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What changed in IDEAYA Biosciences, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of IDEAYA Biosciences, 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.

+636 added−844 removedSource: 10-K (2025-12-31) vs 10-K (2024-12-31)

Top changes in IDEAYA Biosciences, Inc.'s 2025 10-K

636 paragraphs added · 844 removed · 454 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

161 edited+108 added−237 removed231 unchanged
Biggest changeThe purpose of the clinical trial is to evaluate darovasertib in combination with crizotinib, Pfizer’s investigational cMET inhibitor, in patients having metastatic uveal melanoma, or MUM, with human leukocyte antigen-, or HLA-A*02:01 negative, or HLA-A2(-), serotype, as part of a second Clinical Trial Collaboration and Supply Agreement, or the Second Pfizer Agreement, with Pfizer. • In December 2024, we announced the recommendation of a move-forward dose and the completion of the Part 2a dose optimization for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the first-line, or 1L, setting in patients with HLA-A2(-) MUM.
Biggest changeWe are evaluating darovasertib in combination with crizotinib, Pfizer’s oral c-MET inhibitor, in a potentially registration-enabling, Phase 2/3 trial (OptimUM-02) for human leukocyte antigen-A*02:01 negative (HLA*A2(-)), patients with first line (1L) mUM. We expect to report topline data, including progression free survival (PFS) data, from this trial in the first quarter of 2026. Based on our discussions with the U.S.
Pediatric Use Even when not pursuing a pediatric indication, under the Pediatric Research Equity Act, or PREA, an NDA or supplement thereto must contain data that is adequate to assess the safety and effectiveness of the drug product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Pediatric Use Even when not pursuing a pediatric indication, under the Pediatric Research Equity Act (PREA), an NDA or supplement thereto must contain data that is adequate to assess the safety and effectiveness of the drug product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Marketing Exclusivity Market exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity, or NCE.
Marketing Exclusivity Market exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity (NCE).
During the exclusivity period, the FDA may not approve or even accept for review an abbreviated new drug application, or ANDA, or an NDA submitted under Section 505(b)(2) of the FDCA, or 505(b)(2) NDA, submitted by another company for another drug that contains the same active moiety.
During the exclusivity period, the FDA may not approve or even accept for review an abbreviated new drug application (ANDA), or an NDA submitted under Section 505(b)(2) of the FDCA, or 505(b)(2) NDA, submitted by another company for another drug that contains the same active moiety.
Regulation Outside the United States To the extent that any of our product candidates, once approved, are sold in a foreign country, we would be subject to numerous and varying foreign laws and regulations regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, or MA, commercial sales and distribution of our products, and may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.
Regulation Outside the United States To the extent that any of our product candidates, once approved, are sold in a foreign country, we would be subject to numerous and varying foreign laws and regulations regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization (MA), commercial sales and distribution of our products, and may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.
Some Phase 1b studies evaluate biomarkers or surrogate markers that may be associated with efficacy in patients with specific types of diseases. • Phase 2: This phase involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and appropriate dosage. 29 • Phase 3: Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population, generally at geographically dispersed clinical trial sites.
Some Phase 1b studies evaluate biomarkers or surrogate markers that may be associated with efficacy in patients with specific types of diseases. • Phase 2: This phase involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and appropriate dosage. • Phase 3: Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population, generally at geographically dispersed clinical trial sites.
The centralized procedure is mandatory for certain types of medicinal products, such as (i) medicinal products derived from biotechnological processes, (ii) designated orphan medicinal products, (iii) advanced therapy medicinal products, or ATMPs (such as gene therapy, somatic cell therapy and tissue engineered products) and (iv) medicinal products containing a new active substance indicated for the treatment of certain diseases, such as AIDS/HIV, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases and other immune dysfunctions.
The centralized procedure is mandatory for certain types of medicinal products, such as (i) medicinal products derived from biotechnological processes, (ii) designated orphan medicinal products, (iii) advanced therapy medicinal products (ATMPs) (such as gene therapy, somatic cell therapy and tissue engineered products) and (iv) medicinal products containing a new active substance indicated for the treatment of certain diseases, such as AIDS/HIV, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases and other immune dysfunctions.
The centralized procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU; and • “National MAs” are issued by the competent authorities of the EU member states, only cover their respective territory, and are available for products not falling within the mandatory scope of the centralized procedure.
The centralized procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU; and 27 • “National MAs” are issued by the competent authorities of the EU member states, only cover their respective territory, and are available for products not falling within the mandatory scope of the centralized procedure.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: 28 • completion of preclinical laboratory tests, animal studies and formulation studies in accordance with good laboratory practice, or GLP, regulations and other applicable regulations; • submission to the FDA of an IND, which must become effective before clinical trials in humans may begin; • approval by an independent institutional review board, or IRB, at each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practice, or GCP, regulations to establish the safety and efficacy of the proposed drug for its intended use; • submission to the FDA of an NDA; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current good manufacturing practice, or cGMP, regulations to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and • FDA review and approval of the NDA.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory tests, animal studies and formulation studies in accordance with good laboratory practice (GLP), regulations and other applicable regulations; • submission to the FDA of an IND, which must become effective before clinical trials in humans may begin; • approval by an independent institutional review board (IRB), at each clinical site before each clinical trial 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 proposed drug for its intended use; • submission to the FDA of an NDA; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current good manufacturing practice (cGMP), regulations to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and 19 • FDA review and approval of the NDA.
We also expect to pursue breakthrough therapy designation and accelerated approval for darovasertib and may explore some of these opportunities for our other product candidates as appropriate. U.S. Post-approval Requirements Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory standards is not maintained or if problems occur after the product reaches the market.
We also expect to pursue breakthrough therapy designation and accelerated approval for darovasertib and may explore some of these opportunities for our other product candidates as appropriate. U.S. Post-approval Requirements 23 Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory standards is not maintained or if problems occur after the product reaches the market.
While the EU Clinical Trials Directive required a separate clinical trial application, or CTA, to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials.
While the EU Clinical Trials Directive required a separate CTA to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials.
The overall 10-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those 10 years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
The overall 10-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight 28 years of those 10 years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
Other types of non-patent exclusivity include seven-year orphan drug exclusivity and six-month pediatric exclusivity (each discussed above). FDA Regulation of Companion Diagnostics We are collaborating or expect to collaborate with strategic partners or CMOs to manufacture and supply in vitro diagnostics to identify patients with biomarkers associated with the targeted therapeutics we are developing.
Other types of non-patent exclusivity include seven-year orphan drug exclusivity and six-month pediatric exclusivity (each discussed above). FDA Regulation of Companion Diagnostics 24 We are collaborating or expect to collaborate with strategic partners or CMOs to manufacture and supply in vitro diagnostics to identify patients with biomarkers associated with the targeted therapeutics we are developing.
Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the PRIority MEdicines, or PRIME, scheme, which provides incentives similar to the breakthrough therapy designation in the United States.
Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the PRIority MEdicines (PRIME), scheme, which provides incentives similar to the breakthrough therapy designation in the United States.
The regulation of companion diagnostics is subject to further requirements since Regulation (EU) No 2017/746, or IVDR, became applicable on May 26, 2022 but there is a tiered system extending the grace period for many devices (depending on their risk classification) before they have to be fully compliant with the Regulation.
The regulation of companion diagnostics is subject to further requirements since Regulation (EU) No 2017/746 (IVDR) became applicable on May 26, 2022 but there is a tiered system extending the grace period for many devices (depending on their risk classification) before they have to be fully compliant with the Regulation.
Exclusive Option and License Agreement with Cancer Research UK and University of Manchester for IDE161 In April 2017, we entered into the CRUK/Manchester Agreement with Cancer Research UK and University of Manchester, which was amended on April 24, 2019 and on March 3, 2020, for the development and commercialization of licensed products comprising pharmaceutical preparations of PARG inhibitors for all therapeutic uses.
Exclusive Option and License Agreement with Cancer Research UK and University of Manchester for IDE161 16 In April 2017, we entered into the CRUK/Manchester Agreement with Cancer Research UK and University of Manchester, which was amended on April 24, 2019 and on March 3, 2020, for the development and commercialization of licensed products comprising pharmaceutical preparations of PARG inhibitors for all therapeutic uses.
The PMA can include post-approval conditions that the FDA believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution. 35 If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter.
The PMA can include post-approval conditions that the FDA believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution. If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter.
Exclusive License Agreement with Novartis for Darovasertib In September 2018, we entered into a license agreement with Novartis to develop and commercialize Novartis’ LXS196 (also known as IDE196), a Phase 1 PKC inhibitor, for the treatment of cancers having GNAQ and GNA11 mutations. We renamed Novartis’ LXS196 oncology as IDE196, and which has a non-proprietary name of darovasertib.
Exclusive License Agreement with Novartis for Darovasertib In September 2018, we entered into a license agreement with Novartis to develop and commercialize Novartis’ LXS196 (also known as IDE196), a Phase 1 PKC inhibitor, for the treatment of cancers with GNAQ and GNA11 mutations. We renamed Novartis’ LXS196 oncology as IDE196, and which has a non-proprietary name of darovasertib.
If used to make critical treatment decisions, such as patient selection, the diagnostic device generally will be considered a significant risk device under the FDA’s Investigational Device Exemption, or IDE, regulations. Thus, the sponsor of the diagnostic device will be required to submit an IDE application for clinical testing of the device and comply with the applicable IDE requirements.
If used to make critical treatment decisions, such as patient selection, the diagnostic device generally will be considered a significant risk device under the FDA’s Investigational Device Exemption (IDE) regulations. Thus, the sponsor of the diagnostic device will be required to submit an IDE application for clinical testing of the device and comply with the applicable IDE requirements.
The FDA may also place other conditions on approval including the requirement for a risk evaluation and mitigation strategy, or REMS, to assure the safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the NDA without an approved REMS, if required.
The FDA may also place other conditions on approval, including the requirement for a risk evaluation and mitigation strategy (REMS), to assure the safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the NDA without an approved REMS, if required.
Recently, the Food and Drug Omnibus Reform Act, or FDORA, enacted as part of the year-end omnibus spending bill in December 2022, included several reforms intended to expand the FDA’s ability to regulate products receiving accelerated approval, including by increasing the FDA’s oversight over the conduct of confirmatory trials.
Recently, the Food and Drug Omnibus Reform Act (FDORA) enacted as part of the year-end omnibus spending bill in December 2022, included several reforms intended to expand the FDA’s ability to regulate products receiving accelerated approval, including by increasing the FDA’s oversight over the conduct of confirmatory trials.
Class III devices 34 include devices deemed by the FDA to pose the greatest risk such as life-supporting or life-sustaining devices, or implantable devices, in addition to new devices deemed not substantially equivalent following the 510(k) process. The safety and effectiveness of Class III devices cannot be reasonably assured solely by General Controls and Special Controls.
Class III devices include devices deemed by the FDA to pose the greatest risk such as life-supporting or life-sustaining devices, or implantable devices, in addition to new devices deemed not substantially equivalent following the 510(k) process. The safety and effectiveness of Class III devices cannot be reasonably assured solely by General Controls and Special Controls.
Non-clinical (pharmaco-toxicological) studies must be conducted in compliance with the principles of good laboratory practice, or GLP, as set forth in EU Directive 2004/10/EC (unless otherwise justified for certain particular medicinal products, e.g., radio-pharmaceutical precursors for radio-labeling purposes).
Non-clinical (pharmaco-toxicological) studies must be conducted in compliance with the principles of good laboratory practice (GLP), as set forth in EU Directive 2004/10/EC (unless otherwise justified for certain particular medicinal products, e.g., radio-pharmaceutical precursors for radio-labeling purposes).
In addition, exclusive marketing rights in the United States may also 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 also be 22 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.
Option and License Agreement with Biocytogen for IDE034 In July 2024, we entered into the Biocytogen Option and License Agreement with Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license to develop and commercialize products in connection with a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program, or the Option.
Option and License Agreement with Biocytogen for IDE034 In July 2024, we entered into the Biocytogen Option and License Agreement with Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license to develop and commercialize products in connection with a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program (the Option).
On February 12, 2025, we entered into the Second Gilead CSCSA with Gilead pursuant to which we and Gilead will collaborate on a portion of our Phase 1 study for the clinical evaluation of IDE397 in combination with Trodelvy, or the Combination Study, in certain patients with advanced solid tumors in lungs.
On February 12, 2025, we entered into the Second Gilead CSCSA with Gilead pursuant to which we and Gilead will collaborate on a portion of our Phase 1 study for the clinical evaluation of IDE397 in combination with Trodelvy (the Combination Study), in certain patients with advanced solid tumors in lungs.
The resubmitted application also is subject to review before the FDA accepts it for filing. Under the Prescription Drug User Fee Act, or PDUFA, the FDA has agreed to certain performance goals in the review of NDAs through a two-tiered classification system, standard review and priority review.
The resubmitted application also is subject to review before the FDA accepts it for filing. Under the Prescription Drug User Fee Act (PDUFA) the FDA has agreed to certain performance goals in the review of NDAs through a two-tiered classification system, standard review and priority review.
These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties. 39 Regulation of Companion Diagnostics In the EU, in vitro diagnostic medical devices, or IVD MDs, were regulated by the EU Directive on in vitro diagnostic medical devices (Directive No. 98/79/EC, as amended), or IVDD, which regulated the placing on the market, the CE marking, the essential requirements, the conformity assessment procedures, the registration obligations for manufacturers and devices, as well as the vigilance procedure.
These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties. 29 Regulation of Companion Diagnostics In the EU, in vitro diagnostic medical devices (IVD MDs), were regulated by the EU Directive on in vitro diagnostic medical devices (Directive No. 98/79/EC, as amended) (IVDD), which regulated the placing on the market, the CE marking, the essential requirements, the conformity assessment procedures, the registration obligations for manufacturers and devices, as well as the vigilance procedure.
In March 2022, we and Pfizer entered into a Second Clinical Trial Collaboration and Supply Agreement (as amended in May 2023), or the Second Pfizer Agreement, pursuant to which we are evaluating darovasertib and crizotinib as a combination therapy in MUM in a planned Phase 2/3 potential registration-enabling clinical trial.
In March 2022, we and Pfizer entered into a Second Clinical Trial Collaboration and Supply Agreement (as amended in May 2023) (the Second Pfizer Agreement), pursuant to which we are evaluating darovasertib and crizotinib as a combination therapy in mUM in a planned Phase 2/3 potential registration-enabling clinical trial.
A product can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product may demonstrate substantial improvement 32 over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
A product can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
A new drug must be approved by the FDA through the NDA process before it may be legally marketed in the United States. U.S. Drug Development Process In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations.
A new drug must be approved by the FDA through the NDA process before it may be legally marketed in the United States. U.S. Drug Development Process In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (FDCA), and its implementing regulations.
There are two types of MAs: • “Centralized MAs” are issued by the European Commission through the centralized procedure based on the opinion of the Committee for Medicinal Products for Human Use, or CHMP of the European Medicines Agency, or EMA, and are valid throughout the entire territory of the EU.
There are two types of MAs: • “Centralized MAs” are issued by the European Commission through the centralized procedure based on the opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), and are valid throughout the entire territory of the EU.
Non-clinical Studies and Clinical Trials Similarly 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 26 Similarly 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.
In March 2010, the Patient Protection and Affordable Care Act, or ACA, was signed into law which substantially changed the way healthcare is financed by both governmental and private insurers in the United States and significantly affected the pharmaceutical industry.
In March 2010, the Patient Protection and Affordable Care Act (ACA) was signed into law which substantially changed the way healthcare is financed by both governmental and private insurers in the United States and significantly affected the pharmaceutical industry.
Manufacturing We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates and our biomarker diagnostics for preclinical and clinical testing, as well as for future commercial manufacture of any drugs and diagnostics that we may commercialize.
Manufacturing We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates and our biomarker diagnostics for preclinical and clinical testing, as well as for future commercial manufacture of any drugs and 18 diagnostics that we may commercialize.
In the EU, similar developments may affect our ability to profitably commercialize our products, if approved. On December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted.
In the EU, similar developments may affect our ability to profitably commercialize our products, if approved. On December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment (HTA), amending Directive 2011/24/EU, was adopted.
The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to 30 assure and preserve the product’s identity, strength, quality and purity.
The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.
Discovery of previously unknown problems or the failure to comply with the applicable regulatory requirements may result in 33 restrictions on the marketing of a product or withdrawal of the product from the market, as well as possible civil or criminal sanctions.
