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What changed in Nuvation Bio Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Nuvation Bio 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.

+614 added−532 removedSource: 10-K (2026-03-02) vs 10-K (2025-03-06)

Top changes in Nuvation Bio Inc.'s 2025 10-K

614 paragraphs added · 532 removed · 352 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

90 edited+105 added−75 removed192 unchanged
Biggest changeBecause of the extensive time required for development, testing and regulatory review of an investigational product, it is possible that, before a product can be commercialized, any patent protection for such product may expire or remain in force for only a short period following commercialization, thereby reducing the commercial advantage the patent provides.
Biggest changeThese patents families include issued patents as well as pending patent applications in the U.S. and certain foreign jurisdictions, and patents that have issued or may issue from these patent families are expected to expire from 2035 to 2041 (not including patent term adjustment or extension that may be available to extend the term of such patents). 11 Because of the extensive time required for development, testing and regulatory review of an investigational product, it is possible that, before a product can be commercialized, any patent protection for such product may expire or remain in force for only a short period following commercialization, thereby reducing the commercial advantage the patent provides.
Pursuant to the NK Agreement, AHT received a $40.0 million upfront payment. In addition, we may receive $25.0 million upon achievement of a regulatory milestone, up to $35.0 million upon achievement of commercial milestones, and a lower-mid double digit percentage royalty on net sales of taletrectinib in the NK Territory.
Pursuant to the NK Agreement, AHT received a $40.0 million upfront payment. In addition, we received $25.0 million upon achievement of a regulatory milestone and may receive up to $35.0 million upon achievement of commercial milestones, and a lower-mid double digit percentage royalty on net sales of taletrectinib in the NK Territory.
Either party may terminate the agreement in the event of a material breach by the other party that remains uncured for 90 days (or, if such material breach cannot be cured within 90 days, if the other party does not commence and diligently continue actions to cure such breach during such 90 days).
Either party may terminate the agreement in the event of a material breach by the other party that remains uncured for 90 days (or, if such material breach cannot be cured within 90 days, if the other party does not commence and diligently continue actions to cure such breach during such 90 days).
Patent-Term Restoration and Marketing Exclusivity Depending upon the timing, duration and specifics of FDA approval of any future product candidates, some of our U.S. patents, or U.S. patent applications, if issued, may be eligible for limited patent term extension under the Hatch-Waxman Act.
U.S. Patent-Term Restoration and Marketing Exclusivity Depending upon the timing, duration and specifics of FDA approval of any future product candidates, some of our U.S. patents, or U.S. patent applications, if issued, may be eligible for limited patent term extension under the Hatch-Waxman Act.
Moreover, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, (collectively, the “Affordable Care Act”) provides that the government may assert that a claim including items or services 23 resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act. • The federal false claims laws, including the civil False Claims Act that can be enforced by private citizens through civil whistleblower or qui tam actions, and civil monetary penalties law prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government. • The federal Health Insurance Portability and Accountability Act (“HIPAA”) prohibits, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters. • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their implementing regulations also impose obligations on covered entities such as health insurance plans, healthcare clearinghouses, and certain healthcare providers and their respective business associates and their covered subcontractors, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. • The federal Physician Payments Sunshine Act requires applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to annually report to the Centers for Medicare & Medicaid Services (“CMS”) information regarding certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals as well as information regarding ownership and investment interests held by physicians and their immediate family members. • Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, state laws that require biotechnology companies to comply with the biotechnology industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state and local laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures and require the registration of their sales representatives, state laws that require biotechnology companies to report information on the pricing of certain drug products, and state and foreign laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Moreover, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, (collectively, the “Affordable Care Act”) provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act. • The federal false claims laws, including the civil False Claims Act that can be enforced by private citizens through civil whistleblower or qui tam actions, and civil monetary penalties law prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government. 19 • The federal Health Insurance Portability and Accountability Act (“HIPAA”) prohibits, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters. • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their implementing regulations also impose obligations on covered entities such as health insurance plans, healthcare clearinghouses, and certain healthcare providers and their respective business associates and covered subcontractors, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. • The federal Physician Payments Sunshine Act requires applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to annually report to the Centers for Medicare & Medicaid Services (“CMS”) information regarding certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals as well as information regarding ownership and investment interests held by physicians and their immediate family members. • Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, state laws that require biotechnology companies to comply with the biotechnology industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state and local laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures and require the registration of their sales representatives, state laws that require biotechnology companies to report information on the pricing of certain drug products, and state and foreign laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Post-approval Requirements Following approval of a new product, the manufacturer and the approved product are subject to continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, requirements to report adverse events and comply with promotion and advertising requirements, which include restrictions on promoting drugs for unapproved uses or patient populations, known as “off-label promotion,” and limitations on 22 industry-sponsored scientific and educational activities.
Post-approval Requirements Following approval of a new product, the manufacturer and the approved product are subject to continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, requirements to report adverse events and comply with promotion and advertising requirements, which include restrictions on promoting drugs for unapproved uses or patient populations, known as “off-label promotion,” and limitations on industry-sponsored scientific and educational activities.
While we believe that our technology, development experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including large pharmaceutical and biotechnology companies, academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for the research, development, manufacturing and commercialization of cancer therapies.
While we believe that our technology, development experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including large pharmaceutical and biotechnology companies, academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for the research, development, manufacturing and commercialization of 12 cancer therapies.
Phase 1 Study Results A Phase 1 (NCT03030066) multicenter, open-label, dose-escalation study evaluating safusidenib as a monotherapy in 47 patients was conducted in Japan and sponsored by Daiichi Sankyo Co., Ltd. Patients were divided into enhancing and non-enhancing groups based on the presence or absence of tumor contrast enhancement judged by each investigator at the time of enrollment.
Phase 1 Study Results A Phase 1 multicenter, open-label, dose-escalation study evaluating safusidenib as a monotherapy in 47 patients was conducted in Japan and sponsored by Daiichi Sankyo Co., Ltd. Patients were divided into enhancing and non-enhancing groups based on the presence or absence of tumor contrast enhancement judged by each investigator at the time of enrollment.
The process generally involves the following: • completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with GLP; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent institutional review board (“IRB”) or ethics committee at each clinical trial site before each trial may be initiated; • performance of adequate and well controlled human clinical trials in accordance with applicable IND regulations, current Good Clinical Practice ("GCP") requirements and other clinical trial-related protocols and regulations to establish substantial evidence of the safety and efficacy of the investigational product for each proposed indication; • submission to the FDA of an NDA after completion of all pivotal trials; • determination by the FDA within 60 days of its receipt of an NDA to accept the filing for substantive review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug will be produced to assess compliance with current Good Manufacturing Practices (“cGMP”) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; • potential FDA audit of the preclinical study and/or clinical trial sites that generated the data in support of the NDA filing to assess compliance with GCP; • FDA review and approval of the NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the drug in the U.S.; and • compliance with any post-approval requirements, including the potential requirement to implement a risk evaluation and mitigation strategy (“REMS”) and the potential requirement to conduct post-approval studies.
