OFF) inhibitors.
Added
Food and Drug Administration (FDA) granted us a non-transferable voucher for daraxonrasib in pancreatic ductal adenocarcinoma (PDAC) under the Commissioner’s National Priority Voucher (CNPV) pilot program. Also in October 2025, daraxonrasib was granted Orphan Drug Designation by the FDA for the treatment of pancreatic cancer.
Removed
We are evaluating our RAS(ON) Inhibitors alone and in combination with other drugs and investigational drug candidates, particularly in-pathway agents. We believe tailored RAS(ON) Inhibitors will be useful to serve the diverse landscape of RAS-addicted cancers optimally.
Added
In June 2025, daraxonrasib received Breakthrough Therapy Designation from the FDA for previously treated metastatic PDAC in patients with KRAS G12 mutations. Zoldonrasib Zoldonrasib is designed as a RAS(ON) oral G12D-selective tri-complex inhibitor.
Removed
We believe that in some cases, patients may experience maximal clinical benefit from the broad activity of our RAS(ON) multi-selective inhibitor, daraxonrasib (RMC-6236), if approved. In others, we believe treatment with a RAS(ON) mutant-selective inhibitor may be optimal.
Added
In December 2025, zoldonrasib received Breakthrough Therapy Designation from the FDA for the treatment of adult patients with KRAS G12D-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have been previously treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy. Elironrasib Elironrasib is designed as a RAS(ON) oral G12C-selective tri-complex inhibitor.
Removed
We further believe that in some cases, it could be beneficial to combine daraxonrasib with a RAS(ON) mutant-selective inhibitor, with daraxonrasib functioning as the backbone of these RAS(ON) Inhibitor doublets. In addition, we believe that in some cases, combination of our RAS(ON) Inhibitors with standard of care therapies, including immunotherapies, may be optimal.
Added
In July 2025, elironrasib received Breakthrough Therapy Designation from the FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor. 78 RMC-5127 RMC-5127 is designed as a RAS(ON) oral G12V-selective tri-complex inhibitor.
Removed
Daraxonrasib inhibits all three major RAS isoforms, suppressing the mutant cancer driver and cooperating wild-type RAS proteins. A global, randomized Phase 3 registrational trial of daraxonrasib in the second-line (2L) treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC), which we call the RASolute 302 study, is ongoing.
Added
New Class of RAS(ON) Inhibitors We have designed a new class of RAS(ON) Inhibitors in order to overcome RAS-driven drug resistance and thereby extend the clinical benefit of RAS(ON) Inhibitors. We currently expect to initiate a first-in-human clinical trial from this class of RAS(ON) Inhibitors in the fourth quarter of 2026.
Removed
In the RASolute 302 study, we are randomizing patients in a 1:1 ratio to receive either daraxonrasib at a dose of 300 mg daily or the investigator’s choice of chemotherapy.
Added
Clinical development of RMC-8839 is subject to our continuing assessment of portfolio priorities. Clinical Development RAS Mutant Epidemiology in the United States Variants in RAS proteins are among the most common oncogenic drivers of cancer.
Removed
The RASolute 302 study has a nested trial design allowing for a hierarchical sequence of statistical analysis, with patients with tumors harboring RAS G12X mutations serving as the core population which will be tested first and all enrolled patients serving as the secondary population.
Added
Based on tumor mutation frequencies from Foundation Medicine data, scaled to estimated patient numbers using cancer incidence from the American Cancer Society Cancer Facts and Figures, there are an estimated more than 190,000 new RAS mutant cancer diagnoses each year in the U.S.
Removed
We believe this nested design and hierarchical testing increases the probability of trial success based on the core population while creating an opportunity to gain approval for a broader population.
Added
These include approximately 60,000 patients with NSCLC, representing approximately 30% of NSCLC diagnoses, approximately 75,000 patients with colorectal cancer (CRC), representing approximately 50% of CRC diagnoses, and approximately 56,000 patients with PDAC, representing more than 90% of PDAC diagnoses. Pancreatic Cancer Pancreatic cancer is one of the most common and difficult-to-treat cancers and patients have historically had limited treatment options.
Removed
Patients in the RASolute 302 study will be evaluated for the dual primary endpoints of progression-free survival (PFS) and overall survival (OS) in the core 89 population, with secondary endpoints including PFS and OS in the secondary population and objective response rate (ORR) and quality of life measures.
Added
Because of this unmet need and the prevalence of RAS as a driver of PDAC, we believe that pancreatic cancer represents a particularly compelling opportunity for RAS-targeted therapies.
Removed
We currently expect to substantially complete enrollment of the RASolute 302 study in 2025, to enable an expected clinical readout in 2026.
Added
Based on encouraging early-stage clinical results, we are evaluating daraxonrasib and zoldonrasib in the following global, randomized Phase 3 registrational studies in PDAC: • RASolute 302: comparing daraxonrasib against chemotherapy in patients with second line (2L) PDAC; a clinical readout for this study is currently expected in the first half of 2026; • RASolute 303: comparing daraxonrasib with and without chemotherapy against chemotherapy in patients with first line (1L) metastatic PDAC; • RASolute 304: evaluating daraxonrasib as an adjuvant therapy in patients with resectable PDAC; and • RASolute 305: comparing zoldonrasib in combination with the investigator’s choice of either gemcitabine nab-paclitaxel or modified FOLFIRINOX against the investigator’s choice of the chemotherapies in patients with 1L metastatic PDAC in a placebo-controlled study. 79 In addition, we expect to initiate RASolute 309, a global, randomized Phase 3 registrational trial evaluating the combination of daraxonrasib with zoldonrasib in patients with 1L PDAC in the second half of 2026.
Removed
In the RASolve 301 study, we are randomizing patients in a 1:1 ratio to receive either daraxonrasib or docetaxel.
Added
Non-Small Cell Lung Cancer NSCLC is another major cancer type in which RAS mutations are common. While advances in immunotherapy and chemotherapy have improved outcomes for some individuals, many patients with RAS mutant NSCLC continue to experience disease progression, highlighting the need for new targeted approaches.
Removed
The RASolve 301 study has a nested trial design allowing for a hierarchical sequence of statistical analysis, with patients with tumors harboring RAS G12X (other than G12C) mutations serving as the core population which will be tested first, and all enrolled patients serving as the secondary population.
Added
Importantly, RAS mutations in NSCLC extend beyond a single subtype, leaving a significant portion of patients without broadly effective targeted treatment options.
Removed
We believe this nested design and hierarchical testing increases the probability of trial success based on the core population while creating an opportunity to gain approval for a broader population.
Added
We also currently expect to share an update on our registrational strategy for elironrasib in NSCLC in 2026. Colorectal Cancer Colorectal cancers are genetically complex and heterogeneous, and patients with RAS mutant disease typically have limited targeted treatment options, particularly after progression on standard therapies.
Removed
Patients in the RASolve 301 study will be evaluated for the dual primary endpoints of PFS and OS in the core population, with secondary endpoints including PFS and OS in the secondary population and ORR and quality of life measures.
Added
As a result, outcomes remain poor for many patients, underscoring the need for new therapeutic approaches that more effectively address the underlying drivers of the disease. To address this need, we are pursuing a combination-focused strategy designed to maximize clinical impact in this challenging setting. We believe that our early clinical experience supports continued exploration of these strategies.
Removed
On December 2, 2024 we reported updated clinical safety, tolerability, and activity data for daraxonrasib from our first-in-human monotherapy study of daraxonrasib, which we refer to as the RMC-6236-001 study, in patients with previously treated RAS-mutant PDAC as of a data cutoff date of July 23, 2024.
Added
As data mature, we plan to prioritize registrational opportunities with the goal of improving outcomes and expanding treatment options for patients with RAS mutant colorectal cancer. We currently expect to provide updated combination data in CRC in 2026.
Removed
We believe these data showed that daraxonrasib was generally well tolerated and demonstrated encouraging antitumor activity that supported our initiation of the RASolute 302 study.