Discovery of previously unknown problems or the failure to comply with the applicable regulatory requirements may result in restrictions on the marketing of a product or withdrawal of the product from the market, as well as possible civil or criminal sanctions.
Collaboration, Option and License Agreement with GSK for Pol Theta and Werner Helicase In June 2020, we entered into the GSK Collaboration Agreement with GSK, pursuant to which we and GSK have entered into a collaboration for its synthetic lethality programs targeting MAT2A, Pol Theta and WRN.
Collaboration, Option and License Agreement with GSK for Pol Theta and Werner Helicase In June 2020, we entered into the GSK Collaboration Agreement with GSK, pursuant to which we and GSK entered into a collaboration for its synthetic lethality programs targeting MAT2A, Pol Theta and WRN.
The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.
The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation (CTR) which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.
We will have the right to terminate the Biocytogen Option and License Agreement for any reason or no reason upon ninety (90) days written notice to Biocytogen. Upon any termination of the Biocytogen Option and License Agreement after the exercise of the Option, the license granted to us will automatically terminate.
We will have the right to terminate the Biocytogen Option and License Agreement for any reason or no reason upon 90 days written notice to Biocytogen. Upon any termination of the Biocytogen Option and License Agreement after the exercise of the Option, the license granted to us will automatically terminate.
PMAs must generally include the results from extensive preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought.
PMAs must generally include the results from extensive preclinical and adequate and 25 well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought.
Under an Orphan Drug designation, darovasertib may be entitled to certain tax credits for qualifying clinical trial expenses, exemption from certain user fees and, subject to FDA approval of a New Drug Application, or NDA, for darovasertib in UM, eligibility for seven years of statutory marketing exclusivity during which the FDA is prohibited from approving a subsequent same drug for the same rare disease or condition except in limited circumstances, such as a subsequent drug that demonstrates clinical superiority.
Under an Orphan Drug designation, darovasertib may be entitled to certain tax credits for qualifying clinical trial expenses, exemption from certain user fees and, subject to FDA approval of a NDA, for darovasertib in UM, eligibility for seven years of statutory marketing exclusivity during which the FDA is prohibited from approving a subsequent same drug for the same rare disease or condition except in limited circumstances, such as a subsequent drug that demonstrates clinical superiority.
We have an agreement with STA Pharmaceutical Hong Kong Limited, or STA Pharmaceutical, and Yuhan Corporation for the synthesis of the API for darovasertib, and agreements with STA Pharmaceutical and Patheon Inc. for formulation and manufacturing of darovasertib drug product. We have an agreement with STA Pharmaceutical for the synthesis of the API, formulation and manufacturing of IDE397 drug product.
We have an agreement with STA Pharmaceutical Hong Kong Limited Pharmaceutical (STA Pharmaceutical), and Yuhan Corporation for the synthesis of the API for darovasertib, and agreements with STA Pharmaceutical and Patheon Inc. for formulation and manufacturing of darovasertib drug product. We have an agreement with STA Pharmaceutical for the synthesis of the API, formulation and manufacturing of IDE397 drug product.
We have the first right to enforce any exclusively licensed patents, while Novartis retains the right to representation. If we do not bring an action to enforce any exclusively licensed patent, Novartis has the right to bring such action, and we will have the right to representation.
We have the first right to enforce any exclusively licensed patents, while Novartis retains the right to representation. If we do not 15 bring an action to enforce any exclusively licensed patent, Novartis has the right to bring such action, and we will have the right to representation.
In particular, for a diagnostic, the applicant must demonstrate that the diagnostic produces reproducible results when the same sample is tested multiple times by multiple users at multiple laboratories. As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the QSR, which imposes elaborate testing, control, documentation and other quality assurance requirements.
In particular, for a diagnostic, the applicant must demonstrate that the diagnostic produces reproducible results when the same sample is tested multiple times by multiple users at multiple laboratories. As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the QMSR, which imposes elaborate testing, control, documentation and other quality assurance requirements.
Therefore, these devices are generally subject to the premarket approval, or PMA, application process, which is generally more costly and time-consuming than the 510(k) process.
Therefore, these devices are generally subject to the premarket approval (PMA), application process, which is generally more costly and time-consuming than the 510(k) process.
The aforementioned EU rules are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.
The aforementioned EU rules are generally applicable in the European Economic Area (EEA), which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.
The IRA permits the Secretary of the Department of Health 40 and Human Services to implement many of these provisions through guidance, as opposed to regulation, for the initial years.
The IRA permits the Secretary of the Department of Health and Human Services to implement many of these provisions through guidance, as opposed to regulation, for the initial years.
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 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 discounting program (which began in 2025).
A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.
A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QMSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.
We do not own or operate, and currently have no plans to establish, any manufacturing facilities. In general, we plan to establish agreements with contract manufacturing organizations, or CMOs, for synthesis of the active pharmaceutical ingredient, or API, manufacturing of drug product comprising such API, as well as packaging, labeling and distribution.
We do not own or operate, and currently have no plans to establish, any manufacturing facilities. In general, we plan to establish agreements with CMOs for synthesis of the active pharmaceutical ingredient (API) manufacturing of drug product comprising such API, as well as packaging, labeling and distribution.
We believe a moderately sized specialty sales force, supported by effective marketing and sales management organizations, would enable us to reach healthcare practitioners who specialize in the care of the patient populations for darovasertib and our other product candidates.
We believe a moderately sized specialty sales force, supported by effective marketing and sales management organizations, would enable us to reach healthcare professionals who specialize in the care of the patient populations for darovasertib and our other product candidates.
We have an agreement with Pharmaron for the synthesis of the API, and with STA Pharmaceutical for the formulation and drug product manufacturing of IDE161, IDE892 and IDE251. We have established arrangements with CMOs as well for packaging, labeling and distribution of darovasertib, IDE397, and IDE161.
We have an agreement with Pharmaron for the synthesis of the API, and with STA Pharmaceutical for the formulation and drug product manufacturing of IDE161, IDE892 and IDE574. We have established arrangements with CMOs as well for packaging, labeling and distribution of darovasertib, IDE397, and IDE161.
The DECIPHER 1.0 library is focused on DNA Damage Repair targets across various tumor suppressor genes and oncogenes of interest that were selected based on their known prevalence and role in solid tumors, enabling evaluation of approximately 50,000 independent gene knockout combinations of DDR pathway related drug targets across known tumor suppressor genes.
The DECIPHER 1.0 library is focused on DDR targets across various tumor suppressor genes and oncogenes of interest that were selected based on their known prevalence and role in solid tumors, enabling evaluation of approximately 50,000 independent gene knockout combinations of DDR pathway-related drug targets across known tumor suppressor genes.
On August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law.
On August 16, 2022, the Inflation Reduction Act of 2022 (IRA) was signed into law.
Agreements Clinical Trial Collaboration and Supply Agreements with Pfizer for Darovasertib In March 2020, we entered into a Clinical Trial Collaboration and Supply Agreement with Pfizer, Inc., as amended in September 2020, April 2021, September 2021 and May 2023, or the Pfizer Agreement.
Agreements 14 Clinical Trial Collaboration and Supply Agreements with Pfizer for Darovasertib In March 2020, we entered into a Clinical Trial Collaboration and Supply Agreement with Pfizer, Inc., as amended in September 2020, April 2021, September 2021 and May 2023 (the Pfizer Agreement).
We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by any other entity. 43
We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by any other entity. 33
Under the terms of the Biocytogen Option and License Agreement, we paid Biocytogen an upfront fee and, upon our exercise of the Option, an exercise fee totaling up to $6.5 million. In November 2024, we announced the selection of IDE034, a potential first-in-class B7H3/PTK7 topo-I-payload BsADC, as a development candidate and the exercise of the Option.
Under the terms 17 of the Biocytogen Option and License Agreement, we paid Biocytogen an upfront fee and, upon our exercise of the Option, an exercise fee totaling $6.5 million. In November 2024, we announced the selection of IDE034, a potential first-in-class B7H3/PTK7 topo-I-payload BsADC, as a development candidate and the exercise of the Option.
Class I devices are those for which safety and effectiveness can be reasonably assured by adherence to a set of regulations, referred to as General Controls, which require compliance with the applicable portions of the FDA’s Quality System Regulation, or QSR, facility registration and product listing, reporting of AEs and malfunctions, and appropriate, truthful and non-misleading labeling and promotional materials.
Class I devices are those for which safety and effectiveness can be reasonably assured by adherence to a set of regulations, referred to as General Controls, which require compliance with the applicable portions of the FDA’s Quality Management System Regulation (QMSR), facility registration and product listing, reporting of AEs and malfunctions, and appropriate, truthful and non-misleading labeling and promotional materials.
These solely owned or in-licensed patent applications, if granted, would expire between 2039 and 2044, without taking into account any applicable patent term adjustments or extensions.
These solely owned or in-licensed patent applications, if granted, would expire between 2039 and 2045, without taking into account any applicable patent term adjustments or extensions.
In addition, the PKC program portfolio includes two U.S. patent application and two PCT applications which are jointly owned with Pfizer directed to methods of treatment for certain combination treatments.
In addition, the PKC program portfolio includes two U.S. patent application, which are jointly owned with Pfizer directed to methods of treatment for certain combination treatments.
We own all commercial rights to our earlier next-generation synthetic lethality programs, including IDE892 and IDE251, for which our small molecule compounds are being discovered and/or developed internally with our own resources, supplemented by certain service providers, such as CROs. 21 Additionally, in 2024, we entered into two in-licensing agreements for ADCs with topoisomerase-I-inhibitor-payloads to enable combinations with our synthetic lethality programs.
We own all commercial rights to our earlier next-generation synthetic lethality programs, including IDE892 and IDE574, for which our small molecule compounds are being discovered and/or developed internally with our own resources, supplemented by certain service providers, such as CROs. In 2024, we entered into two in-license agreements for ADCs with topoisomerase-I-inhibitor-payloads to enable combinations with our synthetic lethality programs.
Additionally, Windtree Therapeutics is advancing a preclinical-stage atypical PCK iota inhibitor, including both topical and oral formulations, for potential treatment of Basal Cell Carcinoma, or BCC. We are aware of other companies that are conducting research and development of potential therapies for primary UM or for MUM based on other targets and approaches.
Additionally, Windtree Therapeutics is advancing a preclinical-stage atypical PKC iota inhibitor, including both topical and oral formulations, for potential treatment of Basal Cell Carcinoma. We are aware of several other companies conducting research and development of potential therapies for primary UM or for mUM based on other targets and approaches.
To enable our delivery of any approved medicines to patients, we plan to build our own sales force to commercialize them in the United States and potentially in Europe and other selected foreign countries.
To enable our delivery of any approved medicines to patients, we plan to build our own sales force to commercialize them in the United States and potentially in Europe and other selected foreign countries for pipeline products beyond darovasertib.
PAGEO™ Paralogous Gene Evaluation in Ovarian Cancer and Dep Map Consortium – Broad Institute We have an ongoing strategic collaboration with the Broad Institute focused on synthetic lethality target and biomarker discovery. This collaboration will use the large-scale CRISPR paralog screening platform developed at the laboratory of William R.
PAGEO™ Paralogous Gene Evaluation in Ovarian Cancer and Dep Map Consortium We have an ongoing strategic collaboration with the Broad Institute focused on discovery of synthetic lethality targets and biomarkers. This collaboration uses the large-scale CRISPR paralog screening platform developed at the laboratory of William R.
In addition, the MAT2A program portfolio also includes one pending PCT application directed to methods of treatment of cancer which is jointly owned with GSK pursuant to the GSK Collaboration Agreement; one pending US application, one pending PCT application, and two foreign applications directed to methods of treatment of cancer which is jointly owned with Amgen pursuant to the Amgen CTCSA; and one pending US application directed to methods of treatment of cancer which is jointly owned with Gilead pursuant to the Gilead CSCSA.
In addition, the MAT2A program portfolio also includes one pending US application and nine pending foreign applications directed to methods of treatment of cancer which are jointly owned with GSK; one pending US application, one pending PCT application, and five foreign applications directed to methods of treatment of cancer which are jointly owned with Amgen pursuant to the Amgen CTCSA; and one pending PCT application directed to methods of treatment of cancer which is jointly owned with Gilead pursuant to the Gilead CSCSA.
We will be obligated to make payments to CRT aggregating up to a total of £19.5 million upon the achievement of specific development and regulatory approval events for development of a PARG inhibitor in oncologic diseases. We will also pay low single-digit tiered royalties, and potentially also sales-based milestones, to CRT based on net sales of licensed products.
A total of up to £19.5 million in payments to CRT upon the achievement of specific development and regulatory approval events for development of a PARG inhibitor in oncologic diseases are payable under the agreement. We will also pay low single-digit tiered royalties, and potentially also sales-based milestones, to CRT based on net sales of licensed products.
We may also enter into distribution and other marketing arrangements with third parties for any of our approved medicines to support their safe and effective use.
We may also enter into distribution and other marketing or commercialization arrangements with third parties for any of our approved medicines to support their safe and effective use in appropriate patients.
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 Good Manufacturing Practice, or GMP.
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 Good Manufacturing Practice (GMP). Other national and EU-wide regulatory requirements may also apply.
As of January 26, 2025, as relating to our PARG program, including IDE161, we own or have exclusively in-licensed from Cancer Research UK and University of Manchester, patents and patent applications comprising approximately three issued U.S. patents, approximately 14 issued foreign patents, approximately three pending U.S. application, and approximately 61 pending foreign applications in approximately 37 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia.
As of January 30, 2026, as relating to our PARG program, including IDE161, we own or have exclusively in-licensed from Cancer Research UK and University of Manchester, patents and patent applications comprising approximately four issued U.S. patents, approximately 17 issued foreign patents, approximately eight pending U.S. application, and approximately 67 pending foreign applications in approximately 37 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia.
CMS has published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and has published the list of the subsequent 15 drugs that will be subject to negotiation, although the drug price negotiation program is currently subject to legal challenges.
CMS has published the negotiated prices for the initial ten drugs, which went into effect in 2026, and the subsequent 15 drugs, which will first be effective in 2027, although the drug price negotiation program is currently subject to legal challenges.
We have entered into strategic relationships for these programs – for example, to in-license certain intellectual property rights or to enable evaluation of combination therapies, such as through combination drug supply or clinical trial collaborations to evaluate combinations.
We own or control all commercial rights worldwide for IDE397 and IDE161. We have entered into strategic relationships for these programs – for example, to in-license certain intellectual property rights or to enable evaluation of combination therapies, such as through combination drug supply or clinical trial collaborations to evaluate combinations.
Our patent portfolio, including patents owned by or exclusively licensed to us, is built on a program-by-program basis with a goal of establishing broad protection that generally includes, for each product candidate compound and for selected alternative back-up compounds, claims directed to composition of matter, pharmaceutical compositions, and methods of treatment using such pharmaceutical compositions.
We endeavor to establish, maintain and enforce intellectual property rights that protect our business interests. 12 Our patent portfolio, including patents owned by or exclusively licensed to us, is built on a program-by-program basis with a goal of establishing broad protection that generally includes, for each product candidate compound and for selected alternative back-up compounds, claims directed to composition of matter, pharmaceutical compositions, and methods of treatment using such pharmaceutical compositions.
We offer our employees a challenging work environment, ongoing skills development, attractive career advancement, and a culture that rewards entrepreneurial initiative and exceptional execution. We have assembled a team of cancer biologists, drug discovery chemists, translational biologists and drug development professionals with broad experience at leading oncology organizations. Our team is led by our Chief Executive Officer, Yujiro S Hata.
We offer our employees a challenging work 32 environment, ongoing skills development, attractive career advancement, and a culture that rewards entrepreneurial initiative and exceptional execution. We have assembled a team of cancer biologists, drug discovery chemists, translational biologists and drug development professionals with broad experience at leading oncology organizations.
In particular, non-clinical studies, both in vitro and in vivo , must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies.
In particular, non-clinical studies, both in vitro and in vivo , must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies. These GLP standards reflect the Organization for Economic Co-operation and Development requirements.
As of January 26, 2025, as relating to our MAT2A program, including IDE397, we own patents and patent applications comprising approximately four issued U.S. patents, approximately four issued foreign patent, approximately eight pending U.S. applications, approximately five pending PCT applications and approximately 50 pending foreign applications in approximately 28 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia.
As of January 30, 2026, as relating to our MAT2A program, including IDE397, we own patents and patent applications comprising approximately five issued U.S. patents, approximately nine issued foreign patent, approximately 11 pending U.S. applications, approximately three pending PCT applications and approximately 69 pending foreign applications in approximately 26 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia.