The process generally involves the following: • completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with good laboratory practice (“GLP”); • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent institutional review board (“IRB”) or ethics committee at each clinical trial site before each trial may be initiated; • performance of adequate and well controlled human clinical trials in accordance with applicable IND regulations, current GCP requirements and other clinical trial-related protocols and regulations to establish substantial evidence of the safety and efficacy of the investigational product for each proposed indication; • submission to the FDA of an NDA after completion of all pivotal trials; • determination by the FDA within 60 days of its receipt of an NDA to accept the filing for substantive review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug will be produced to assess compliance with current Good Manufacturing Practices (“cGMP”) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; • potential FDA audit of the preclinical study and/or clinical trial sites that generated the data in support of the NDA filing to assess compliance with GCP; • FDA review and approval of the NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the drug in the U.S.; and • compliance with any post-approval requirements, including the potential requirement to implement a risk evaluation and mitigation strategy (“REMS”) and the potential requirement to conduct post-approval studies.
The CTR foresaw a three-year transition period that ended on January 31, 2025. Since this date, all new or 25 ongoing trials are 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.
The CTR foresaw a three-year transition period that ended on January 31, 2025. Since this date, all new or ongoing trials are 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.
It is uncertain whether the issuance of any third-party patent would require us to alter our development or commercial 15 strategies, obtain licenses or cease certain activities. Our failure to obtain a license to proprietary rights that we may require to develop or commercialize our future drug products may have a material adverse impact on us.
It is uncertain whether the issuance of any third-party patent would require us to alter our development or commercial strategies, obtain licenses or cease certain activities. Our failure to obtain a license to proprietary rights that we may require to develop or commercialize our future drug products may have a material adverse impact on us.
Other EEA countries allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products.
Other EEA countries allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. 27 There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products.
Any agency or judicial enforcement action could have a material adverse effect on us. Our product candidates are considered small molecule drugs and must be approved by the FDA through the new drug application (“NDA”) process before they may be legally marketed in the U.S.
Any agency or judicial enforcement action could have a material adverse effect on us. 13 Our product candidates are considered small molecule drugs and must be approved by the FDA through the new drug application (“NDA”) process before they may be legally marketed in the U.S.
Orphan drug exclusivity also could block the approval of one of our product candidates for seven years if a competitor obtains approval before we do for the same product, as defined by the FDA, for the same indication we are seeking approval, or if a product candidate is determined to be contained within the scope of the competitor’s product for the same indication.
Orphan drug exclusivity also could block the approval of one of our product candidates for seven years if a competitor 17 obtains approval before we do for the same product, as defined by the FDA, for the same indication we are seeking approval, or if a product candidate is determined to be contained within the scope of the competitor’s product for the same indication.
Either party may terminate the agreement in the event of a material breach by the other party that remains uncured for 90 days (or, if such material breach cannot be cured within 90 days, if the other 8 party does not commence and diligently continue actions to cure such breach during such 90 days), or due to insolvency or bankruptcy of the other party.
Either party may terminate the agreement in the event of a material breach by the other party that remains uncured for 90 days (or, if such material breach cannot be cured within 90 days, if the other party does not commence and diligently continue actions to cure such breach during such 90 days), or due to insolvency or bankruptcy of the other party.
FDA approval of an NDA must be obtained before a drug may be legally marketed in the U.S. Under the Prescription Drug User Fee Act (“PDUFA”), as amended, each NDA must be accompanied by a user fee. FDA adjusts the PDUFA user fees on an annual basis. PDUFA also imposes an annual program fee for each marketed human drug.
FDA approval of an NDA must be obtained before a drug may be legally marketed in the U.S. 16 Under the Prescription Drug User Fee Act (“PDUFA”), as amended, each NDA must be accompanied by a user fee. FDA adjusts the PDUFA user fees on an annual basis. PDUFA also imposes an annual program fee for each marketed human drug.
The patent-term restoration period is generally one-half the time between the effective date of an IND or the issue date of the patent, whichever is later, and the submission date of an NDA plus the time between the submission date of an NDA or the issue date of the patent, whichever is later, and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence.
The patent-term restoration period is generally one-half the time between the effective date of an IND or the issue date of the patent, whichever is later, and the submission date of an NDA plus the time between the submission date of an NDA or the issue date of the patent, whichever is later, and the approval of that application, 20 except that the review period is reduced by any time during which the applicant failed to exercise due diligence.
Preclinical studies include laboratory evaluation of product chemistry and formulation, as well as in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use. 18 The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations for safety/toxicology studies.
Preclinical studies include laboratory evaluation of product chemistry and formulation, as well as in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations for safety/toxicology studies.
Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. 21 Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
Our obligation to pay royalties under 10 the Safusidenib In-License Agreement will expire on a country-by-country basis upon the later of the expiration of the last valid claim of a patent licensed under the Safusidenib In-License Agreement covering safusidenib, and ten years after the first commercial sale of safusidenib in such country.
Our obligation to pay royalties under the Safusidenib In-License Agreement will expire on a country-by-country basis upon the later of the expiration of the last valid claim of a patent licensed under the Safusidenib In-License Agreement covering safusidenib, and ten years after the first commercial sale of safusidenib in such country.
The European Commission or the competent authorities 26 of the EEA countries may decide on justified grounds relating to pharmacovigilance, to proceed with one further five- year renewal period for the MA. Once subsequently definitively renewed, the MA shall be valid for an unlimited period.
The European Commission or the competent authorities of the EEA countries may decide on justified grounds relating to pharmacovigilance, to proceed with one further five- year renewal period for the MA. Once subsequently definitively renewed, the MA shall be valid for an unlimited period.
Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.
Similarly, an IRB can 15 suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.
However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. Any formulary used by a Part D prescription drug plan must be developed and reviewed by a pharmacy and therapeutic committee.
However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. Any formulary used by a Part D prescription drug plan must be developed and reviewed by a 26 pharmacy and therapeutic committee.
Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.
Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing 18 of products. Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.
The Innovent Agreement will continue in effect until Innovent ceases all commercial activity related to taletrectinib in the Innovent Territory or termination of the Taletrectinib In-License Agreement. We may terminate the Innovent Agreement if Innovent challenges any patents licensed to it under the Innovent Agreement.
The Innovent Agreement will continue in effect until Innovent ceases all commercial activity related to taletrectinib in the Innovent Territory or termination of the Taletrectinib In-License 7 Agreement. We may terminate the Innovent Agreement if Innovent challenges any patents licensed to it under the Innovent Agreement.
The results of preclinical studies and clinical trials are then 20 submitted to the FDA as part of an NDA, along with proposed labeling, chemistry and manufacturing information to ensure product quality and other relevant data.
The results of preclinical studies and clinical trials are then submitted to the FDA as part of an NDA, along with proposed labeling, chemistry and manufacturing information to ensure product quality and other relevant data.
As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality System Regulation, which imposes elaborate testing, control, documentation and other quality assurance requirements.
As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality Management System Regulation, which imposes elaborate testing, control, documentation and other quality assurance requirements.
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) advanced therapy medicinal products, or ATMPs, and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases.
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) advanced therapy medicinal products, and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases.
For our product candidates, we generally seek patent protection in the U.S. and in certain foreign jurisdictions. As of December 31, 2024, taletrectinib is covered by patent families that we either own or have exclusively licensed from Daiichi Sankyo worldwide. These patent families cover the composition of matter of taletrectinib, methods of use thereof, or methods of manufacturing thereof.
For our product candidates, we generally seek patent protection in the U.S. and in certain foreign jurisdictions. As of December 31, 2025, taletrectinib is covered by patent families that we either own or have exclusively licensed from Daiichi Sankyo worldwide. These patent families cover the composition of matter of taletrectinib, methods of use thereof, or methods of manufacturing thereof.
Depending on the circumstances, failure to comply can result in significant civil, criminal and administrative penalties, including damages, fines, disgorgement, imprisonment, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings, injunctions, requests for recall, seizure of products, total or partial suspension of production, denial or withdrawal of product approvals or refusal to allow a firm to enter into supply contracts, including government contracts. 24 U.S.