… 89 more changes not shown on this page.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

3 edited+0 added−0 removed3 unchanged
Biggest changeWe held cash, cash equivalents and marketable securities of $2.3 billion and $1.9 billion as of December 31, 2024 and 2023, respectively, which consisted of bank deposits, money market funds, U.S. government debt securities, U.S. government agency bonds, commercial paper and corporate bonds.
Biggest changeWe held cash, cash equivalents and marketable securities of $2.0 billion and $2.3 billion as of December 31, 2025 and 2024, respectively, which consisted of bank deposits, money market funds, U.S. government debt securities, U.S. government agency bonds, commercial paper and corporate bonds.
To date, foreign currency transaction gains and losses have not been material to our consolidated financial statements, and we have not had a formal hedging program with respect to foreign currency. A 10% increase or decrease in current exchange rates would not have a material effect on our financial results.
To date, foreign currency transaction gains and losses have not been material to our consolidated financial statements, and we have not had a formal hedging program with respect to foreign currency. A 10% increase or decrease in current exchange rates would not have a material effect on our financial results. 87
We also seek to maximize income 100 from our investments without assuming significant risk. To achieve our objectives, we maintain a portfolio of investments in a variety of securities of high credit quality and short-term duration, invested in compliance with our policy.
We also seek to maximize income from our investments without assuming significant risk. To achieve our objectives, we maintain a portfolio of investments in a variety of securities of high credit quality and short-term duration, invested in compliance with our policy.

Other RVMD 10-K year-over-year comparisons