As of January 26, 2025, we own or exclusively in-license patents and patent applications, comprising approximately 59 distinct patent families, protecting our technology across our pipeline.
As of January 30, 2026, we own or exclusively in-license patents and patent applications, comprising approximately 71 distinct patent families, protecting our technology across our pipeline.
For example, Aura Biosciences is developing AU-011, a virus-like drug conjugate (VDC), as local treatment for early-stage choroidal melanoma.
Aura Biosciences is developing bel-sar, a virus-like drug conjugate (VDC), as local treatment for early-stage choroidal melanoma.
As of January 26, 2025, as relating to our PKC program, including darovasertib, we own or have exclusively in-licensed from Novartis patents and patent applications comprising approximately six issued U.S. patents, approximately 33 issued foreign patents, approximately nine pending U.S. applications, approximately four pending 20 PCT application, and approximately 33 pending applications in approximately 18 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia.
As of January 30, 2026, as relating to our PKC program, including darovasertib, we own or have exclusively in-licensed from Novartis patents and patent applications comprising approximately seven issued U.S. patents, approximately 34 issued foreign patents, approximately eight pending U.S. applications, approximately two pending PCT application, and approximately 48 pending applications in approximately 20 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeOur future capital requirements will depend on many factors, including: • the scope, progress, results and costs of developing our product candidates or any other future product candidates, and conducting preclinical studies and clinical trials, including our ongoing clinical trials for IDE397, darovasertib, IDE161, and IDE849/SHR-4849; • the scope, progress, results and costs related to the research and development of our precision medicine target and biomarker discovery platform, including costs related to the development of our proprietary libraries and database of tumor genetic information and specific cancer-target dependency networks; • the timing of, and the costs involved in, obtaining regulatory approvals for our product candidates or any future product candidates, or any applicable diagnostics; • the number and characteristics of any additional product candidates we develop or acquire; • the cost of coordinating and/or collaborating with certain diagnostic companies for manufacturing and supply of companion diagnostics for biomarkers associated with our product candidates and any future product candidates; • the timing and amount of any milestone, royalty or other payments we are required to make pursuant to any current or future collaboration or license agreement, including under the License Agreement with Novartis or the Option and License Agreement with CRT and University of Manchester; Option and License Agreement with Biocytogen Pharmaceuticals Co., Ltd.; and License Agreement with Jiangsu Hengrui Pharmaceuticals Co., Ltd.; • the timing and amount of any option exercise, milestone, royalty or other payments we may or may not receive pursuant to any current or future collaboration or license agreement, including under the GSK Collaboration Agreement; • the timing and amount of any milestone, royalty or other payments we are required to make pursuant to any current or future collaboration or license agreement, including under the License Agreement with Novartis or the Option and License Agreement with CRT and University of Manchester; • potential delays in our ongoing clinical programs as a result of any public health outbreaks, epidemics or pandemics (such as the COVID-19 pandemic); • the cost of manufacturing our product candidates and any future products we successfully commercialize; • the cost of commercialization activities, including the cost of building a sales force in anticipation of product commercialization and distribution costs; • any product liability or other lawsuits related to our product candidates or future approved products; • the expenses needed to attract, hire and retain skilled personnel; • the costs associated with being a public company; • the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing our intellectual property portfolio; and • the timing, receipt and amount of sales of any future approved products, if any.
Biggest changeIn addition, we cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all. 35 Our future capital requirements will depend on many factors, including: • the scope, progress, results and costs of developing our product candidates or any other future product candidates, and conducting preclinical studies and clinical trials, including our ongoing clinical trials; • the scope, progress, results and costs related to the research and development of our precision medicine target and biomarker discovery platform, including costs related to the development of our proprietary libraries and database of tumor genetic information and specific cancer-target dependency networks; • the timing of, and the costs involved in, obtaining regulatory approvals for our product candidates or any future product candidates, or any applicable diagnostics; • the number and characteristics of any additional product candidates we develop or acquire; • the cost of coordinating and/or collaborating with certain diagnostic companies for manufacturing and supply of companion diagnostics for biomarkers associated with our product candidates and any future product candidates; • the timing and amount of any milestone, royalty or other payments we are required to make pursuant to any current or future collaboration or license agreement, including under the License Agreement with Novartis or the Option and License Agreement with CRT and University of Manchester; Option and License Agreement with Biocytogen Pharmaceuticals Co., Ltd.; and License Agreement with Jiangsu Hengrui Pharmaceuticals Co., Ltd.; • the timing and amount of any option exercise, milestone, royalty or other payments we may or may not receive pursuant to any current or future collaboration or license agreement, including under the Servier Agreement; • potential delays in our ongoing clinical programs as a result of any public health outbreaks or geopolitical conflicts; • the cost of manufacturing our product candidates and any future products we successfully commercialize; • the cost of commercialization activities, including the cost of building a sales force in anticipation of product commercialization and distribution costs; • any product liability or other lawsuits related to our product candidates or future approved products; • the expenses needed to attract, hire and retain skilled personnel; • the costs associated with being a public company; • the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing our intellectual property portfolio; and • the timing, receipt and amount of sales of any future approved products, if any.
We and our strategic collaborators could also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board, or DSMB, for such trial or by the FDA or another comparable foreign regulatory authority.
We and our strategic collaborators could also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board (DSMB) for such trial or by the FDA or another comparable foreign regulatory authority.
If unacceptable side effects arise in the further development of our product candidates, we, the FDA or comparable foreign regulatory authorities, or the IRBs at the institutions in which the clinical trials are being conducted could suspend or terminate our clinical trials or the FDA or a comparable foreign regulatory authority could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
If unacceptable side effects arise in the further development of our product candidates, we, the FDA or comparable foreign regulatory authorities (the IRBs) at the institutions in which the clinical trials are being conducted could suspend or terminate our clinical trials or the FDA or a comparable foreign regulatory authority could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
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 restrict the use of the product, including implementing a Risk Evaluation and Mitigation Strategy, or REMS, or to create a Medication Guide outlining the risks of such side effects for distribution to patients or similar risk management measures; • 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 restrict the use of the product, including implementing a Risk Evaluation and Mitigation Strategy (REMS), or to create a Medication Guide outlining the risks of such side effects for distribution to patients or similar risk management measures; • we could be sued and held liable for harm caused to patients; • the product may become less competitive; and • our reputation may suffer.
Further, approval, clearance or certification of companion diagnostics may be subject to further legislative or regulatory reforms notably in the EU. On May 25, 2017, the new In Vitro Medical Devices Regulation, or IVDR, entered into force. The IVDR repeals and replaces the EU In Vitro Diagnostic Medical Devices Directive.
Further, approval, clearance or certification of companion diagnostics may be subject to further legislative or regulatory reforms notably in the EU. On May 25, 2017, the new In Vitro Medical Devices Regulation (IVDR) entered into force. The IVDR repeals and replaces the EU In Vitro Diagnostic Medical Devices Directive.
In addition, the government may assert that a claim including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act; • the Health Insurance Portability and Accountability Act, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HIPAA, which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items or services.
In addition, the government may assert that a claim including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act; • the Health Insurance Portability and Accountability Act, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HIPAA), which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items or services.
Similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the healthcare fraud statute implemented under HIPAA or specific intent to violate it in order to have committed a violation; • the Federal Food Drug or Cosmetic Act, or FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; • the U.S.
Similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the healthcare fraud statute implemented under HIPAA or specific intent to violate it in order to have committed a violation; • the Federal Food Drug or Cosmetic Act (FDCA), which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; • the U.S.
The GDPR applies to any company established in the European Economic Area, or EEA, as well as to those outside the EEA if they collect and use personal data in connection with the offering of goods or services to individuals in the EEA or the monitoring of their behavior.
The GDPR applies to any company established in the European Economic Area (EEA), as well as to those outside the EEA if they collect and use personal data in connection with the offering of goods or services to individuals in the EEA or the monitoring of their behavior.
In addition, a data breach could result in negative publicity which could damage our reputation and have an adverse effect on our business, financial condition or results of operations. In addition, we use artificial intelligence, including machine learning, and automated decision-making technologies, or collectively, AI Technologies, in our business.
In addition, a data breach could result in negative publicity which could damage our reputation and have an adverse effect on our business, financial condition or results of operations. In addition, we use artificial intelligence, including machine learning, and automated decision-making technologies (collectively, AI Technologies) in our business.
These risks and uncertainties include the following: • the United States Patent and Trademark Office, or USPTO, and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other requirements during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdiction; • patent applications may not result in any patents being issued; • our competitors, many of whom have substantially greater resources than we do and many of whom have made significant investments in competing technologies, may seek or may have already obtained or licensed patents that will limit, interfere with or eliminate our ability to make, use and sell our product candidates; • other parties may have designed or may design around our claims or developed technologies that may be related or competitive to our platform, may have filed or may file patent applications and may have received or may receive patents that overlap or conflict with our patent applications, either by claiming the same methods or devices or by claiming subject matter that could dominate our patent position; • any successful opposition to any patents owned by or licensed to us could deprive us of rights necessary for the practice of our technologies or the successful commercialization of any product candidates that we may develop; • because patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that we or our licensors were the first to file any patent application related to our product candidates and proprietary technologies; • an interference proceeding can be provoked by a third-party or instituted by the USPTO to determine who was the first to invent any of the subject matter covered by the patent claims of our applications for any application with an effective filing date before March 16, 2013; • there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and • countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity to create, develop and market competing product candidates.
These risks and uncertainties include the following: • the United States Patent and Trademark Office (USPTO) and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other requirements during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdiction; • patent applications may not result in any patents being issued; • our competitors, many of whom have substantially greater resources than we do and many of whom have made significant investments in competing technologies, may seek or may have already obtained or licensed patents that will limit, interfere with or eliminate our ability to make, use and sell our product candidates; • other parties may have designed or may design around our claims or developed technologies that may be related or competitive to our platform, may have filed or may file patent applications and may have received or may receive patents that overlap or conflict with our patent applications, either by claiming the same methods or devices or by claiming subject matter that could dominate our patent position; • any successful opposition to any patents owned by or licensed to us could deprive us of rights necessary for the practice of our technologies or the successful commercialization of any product candidates that we may develop; • because patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that we or our licensors were the first to file any patent application related to our product candidates and proprietary technologies; 67 • an interference proceeding can be provoked by a third-party or instituted by the USPTO to determine who was the first to invent any of the subject matter covered by the patent claims of our applications for any application with an effective filing date before March 16, 2013; • there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and • countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity to create, develop and market competing product candidates.
Collaborations are subject to numerous risks, which may include risks that: • collaborators may have significant discretion in determining the efforts and resources that they will apply to collaborations; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in their strategic focus due to their acquisition of competitive products or their internal development of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; • 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; • a collaborator with marketing, manufacturing and distribution rights to one or more products may not commit sufficient resources to or otherwise not perform satisfactorily in carrying out these activities; • we could grant exclusive rights to our collaborators that would prevent us from collaborating with others; • collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or 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 liability; • disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our current or future product candidates or that results in costly litigation or arbitration that diverts management attention and resources; • collaborations may be terminated, which may result in a need for additional capital to pursue further development or commercialization of the applicable current or future product candidates; • collaborators may own or co-own intellectual property covering products that result from our collaboration with them, and in such cases, we would not have the exclusive right to develop or commercialize such intellectual property; • disputes may arise with respect to the ownership or inventorship of any intellectual property developed pursuant to our collaborations; and • a collaborator’s sales and marketing activities or other operations may not be in compliance with applicable laws resulting in civil or criminal proceedings.
Collaborations are subject to numerous risks, which may include risks that: • collaborators may have significant discretion in determining the efforts and resources that they will apply to collaborations; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in their strategic focus due to their acquisition of competitive products or their internal development of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; • 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; • a collaborator with marketing, manufacturing and distribution rights to one or more products may not commit sufficient resources to or otherwise not perform satisfactorily in carrying out these activities; • we could grant exclusive rights to our collaborators that would prevent us from collaborating with others; • collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or 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 liability; 62 • disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our current or future product candidates or that results in costly litigation or arbitration that diverts management attention and resources; • collaborations may be terminated, which may result in a need for additional capital to pursue further development or commercialization of the applicable current or future product candidates; • collaborators may own or co-own intellectual property covering products that result from our collaboration with them, and in such cases, we would not have the exclusive right to develop or commercialize such intellectual property; • disputes may arise with respect to the ownership or inventorship of any intellectual property developed pursuant to our collaborations; and • a collaborator’s sales and marketing activities or other operations may not be in compliance with applicable laws resulting in civil or criminal proceedings.
The FDA or a comparable foreign regulatory authority can delay, limit or deny approval of a product candidate for many reasons, including, but not limited to: • such authorities may disagree with the design or implementation of our clinical trials; • negative or ambiguous results from our clinical trials, or results may not meet the level of statistical significance required by the FDA or a comparable foreign regulatory agency for approval; • serious and unexpected drug-related side effects may be experienced by participants in our clinical trials or by individuals using drugs similar to our product candidates; • the population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; • such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; • we are unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA’s or the applicable comparable foreign regulatory agency’s non-approval of the formulation, labeling or specifications of our product candidates or any of our future product candidates; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • such authorities could question the integrity of data obtained in our current or future clinical trials, for example, due to missed protocol procedures; • such authorities may not agree that the data collected from clinical trials of our product candidates are acceptable or sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States or elsewhere, and such authorities may impose requirements for additional preclinical studies or clinical trials; • such authorities may disagree regarding the formulation, labeling and/or the specifications of our product candidates; • such authorities may only approve indications that are significantly more limited than what we apply for and/or with other significant restrictions on distribution and use; • such authorities may find deficiencies in the manufacturing processes or facilities of our third-party manufacturers with which we or any of our collaborators or any potential future collaborators, contract for clinical and commercial supplies; and • the approval policies or regulations of such authorities may significantly change in a manner rendering our or any of our collaborators’ clinical data insufficient for approval.
The FDA or a comparable foreign regulatory authority can delay, limit or deny approval of a product candidate for many reasons, including, but not limited to: • such authorities may disagree with the design or implementation of our clinical trials; • negative or ambiguous results from our clinical trials, or results may not meet the level of statistical significance required by the FDA or a comparable foreign regulatory agency for approval; • serious and unexpected drug-related side effects may be experienced by participants in our clinical trials or by individuals using drugs similar to our product candidates; 48 • the population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; • such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; • we are unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA’s or the applicable comparable foreign regulatory agency’s non-approval of the formulation, labeling or specifications of our product candidates or any of our future product candidates; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • such authorities could question the integrity of data obtained in our current or future clinical trials, for example, due to missed protocol procedures; • such authorities may not agree that the data collected from clinical trials of our product candidates are acceptable or sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States or elsewhere, and such authorities may impose requirements for additional preclinical studies or clinical trials; • such authorities may disagree regarding the formulation, labeling and/or the specifications of our product candidates; • such authorities may only approve indications that are significantly more limited than what we apply for and/or with other significant restrictions on distribution and use; • such authorities may find deficiencies in the manufacturing processes or facilities of our third-party manufacturers with which we or any of our collaborators or any potential future collaborators, contract for clinical and commercial supplies; and • the approval policies or regulations of such authorities may significantly change in a manner rendering our or any of our collaborators’ clinical data insufficient for approval.
Physician Payments Sunshine Act and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the government information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (nurse practitioners, certified nurse anesthetists, physician assistants, clinical nurse specialists, anesthesiology assistants and certified nurse midwives), and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, 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 U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing 92 information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; • the U.S.
Physician Payments Sunshine Act and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid (the Children’s Health Insurance Program), with specific exceptions, to report annually to the government information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (nurse practitioners, certified nurse anesthetists, physician assistants, clinical nurse specialists, anesthesiology assistants and certified nurse midwives), and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, 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 U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; • the U.S.