Depending on the circumstances, failure to comply can result in significant civil, criminal and administrative penalties, including damages, fines, disgorgement, imprisonment, exclusion from participation in government funded healthcare programs, such as Medicare and Medicaid, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings, injunctions, requests for recall, seizure of products, total or partial suspension of production, denial or withdrawal of product approvals or refusal to allow a firm to enter into supply contracts, including government contracts.
DRUG-DRUG CONJUGATES ARE DESIGNED TO BIND TWO DIFFERENT TARGETS SIMULTANEOUSLY Key potential benefits of our DDCs include: • Tissue-selective targeting improves therapeutic index vs. untargeted warhead; • Oral or IV delivery; • Binds intracellular and cell membrane targets; • Highly cell permeable; and 11 • Simpler and less expensive to manufacture than antibody-drug conjugates.
DRUG-DRUG CONJUGATES ARE DESIGNED TO BIND TWO DIFFERENT TARGETS SIMULTANEOUSLY 10 Key potential benefits of our DDCs include: • Tissue-selective targeting improves therapeutic index vs. untargeted warhead; • Oral or IV delivery; • Binds intracellular and cell membrane targets; • Highly cell permeable; and • Simpler and less expensive to manufacture than antibody-drug conjugates.
PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet medical needs.
PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet 22 medical needs.
Coverage and Reimbursement Sales of our products, if approved, will depend, in part, on the extent to which our products will be covered by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations. There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products.
Coverage and Reimbursement Sales of our products and our product candidates, if approved, will depend, in part, on the extent to which our products will be covered by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations. There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products.
In addition, we are obligated to pay up to $6.0 million upon achievement of additional development milestones, up to $50.0 million upon achievement of regulatory milestones, up to $45.0 million upon achievement of commercial sales milestones, and a high single-digit percentage royalty based on worldwide net sales subject to certain adjustments.
In addition, we are obligated to pay up to $3.0 million upon achievement of additional development milestones, up to $50.0 million upon achievement of regulatory milestones, up to $45.0 million upon achievement of commercial sales milestones, and a high single-digit percentage royalty based on worldwide net sales subject to certain adjustments.
For safusidenib, as of December 31, 2024, we have an exclusive worldwide (other than Japan) license from Daiichi Sankyo to patent families that cover the composition of matter of safusidenib, methods of use thereof, or methods of manufacturing thereof.
For safusidenib, as of December 31, 2025, we have an exclusive worldwide (other than Japan) license from Daiichi Sankyo to patent families that cover the composition of matter of safusidenib, methods of use thereof, or methods of manufacturing thereof.
We have no collective bargaining agreements with our employees and we have not experienced any work stoppages nor are we aware of any employment circumstances that are likely to disrupt work at any of our facilities. We consider our relationship with our employees to be good.
We have no collective bargaining agreements with our employees, and we have not experienced any work stoppages nor are we aware of any employment circumstances that are likely to disrupt work at any of our facilities. We consider our relationship with our employees to be strong.
We also occupy office space located in Burlington, Massachusetts, where we lease approximately 2,235 square feet of office space under a lease that terminates in 2027, as well as a total of approximately 1,735 square meters of office space in the People’s Republic of China, in the cities of Beijing, Guangzhou, Hangzhou and Shanghai, under leases that terminate in 2026 through 2027.
We also occupy office space located in Burlington, Massachusetts, where we lease approximately 2,235 square feet of office space under a lease that terminates in 2027, as well as a total of approximately 1,799 square meters of office space in the People’s Republic of China, in the cities of Beijing, Guangzhou, Hangzhou and Shanghai, under leases that terminate in 2026 through 2029.
Drug Development In the U.S., the FDA regulates drugs under the Food, Drug, and Cosmetic Act (“FDCA”). Drugs also are subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the 17 subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.
Drug Development In the U.S., the FDA regulates drugs under the Food, Drug, and Cosmetic Act (“FDCA”). Drugs also are subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.
We value agility, passion and teamwork, and are building a diverse environment where our employees can thrive and one that inspires exceptional contributions and professional and personal development in order to achieve our mission to significantly change the practice of oncology.
We value agility, passion and teamwork, and are building an engagement environment where our employees can thrive and one that inspires exceptional contributions and professional and personal development in order to achieve our mission to significantly change the practice of oncology.
Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the "EU portal", the Clinical Trials Information System, or CTIS; a single set of documents to be prepared and submitted for the application; as well as simplified reporting procedures for clinical trial sponsors.
Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the “EU portal”, the Clinical Trials Information System; a single set of documents to be prepared and submitted for the application; as well as simplified reporting procedures for clinical trial sponsors.
This Regulation, which entered into application on January 12, 2025 and has a phased implementation, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.
This Regulation, which entered into application on January 12, 2025 and has a phased implementation, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas. The Regulation initially applies to new active substances for oncology and ATMPs.
On April 9, 2024 (the "Acquisition Date"), the Company completed its acquisition of AnHeart Therapeutics Ltd., an exempted company incorporated under the laws of the Cayman Islands (“AnHeart”), pursuant to that certain Agreement and Plan of Merger (the "AnHeart Merger Agreement"), by and among the Company, AnHeart, Artemis Merger Sub I, Ltd., an exempted company incorporated under the laws of the Cayman Islands and a wholly owned subsidiary of the Company, and Artemis Merger Sub II, Ltd., an exempted company incorporated under the laws of the Cayman Islands and a wholly owned subsidiary of the Company.
On April 9, 2024 (the “Acquisition Date”), the Company completed its acquisition of AnHeart Therapeutics Ltd., an exempted company incorporated under the laws of the Cayman Islands (“AnHeart”), pursuant to that certain Agreement and Plan of Merger (the “AnHeart Merger Agreement”), by and among the Company, AnHeart, Artemis Merger Sub I, Ltd., an exempted company incorporated under the laws of the Cayman Islands and a wholly owned 3 subsidiary of the Company, and Artemis Merger Sub II, Ltd., an exempted company incorporated under the laws of the Cayman Islands and a wholly owned subsidiary of the Company.
HTAs of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets. The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country.
HTAs of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in EEA countries, including those representing the larger markets. The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country.
These new laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our drugs, if approved, and accordingly, our financial operations.
These and other future healthcare reform measures may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our drugs, if approved, and accordingly, our financial operations.
To date, pursuant to the Innovent Agreement, AHT Hangzhou has received $67.0 million in connection with an upfront payment, reimbursement of research and development expenses, and achievement of regulatory milestones.
To date, pursuant to the Innovent Agreement, Nuvation Bio China has received $67.0 million in connection with an upfront payment, reimbursement of research and development expenses, and achievement of regulatory milestones.
Safusidenib Phase 1 and Phase 2 Clinical Study Overview Safusidenib In-License Agreement In September 2020, AHT entered into a license agreement with Daiichi Sankyo, pursuant to which Daiichi Sankyo granted to AHT exclusive worldwide (other than Japan) rights to develop and commercialize safusidenib for all human prophylactic or therapeutic uses (the “Safusidenib In-License Agreement”).
Safusidenib In-License Agreement In September 2020, AHT entered into a license agreement with Daiichi Sankyo, pursuant to which Daiichi Sankyo granted to AHT exclusive worldwide (other than Japan) rights to develop and commercialize safusidenib for all human prophylactic or therapeutic uses (the “Safusidenib In-License Agreement”). Daiichi Sankyo retains the right to develop and commercialize safusidenib in Japan.
(“AHT Hangzhou”), a wholly owned subsidiary of AnHeart, entered into a collaboration and license agreement with Innovent (the “Innovent Agreement”), pursuant to which AHT Hangzhou granted to Innovent exclusive rights to commercialize taletrectinib in mainland China, Hong Kong, Macau and Taiwan (collectively, the “Innovent Territory”), as well as certain development rights within the Innovent Territory.
Ltd.) (“Nuvation Bio China”), a wholly owned subsidiary of AnHeart, entered into a collaboration and license agreement with Innovent (the “Innovent Agreement”), pursuant to which Nuvation Bio China granted to Innovent exclusive rights to commercialize taletrectinib in mainland China, Hong Kong, Macau and Taiwan (collectively, the “Innovent Territory”), as well as certain development rights within the Innovent Territory.
Clinical Trials The clinical stage of development involves the administration of the investigational product to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.
As a result, submission of an IND may not result in the FDA allowing clinical trials to commence. 14 Clinical Trials The clinical stage of development involves the administration of the investigational product to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.
We believe that this strategy allows us to maintain a more efficient infrastructure by eliminating the need for us to invest in our own manufacturing facilities, equipment and personnel while also enabling us to focus our expertise and resources on the development of our investigational products.
We believe that this strategy allows us to maintain a more efficient infrastructure by eliminating the need for us to invest in our own manufacturing facilities, equipment and personnel while also enabling us to focus our expertise and resources on the development of our investigational products. We obtain taletrectinib API and drug product pursuant to long-term supply agreements.
(“AHT”), a wholly owned subsidiary of AnHeart, entered into a license agreement with Daiichi Sankyo, pursuant to which Daiichi Sankyo granted to AHT exclusive worldwide rights to develop and commercialize taletrectinib (the “Taletrectinib In-License Agreement”).
Taletrectinib In-License Agreement In December 2018, AnHeart Therapeutics Inc. (“AHT”), a wholly owned subsidiary of AnHeart, entered into a license agreement with Daiichi Sankyo Company, Limited (“Daiichi Sankyo”), pursuant to which Daiichi Sankyo granted to AHT exclusive worldwide rights to develop and commercialize taletrectinib (the “Taletrectinib In-License Agreement”).
Daiichi Sankyo retains the right to develop and commercialize safusidenib in Japan. To date, under the Safusidenib In-License Agreement, AHT has paid Daiichi Sankyo $9.0 million in connection with an upfront payment and the achievement of a development milestone.
To date, under the Safusidenib In-License Agreement, AHT has paid Daiichi Sankyo $12.0 million in connection with an upfront payment and the achievement of a development milestone.
Additionally, there has been heightened governmental scrutiny recently over the manner in which drug manufacturers set prices for their marketed products, which has resulted in several Presidential executive orders, Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for drug products.
Additionally, there has been heightened governmental scrutiny recently over the manner in which drug manufacturers set prices for their marketed products, which has resulted in reform measures designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for drug products.
(“NK”, and such agreement, the “NK Agreement”), pursuant to which AHT granted to NK exclusive rights to commercialize taletrectinib for all human indications in Japan (the “NK Territory”), and exclusive rights to research and develop taletrectinib for any indication other than ROS1+ NSCLC in Japan subject to AnHeart’s prior approval.
In October 2023, AHT entered into a collaboration and license agreement with NK (the “NK Agreement”), pursuant to which AHT granted to NK exclusive rights to commercialize taletrectinib for all human indications in Japan (the “NK Territory”), and exclusive rights to research and develop taletrectinib for any indication other than ROS1+ NSCLC in Japan subject to AnHeart’s prior approval.
Other ROS1 inhibitors currently in clinical-stage development include Nuvalent’s zidesamtinib. If approved for the treatment of mIDH1 low grade glioma, we expect that safusidenib would compete against Servier’s Voranigo® (vorasidenib). Another mIDH1 currently in clinical development for mIDH1 glioma is Rigel’s olutasidenib.
Taletrectinib competes against approved drugs including Pfizer’s Xalkori®, Roche’s Rozlytrek®, and BMS’s Augtyro®. Other ROS1 inhibitors currently in clinical-stage development include Nuvalent’s zidesamtinib. If approved for the treatment of mIDH1 low grade glioma, we expect that safusidenib would compete against Servier’s Voranigo® (vorasidenib). Another mIDH1 currently in clinical development for mIDH1 glioma is Rigel’s olutasidenib.
To obtain an MA for a product in the EEA, an applicant must submit a Marketing Authorization Application (“MAA”) either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EEA countries (decentralized procedure, national procedure or mutual recognition procedure).
To obtain an MA for a product in the EEA, an applicant must submit a MAA either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EEA countries 21 (decentralized procedure, national procedure or mutual recognition procedure). An MA may be granted only to an applicant established in the EEA.
We leverage our team’s extensive expertise in medicinal chemistry, preclinical development, drug development, business development, manufacturing, and commercialization to pursue oncology targets validated by strong clinical or preclinical data and develop novel small molecules that improve the activity and overcome the liabilities of currently marketed drugs. 3 The foundations of our approach include: • The pursuit of validated targets: We identify and pursue oncology targets validated by strong clinical or preclinical data that provide a high degree of confidence in generating clinically meaningful benefit.
We leverage our team’s extensive expertise in medicinal chemistry, preclinical development, drug development, business development, manufacturing, and commercialization to pursue oncology targets validated by strong clinical or preclinical data and develop novel small molecules that improve the activity and overcome the liabilities of currently marketed drugs.
The data required to support an NDA are generated in two distinct developmental stages: preclinical and clinical. The preclinical and clinical testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for any current and future product candidates will be granted on a timely basis, or at all.
The preclinical and clinical testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for any current and future product candidates will be granted on a timely basis, or at all.
The Central Brain Tumor Registry of the United States estimated that the incidence of IDH-mutant glioma in the United States in 2018-2021 to be approximately 9,600 total cases (approximately 2,400 new cases per year). Safusidenib has high blood–brain barrier (“BBB”) permeability and inhibits mIDH1, including the subtype IDH1R132H.
The Central Brain 8 Tumor Registry of the United States estimated that the incidence of IDH-mutant glioma in the United States in 2018-2021 to be approximately 2,500 new cases per year, with approximately half of such patients classified as low-grade and the other half as high-grade. Safusidenib has high blood–brain barrier (“BBB”) permeability and inhibits mIDH1, including the subtype IDH1R132H.
These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, effective April 1, 2013, which, due to subsequent legislative amendments, will stay in effect until 2032, unless additional congressional action is taken.
Other legislative changes have been proposed and adopted in the U.S. since the Affordable Care Act was enacted. These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, effective April 1, 2013, which, due to subsequent legislative amendments, will stay in effect until 2032, unless additional congressional action is taken.
We believe that a rich culture of inclusion and diversity enables us to create, develop and fully leverage the strengths of our workforce. Our workforce comprises approximately 52% female employees and approximately 33% racial/ethnic minority employees.
We believe that a rich culture of inclusion and diversity enables us to create, develop and fully leverage the strengths of our workforce.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program. 28 At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
We currently have a single source for taletrectinib API and drug product, and we obtain taletrectinib API pursuant to a long-term supply agreement. We are currently developing a second source for taletrectinib API and drug product, respectively. For our other investigational products, we have obtained APIs and drug product from various single-source third-party CMOs.
We currently rely upon a single source for taletrectinib API and are working to develop a second source. For our other investigational products, we have obtained APIs and drug product from various single-source third-party CMOs.