For a variety of reasons, including among other things, competitive factors, pricing or physician preference, reimbursement by insurers, the degree and rate of physician and patient adoption of any products, if approved, commercial success will depend on a number of factors, including: • the clinical indications for which the product is approved and patient demand for approved products that treat those indications; • the safety and efficacy of our product as compared to other available therapies; • the availability of companion diagnostics for biomarkers associated with our product candidates or any other future product candidates; • the time required for manufacture and release of our products; • the availability of coverage and adequate reimbursement from managed care plans, private insurers, government payors (such as Medicare and Medicaid) and other third-party payors for any of our products that may be approved; • acceptance by physicians, operators of hospitals and clinics and patients of the product as a safe and effective treatment; • physician and patient willingness to adopt a new therapy over other available therapies for a particular indication; • proper training and administration of our product candidates by physicians and medical staff; • patient satisfaction with the results and administration of our product candidates and overall treatment experience, including, for example, the convenience of any dosing regimen; • the cost of treatment with our product candidates in relation to alternative treatments and reimbursement levels, if any, and willingness to pay for the product, if approved, on the part of insurance companies and other third-party payors, physicians and patients; • the prevalence and severity of side effects; • limitations or warnings contained in the FDA-approved labeling for our products or similar foreign requirements; • the willingness of physicians, operators of hospitals and clinics and patients to utilize or adopt our products as a solution; • any FDA requirement for a REMS or similar foreign risk mitigation measures; • the effectiveness of our sales, marketing and distribution efforts; • adverse publicity about our products or favorable publicity about competitive products; and • potential product liability claims.
For a variety of reasons, including among other things, competitive factors, pricing or physician preference, reimbursement by insurers, the degree and rate of physician and patient adoption of any products, if approved, commercial success will depend on a number of factors, including: • the clinical indications for which the product is approved and patient demand for approved products that treat those indications; • the safety and efficacy of our product as compared to other available therapies; • the availability of companion diagnostics for biomarkers associated with our product candidates or any other future product candidates; • the time required for manufacture and release of our products; • the availability of coverage and adequate reimbursement from managed care plans, private insurers, government payors (such as Medicare and Medicaid) and other third-party payors for any of our products that may be approved; • acceptance by physicians, operators of hospitals and clinics and patients of the product as a safe and effective treatment; 64 • physician and patient willingness to adopt a new therapy over other available therapies for a particular indication; • proper training and administration of our product candidates by physicians and medical staff; • patient satisfaction with the results and administration of our product candidates and overall treatment experience, including, for example, the convenience of any dosing regimen; • the cost of treatment with our product candidates in relation to alternative treatments and reimbursement levels, if any, and willingness to pay for the product, if approved, on the part of insurance companies and other third-party payors, physicians and patients; • the prevalence and severity of side effects; • limitations or warnings contained in the FDA-approved labeling for our products or similar foreign requirements; • the willingness of physicians, operators of hospitals and clinics and patients to utilize or adopt our products as a solution; • any FDA requirement for a REMS or similar foreign risk mitigation measures; • the effectiveness of our sales, marketing and distribution efforts; • adverse publicity about our products or favorable publicity about competitive products; and • potential product liability claims.
These provisions include the following: • a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors; • no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates; • the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from being able to fill vacancies on our board of directors; • the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the price and other terms of those shares, including preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a hostile acquiror; • the ability of our board of directors to alter our amended and restated bylaws without obtaining stockholder approval; • the required approval of at least 66 2/3% of the shares entitled to vote at an election of directors to adopt, amend or repeal our amended and restated bylaws or repeal the provisions of our amended and restated certificate of incorporation regarding the election and removal of directors; • a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders; • the requirement that a special meeting of stockholders may be called only by our chief executive officer or president or by the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and • advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquiror from conducting a solicitation of proxies to elect the acquiror’s own slate of directors or otherwise attempting to obtain control of us.
These provisions include the following: • a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors; • no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates; 90 • the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from being able to fill vacancies on our board of directors; • the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the price and other terms of those shares, including preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a hostile acquiror; • the ability of our board of directors to alter our amended and restated bylaws without obtaining stockholder approval; • the required approval of at least 66 2/3% of the shares entitled to vote at an election of directors to adopt, amend or repeal our amended and restated bylaws or repeal the provisions of our amended and restated certificate of incorporation regarding the election and removal of directors; • a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders; • the requirement that a special meeting of stockholders may be called only by our chief executive officer or president or by the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and • advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquiror from conducting a solicitation of proxies to elect the acquiror’s own slate of directors or otherwise attempting to obtain control of us.
We and our strategic collaborators also may experience numerous unforeseen events during, or as a result of, any preclinical studies or clinical trials that could delay or prevent us or our strategic collaborators from successfully developing our product candidates, including: • we may be unable to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation of clinical trials; • the FDA or a comparable foreign regulatory authority disagreeing as to the design or implementation of our clinical trials; • delays in obtaining regulatory authorization to commence a clinical trial; • reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • obtaining IRB or ethics committee approval or positive opinion at each clinical trial site; • recruiting an adequate number of suitable patients to participate in a clinical trial, particularly if any public health outbreak, epidemic or pandemic leads to clinical site closures; • having patients complete a clinical trial or return for post-treatment follow-up; • clinical sites deviating from clinical trial protocol or dropping out of a clinical trial; • addressing subject safety concerns that arise during the course of a clinical trial; • adding a sufficient number of clinical trial sites; • obtaining sufficient quantities of product candidate for use in preclinical studies or clinical trials from third-party suppliers; or 52 • accessing third-party products or product candidates for use in combination with our product candidates in preclinical studies or clinical trials, including third-party product candidates that have not yet been approved by the FDA or comparable foreign regulatory authorities.
We and our strategic collaborators also may experience numerous unforeseen events during, or as a result of, any preclinical studies or clinical trials that could delay or prevent us or our strategic collaborators from successfully developing our product candidates, including: • we may be unable to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation of clinical trials; • the FDA or a comparable foreign regulatory authority disagreeing as to the design or implementation of our clinical trials; • delays in obtaining regulatory authorization to commence a clinical trial; • reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • obtaining IRB or ethics committee approval or positive opinion at each clinical trial site; • recruiting an adequate number of suitable patients to participate in a clinical trial, particularly if any public health outbreak, epidemic or pandemic leads to clinical site closures; • having patients complete a clinical trial or return for post-treatment follow-up; • clinical sites deviating from clinical trial protocol or dropping out of a clinical trial; • addressing subject safety concerns that arise during the course of a clinical trial; • adding a sufficient number of clinical trial sites; • obtaining sufficient quantities of product candidate for use in preclinical studies or clinical trials from third-party suppliers; or • accessing third-party products or product candidates for use in combination with our product candidates in preclinical studies or clinical trials, including third-party product candidates that have not yet been approved by the FDA or comparable foreign regulatory authorities.
We and our strategic collaborators may experience numerous adverse or unforeseen events during, or as a result of, preclinical studies and clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including: • we may receive feedback from regulatory authorities that requires us to modify the design of our clinical trials; • clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon our development programs; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate; • we or our third-party contractors may fail to comply with regulatory requirements, fail to maintain adequate quality controls, or be unable to produce sufficient product supply to conduct and complete preclinical studies or clinical trials of our product candidates in a timely manner, or at all; • we or our investigators might have to suspend or terminate clinical trials of our product candidates for various reasons, including non-compliance with regulatory requirements, a finding that our product candidates have undesirable side effects or other unexpected characteristics, or a finding that the participants are being exposed to unacceptable health risks; • the cost of clinical trials of our product candidates may be greater than we anticipate; • the quality of our product candidates or other materials necessary to conduct preclinical studies or clinical trials of our product candidates may be insufficient or inadequate; • regulators may revise the requirements for approving our product candidates, or such requirements may not be as we anticipate; and • collaborators may conduct clinical trials in ways they view as advantageous to them but that are suboptimal for us.
We and our strategic collaborators may experience numerous adverse or unforeseen events during, or as a result of, preclinical studies and clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including: • we may receive feedback from regulatory authorities that requires us to modify the design of our clinical trials; • clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon our development programs; 41 • the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate; • we or our third-party contractors may fail to comply with regulatory requirements, fail to maintain adequate quality controls, or be unable to produce sufficient product supply to conduct and complete preclinical studies or clinical trials of our product candidates in a timely manner, or at all; • we or our investigators might have to suspend or terminate clinical trials of our product candidates for various reasons, including non-compliance with regulatory requirements, a finding that our product candidates have undesirable side effects or other unexpected characteristics, or a finding that the participants are being exposed to unacceptable health risks; • the cost of clinical trials of our product candidates may be greater than we anticipate; • the quality of our product candidates or other materials necessary to conduct preclinical studies or clinical trials of our product candidates may be insufficient or inadequate; • regulators may revise the requirements for approving our product candidates, or such requirements may not be as we anticipate; and • collaborators may conduct clinical trials in ways they view as advantageous to them but that are suboptimal for us.
The degree of future protection for our patent rights is uncertain, and we cannot ensure that: • any of our patents, or any of our pending patent applications, if issued, or those of our licensors, will include claims having a scope sufficient to protect our product candidates; • any of our pending patent applications will issue as patents; • any of the patents we own or license will be found to ultimately be valid and enforceable if subject to challenge; • we were the first to make the inventions covered by each of our patents and pending applications; • we were the first to file patent applications for these inventions; • we will be able to successfully manufacture and commercialize our products on a substantial scale, if approved, before relevant patents we may have expire; • any patents issued to us or our licensors will provide a basis for an exclusive market for any commercially viable products we may develop or will provide us with any competitive advantages; • we will develop or in-license additional proprietary technologies that are patentable; • the patents of others will not have an adverse effect on our business; • others will not develop, manufacture and/or commercialize similar or alternative products or technologies that do not infringe our patents; • our competitors do not conduct research and development activities in countries where we do not have enforceable patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; and • our commercial activities or products will not infringe upon the patents of others.
The degree of future protection for our patent rights is uncertain, and we cannot ensure that: • any of our patents, or any of our pending patent applications, if issued, or those of our licensors, will include claims having a scope sufficient to protect our product candidates; • any of our pending patent applications will issue as patents; 68 • any of the patents we own or license will be found to ultimately be valid and enforceable if subject to challenge; • we were the first to make the inventions covered by each of our patents and pending applications; • we were the first to file patent applications for these inventions; • we will be able to successfully manufacture and commercialize our products on a substantial scale, if approved, before relevant patents we may have expire; • any patents issued to us or our licensors will provide a basis for an exclusive market for any commercially viable products we may develop or will provide us with any competitive advantages; • we will develop or in-license additional proprietary technologies that are patentable; • the patents of others will not have an adverse effect on our business; • others will not develop, manufacture and/or commercialize similar or alternative products or technologies that do not infringe our patents; • our competitors do not conduct research and development activities in countries where we do not have enforceable patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; and • our commercial activities or products will not infringe upon the patents of others.
Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption or incurrence of additional indebtedness or contingent liabilities; • the issuance of our equity securities; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing product programs and initiatives in pursuing such a strategic merger or acquisition; • loss of key personnel, and uncertainties in our ability to maintain key business relationships; 97 • uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and • our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption or incurrence of additional indebtedness or contingent liabilities; • the issuance of our equity securities; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing product programs and initiatives in pursuing such a strategic merger or acquisition; • loss of key personnel, and uncertainties in our ability to maintain key business relationships; • uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and • our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
We have recently adopted an AI Acceptable Use Policy, however, if the models underlying the AI Technologies we use are incorrectly designed or implemented; trained or reliant on incomplete, inadequate, inaccurate, biased or otherwise poor quality data, or on data to which we do not have sufficient rights or in relation to which we and/or the providers of such data have not implemented sufficient legal compliance measures; used without sufficient oversight and governance to ensure their responsible use; and/or adversely impacted by unforeseen defects, technical challenges, cybersecurity threats or material performance issues, the performance of our products, services and business, as well as our reputation, could suffer or we could incur liability resulting from the violation of laws or contracts to which we are a party or civil claims.
We have adopted an AI Acceptable Use Policy, however, if the models underlying the AI Technologies we use are incorrectly designed or implemented; trained or reliant on incomplete, inadequate, inaccurate, biased or otherwise poor quality data, or on data to which we do not have sufficient rights or in relation to which we and/or the providers of such data have not implemented sufficient legal compliance measures; used without sufficient oversight and governance to ensure their responsible use; and/or adversely impacted by unforeseen defects, technical challenges, cybersecurity threats or material performance issues, the performance of our products, services and business, as well as our reputation, could suffer or we could incur liability resulting from the violation of laws or contracts to which we are a party or civil claims.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and financial results, including, without limitation, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgement, possible exclusion from participation in Medicare, Medicaid and other U.S. federal healthcare programs or healthcare programs in other jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, individual imprisonment, other sanctions, contractual damages, reputational harm, diminished profits and future earnings and curtailment of our operations, any of which could adversely affect our business, financial condition, results of operations and prospects.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and financial results, including, without limitation, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgement, possible exclusion from participation in Medicare, Medicaid and other U.S. federal healthcare 55 programs or healthcare programs in other jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, individual imprisonment, other sanctions, contractual damages, reputational harm, diminished profits and future earnings and curtailment of our operations, any of which could adversely affect our business, financial condition, results of operations and prospects.
Our internal information technology systems and infrastructure, and those of our current and any future collaborators, contractors and consultants and other third parties on which we rely, are vulnerable to attack, damage and interruption from computer viruses, malware (e.g. ransomware), malicious code, misconfigurations, “bugs” or other vulnerabilities, natural disasters, terrorism, war, telecommunication and electrical failures, hacking, cyberattacks or intrusions over the Internet, phishing attacks and other social engineering schemes, attachments to emails, human error, fraud, denial or degradation of service 96 attacks, sophisticated nation-state and nation-state-supported actors, employee theft or misuse, persons inside our organization, or persons with access to systems inside our organization.
Our internal information technology systems and infrastructure, and those of our current and any future collaborators, contractors and consultants and other third parties on which we rely, are vulnerable to attack, damage and interruption from computer viruses, malware (e.g. ransomware), malicious code, misconfigurations, “bugs” or other vulnerabilities, natural disasters, terrorism, war, telecommunication and electrical failures, hacking, cyberattacks or intrusions over the Internet, phishing attacks and other social engineering schemes, attachments to emails, human error, fraud, denial or degradation of service attacks, sophisticated nation-state and nation-state-supported actors, employee theft or misuse, persons inside our organization, or persons with access to systems inside our organization.
Among other things, such delays may be caused by slow enrollment in clinical trials, patients dropping out of trials, length of time to achieve trial endpoints, additional time requirements for data analysis, IND preparation, discussions with the FDA or similar foreign regulatory authorities, an FDA or similar foreign regulatory authority request for additional preclinical or clinical data, or unexpected safety or manufacturing issues; • manufacturing costs, formulation issues, pricing or reimbursement issues, or other factors that may make our targeted therapeutic small molecule inhibitors uneconomical; and • proprietary rights of others and their competing products and technologies that may prevent our targeted therapeutic small molecule inhibitors, or the diagnostics for biomarkers associated with such small molecule inhibitors, from being commercialized.
Among other things, such delays may be caused by slow enrollment in clinical trials, patients dropping out of trials, length of time to achieve trial endpoints, additional time requirements for data analysis, IND preparation, discussions with the FDA or similar foreign regulatory authorities, an FDA or similar foreign regulatory authority request for additional preclinical or clinical data, or unexpected safety or manufacturing issues; 39 • manufacturing costs, formulation issues, pricing or reimbursement issues, or other factors that may make our targeted therapeutic small molecule inhibitors uneconomical; and • proprietary rights of others and their competing products and technologies that may prevent our targeted therapeutic small molecule inhibitors, or the diagnostics for biomarkers associated with such small molecule inhibitors, from being commercialized.
Targeted therapeutics that appear promising in the early phases of development may fail to reach the market for several reasons, including: • research or preclinical studies may show our targeted small molecule inhibitors or antagonists to be less effective than desired or to have harmful or problematic side effects or toxicities; • failure to accurately identify, validate or develop clinically relevant biomarkers for our targeted therapeutic product candidates; 50 • clinical trial results may show our targeted therapeutic small molecule inhibitors to be less effective than expected based on preclinical studies (e.g., a clinical trial could fail to meet its primary endpoint(s)) or to have unacceptable side effects or toxicities; • failure to receive the necessary regulatory approvals or a delay in receiving such approvals.
Targeted therapeutics that appear promising in the early phases of development may fail to reach the market for several reasons, including: • research or preclinical studies may show our targeted small molecule inhibitors or antagonists to be less effective than desired or to have harmful or problematic side effects or toxicities; • failure to accurately identify, validate or develop clinically relevant biomarkers for our targeted therapeutic product candidates; • clinical trial results may show our targeted therapeutic small molecule inhibitors to be less effective than expected based on preclinical studies (e.g., a clinical trial could fail to meet its primary endpoint(s)) or to have unacceptable side effects or toxicities; • failure to receive the necessary regulatory approvals or a delay in receiving such approvals.