The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Two complete responses were observed: one complete response in a grade 4 astrocytoma and one complete response in the target lesions of a grade 3 oligodendroglioma (with stable disease in non-target lesions). The maximum tolerated dose was not reached. Most adverse events (AEs) were grade 1-2.
As reported in the journal of Neuro-Oncology in February 2023, the objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors, including one complete response in a grade 4 astrocytoma and one complete response in the target lesions of a grade 3 oligodendroglioma (with stable disease in non-target lesions). The maximum tolerated dose was not reached.
An MA may be granted only to an applicant established in the EEA. The centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EEA countries.
The centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EEA countries.
Taletrectinib Out-License Agreements In May 2021, AnHeart Therapeutics (Hangzhou) Co. Ltd.
Taletrectinib Out-License Agreements In May 2021, Nuvation Bio China Ltd. (formerly known as AnHeart Therapeutics (Hangzhou) Co.
There are many other companies that have commercialized and/or are developing such treatments for cancer including large pharmaceutical and biotechnology companies, such as AstraZeneca plc, Bristol-Myers Squibb Company (“BMS”), Eli Lilly, Merck, Novartis Pharmaceuticals Corporation (“Novartis”), Pfizer, Regeneron Pharmaceuticals, Inc. in partnership with Sanofi Genzyme (“Sanofi”) and Roche. 16 If approved for the treatment of advanced ROS1+ NSCLC, we expect that taletrectinib would compete against approved drugs including Pfizer’s Xalkori®, Roche’s Rozlytrek®, and BMS’s Augtyro®.
There are many other companies that have commercialized and/or are developing such treatments for cancer including large pharmaceutical and biotechnology companies, such as AstraZeneca plc, Bristol-Myers Squibb Company (“BMS”), Eli Lilly, Merck, Novartis Pharmaceuticals Corporation (“Novartis”), Pfizer, Regeneron Pharmaceuticals, Inc. in partnership with Sanofi Genzyme (“Sanofi”) and Roche.
We believe taletrectinib has a potentially best-in-class efficacy and safety profile, including overall response rate, durable responses, prolonged progression-free survival, brain penetrance to improve outcomes for patients with brain metastases, activity against tumors that have developed resistance mutations to approved ROS1 TKIs such as G2032R, and a low rate of treatment discontinuation.
We believe IBTROZI is becoming the new standard of care in advanced ROS1+ NSCLC, which is supported by IBTROZI’s best-in-class efficacy and safety profile including objective response rate, durable responses, prolonged progression-free survival, brain penetrance to improve outcomes for patients with brain metastases, activity against tumors that have developed resistance mutations to approved ROS1 tyrosine kinase inhibitors (“TKIs”) such as G2032R, and a low rate of treatment discontinuation.
Up to 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that spread to their brain, increasing up to 55% for those whose cancer has progressed following initial treatment (Ou et al 2019). There are currently three FDA approved TKIs for the treatment of patients with ROS1+ NSCLC: Xalkori (crizotinib), Rozlytrek (entrectinib) and, most recently, Augtyro (repotrectinib).
Up to 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that spread to their brain, increasing up to 55% for those whose cancer has progressed following initial treatment (Ou et al 2019).
In addition, we are obligated to pay up to $14.0 million upon achievement of additional regulatory milestones, up to $20.0 million upon achievement of commercial sales milestones, and a high single-digit percentage royalty based on worldwide net sales subject to certain adjustments.
To date, under the Taletrectinib In-License Agreement, we have paid Daiichi Sankyo $23.0 million in connection with an upfront payment and the achievement of development and regulatory milestones. In addition, we are obligated to pay up to $20.0 million upon achievement of commercial sales milestones, and a high single-digit percentage royalty based on worldwide net sales subject to certain adjustments.
Human Capital Employees 29 As of December 31, 2024, we had 220 full-time employees, 49 of whom hold Ph.D.s, M.D.s or both. Of our total workforce, 135 employees are engaged in research and development, and 85 employees in general and administrative. Our workforce also includes 43 independent contractors.
Human Capital Employees As of December 31, 2025, we had 298 full-time employees, 58 of whom hold Ph.Ds, M.Ds or Pharm.Ds. Of our total workforce, 147 employees are engaged in research and development, and 151 employees in selling, general and administrative. Our workforce also includes 67 independent contractors.
Twenty patients (42.6%) experienced at least one grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, back pain, and dry skin. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples.
Most adverse events (AEs) were grade 1-2. Twenty (42.6%) patients experienced at least one grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, back pain, and dry skin.
For example, in the EEA, some countries provide that products may be marketed only after a reimbursement price has been agreed, and other countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies (so called Health Technology Assessments (“HTAs”) in order to obtain reimbursement or pricing approval.
Political, economic and regulatory developments may further complicate pricing negotiations. In addition, other countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies (so called Health Technology Assessments (“HTAs”)) in order to obtain reimbursement or pricing approval.
“Nuvation Bio” is a registered trademark of Nuvation Bio Inc. in the U.S. and other countries. Other trademarks or service marks appearing in this report may be trademarks or service marks of other owners. Business Overview We are a global biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel product candidates.
“Nuvation Bio” is a registered trademark of Nuvation Bio Inc. in the U.S. and other countries. Other trademarks or service marks appearing in this report may be trademarks or service marks of other owners.
Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private third-party payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. 27 In addition, in case a drug product needs companion diagnostics, then companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products.
Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private third-party payors often follow Medicare coverage policy and payment limitations in setting their own payment rates.
We are unable to predict the future course of federal or state healthcare legislation in the U.S. directed at broadening the availability of healthcare and containing or lowering the cost of healthcare.
Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs. We are unable to predict the future course of federal or state healthcare legislation in the U.S. directed at broadening the availability of healthcare and containing or lowering the cost of healthcare.
We are evaluating next steps for the NUV-868 program, including external partnership opportunities or further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients. 14 Intellectual Property Our commercial success depends in large part on our ability to obtain and maintain patent protection in the U.S. and other countries for our investigational products, to operate without infringing valid and enforceable patents and proprietary rights of others, and to prevent others from infringing on our proprietary or intellectual property rights.
Intellectual Property Our commercial success depends in large part on our ability to obtain and maintain patent protection in the U.S. and other countries for our investigational products, to operate without infringing valid and enforceable patents and proprietary rights of others, and to prevent others from infringing on our proprietary or intellectual property rights.
In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA. 19 Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA.
Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA.
We are building a culture that fosters a productive, professional and inclusive work environment, where people can thrive, have fun, and be inspired to perform their best work.
We are building a culture that fosters a productive, professional and inclusive work environment, where people can thrive, have fun, and be inspired to perform their best work. 4 The following table summarizes our product candidate pipeline: We commercially launched IBTROZI in the U.S. in June 2025, following its approval by the U.S.
Taletrectinib Phase 2 Clinical Studies Overview Taletrectinib is currently being evaluated for the treatment of patients with advanced ROS1+ NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study.
Taletrectinib continues to be evaluated for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I in China, and TRUST-II, a global study, as well as in a confirmatory randomized Phase 3 study versus crizotinib in China known as TRUST-III.
It is unclear how any such challenges and other litigation, and the healthcare reform measures of the second Trump administration will impact the Affordable Care Act. Other legislative changes have been proposed and adopted in the U.S. since the Affordable Care Act was enacted.
It is possible that the Affordable Care Act will be subject to judicial or Congressional challenges in the future. It is unclear how any such challenges and other litigation, and the healthcare reform measures of the second Trump administration will impact the Affordable Care Act.