A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. federal civil and criminal false claims and civil monetary penalties laws, including the civil False Claims Act, which prohibit, among other things, including through civil whistleblower or qui tam actions, individuals or entities from knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the U.S. federal government.
A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; 80 • the U.S. federal civil and criminal false claims and civil monetary penalties laws, including the civil False Claims Act, which prohibit, among other things, including through civil whistleblower or qui tam actions, individuals or entities from knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the U.S. federal government.
A medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five 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 investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment, of such condition authorized for marketing in the EU, or if such a method exists, the product will be 61 of significant benefit to those affected by the condition.
A medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five 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 investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment, of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.
If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations.
If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare 81 programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations.
Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its stock ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards, or NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change taxable income may be limited.
Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its stock ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards (NOLs) and other pre-change tax attributes (such as research and development tax credits) to offset its post-change taxable income may be limited.
AEs in future clinical trials of our product candidates or in clinical trials of others developing similar products and the resulting publicity, as well as any other AEs in the field of synthetic lethality, or other products that are perceived to be similar to synthetic lethality, such as those related to gene therapy or gene editing, could result in a decrease in the perceived benefit of one or more of our programs, increased regulatory scrutiny, decreased confidence by patients and CROs in our product candidates, and less demand for any product that we may develop.
AEs in future clinical trials of our product candidates or in clinical trials of others developing similar products and the resulting publicity, as well as any other 43 AEs in the field of synthetic lethality, or other products that are perceived to be similar to synthetic lethality, such as those related to gene therapy or gene editing, could result in a decrease in the perceived benefit of one or more of our programs, increased regulatory scrutiny, decreased confidence by patients and CROs in our product candidates, and less demand for any product that we may develop.
Furthermore, if any of our product candidates are approved and contract manufacturers fail to deliver the required commercial quantities of finished product on a timely basis and at commercially reasonable prices, and we are unable to find one or more replacement manufacturers capable of production at a substantially equivalent cost, in substantially equivalent volumes and quality and on a timely basis, we would likely be unable to meet demand for our products and could lose potential revenue.
Furthermore, if any of our product candidates are approved and contract manufacturers fail to deliver the required commercial quantities of finished product on a timely basis and at 61 commercially reasonable prices, and we are unable to find one or more replacement manufacturers capable of production at a substantially equivalent cost, in substantially equivalent volumes and quality and on a timely basis, we would likely be unable to meet demand for our products and could lose potential revenue.
Even if any product candidate we develop were to receive marketing approval or be commercialized for use in combination with other existing therapies, we would continue to be subject to the risks that the FDA or similar regulatory authorities outside of the United States could revoke approval of the therapy used in combination with our product candidates or that safety, efficacy, manufacturing or supply issues could arise with these existing therapies.
Even if any product candidate we develop were to receive marketing approval or be commercialized for use in combination with other existing therapies, we would continue to be subject to the risks that the FDA or similar regulatory authorities 49 outside of the United States could revoke approval of the therapy used in combination with our product candidates or that safety, efficacy, manufacturing or supply issues could arise with these existing therapies.
Since we do not intend to pay dividends, your ability to receive a return on your investment will depend on any future appreciation in the market value of our common stock. There is no guarantee that our common stock will appreciate or even maintain the price at which our holders have purchased it. 103 Item 1B. Unre solved Staff Comments.
Since we do not intend to pay dividends, your ability to receive a return on your investment will depend on any future appreciation in the market value of our common stock. There is no guarantee that our common stock will appreciate or even maintain the price at which our holders have purchased it. Item 1B. Unre solved Staff Comments.
Misconduct by these 66 parties could include intentional, reckless and/or negligent conduct or other unauthorized activities that violate: the laws and regulations of the FDA and other similar regulatory bodies, including those laws that require the reporting of true, complete and accurate information to such regulatory bodies; manufacturing standards; U.S. federal and state healthcare fraud and abuse laws, data privacy and security laws and other similar non-U.S. laws; or laws that require the true, complete and accurate reporting of financial information or data.
Misconduct by these parties could include intentional, reckless and/or negligent conduct or other unauthorized activities that violate the laws and regulations of the FDA and other similar regulatory bodies, including those laws that require the reporting of true, complete and accurate information to such regulatory bodies; manufacturing standards; U.S. federal and state healthcare fraud and abuse laws, data privacy and security laws and other similar non-U.S. laws; or laws that require the true, complete and accurate reporting of financial information or data.
The costs to us to mitigate network security problems, bugs, viruses, worms, malicious software programs and security vulnerabilities could be significant, and while we have implemented security measures to protect our data security and information technology systems, our efforts to address these problems may not be successful, and these problems could result in unexpected interruptions, delays, cessation of service and other harm to our business and our competitive position.
The costs to us to mitigate network security problems, bugs, viruses, worms, malicious software programs and security vulnerabilities could be significant, and while we have implemented security measures to protect our data security and information technology systems, our efforts to address 85 these problems may not be successful, and these problems could result in unexpected interruptions, delays, cessation of service and other harm to our business and our competitive position.
The intellectual property laws and other statutory and contractual arrangements in the United States and other jurisdictions we depend upon may not provide sufficient protection in the future to prevent the infringement, use, violation or misappropriation of our patents, trademarks, data, technology and 78 other intellectual property rights and products by others, and may not provide an adequate remedy if our intellectual property rights are infringed, misappropriated or otherwise violated by others.
The intellectual property laws and other statutory and contractual arrangements in the United States and other jurisdictions we depend upon may not provide sufficient protection in the future to prevent the infringement, use, violation or misappropriation of our patents, trademarks, data, technology and other intellectual property rights and products by others, and may not provide an adequate remedy if our intellectual property rights are infringed, misappropriated or otherwise violated by others.
The determinable prevalence may vary depending on the source and quality of the underlying data and in 75 some cases, insufficient data or poorly curated data may impact our ability to accurately estimate the prevalence of our target patient populations for each indication and in the aggregate across multiple indications both in the clinical trial setting, as well as in the commercial setting, if our product is approved.
The determinable prevalence may vary depending on the source and quality of the underlying data and in some cases, insufficient data or poorly curated data may impact our ability to accurately estimate the prevalence of our target patient populations for each indication and in the aggregate across multiple indications both in the clinical trial setting, as well as in the commercial setting, if our product is approved.
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. Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans.
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. Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our development plans.
The enrollment of patients depends on many factors, including: • the patient eligibility and exclusion criteria defined in the protocol; • the size and nature of the patient population required for analysis of the clinical trial’s primary endpoints; • the proximity of patients to clinical trial sites; 55 • the design of the clinical trial; • the risk that enrolled patients will not complete a clinical trial; • our ability to recruit clinical trial investigators with the appropriate competencies and experience; • clinical trial investigators’ willingness to continue enrolling patients and patients’ willingness to complete protocol assessments during any public health outbreak, epidemic or pandemic; • clinicians’ and patients’ perceptions as to the safety of the product candidate; • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new therapies that may be approved for the indications we are investigating as well as any drugs under development; and • our ability to obtain and maintain patient consents.
The enrollment of patients depends on many factors, including: • the patient eligibility and exclusion criteria defined in the protocol; • the size and nature of the patient population required for analysis of the clinical trial’s primary endpoints; • the proximity of patients to clinical trial sites; • the design of the clinical trial; • the risk that enrolled patients will not complete a clinical trial; • our ability to recruit clinical trial investigators with the appropriate competencies and experience; • clinical trial investigators’ willingness to continue enrolling patients and patients’ willingness to complete protocol assessments during any public health outbreak, epidemic or pandemic; • clinicians’ and patients’ perceptions as to the safety of the product candidate; • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new therapies that may be approved for the indications we are investigating as well as any drugs under development; and 44 • our ability to obtain and maintain patient consents.
We believe that 63 while our precision medicine target and biomarker discovery platform and our scientific and technical know-how give us a competitive advantage in this space, competition from many sources remains. Our competitors include larger and better funded biopharmaceutical, biotechnological and oncology therapeutics companies, as well as universities and other research institutions.
We believe that while our precision medicine target and biomarker discovery platform and our scientific and technical know-how give us a competitive advantage in this space, competition from many sources remains. Our competitors include larger and better funded biopharmaceutical, biotechnological and oncology therapeutics companies, as well as universities and other research institutions.
In the future, we may also become dependent on other product candidates that we may develop or acquire; however, given the current stages of development for our product candidates, it may be several years, if at all, before we have demonstrated the safety and efficacy of a product candidate sufficient to support approval for commercialization.
In the future, we may also become dependent on other product candidates that we may develop or acquire; however, given the current stages of development for most of our product candidates, it may be several years, if at all, before we have demonstrated the safety and efficacy of a product candidate sufficient to support approval for commercialization.
Although we have obtained and intend to maintain product liability insurance covering our clinical trials, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.
Although we have obtained and intend to maintain product liability insurance covering our clinical trials, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our 66 insurance or that is in excess of the limits of our insurance coverage.
We attempt to distribute our technology, biology, execution and financing risks across a range of therapeutic classes, disease states, programs and technologies. Due to the significant resources required for the development of our broad portfolio of programs, and depending on our ability to access capital, we must make certain risk assessments and prioritize 67 development of certain product candidates.
We attempt to distribute our technology, biology, execution and financing risks across a range of therapeutic classes, disease states, programs and technologies. Due to the significant resources required for the development of our broad portfolio of programs, and depending on our ability to access capital, we must make certain risk assessments and prioritize development of certain product candidates.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find 59 alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we could lose at least part, and perhaps all, of the patent protection on an affected product candidate. Such a loss of patent protection would have a material adverse impact on our business, financial condition, results of operations and prospects.
If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we could lose at least part, and perhaps all, of the patent protection on an 74 affected product candidate. Such a loss of patent protection would have a material adverse impact on our business, financial condition, results of operations and prospects.
In markets outside of the United States and EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. On December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted.
In markets outside of the United States and EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. On December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment (HTA), amending Directive 2011/24/EU, was adopted.
In addition, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial 53 protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs or other foreign regulatory authorities or ethics committees for reexamination, which may impact the costs, timing or successful completion of a clinical trial.
In addition, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs or other foreign regulatory authorities or ethics committees for reexamination, which may impact the costs, timing or successful completion of a clinical trial.
Because from time to time we expect to rely on third parties in the development, manufacture, and distribution of our products and provision of our services, we must, at times, share trade secrets with them. 88 In addition, some courts inside and outside the United States are less willing or unwilling to protect trade secrets.
Because from time to time we expect to rely on third parties in the development, manufacture, and distribution of our products and provision of our services, we must, at times, share trade secrets with them. In addition, some courts inside and outside the United States are less willing or unwilling to protect trade secrets.
Multiple established companies have been involved with research and development in synthetic lethality, such as AstraZeneca (Lynparza), Pfizer (Talzenna), GSK (Zejula) and Roche. Additionally, several other early-stage companies are developing synthetic lethality therapeutics, including 858 Therapeutics, Artios, Breakpoint Therapeutics, Eikon, FoRx Therapeutics, Repare Therapeutics, Ryvu Therapeutics, Tango, Vividion and Xpose.
Multiple established companies have been involved with research and development in synthetic lethality, such as AstraZeneca (Lynparza), Pfizer (Talzenna), GSK (Zejula) and Roche. Additionally, several other early-stage companies are developing synthetic lethality therapeutics, including 858 Therapeutics, 53 Artios, Breakpoint Therapeutics, Eikon, FoRx Therapeutics, Repare Therapeutics, Ryvu Therapeutics, Tango, Vividion, and Xpose.
Therefore, these patents and patent applications may not be prosecuted, maintained and/or enforced in a manner consistent with the best 79 interests of our business. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
Therefore, these patents and patent applications may not be prosecuted, maintained and/or enforced in a manner consistent with the best interests of our business. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded if we were to prevail may not be commercially meaningful. If we initiate 80 lawsuits to protect or enforce our patents, or litigate against third-party claims, such proceedings would be expensive and would divert the attention of our management and technical personnel.
We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded if we were to prevail may not be commercially meaningful. If we initiate lawsuits to protect or enforce our patents, or litigate against third-party claims, such proceedings would be expensive and would divert the attention of our management and technical personnel.
Outside the United States, an increasing number of laws, regulations, and industry standards apply to data privacy and security. For example, in Europe, the European Union General Data Protection Regulation, or GDPR, went into effect in May 2018, implementing more stringent requirements in relation to our use of personal data.
Outside the United States, an increasing number of laws, regulations, and industry standards apply to data privacy and security. For example, in Europe, the European Union General Data Protection Regulation (GDPR) went into effect in May 2018, implementing more stringent requirements in relation to our use of personal data.
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 50 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.
Data analytics and information from databases that we rely on for identifying or validating some of our biomarker-target relationships may not accurately reflect potential patient populations. Potential biomarkers, even if validated preclinically, may not be functionally effective or validated in human clinical trials.
Data analytics and information from databases that we rely on for 46 identifying or validating some of our biomarker-target relationships may not accurately reflect potential patient populations. Potential biomarkers, even if validated preclinically, may not be functionally effective or validated in human clinical trials.
Even if we receive accelerated approval from the FDA, if our confirmatory trials do not verify clinical benefit, or if we do not comply with rigorous post-marketing requirements, the FDA may seek to withdraw any accelerated approval we have obtained. We may in the future seek accelerated approval for our one or more of our product candidates.
Even if we receive accelerated approval from the FDA, if our confirmatory trials do not verify clinical benefit, or if we do not comply with rigorous post-marketing requirements, the FDA may seek to withdraw any accelerated approval we have obtained. 51 We may in the future seek accelerated approval for our one or more of our product candidates.
There is no assurance that any of these increases in scale, expansion of personnel, equipment, software and computing capacities, or process enhancements will be successfully implemented, or that we will have adequate space in our laboratory facilities to accommodate such required expansion. We currently have no sales organization.
There is no assurance that any of these increases in scale, expansion of personnel, equipment, software and computing capacities, or process enhancements will be successfully implemented, or that we will have adequate space in our laboratory facilities to accommodate such required expansion. 54 We currently have no sales organization.
Therefore, the IVDR applies since May 26, 2022 58 but there is a tiered system extending the grace period for many in vitro diagnostic medical devices (depending on their risk classification) before they have to be fully compliant with the Regulation.
Therefore, the IVDR applies since May 26, 2022 but there is a tiered system extending the grace period for many in vitro diagnostic medical devices (depending on their risk classification) before they have to be fully compliant with the Regulation.
We employ reputable professionals and rely on such third parties to help us comply with these requirements and effect payment of these fees with respect to the patents and patent applications that we own, and if we license intellectual property we may have to rely upon our licensors to comply with these requirements and effect payment of these fees with respect to any patents and patent applications that we license.
We employ reputable professionals and rely on such third parties to help us comply with these requirements and effect payment of these fees with respect to the patents and patent applications that we own, and if we license intellectual property we may have to rely upon our licensors to comply with these requirements and effect payment of these fees with 88 respect to any patents and patent applications that we license.
Some adverse effects of our product candidates will not be uncovered until a significantly larger number of patients are exposed to the product candidate. Further, any clinical trials may not be sufficient to determine the effect and safety consequences of taking our product candidates over a multi-year period.
Some adverse effects of our product candidates may not be uncovered until a significantly larger number of patients are exposed to the product candidate. Further, any clinical trials may not be sufficient to determine the effect and safety consequences of taking our product candidates over a multi-year period.
If we seek to acquire or license additional intellectual property rights, we may face substantial competition from a number of more established companies, some of which have acknowledged strategies to license or acquire products, and many of which have more institutional experience and greater financial and other resources than we have.
If we seek to acquire or license additional intellectual property rights, we may face substantial competition from a number of more established companies, some of which have acknowledged strategies to license or acquire products, and many of which have 86 more institutional experience and greater financial and other resources than we have.
As a public company, we are subject to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, and the related rules of the SEC, which generally require our management and independent registered public accounting firm to report on the effectiveness of our internal control over financial reporting.
As a public company, we are subject to Section 404 of the Sarbanes-Oxley Act of 2002 (Section 404) and the related rules of the SEC, which generally require our management and independent registered public accounting firm to report on the effectiveness of our internal control over financial reporting.
Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to our management team. We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property rights.
Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to our management team. 75 We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property rights.
In the future, we may seek to enter into additional collaboration arrangements for the development or commercialization of certain of our product candidates or diagnostics for biomarkers associated with our product candidates. To the extent that we 73 decide to enter into additional collaboration agreements in the future, we may face significant competition in seeking appropriate collaborators.