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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, rate of progress, results and costs of drug discovery, preclinical development, laboratory testing and clinical trials for our product candidates; • the number and development requirements of product candidates that we may pursue, and other indications for our current product candidates that we may pursue; • the costs, timing and outcome of regulatory review of our product candidates; • the scope and costs of manufacturing development and commercial manufacturing activities; • the cost associated with commercializing any approved product candidates; • the cost and timing of developing our ability to establish sales and marketing capabilities, if any; • the costs of preparing, filing and prosecuting patent applications, maintaining, enforcing and protecting our intellectual property rights, defending intellectual property-related claims and obtaining licenses to third-party intellectual property; • our ability to establish and maintain collaborations on favorable terms, if at all; and • the extent to which we acquire or in-license other product candidates and technologies and associated intellectual property, and payments required under such acquisitions or in-licenses.
Biggest changeOur future capital requirements will depend on many factors, including: • the level of demand for IBTROZI; • the extent to which coverage and reimbursement for IBTROZI is available from government and health administration authorities, private health insurers, managed care programs and other third-party payors; 39 • changes in the amount of deductions from gross sales, including government-mandated rebates, chargebacks and discounts that can vary because of changes to the government discount percentage, including increases in the government discount percentage resulting from price increases we may take in the future, or due to different levels of utilization by entities entitled to government rebates and discounts and changes in patient demographics; • increases in the scope of eligibility for customers to purchase IBTROZI at the discounted government price or to obtain government-mandated rebates on purchases of IBTROZI; • changes in our cost of sales; • the timing, cost and level of investment in our sales and marketing efforts to support IBTROZI sales; • the timing and level of royalty payments under the RIF Agreement and Loan Agreement with Sagard; • the scope, rate of progress, results and costs of drug discovery, preclinical development, laboratory testing and clinical trials for our product candidates; • the number and development requirements of product candidates that we may pursue, and other indications for our current product candidates that we may pursue; • the costs, timing and outcome of regulatory review of our product candidates; • the scope and costs of manufacturing development and commercial manufacturing activities; • the cost associated with commercializing any approved product candidates; • the cost and timing of developing our ability to establish sales and marketing capabilities, if any; • the costs of preparing, filing and prosecuting patent applications, maintaining, enforcing and protecting our intellectual property rights, defending intellectual property-related claims and obtaining licenses to third-party intellectual property; • our ability to establish and maintain collaborations on favorable terms, if at all; and • the extent to which we acquire or in-license other product candidates and technologies and associated intellectual property, and payments required under such acquisitions or in-licenses.
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 False Claims Act; • the U.S. federal Health Insurance Portability and Accountability Act of 1996, (“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 statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, (“HITECH”), and its implementing regulations, which imposes certain obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by “covered entities”, i.e. health plans, healthcare clearinghouses and certain healthcare providers, as well as their “business associates” and covered subcontractors that perform certain services for or on their behalf involving the use or disclosure of individually identifiable health information; • the U.S.
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 False Claims Act; • the U.S. federal Health Insurance Portability and Accountability Act of 1996, (“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 statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, (“HITECH”), and its implementing regulations, which imposes certain obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by “covered entities”, i.e. health plans, healthcare clearinghouses and certain healthcare providers, as well as their “business associates” and covered subcontractors that perform certain services for or on their behalf involving the use or disclosure of individually identifiable health information; 60 • the U.S.
See also the risk factor titled “—Our business, operations and clinical development plans and timelines and supply chain could be adversely affected by the effects of health epidemics, on the manufacturing, clinical trial and other business activities performed by us or by third parties with whom we conduct business, including our CMOs, CROs, shippers and others.” Further, our reliance on third-party manufacturers exposes us to risks beyond our control, including the risk of: • inability to meet our product specifications and quality requirements consistently; • delay or inability to procure or expand sufficient manufacturing capacity; • manufacturing and quality issues, including related to scale-up of manufacturing; • costs and validation of new equipment and facilities required for additional scale-up; 51 • failure of the manufacturer to comply with cGMP and similar foreign standards; • inability to negotiate manufacturing agreements with third parties on commercially reasonable terms; • termination or nonrenewal of manufacturing agreements with third parties in a manner or at a time that is costly or damaging to us; • reliance on a limited number of sources, and in some cases, single sources for components, such that if we are unable to secure a sufficient supply of these drug components, we will be unable to manufacture and sell our product candidates in a timely fashion, in sufficient quantities or under acceptable terms; • lack of qualified backup suppliers for those components that are currently purchased from a sole or single source supplier; • operations of our third-party manufacturers or suppliers could be disrupted by conditions unrelated to our business or operations, including the bankruptcy of the manufacturer or supplier or the issuance of a FDA Form 483 notice, warning letter, or cease and desist order; • carrier disruptions or increased costs that are beyond our control; and • failure to deliver our products under specified storage conditions and in a timely manner.
See also the risk factor titled “—Our business, operations and clinical development plans and timelines and supply chain could be adversely affected by the effects of health epidemics, on the manufacturing, clinical trial and other business activities performed by us or by third parties with whom we conduct business, including our CMOs, CROs, shippers and others.” Further, our reliance on third-party manufacturers exposes us to risks beyond our control, including the risk of: • inability to meet our product specifications and quality requirements consistently; • delay or inability to procure or expand sufficient manufacturing capacity; • manufacturing and quality issues, including related to scale-up of manufacturing; • costs and validation of new equipment and facilities required for additional scale-up; • failure of the manufacturer to comply with cGMP and similar foreign standards; 55 • inability to negotiate manufacturing agreements with third parties on commercially reasonable terms; • termination or nonrenewal of manufacturing agreements with third parties in a manner or at a time that is costly or damaging to us; • reliance on a limited number of sources, and in some cases, single sources for components, such that if we are unable to secure a sufficient supply of these drug components, we will be unable to manufacture and sell our product candidates in a timely fashion, in sufficient quantities or under acceptable terms; • lack of qualified backup suppliers for those components that are currently purchased from a sole or single source supplier; • operations of our third-party manufacturers or suppliers could be disrupted by conditions unrelated to our business or operations, including the bankruptcy of the manufacturer or supplier or the issuance of a FDA Form 483 notice, warning letter, or cease and desist order; • carrier disruptions or increased costs that are beyond our control; and • failure to deliver our products under specified storage conditions and in a timely manner.
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; 55 • the U.S. federal false claims, including the False Claims Act, which can be enforced through whistleblower actions, and Civil Monetary Penalties Laws, which, among other things, impose criminal and civil penalties against individuals or entities for 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; • the U.S. federal false claims, including the False Claims Act, which can be enforced through whistleblower actions, and Civil Monetary Penalties Laws, which, among other things, impose criminal and civil penalties against individuals or entities for 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.
Before you make a decision to buy our securities, in addition to the risks and uncertainties discussed in the section titled 30 “Cautionary Information Regarding Forward-Looking Statements,” you should carefully consider the risks and uncertainties described below together with all of the other information contained in this Annual Report on Form 10-K, including our financial statements and related notes and in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” The occurrence of any of the events or developments described in the following risk factors and the risks described elsewhere in this report could harm our business, financial condition, results of operations, cash flows, the trading price of our common stock and our growth prospects.
Before you make a decision to buy our securities, in addition to the risks and uncertainties discussed in the section titled “Cautionary Information Regarding Forward-Looking Statements,” you should carefully consider the risks and uncertainties described below together with all of the other information contained in this Annual Report on Form 10-K, including our financial statements and related notes and in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” The occurrence of any of the events or developments described in the following risk factors and the risks described elsewhere in this report could harm our business, financial condition, results of operations, cash flows, the trading price of our common stock and our growth prospects.