In the future, we may seek to enter into additional collaboration arrangements for the development or commercialization of certain of our product candidates or diagnostics for biomarkers associated with our product candidates. To the extent that we decide to enter into additional collaboration agreements in the future, we may face significant competition in seeking appropriate collaborators.
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited. 101 We have incurred substantial losses during our history and do not expect to become profitable in the near future, and we may never achieve profitability.
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited. We have incurred substantial losses during our history and do not expect to become profitable in the near future, and we may never achieve profitability.
Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies. To date, we have primarily financed our operations through the sale of equity securities and payments received under our collaboration agreements.
Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies. To date, we have primarily financed our operations through the sale of equity securities and payments received under our collaboration and licensing agreements.
We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which, particularly when taken together with our lack of earthquake insurance, could have a material adverse effect on our business.
We may incur substantial expenses as a result of the limited nature of our disaster recovery and business 57 continuity plans, which, particularly when taken together with our lack of earthquake insurance, could have a material adverse effect on our business.
Any performance failure on the part of our suppliers could delay the development and 72 potential commercialization of our product candidates, including limiting supplies necessary for clinical trials and regulatory approvals, which would have a material adverse effect on our business.
Any performance failure on the part of our suppliers could delay the development and potential commercialization of our product candidates, including limiting supplies necessary for clinical trials and regulatory approvals, which would have a material adverse effect on our business.
A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only those claims covering such approved drug product, a method for using it or a method for 81 manufacturing it may be extended.
A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only those claims covering such approved drug product, a method for using it or a method for manufacturing it may be extended.
In addition, some of our 82 agreements with our licensors require us to obtain consent from the licensor before we can enforce patent rights, and our licensor may withhold such consent or may not provide it on a timely basis.
In addition, some of our agreements with our licensors require us to obtain consent from the licensor before we can enforce patent rights, and our licensor may withhold such consent or may not provide it on a timely basis.
Even if we believe such claims are without merit, we cannot predict whether we would prevail in any such actions or that any license required under any of these patents would be made available on commercially acceptable terms, if at all.
Even if we believe such claims are without merit, we cannot predict whether we would prevail in any such actions or that any license required under any of these patents would be made available on commercially 73 acceptable terms, if at all.
If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our 86 common stock. Any of the foregoing could harm our business, financial condition, results of operations and prospects.
If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our common stock. Any of the foregoing could harm our business, financial condition, results of operations and prospects.
On July 10, 2023, the European Commission adopted its Adequacy Decision in relation to the new EU-US Data Privacy Framework, or the DPF, rendering the DPF effective as a GDPR transfer mechanism to U.S. entities self-certified under the DPF.
On July 10, 2023, the European Commission adopted its Adequacy Decision in relation to the new EU-US Data Privacy Framework, (the DPF), rendering the DPF effective as a GDPR transfer mechanism to U.S. entities self-certified under the DPF.
For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, was enacted, which substantially changed the way healthcare is financed by both governmental and private payors.
For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively the ACA) was enacted, which substantially changed the way healthcare is financed by both governmental and private payors.
Our stock currently trades on the Nasdaq Global Select Market, but we can provide no assurance that we will be able to maintain an active trading market on the Nasdaq Global Select Market or any other exchange in the future.
Our stock currently trades on the Nasdaq Global Select Market, but we can provide no assurance that we will be able to maintain an 84 active trading market on the Nasdaq Global Select Market or any other exchange in the future.
In contrast, in the event of an adverse safety issue, clinical hold, or other adverse finding in one or more indications being tested, such event 54 could adversely affect our trials in the other indications and may delay or prevent completion of the clinical trials.
In contrast, in the event of an adverse safety issue, clinical hold, or other adverse finding in one or more indications being tested, such event could adversely affect our trials in the other indications and may delay or prevent completion of the clinical trials.
Foreign regulatory authorities may require a similar demonstration before we can obtain approval to commercialize a product candidate abroad. Results from preclinical 59 studies and clinical trials can be interpreted in different ways.
Foreign regulatory authorities may require a similar demonstration before we can obtain approval to commercialize a product candidate abroad. Results from preclinical studies and clinical trials can be interpreted in different ways.
To prevent infringement or unauthorized use, we may be required to file lawsuits or initiate other proceedings to protect or enforce our patents or other intellectual property 85 rights, which can be expensive, time-consuming and unsuccessful.
To prevent infringement or unauthorized use, we may be required to file lawsuits or initiate other proceedings to protect or enforce our patents or other intellectual property rights, which can be expensive, time-consuming and unsuccessful.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents once obtained. Depending on decisions by the U.S.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the 87 value of patents once obtained. Depending on decisions by the U.S.
Such resolution could narrow what we believe 83 to be the scope of our rights to the relevant intellectual property or technology, increase what we believe to be our financial or other obligations under the relevant agreement or decrease the third-party’s financial or other obligations under the relevant agreement.
Such resolution could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, increase what we believe to be our financial or other obligations under the relevant agreement or decrease the third-party’s financial or other obligations under the relevant agreement.
As the biotechnology industry expands and more patents are issued, the risk increases that our product candidates may be subject to claims of infringement of the patent rights of third parties.
As the biotechnology industry expands and more patents are issued, the risk increases that our product candidates may be subject to claims of infringement of the patent rights of third 72 parties.
If any of these strategic collaborators delay or fail to supply their compound in support of these combination trials, fail to sponsor or appropriately conduct the combination trial (in the case of Amgen), or we fail to reach an agreement with any of these strategic collaborators for the continued supply of their compound beyond the terms of the current supply agreements, the development programs as pertaining to these combinations may be significantly delayed, and our development costs may increase.
If any of these strategic collaborators delay or fail to supply their compound in support of these combination trials, fail to sponsor or appropriately conduct the combination trial, or we fail to reach an agreement with any of these strategic collaborators for the continued supply of their compound beyond the terms of the current supply agreements, the development programs as pertaining to these combinations may be significantly delayed, and our development costs may increase.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeAndres Briseno, our SVP, Head of Finance and Investor Relations and, Douglas Snyder, our Senior Vice President, General Counsel, are primarily responsible for assessing and managing our material risks from cybersecurity threats. Mr. Briseno and Mr. Snyder have primary responsibility for our overall cybersecurity risk management program and supervises both our internal cybersecurity personnel and our retained external cybersecurity consultants.
Biggest changeSnyder have primary responsibility for our overall cybersecurity risk management program and supervise both our internal cybersecurity personnel and our retained external cybersecurity consultants. Mr.
Security breaches, loss of data or financial assets, and other disruptions could compromise sensitive information related to our business or prevent us from accessing critical information and expose us to liability.” Cybersecurity Governance Our board of directors considers cybersecurity risk as part of its risk oversight function and has delegated to the Audit Committee, or the Committee, oversight of cybersecurity risks, including oversight of management’s implementation of our cybersecurity risk management program.
Security breaches, loss of data or financial assets, and other disruptions could compromise sensitive information related to our business or prevent us from accessing critical information and expose us to liability.” Cybersecurity Governance Our board of directors considers cybersecurity risk as part of its risk oversight function and has delegated to the Audit Committee (the Committee) oversight of cybersecurity risks, including oversight of management’s implementation of our cybersecurity risk management program.
Our management team takes steps to stay informed about and monitor efforts to prevent, detect, mitigate, and remediate cybersecurity risks and incidents through various means, which may include briefings from internal security personnel; threat intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in the information technology environment.
Our management team takes steps to stay informed about and monitor efforts to prevent, detect, mitigate, and remediate cybersecurity risks and incidents through various means, which may include briefings from internal security personnel; threat 93 intelligence and other information obtained from governmental, public or private sources, including external consultants engaged by us; and alerts and reports produced by security tools deployed in the information technology environment.
Snyder has served in a number of significant leadership roles in various companies in the healthcare industry, and provided an oversight to legal and compliance teams with his broad legal background. Prior to joining our company, Mr. Snyder served in senior leadership and operations roles across healthcare field, including biotechnology, pharmaceuticals and the FDA .
Snyder has served in a number of significant leadership roles in various companies in the healthcare industry, and provided oversight to legal and compliance teams with his broad legal background. Prior to joining our company, Mr. Snyder served in senior leadership and operations roles across the healthcare field, including biotechnology, pharmaceuticals and the FDA .
In addition, management updates the Committee where it deems appropriate, regarding any cybersecurity incidents it considers to be significant or potentially significant. 104 The Committee reports to our full board of directors regarding its activities, including those related to cybersecurity. The full board of directors also receives briefings from management on our cybersecurity risk management program.
In addition, management updates the Committee where it deems appropriate, regarding any cybersecurity incidents it considers to be significant or potentially significant. The Committee reports to our full board of directors regarding its activities, including those related to cybersecurity. The full board of directors also receives briefings from management on our cybersecurity risk management program.
Key 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; • a documented set of cybersecurity policies and procedures that specifies the manner in which security controls are implemented; • the use of external service providers, where appropriate, to assess, test or otherwise assist with aspects of our security processes ; • cybersecurity awareness training of our employees, including incident response personnel, and senior management; • a cybersecurity incident response plan that includes procedures for responding to cybersecurity incidents; and • a third-party risk management process for key service providers based on our assessment of their criticality to our operations and respective risk profile,, suppliers, and vendors who have access to our critical systems and information.
Key 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; 92 • a security team principally responsible for managing (1) our cybersecurity risk assessment processes, (2) our security controls, and (3) our response to cybersecurity incidents; • a documented set of cybersecurity policies and procedures that specifies the manner in which security controls are implemented; • the use of external service providers, where appropriate, to assess, test or otherwise assist with aspects of our security processes ; • periodic and role-based cybersecurity awareness training of our employees, including incident response personnel and senior management; • a cybersecurity incident response plan that includes procedures for responding to cybersecurity incidents, including escalation to senior management for evaluation of potential materiality and related disclosure obligations; and • a third-party risk management process for key service providers based on our assessment of their criticality to our operations and respective risk profile, suppliers, and vendors who have access to our critical systems and information.
Mr. Briseno has served in a number of significant leadership roles at our company since 2016, including oversight of investor relations, business operations and corporate developments, and was appointed as SVP, Head of Finance and Investor Relations in 2023. Mr.
Briseno has served in a number of significant leadership roles at our company since 2016, including oversight of investor relations, business operations and corporate developments, and was appointed as SVP, Head of Finance and Investor Relations in 2023, and Chief Accounting Officer in 2025. Mr.
Item 1C. Cybersecurity. Cybersecurity Risk Management and Strategy We have developed and implemented a cybersecurity risk management program intended to protect the confidentiality, integrity, and availability of our critical systems and information. We design and assess our program based on the National Institute of Standards and Technology Cybersecurity Framework (NIST CSF).
Item 1C. Cybersecurity. Cybersecurity Risk Management and Strategy We have developed and implemented a cybersecurity risk management program intended to protect the confidentiality, integrity, and availability of our critical systems and information. We design and assess our program based on the National Institute of Standards and Technology Cybersecurity Framework (NIST CSF v1.1, update to v2.0 planned).
Board members receive presentations on cybersecurity topics from our Senior Vice President, or SVP, Head of Finance and Investor Relations, Senior Vice President, General Counsel, internal security staff and external experts as part of the board of directors’ continuing education on topics that impact public companies.
Board members receive presentations on cybersecurity topics from our Chief Accounting Officer, Chief Legal Officer, internal security staff and external experts as part of the board of directors’ continuing education on topics that impact public companies.
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Andres Ruiz Briseno, our Chief Accounting Officer and Douglas Snyder, our Chief Legal Officer, are primarily responsible for assessing and managing our material risks from cybersecurity threats. Day-to-day operational cybersecurity activities are executed by internal security personnel and external specialists under management oversight. Mr. Briseno and Mr.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeThe amendment to the lease term commenced in January 2025. Our lease at 7000 Shoreline Court, South San Francisco, California, expired in September 2024. In November 2023, we entered into a lease agreement for approximately 5,700 square feet of space at 11710 El Camino Real, San Diego, California for corporate office space.
Biggest changeIn November 2023, we entered into a lease agreement for approximately 5,700 square feet of space at 11710 El Camino Real, San Diego, California for corporate office space. The lease commenced in December 2023 and expires in March 2028. We have an option to renew the lease for three years.
To meet the future needs of our business, we may lease additional or alternate space, and we believe suitable additional or alternative space will be available in the future on commercially reasonable terms.
We believe our existing facilities are sufficient for our needs for the foreseeable future. To meet the future needs of our business, we may lease additional or alternate space, and we believe suitable additional or alternative space will be available in the future on commercially reasonable terms.
The lease term is 120 months, and we have an option to extend the lease term for a total of two consecutive five-year periods. The lease commenced in August 2024. In May 2024, we amended our 5000 Shoreline Court facility lease agreement to expand the size of the original premises by adding approximately 11,321 rentable square feet of additional space.
The lease term is 120 months, and we have an option to extend the lease term for a total of two consecutive five-year periods. This lease agreement commenced in August 2024.
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The lease commenced in December 2023 and expires in March 2028. We have an option to renew the lease for three years. We believe our existing facilities are sufficient for our needs for the foreseeable future.
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In May 2024, we amended our 5000 Shoreline Court facility lease agreement to expand the size of the original premises by adding approximately 11,321 rentable square feet of additional space. The amendment to the lease term commenced in January 2025. Our lease at 7000 Shoreline Court, South San Francisco, California, expired in September 2024.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeRegardless of outcome, litigation can have an adverse impact on our business, financial condition, results of operations and prospects because of defense and settlement costs, diversion of management resources and other factors. Item 4. Mine S afety Disclosures. Not applicable. 105 PART II
Biggest changeRegardless of outcome, litigation can have an adverse impact on our business, financial condition, results of operations and prospects because of defense and settlement costs, diversion of management resources and other factors. Item 4. Mine S afety Disclosures. Not applicable. 94 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock trades on the Nasdaq Global Select Market under the symbol “IDYA.” Stockholders As of February 14, 2025, we had 8 record holders of our common stock.
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock trades on the Nasdaq Global Select Market under the symbol “IDYA.” Stockholders As of February 13, 2026, we had 8 record holders of our common stock.
Securities Authorized for Issuance under Equity Compensation Plans Information about our equity compensation plans is incorporated by reference to Item 12 of Part III of this Annual Report on Form 10-K. Sale of Unregistered Securities None. Use of Proceeds from the Sale of Registered Securities Not applicable. Issuer Purchases of Equity Securities None. Ite m 6. Reserved 106
Securities Authorized for Issuance under Equity Compensation Plans Information about our equity compensation plans is incorporated by reference to Item 12 of Part III of this Annual Report on Form 10-K. Sale of Unregistered Securities None. Use of Proceeds from the Sale of Registered Securities Not applicable. Issuer Purchases of Equity Securities None. Ite m 6. Reserved 95

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe net change in our operating assets and liabilities consisted primarily of decreases of $13.8 million in contract liabilities due to revenue recognized under the GSK Collaboration Agreement, $2.0 million in prepaid and other assets, and $1.9 million in lease liabilities, partially offset by $1.6 million accrued and other liabilities due to CRO fees in support of 117 research and manufacturing activities, $2.6 million in accounts payable, and $0.2 million in accounts receivable from GSK for estimated program costs under the GSK Collaboration Agreement.
Biggest changeThe net change in our operating assets and liabilities consisted primarily of cash inflows resulting from a $2.6 million increase in lease liabilities, $2.7 million increase in accounts payable and $10.4 million increase in accrued and other liabilities due to fees paid to CROs, CMOs and consultants in support of research and manufacturing activities, partially offset by cash outflows resulting from a $7.8 million increase in prepaid and other assets and $6.0 million increase in contract assets related to the Servier License Agreement.
From January 1, 2024 through January 17, 2024, we sold an aggregate of 6,115,516 shares of our common stock for aggregate net proceeds of $215.9 million at a weighted average sales price of approximately $36.39 per share under the at-the-market offering pursuant to the June 2023 Sales Agreement with Jefferies as sales agent.
From January 1, 2024 through January 17, 2024, pursuant to the June 2023 Sales Agreement, we sold an aggregate of 6,115,516 shares of our common stock for aggregate net proceeds of $215.9 million at a weighted average sales price of approximately $36.39 per share under the at-the-market offering pursuant to the June 2023 Sales Agreement with Jefferies as sales agent.
On June 26, 2023, we also entered into an Open Market Sales Agreement, or the June 2023 Sales Agreement, with Jefferies LLC, or Jefferies, relating to an at-the-market offering program under which we may offer and sell, from time to time at our sole discretion, shares of our common stock, par value $0.0001 per share, having aggregate gross proceeds of up to $250.0 million through Jefferies as sales agent.