If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.
If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, 62 and injunctions against our processing or transferring of personal data necessary to operate our business.
Accordingly, our future results could be harmed by a variety of factors, including: • economic weakness, including inflation, or political instability in particular non-U.S. economies and markets; • differing and changing regulatory requirements for product approvals; • differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions; • potentially reduced protection for intellectual property rights; • difficulties in compliance with different, complex and changing laws, regulations and court systems of multiple jurisdictions and compliance with a wide variety of foreign laws, treaties and regulations; • changes in non-U.S. regulations and customs, tariffs and trade barriers; • changes in non-U.S. currency exchange rates of the RMB; • increasing geopolitical tensions between the U.S. and China and changes in a specific country’s or region’s political or economic environment especially with respect to a particular country’s treatment of or stance towards other countries; • trade protection measures, import or export licensing requirements or other restrictive actions by governments; • differing reimbursement regimes and price controls in certain non-U.S. markets; • negative consequences from changes in tax laws; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • variable tax treatment in different jurisdictions of options granted under our equity incentive plans; • workforce uncertainty in countries where labor unrest is more common than in the United States; and • business interruptions resulting from geo-political actions, including war and terrorism, health epidemics, or natural disasters including earthquakes, typhoons, floods and fires.
Accordingly, our future results could be harmed by a variety of factors, including: • economic weakness, including inflation, or political instability in particular non-U.S. economies and markets; • differing and changing regulatory requirements for product approvals; • differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions; • potentially reduced protection for intellectual property rights; • difficulties in compliance with different, complex and changing laws, regulations and court systems of multiple jurisdictions and compliance with a wide variety of foreign laws, treaties and regulations; • changes in non-U.S. regulations and customs, tariffs and trade barriers; • changes in non-U.S. currency exchange rates of the RMB; • increasing geopolitical tensions between the U.S. and China and changes in a specific country’s or region’s political or economic environment especially with respect to a particular country’s treatment of or stance towards other countries; • trade protection measures, import or export licensing requirements or other restrictive actions by governments; • differing reimbursement regimes and price controls in certain non-U.S. markets; • negative consequences from changes in tax laws; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • different tax treatment in various jurisdictions of options granted under our equity incentive plans; • workforce uncertainty in countries where labor unrest is more common than in the United States; and • business interruptions resulting from geo-political actions, including war and terrorism, health epidemics, or natural disasters including earthquakes, typhoons, floods and fires.
Foreign organizations and the entities established or actually controlled by foreign organizations or individuals may only utilize and be provided with China’s human genetic resources after satisfaction of all requirements under the HGR Regulation and other applicable laws, such as (i) China’s human genetic resources being utilized only in international cooperation with Chinese scientific research institutions, universities, medical institutions, and enterprises for scientific research and clinical trials after completion of requisite approval or filing formalities with competent governmental authorities, and (ii) China’s human genetic resources 75 information being provided after required filing and information backup procedures have been gone through.
Foreign organizations and the entities established or actually controlled by foreign organizations or individuals may only utilize and be provided with China’s human genetic resources after satisfaction of all requirements under the HGR Regulation and other applicable laws, such as (i) China’s human genetic resources being utilized only in international cooperation with Chinese scientific research institutions, universities, medical institutions, and enterprises for scientific research and clinical trials after completion of requisite approval or filing formalities with competent governmental authorities, and (ii) China’s human genetic resources information being provided after required filing and information backup procedures have been gone through.
For example: 67 • others may be able to make products that are similar to any product candidates we may develop or utilize similar technology but that are not covered by the claims of the patents that we own or license now or in the future; • we, or our current or future licensors, might not have been the first to make the inventions covered by the issued patents or pending patent applications that we own or license now or in the future; • we, or our current or future licensors, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • it is possible that our pending owned or licensed patent applications or those that we may own or license in the future will not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by other persons; • our competitors might conduct research and development activities in the U.S. under FDA-related safe harbor patent infringement exemptions and/or in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents or pending patent applications of others may harm our business; and • we may choose not to file for patent protection in order to maintain certain trade secrets or know-how, and a third party may subsequently file for and obtain a patent covering such intellectual property.
For example: • others may be able to make products that are similar to any product candidates we may develop or utilize similar technology but that are not covered by the claims of the patents that we own or license now or in the future; • we, or our current or future licensors, might not have been the first to make the inventions covered by the issued patents or pending patent applications that we own or license now or in the future; • we, or our current or future licensors, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • it is possible that our pending owned or licensed patent applications or those that we may own or license in the future will not lead to issued patents; 72 • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by other persons; • our competitors might conduct research and development activities in the U.S. under FDA-related safe harbor patent infringement exemptions and/or in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents or pending patent applications of others may harm our business; and • we may choose not to file for patent protection in order to maintain certain trade secrets or know-how, and a third party may subsequently file for and obtain a patent covering such intellectual property.
Federal Food, Drug and Cosmetic Act, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; • the U.S. federal legislation commonly referred to as Physician Payments Sunshine Act, enacted as part of the Affordable Care 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 to report annually to the Centers for Medicare & Medicaid Services ("CMS") information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; • analogous 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; 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; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and • European, Chinese and other foreign law equivalents of each of the laws, including reporting requirements detailing interactions with and payments to healthcare providers.
Federal Food, Drug and Cosmetic Act, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; • the U.S. federal legislation commonly referred to as Physician Payments Sunshine Act, enacted as part of the Affordable Care 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 to report annually to CMS information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; • analogous 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; 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; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and • European and other foreign law equivalents of each of the laws, including reporting requirements detailing interactions with and payments to healthcare providers.
Events that may prevent successful or timely completion of preclinical or clinical development include: • delays in conducting experiments or preclinical studies or unsatisfactory results from such experiments or studies; • delays in reaching a consensus with regulatory authorities on trial design, dose optimization or dose selection; • delays in reaching agreement or failing to agree on acceptable terms with prospective CROs and clinical trial sites; 40 • delays in opening sites and recruiting suitable patients to participate in our clinical trials; • delays in enrollment due to travel or quarantine policies, or other factors, related to health epidemics, other pandemics or other events outside our control; • imposition of a clinical hold by regulatory authorities as a result of a serious adverse event, concerns with a class of product candidates or after an inspection of our clinical trial operations or trial sites; • delays in having patients complete participation in a trial or return for post-treatment follow-up; • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; or • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols.
Events that may prevent successful or timely completion of preclinical or clinical development include: • delays in conducting experiments or preclinical studies or unsatisfactory results from such experiments or studies; • delays in reaching a consensus with regulatory authorities on trial design, dose optimization or dose selection; • delays in reaching agreement or failing to agree on acceptable terms with prospective CROs and clinical trial sites; • delays in opening sites and recruiting suitable patients to participate in our clinical trials; • delays in enrollment due to travel or quarantine policies, or other factors, related to health epidemics, other pandemics or other events outside our control; • imposition of a clinical hold by regulatory authorities as a result of a serious adverse event, concerns with a class of product candidates or after an inspection of our clinical trial operations or trial sites; • delays in having patients complete participation in a trial or return for post-treatment follow-up; 48 • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; or • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to: interruptions or stoppages in our business operations (including, as relevant, clinical 58 trials); inability to process sensitive data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to: interruptions or stoppages in our business operations (including, as relevant, clinical trials); inability to process sensitive data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations.