On June 26, 2023, we also entered into an Open Market Sales Agreement (the June 2023 Sales Agreement) with Jefferies LLC (Jefferies) relating to an at-the-market offering program under which we may offer and sell, from time to time at our sole discretion, shares of our common stock, par value $0.0001 per share, having aggregate gross proceeds of up to $250.0 million through Jefferies as sales agent.
On January 19, 2024, we entered into a new Open Market Sales Agreement, or the January 2024 Sales Agreement, with Jefferies, relating to an at-the-market offering program under which we may offer and sell, from time to time at our sole discretion, shares of common stock having aggregate gross proceeds of up to $350.0 million through Jefferies as sales agent.
On January 19, 2024, we entered into a new Open Market Sales Agreement (the January 2024 Sales Agreement) with Jefferies, relating to an at-the-market offering program under which we may offer and sell, from time to time at our sole discretion, shares of common stock having aggregate gross proceeds of up to $350.0 million through Jefferies as sales agent.
Payments made to CMOs and CROs under these arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered. 113 Costs of certain activities, such as preclinical studies, are generally recognized based on an evaluation of the progress to completion of specific tasks.
Payments made to CMOs and CROs under these arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered. Costs of certain activities, such as preclinical studies, are generally recognized based on an evaluation of the progress to completion of specific tasks.
For example, if the FDA or other regulatory authorities were to require us to conduct clinical trials beyond those that we currently anticipate, or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development.
For example, if the FDA or other regulatory authorities were to require us to conduct clinical trials beyond those that we currently anticipate, or if we experience significant delays in enrollment in any of our clinical trials, we 99 could be required to expend significant additional financial resources and time on the completion of clinical development.
Prospectus Supplement - At-the-Market Facility On June 26, 2023, we filed a new Registration Statement on Form S-3 (File No. 333- 272936) under the Securities Act as an automatic shelf registration statement as a “well-known seasoned issuer,” as defined in Rule 405 under the Securities Act.
Prospectus Supplement - At-the-Market Facility On June 26, 2023, we filed a Registration Statement on Form S-3 (File No. 333- 272936) under the Securities Act as an automatic shelf registration statement as a “well-known seasoned issuer,” as defined in Rule 405 under the Securities Act.
The estimated costs of research and development provided, but not yet invoiced, are included in accrued liabilities on the balance sheet. If the actual timing of the performance of services or the level of effort varies from the original estimates, we will adjust the accrual accordingly.
The estimated costs of research and development provided, but not yet invoiced, are included in accrued liabilities on our balance sheet. If the actual timing of the performance of services or the level of effort varies from the original estimates, we will adjust the accrual accordingly.
Furthermore, our operating plans may change in the future, and we will continue to require additional capital to meet operational needs and capital requirements associated with such operating plans. If we raise additional funds by issuing equity securities, our stockholders may experience dilution.
Furthermore, our 102 operating plans may change in the future, and we will continue to require additional capital to meet operational needs and capital requirements associated with such operating plans. If we raise additional funds by issuing equity securities, our stockholders may experience dilution.
Our non-cash charges consisted of $34.7 million in stock-based compensation, $2.4 million in depreciation and $1.4 million of the amortization of right of use assets, partially offset by $23.2 million accretion of discounts on marketable securities.
Our non-cash charges consisted of $34.7 million in stock-based compensation, $2.4 million in depreciation and $1.4 103 million of the amortization of right of use assets, partially offset by $23.2 million accretion of discounts on marketable securities.
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. For more detail on our critical accounting policies, refer to Note 2 to the financial statements appearing elsewhere in this Annual Report on Form 10-K.
We believe that the accounting policies are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates. For more detail on our critical accounting policies, refer to Note 2 to the financial statements appearing elsewhere in this Annual Report on Form 10-K.
Critical Accounting Policies and Estimates Our financial statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP.
Critical Accounting Policies and Estimates Our financial statements have been prepared in accordance with U.S. generally accepted accounting principles (GAAP).
Cash Flows from Investing Activities Net cash used in investing activities was $502.6 million for the year ended December 31, 2024, which consisted primarily of $1.2 billion used to purchase marketable securities and $3.9 million used to purchase property and equipment, partially offset by $692.6 million provided by maturities of marketable securities.
Net cash used in investing activities was $502.6 million for the year ended December 31, 2024, which consisted primarily of $1.2 billion used to purchase marketable securities and $3.9 million used to purchase property and equipment, partially offset by $692.6 million provided by maturities of marketable securities.
We anticipate that our general and administrative expenses will increase, as a result of increased personnel costs, including salaries, benefits and stock-based compensation expense, patent costs for our product candidates, expanded infrastructure and higher consulting, legal and accounting services associated with maintaining compliance with our Nasdaq stock exchange listing and requirements of the Securities and Exchange Commission, or the SEC, investor relations costs and director and officer insurance policy premiums associated with being a public company.
We anticipate that our general and administrative expenses will increase, as a result of increased personnel costs, including salaries, benefits and stock-based compensation expense, patent costs for our product candidates, expanded infrastructure and higher consulting, legal and accounting services associated with maintaining compliance with our Nasdaq stock exchange listing and requirements of the SEC, investor relations costs and director and officer insurance policy premiums associated with being a public company.
Corporate Update We do not have any products approved for sale and have not generated any product revenue since inception. We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK.
Corporate Update 97 We do not have any products approved for sale and have not generated any product revenue since inception. We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK and Servier.
Cash Flows from Financing Activities Net cash provided by financing activities was $677.6 million for the year ended December 31, 2024, which consisted primarily of $274.4 million of net proceeds from our follow-on offering, $9.4 million of proceeds from issuance of pre-funded warrants, $379.9 million of proceeds from ATM offering, $12.5 million of proceeds from exercise of common stock options and $1.4 million of proceeds from ESPP purchase.
Net cash provided by financing activities was $677.6 million for the year ended December 31, 2024, which consisted primarily of $274.4 million of net proceeds from our follow-on offering, $9.4 million of proceeds from issuance of pre-funded warrants, $379.9 million of proceeds from ATM offering, $12.5 million of proceeds from exercise of common stock options and $1.4 million of proceeds from ESPP purchases.
Other Income Interest Income and Other Income, Net Interest income and other income, net consists primarily of interest income earned on our cash, cash equivalents and marketable securities. Results of Operations 114 A discussion regarding our financial condition and results of operations for fiscal year 2024 compared to fiscal year 2023 is presented below.
Other Income Interest Income and Other Income, Net Interest income and other income, net consists primarily of interest income earned on our cash, cash equivalents and marketable securities. Results of Operations A discussion regarding our financial condition and results of operations for fiscal year 2025 compared to fiscal year 2024 is presented below.
As of December 31, 2024, we had cash, cash equivalents and marketable securities of $1.1 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds. Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates.
As of December 31, 2025, we had cash, cash equivalents and marketable securities of approximately $1.05 billion, consisting primarily of money market funds, U.S. government securities, commercial paper and corporate bonds. Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates.
These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib, IDE397, IDE849, IDE275 (GSK959), IDE161, IDE705 (GSK 101), and consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities.
These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib, IDE397, IDE849, IDE161, IDE275, IDE705, IDE892, IDE034, and IDE574 and consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities.
A discussion regarding our financial condition and results of operations for fiscal year 2023 compared to fiscal year 2022 can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K filed with the SEC on February 20, 2024.
A discussion regarding our financial condition and results of operations for fiscal year 2024 compared to fiscal year 2023 can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K filed with the SEC on February 18, 2025.
Components of Operating Results Collaboration Revenues To date, we have not generated any revenue from product sales, and we do not expect to generate any revenue from product sales unless and until we are able to initiate a registrational clinical trial, obtain regulatory approval and commercialize one of our product candidates in the future.
Components of Operating Results Collaboration Revenues To date, we have not generated any revenue from product sales, and we do not expect to generate any revenue from product sales unless and until we are able to obtain regulatory approval and commercialize one of our product candidates in the future.
During the year ended December 31, 2024, pursuant to the January 2024 Sales Agreement, we sold an aggregate of 4,066,866 shares of our common stock for aggregate net proceeds of $164.0 million at a weighted average sales price of approximately $41.28 per share under the at-the-market offering pursuant to the January 2024 Sales Agreement with Jefferies as sales agent.
During the year ended December 31, 2024, pursuant to the January 2024 Sales Agreement, we sold an aggregate of 4,066,866 shares of our common stock for aggregate net proceeds of $164.0 million at a weighted average sales price of approximately $41.28 per share under the at-the-market offering pursuant to the January 2024 Sales Agreement with Jefferies as sales agent. 101 During the year ended December 31, 2025, we sold an aggregate of 984,000 shares of our common stock for aggregate net proceeds of $25.0 million at a weighted average sales price of approximately $26.00 per share under the at-the-market offering pursuant to the January 2024 Sales Agreement with Jefferies as sales agent.
As of January 6, 2025, approximately $156.6 million of common stock remained available to be sold under the ATM facility. We may cancel our at-the-market program at any time upon written notice, pursuant to its terms. 2024 July Public Offering and Sale of IDEAYA Common Stock On July 11, 2024, we completed an underwritten public follow-on offering.
As of December 31, 2025, approximately $156.6 million of common stock remained available to be sold pursuant to the January 2024 Sales Agreement. We may cancel our at-the-market program at any time upon written notice, pursuant to its terms. 2024 July Public Offering and Sale of IDEAYA Common Stock On July 11, 2024, we completed an underwritten public follow-on offering.
Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $113.0 million, adjusted for net non-cash charges of $10.9 million and changes in net operating assets and liabilities of $13.2 million.
Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $113.7 million, adjusted for net non-cash charges of $40.7 million and changes in net operating assets and liabilities of $1.9 million.
For the years ended December 31, 2024 and December 31, 2023, we had net losses of $274.5 million and $113.0 million, respectively, and we expect to incur substantial additional losses in future periods. As of December 31, 2024, we had an accumulated deficit of $622.8 million.
For the years ended December 31, 2025 and 2024, we had net losses of $113.7 million and $274.5 million, respectively, and we expect to incur substantial additional losses in future periods. As of December 31, 2025, we had an accumulated deficit of $736.5 million.
The increase in general and administrative expenses was primarily due to increases of $7.0 million in personnel-related expenses, including salaries, benefits and stock-based compensation and $4.0 million in consulting and legal services.
The increase in general and administrative expenses was primarily due to increases of $11.3 million in personnel-related expenses, including salaries, benefits and stock-based compensation and $12.7 million in consulting and legal services related to company growth.
Our revenue consists exclusively of collaboration revenue under the GSK Collaboration Agreement, including amounts that are recognized related to previously received upfront payments and amounts due and payable to us for research and development services.
Our revenue consists exclusively of collaboration revenue under the Servier License Agreement for the year ended December 31, 2025 and the GSK Collaboration Agreement for the year ended December 31, 2024, including amounts that are recognized related to previously received upfront payments, development and regulatory milestone payments and amounts due and payable to us for research and development services.
Please also see the section of this Annual Report on Form 10-K titled “Note Regarding Forward-Looking Statements.” Overview We are a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics.
Please also see the section of this Annual Report on Form 10-K titled “Note Regarding Forward-Looking Statements.” Overview We are a precision medicine oncology company committed to the discovery, development and commercialization of transformative therapies for cancer.
Our non-cash charges consisted of $18.5 million in stock-based compensation, and $2.5 million in depreciation and amortization of right of use assets of $1.5 million, partially offset by $11.6 million accretion of discounts on marketable securities.
Our non-cash charges consisted of $46.1 million in stock-based compensation, $2.7 million in depreciation and $1.9 million of the amortization of right of use assets, partially offset by $10.0 million accretion of discounts on marketable securities.
Summary Statement of Cash Flows The following table sets forth the primary sources and uses of cash, cash equivalents, and restricted cash for each of the periods presented below (in thousands): Year Ended December 31, 2024 2023 Net cash (used in) provided by: Operating activities $ (247,584 ) $ (115,224 ) Investing activities (502,559 ) (158,456 ) Financing activities 677,551 362,717 Net (decrease) increase in cash, cash equivalents and restricted cash $ (72,592 ) $ 89,037 Cash Flows from Operating Activities Net cash used in operating activities was $247.6 million for the year ended December 31, 2024.
Summary Statement of Cash Flows The following table sets forth the primary sources and uses of cash, cash equivalents, and restricted cash for each of the periods presented below (in thousands): Year Ended December 31, 2025 2024 Net cash (used in) provided by: Operating activities $ (71,098 ) $ (247,584 ) Investing activities 69,976 (502,559 ) Financing activities 29,779 677,551 Net increase (decrease) in cash, cash equivalents and restricted cash $ 28,657 $ (72,592 ) Cash Flows from Operating Activities Net cash used in operating activities was $71.1 million for the year ended December 31, 2025.
Net cash used in operating activities was $115.2 million for the year ended December 31, 2023.
Net cash used in operating activities was $247.6 million for the year ended December 31, 2024.
Net cash used in investing activities was $158.5 million for the year ended December 31, 2023, which consisted primarily of $596.0 million used to purchase marketable securities and $2.4 million used to purchase property and equipment, partially offset by $439.9 million provided by maturities of marketable securities.
Cash Flows from Investing Activities Net cash provided by investing activities was $70.0 million for the year ended December 31, 2025, which consisted primarily of $680.2 million provided by maturities of marketable securities, offset by $607.9 billion used to purchase marketable securities and $2.4 million used to purchase property and equipment.
We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least twelve months from the date of the issuance of our Annual Report on Form 10-K filed February 18, 2025 These funds will support our efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.
We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least twelve months from the date of the issuance of our Annual Report on Form 10-K filed on February 17, 2026.
The increase in research and development expenses was primarily due to $75.0 million upfront payment under the Hengrui Pharma License Agreement for IDE849, $6.5 million in upfront and option exercise fees under the Biocytogen Option and License Agreement for IDE034, increases of $64.1 million in fees paid to CROs, CMOs and consultants related to the advancement of our lead product candidates through preclinical and clinical studies, $15.6 million in personnel-related expenses, including salaries, benefits and stock-based compensation, to support our growth, and $4.0 million in costs for laboratory supplies, facilities and information technology costs to support our research and development programs.
The increase in research and development expenses was primarily due to increases of $74.1 million in fees paid to CROs, CMOs and consultants related to the advancement of our lead product candidates through preclinical and clinical studies, $12.7 million in personnel-related expenses, including salaries, benefits and stock-based compensation, to support our growth, and $8.2 million in costs for laboratory supplies, facilities and information technology costs to support our research and development programs.
These contracts generally provide for termination following a certain period after notice, and therefore, we believe that our non-cancelable obligations under these agreements are not material. See Notes 5. Operating Leases, 6. Commitments and Contingencies, 7. Income Taxes and 10. Significant Agreements. Adequate additional funding may not be available to us on acceptable terms or at all.
These contracts generally provide for termination following a certain period after notice, and therefore, we believe that our non-cancelable obligations under these agreements are not material. For more information, see Note 5. Operating Leases, Note 6. Commitments and Contingencies, Note 7. Income Taxes and Note 10.
IDE251 - KAT6/7 inhibitor In December 2024, we announced the selection of IDE251, a potential first-in-class KAT6/7 inhibitor. IDE251 is an equipotent, highly selective, small molecule dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival.
Next Generation Therapies • IDE574 is a potential first-in-class, oral small molecule equipotent dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival.
If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of our product candidates.
If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of our product candidates. As of December 31, 2025, we had cash, cash equivalents and short-term and long-term marketable securities of approximately $1.05 billion.
As of December 31, 2024, we had cash, cash equivalents and marketable securities of $1.1 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds. Material Cash Requirements We have incurred net losses since our inception.
As of December 31, 2025, we had cash, cash equivalents and marketable securities of approximately $1.05 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds.
We are collaborating with Gilead Sciences, Inc., or Gilead, to clinically evaluate IDE397 in combination with Trodelvy (sacituzumab-govitecan-hziy), Gilead’s Trop-2 directed antibody drug conjugate, or ADC, in patients having MTAP-deletion UC, in our Phase 1 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement, or the Gilead CSCSA, with Gilead.
We are conducting a Phase 1/2 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement (CSCSA) with Gilead to evaluate IDE397 in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2 directed TOP1 ADC, in patients with MTAP-deletion urothelial cancer (UC), and non-small cell lung cancer (NSCLC).
Significant Agreements. Our net losses were $274.5 million and $113.0 million for the years ended December 31, 2024 and 2023, respectively. As of December 31, 2024, we had an accumulated deficit of $622.8 million.
For information about our specific program costs and expenses, see Note 10. Significant Agreements. Our net losses were $113.7 million and $274.5 million for the years ended December 31, 2025 and 2024, respectively. As of December 31, 2025, we had an accumulated deficit of $736.5 million.
General and Administrative Expenses General and administrative expenses increased by $11.0 million, or 39%, during the year ended December 31, 2024 compared to the year ended December 31, 2023.
Research and Development Expenses Research and development expenses increased by $20.0 million, or 7%, during the year ended December 31, 2025 compared to the year ended December 31, 2024.
The following table summarizes our external clinical development expenses by program: Year Ended December 31, 2024 2023 External clinical development expenses (1) : Darovasertib 55,335 $ 25,829 IDE397 (2) 16,629 11,985 IDE161 9,743 7,104 Personnel related and stock-based compensation 54,543 38,948 Other research and development expenses (3) : 158,423 45,642 Total research and development expenses $ 294,673 $ 129,508 (1) External clinical development expenses include manufacturing and clinical trial costs.
The following table summarizes our external clinical development expenses by program: Year Ended December 31, 2025 2024 External clinical development expenses (1) : Darovasertib $ 98,071 $ 55,335 IDE397 14,662 16,629 IDE161 7,598 9,743 IDE849 11,457 75,000 Personnel related and stock-based compensation 67,192 54,543 Other research and development expenses (2) 115,724 83,423 Total research and development expenses $ 314,704 $ 294,673 (1) External clinical development expenses include manufacturing and clinical trial costs.
Recent Accounting Pronouncements See the section titled “Summary of Significant Accounting Policies—Recent Accounting Pronouncements” in Note 2 to our financial statements included elsewhere in this Annual Report on Form 10-K for additional information. 120
Recent Accounting Pronouncements See the section titled “Summary of Significant Accounting Policies—Recent Accounting Pronouncements” in Note 2 to the financial statements included elsewhere in this Annual Report on Form 10-K for a description of recent accounting pronouncements that are applicable to our business and may potentially have an impact on our financial position and results of operations. 104
Pursuant to the offering, we received aggregate gross proceeds of approximately $201.3 million, before deducting underwriting discounts and commissions and other offering expenses, resulting in net proceeds of approximately $188.7 million, after deducting underwriting discounts and commissions and other offering expenses.
Pursuant to the offering, we received aggregate gross proceeds of approximately $302.4 million, before deducting underwriting discounts and commissions and other offering expenses, resulting in net proceeds of approximately $283.8 million, after deducting underwriting discounts and commissions and other offering expenses. Material Cash Requirements We have primarily incurred net losses since our inception.
Net cash provided by financing activities was $362.7 million for the year ended December 31, 2023, which consisted primarily of $281.2 million of net proceeds from our follow-on offering, $42.2 million of proceeds from issuance of pre-funded warrants, $28.6 million of proceeds from ATM offering, $9.6 million of proceeds from exercise of common stock options, and $1.2 million of proceeds from ESPP purchase.
Cash Flows from Financing Activities Net cash provided by financing activities was $29.8 million for the year ended December 31, 2025, which consisted primarily of $24.9 million of proceeds from ATM offering, $3.4 million of proceeds from exercise of common stock options and $1.5 million of proceeds from ESPP purchases.
Interest Income and Other Income, Net Interest income increased by $31.0 million, or 145%, during the year ended December 31, 2024 compared to the year ended December 31, 2023, primarily due to higher interest rates and investment balances. 115 Liquidity and Capital Resources; Plan of Operations Sources of Liquidity We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK.
Liquidity and Capital Resources; Plan of Operations Sources of Liquidity We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK and Servier.
We may also be required to sell or license to others rights to our product candidates in certain territories or indications that we would prefer to develop and commercialize ourselves. 116 In June 2023, we entered into a lease agreement for approximately 44,000 square feet of laboratory and office facilities at 5000 Shoreline Court, South San Francisco, California.
We may also be required to sell or license to others rights to our product candidates in certain territories or indications that we would prefer to develop and commercialize ourselves.
See the section of this Annual Report on Form 10-K titled “Part I, Item 1A. – Risk Factors” for additional risks associated with our substantial capital requirements. Off-Balance Sheet Arrangements We have not entered into any off-balance sheet arrangements as defined in the rules and regulations of the SEC.
Significant Agreements, each in the financial statements appearing elsewhere in this Annual Report on Form 10-K. Adequate additional funding may not be available to us on acceptable terms or at all. See the section of this Annual Report on Form 10-K titled “Part I, Item 1A. – Risk Factors” for additional risks associated with our substantial capital requirements.
Comparison of the Years Ended December 31, 2024 and December 31, 2023 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended December 31, 2024 2023 Change % Change Revenue Collaboration revenue $ 7,000 $ 23,385 $ (16,385 ) (70 %) Operating expenses Research and development 294,673 129,508 165,165 128 % General and administrative 39,302 28,306 10,996 39 % Total operating expenses 333,975 157,814 176,161 112 % Loss from operations (326,975 ) (134,429 ) (192,546 ) 143 % Other income Interest income and other income, net 52,498 21,468 31,030 145 % Net loss $ (274,477 ) $ (112,961 ) $ (161,516 ) 143 % Collaboration Revenue Collaboration revenue decreased by $16.4 million, or 70%, during the year ended December 31, 2024 compared to the year ended December 31, 2023.
Comparison of the Years Ended December 31, 2025 and December 31, 2024 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended December 31, 2025 2024 Change % Change Revenue Collaboration revenue $ 218,710 $ 7,000 $ 211,710 3,024% Operating expenses Research and development 314,704 294,673 20,031 7 % General and administrative 63,319 39,302 24,017 61 % Total operating expenses 378,023 333,975 44,048 13 % Loss from operations (159,313 ) (326,975 ) 167,662 51 % Other income Interest income and other income, net 45,615 52,498 (6,883 ) (13 %) Net loss $ (113,698 ) $ (274,477 ) $ 160,779 59 % Collaboration Revenue Collaboration revenue increased by $211.7 million, or 3,024%, during the year ended December 31, 2025 compared to the year ended December 31, 2024.
In October 2024, we earned a $7.0 million milestone payment for the IND clearance of IDE275 (GSK 959), a potential first-in-class WRN inhibitor. Research and Development Expenses Research and development expenses increased by $165.2 million, or 128%, during the year ended December 31, 2024 compared to the year ended December 31, 2023.
We also recognized revenue related to amounts allocated to the two research and development service milestones over time, as the underlying services are performed over the period through the completion of program development activities. 100 Pursuant to the GSK Collaboration Agreement, in October 2024, we earned a $7.0 million milestone payment for the IND clearance of IDE275 (GSK 959), a potential first-in-class WRN inhibitor.
We completed all performance obligations related to the upfront payment under the GSK Collaboration Agreement as of December 31, 2023 for the Pol Theta and WRN programs. Future collaboration revenue recognized under the GSK Collaboration Agreement is related to milestone payments as they are earned.
We completed all performance obligations under the GSK Collaboration Agreement as of December 31, 2023 for the Pol Theta and WRN programs. In December 2025, GSK notified us of its intention to terminate the Collaboration, Option and License Agreement, dated June 15, 2020, which will be effective 90 days following the date of GSK’s notice, or March 9, 2026.
In December 2024, we announced the recommendation of a move-forward dose and the completion of the Part 2a dose optimization for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the first-line, or 1L setting in patients with HLA-A2(-) MUM.
We are evaluating darovasertib in combination with crizotinib, Pfizer’s oral c-MET inhibitor, in a potentially registration-enabling, Phase 2/3 trial (OptimUM-02) for human leukocyte antigen-A*02:01 negative (HLA*A2(-)), patients with first line (1L) mUM. We expect to report topline data, including progression free survival (PFS) data, from this trial in the first quarter of 2026.
We are focusing substantially all of our resources on the development of our product candidates.
These expenses are primarily for services provided by external consultants, CMOs and CROs. (2) Other research and development expenses include manufacturing and clinical trial costs for preclinical and earlier clinical stage programs. These expenses are primarily for services provided by external consultants, CMOs and CROs. We are focusing substantially all of our resources on the development of our product candidates.
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Our approach integrates small molecule drug discovery with extensive capabilities in identifying and validating translational biomarkers to develop targeted therapies for select patient populations that are most likely to benefit from these targeted therapies. Our small molecule drug discovery expertise includes discovery and development of small molecule therapeutics.
Added
Our approach integrates expertise in small-molecule drug discovery, structural biology and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease. We have built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates (ADCs), for molecularly defined solid tumor indications.
Removed
We are applying these capabilities and approach to develop a robust pipeline in precision medicine oncology. Our clinical pipeline includes six potential first-in-class clinical-stage product candidates – darovasertib (PKC), IDE397 (MAT2A), IDE849(DLL3), IDE275 / GSK959 (Werner Helicase), IDE161 (PARG), and IDE705 / GSK101 (Pol Theta Helicase).
Added
Our clinical development strategy is to evaluate our product candidates in rational combinations, where appropriate, and earlier in the course of disease in the adjuvant and neoadjuvant settings, which we believe has the potential to maximize their impact.
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We own or control all commercial rights of three of these product candidates: darovasertib, IDE397, and IDE161, and own or control all commercial rights outside of greater China for IDE849.
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Our mission is to bring forth the next wave of precision oncology therapies that are more selective, more effective, and deeply personalized with the goal of altering the course of disease and improving clinical outcomes for patients with cancer. Our current clinical pipeline consists of nine potential first-in-class product candidates across four clinical focus areas, as described below.
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We are also advancing several development candidates, including IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor for which we are targeting an investigational new drug, or IND, filing in mid-year 2025; IDE034, a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload bispecific antibody drug conjugate, or BsADC, program for which we are targeting an IND filing in the second half of 2025; and IDE251, a potential first-in-class KAT6/7 dual inhibitor program for which we are targeting an IND filing in the second half of 2025.
Added
Darovasertib for Uveal Melanoma Darovasertib is an oral, potent and selective small molecule inhibitor of protein kinase C (PKC) and our most advanced clinical program. We are developing darovasertib for uveal melanoma (UM), a rare, aggressive form of ocular cancer in both the metastatic and pre-metastatic settings of UM, as described below. • Metastatic UM (mUM).
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We also have multiple earlier-stage preclinical programs. We have established selective, value-accretive collaborations with leading pharmaceutical companies to support our clinical development activities. Darovasertib – PKC Inhibitor Clinical Candidate in Uveal Melanoma Darovasertib (IDE196) is our most advanced clinical-stage product candidate, which we in-licensed from Novartis.
Added
The data from OptimUM-02 may enable an accelerated approval filing in the United States. In December 2025, we completed full enrollment of 437 patients in OptimUM-02, and plan to submit overall survival (OS) data from these patients, when available, to support a full approval filing in this indication.
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Darovasertib is a potent, selective small molecule inhibitor of protein kinase C, or PKC, which we are developing for genetically-defined cancers having GNAQ or GNA11 gene mutations. PKC is a protein kinase that functions downstream of the GTPases GNAQ and GNA11.
Added
We are also evaluating the combination of darovasertib and crizotinib in HLA*A2:01 positive (HLA*A2(+)), mUM patients in our ongoing, single-arm Phase 2 OptimUM-01 trial.
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We have enrolled over 230 patients as of February 7, 2025, and have opened multiple clinical sites, including international sites, in our potential registration-enabling Phase 2/3 clinical trial, designated as IDE196-002.
Added
We expect to complete enrollment of approximately 100 patients in this trial by the second quarter of 2026 with data used to support a potential future submission to the FDA to expand the labeled use for darovasertib and/or a national comprehensive cancer network (NCCN) compendia listing to enable use of the combination in these patients. • Neoadjuvant UM .
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The purpose of the clinical trial is to evaluate darovasertib in combination with crizotinib, Pfizer’s investigational cMET inhibitor, in patients having metastatic uveal melanoma, or MUM, with human leukocyte antigen-, or HLA-A*02:01 negative, or HLA-A2(-), serotype, as part of the second Clinical Trial Collaboration and Supply Agreement, or Second Pfizer Agreement, with Pfizer.
Added
We are also evaluating darovasertib as a monotherapy in the neoadjuvant setting of primary UM, where the goal of treatment is to prevent enucleation (surgical eye removal), preserve vision prior to and post-plaque brachytherapy and potentially delay or prevent progression to metastatic disease.
Removed
We are enrolling additional HLA-A*02:01 positive, or HLA-A2(+), patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001. We are targeting a median overall survival, or OS, readout from our Phase 2 clinical trial, designated as IDE196-001, in approximately 40 1L MUM patients in 2025.
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In 2025, we initiated a randomized Phase 3 trial of darovasertib in the neoadjuvant setting (OptimUM-10), which will enroll approximately 450 patients across two cohorts of plaque brachytherapy-eligible (PB) and enucleation-eligible (EN) patients. We plan to complete enrollment in this trial by the first half of 2027. • Adjuvant UM .
Removed
We have enrolled 95 patients as of December 31, 2024, in our Phase 2 clinical trial, designated as IDE196-009, evaluating darovasertib as single-agent neoadjuvant and adjuvant therapy in patients having primary uveal melanoma, or UM, with ongoing enrollment and multiple clinical sites open.
Added
We plan to initiate a global Phase 3 combination trial (OptimUM-11) of darovasertib and crizotinib in the adjuvant setting of primary UM in the first half of 2026. The trial is expected to enroll approximately 450 patients with high to medium-high risk of metastasis, randomized 1:1 to the combination of darovasertib and crizotinib or placebo.
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We are targeting a clinical data update in over 75 patients and regulatory update(s) in in the first half of 2025, including vision data in plaque brachytherapy patients. 107 In September 2024, we announced interim clinical data from the ongoing Phase 2 Company-sponsored trial and provided a regulatory update on a potential Phase 3 registration-enabling clinical trial in neoadjuvant UM patients based on a Type C meeting held with the U.S.
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The primary endpoint of this trial is relapse-free survival (RFS). 96 In August 2025, we entered into an exclusive license agreement with Les Laboratoires Servier (Servier), for the development and commercialization of darovasertib outside of the United States.
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Food and Drug Administration, or FDA. Based on the FDA meeting, we currently project approximately 400 patients will be randomized for treatment with darovasertib in the treatment arm or the control arm, with potential modifications pending further feedback from the FDA.
Added
We received an upfront payment of $210.0 million and are eligible to receive up to $320.0 million in milestone payments, clinical trial cost sharing and clinical trial cost reimbursement, as well as double-digit royalties on net sales in all territories outside of the United States.
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We are currently finalizing the trial protocol for neoadjuvant UM and are targeting to initiate the study in the first half of 2025.
Added
Antibody-Drug Conjugates (ADC) / DNA Damage Response (DDR) Combinations • IDE849 is a potential first-in-class, DLL3 TOP1 ADC being evaluated by our partner, Hengrui Pharma, in a multi-site, open label Phase 1 clinical trial in China in patients with small-cell lung cancer (SCLC) and neuroendocrine carcinomas (NEC).
Removed
We are also supporting evaluation of darovasertib as single-agent neoadjuvant and adjuvant therapy in primary UM in an ongoing investigator-sponsored clinical trial, or IST, captioned as “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma,” or NADOM, led by St. Vincent’s Hospital in Sydney with the participation of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeWhile we are seeing, and expect to continue to see, record inflation due to geopolitical and macroeconomic events, such as the ongoing Ukraine-Russia conflict and related sanctions, the Israel-Hamas conflict, and the banking sector volatility, we do not believe that inflation, or exchange rate fluctuations have had a significant impact on our results of operations for any periods presented herein.
Biggest changeWhile we have seen higher inflation in the past few years, we do not believe that inflation, or exchange rate fluctuations have had a significant impact on our results of operations for any periods presented herein.
As of December 31, 2024, we had cash, cash equivalents and marketable securities of $1.1 billion, consisting of bank deposits, interest-bearing money market funds, investments in U.S. government securities, commercial paper, and corporate bonds, for which the fair value would be affected by changes in the general level of U.S. interest rates.
As of December 31, 2025, we had cash, cash equivalents and marketable securities of approximately $1.05 billion, consisting of bank deposits, interest-bearing money market funds, investments in U.S. government securities, commercial paper and corporate bonds, for which the fair value would be affected by changes in the general level of U.S. interest rates.

Other IDYA 10-K year-over-year comparisons