Depending upon the timing, duration and conditions of any FDA marketing approval of our product candidates, one or more of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments, and one or more of our 63 foreign patents may be eligible for patent term extension under similar legislation, for example, in the European Union.
Depending upon the timing, duration and conditions of any FDA marketing approval of our product candidates, one or more of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments, and one or more of our foreign patents may be eligible for patent term extension under similar legislation, for example, in the European Union.
Section 302 of the Sarbanes-Oxley Act requires, among other things, that public companies report on the effectiveness of our disclosure controls and procedures in our quarterly and annual reports and, beginning with this report, Section 404 of the Sarbanes-Oxley Act requires that we perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal control over financial reporting in our Annual Report 85 on Form 10-K for that year.
Section 302 of the Sarbanes-Oxley Act requires, among other things, that public companies report on the effectiveness of our disclosure controls and procedures in our quarterly and annual reports and, beginning with this report, Section 404 of the Sarbanes-Oxley Act requires that we perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal control over financial reporting in our Annual Report on Form 10-K for that year.
Although we try to ensure that our employees, consultants and advisors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these individuals have used or disclosed intellectual property, including trade secrets or other proprietary information, of others, such as any such individual’s former employer.
Although we try to ensure that our employees, consultants and advisors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these individuals have used or 70 disclosed intellectual property, including trade secrets or other proprietary information, of others, such as any such individual’s former employer.
Moreover, increasing efforts by governmental and third-party payors in the U.S. and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for newly approved products and, as a result, they may not cover or provide adequate payment for our product candidates.
Moreover, increasing efforts by governmental and third-party payors in the U.S. and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for newly 33 approved products and, as a result, they may not cover or provide adequate payment for our product candidates.
Potential proceedings include re-examination, post-grant review, inter partes review, interference proceedings, derivation proceedings and equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings). Such proceedings could result in the revocation of, cancellation of, or amendment to our patents in such a way that they no longer cover our technology or any product candidates that we may develop.
Potential proceedings include re-examination, post-grant review, inter partes review, interference 65 proceedings, derivation proceedings and equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings). Such proceedings could result in the revocation of, cancellation of, or amendment to our patents in such a way that they no longer cover our technology or any product candidates that we may develop.
If we or any of our CROs or vendors fail to comply with applicable regulations, the data generated in our preclinical studies and clinical trials may be deemed unreliable and the FDA, European Commission, MHRA, NMPA or any other comparable foreign regulatory authority may require us to perform additional preclinical studies and clinical trials before approving our marketing applications.
If we or any of our CROs or vendors fail to comply with applicable regulations, the data generated in our preclinical studies and clinical trials may be deemed unreliable and the FDA, the EMA and the European Commission, MHRA, NMPA or any other comparable foreign regulatory authority may require us to perform additional preclinical studies and clinical trials before approving our marketing applications.
In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties and other fees, redesign 65 our infringing drug or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.
In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties and other fees, redesign our infringing drug or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.
As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific 47 and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
Our (or the third parties with whom we work) actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions; litigation (including class claims) and mass arbitration demands; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue or profits; loss of revenue or profits; and other adverse business consequences.
Our (or the third parties with whom we work) actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions; litigation (including class claims) and mass 61 arbitration demands; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue or profits; loss of revenue or profits; and other adverse business consequences.
We seek to protect these trade secrets and other proprietary technology, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, collaborators, CROs, contract manufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and 66 consultants.
We seek to protect these trade secrets and other proprietary technology, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, collaborators, CROs, contract manufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants.
If any of these 38 events occur, we may be forced to abandon our development efforts for a program or programs, which would harm our business. Our DDC platform-based product candidates are based on a novel technology, which makes it difficult to predict the time and cost of product candidate development.
If any of these events occur, we may be forced to abandon our development efforts for a program or programs, which would harm our business. Our DDC platform-based product candidates are based on a novel technology, which makes it difficult to predict the time and cost of product candidate development.
Periodic maintenance fees, renewal fees, annuity fees and various other government fees on any issued patents and certain pending patent applications are required to be paid to the USPTO or foreign patent agencies in several 64 stages over the lifetime of a patent. In certain circumstances, we may rely on our licensors to pay these fees.
Periodic maintenance fees, renewal fees, annuity fees and various other government fees on any issued patents and certain pending patent applications are required to be paid to the USPTO or foreign patent agencies in several stages over the lifetime of a patent. In certain circumstances, we may rely on our licensors to pay these fees.
If any of our trade secrets were to be disclosed to or independently developed by a competitor or other third party, our competitive position would be materially and adversely harmed. We may not be able to protect and enforce our trademarks and trade names, or build name recognition in our markets of interest thereby harming our competitive position.
If any of our trade secrets were to be disclosed to or independently developed by a competitor or other third party, our competitive position would be materially and adversely harmed. 71 We may not be able to protect and enforce our trademarks and trade names, or build name recognition in our markets of interest thereby harming our competitive position.
Applicable data privacy and security obligations may require us to notify relevant stakeholders, including affected individuals, regulators, and investors, of security incidents, or to implement other requirements, such as 72 providing credit monitoring. Such disclosures and compliance with such requirements are costly, and the disclosure or the failure to comply with such requirements could lead to adverse consequences.
Applicable data privacy and security obligations may require us to notify relevant stakeholders, including affected individuals, regulators, and investors, of security incidents, or to implement other requirements, such as providing credit monitoring. Such disclosures and compliance with such requirements are costly, and the disclosure or the failure to comply with such requirements could lead to adverse consequences.
Outside the United States, an increasing number of laws, regulations, and industry standards may govern data privacy and security. For example, the European Union’s General Data Protection Regulation, or EU GDPR, the 57 United Kingdom’s GDPR, or UK GDPR, Australia’s Privacy Act, and China’s Personal Information Protection Law, or PIPL, impose strict requirements for processing personal data.
Outside the United States, an increasing number of laws, regulations, and industry standards may govern data privacy and security. For example, the European Union’s General Data Protection Regulation, or EU GDPR, the United Kingdom’s GDPR, or UK GDPR, Australia’s Privacy Act, and China’s Personal Information Protection Law, or PIPL, impose strict requirements for processing personal data.
Such proceedings also may result in substantial cost and require significant time from our scientists and management, even if the eventual outcome is favorable to us. Moreover, there could be public announcements of the results of hearings, motions or other developments related to any of the foregoing proceedings.
Such proceedings also may result in substantial cost and require significant time from our scientists and management, even if the eventual outcome is favorable to us. Moreover, there could be public announcements of the results of hearings, motions or other 64 developments related to any of the foregoing proceedings.
Despite our efforts to comply with applicable laws, regulations and other obligations relating to privacy, data protection and information security, it is possible that our practices, offerings or platform could fail to meet all of the requirements imposed on us by the Cyber Security Law, the Data Security Law and/or related implementing regulations.
Despite our efforts to comply with applicable laws, regulations and other obligations relating to privacy, data protection and information security, it is possible that our practices, offerings or platform could fail to meet all of the requirements imposed on us by the Cyber Security Law, the Data Security Law, the Personal Information Protection Law and/or related implementing regulations.
In a patent infringement proceeding, a court may decide that a patent of ours is invalid and/or 60 unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology.
In a patent infringement proceeding, a court may decide that a patent of ours is invalid and/or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology.
If we are unable to obtain patent term extension or the term of any such extension is less than we request, the period during which we can enforce our patent rights for the applicable product candidate will be shortened, and our competitors may obtain approval to market competing products sooner.
If we are unable to obtain patent term extension or the term of any such extension is less than we request, 68 the period during which we can enforce our patent rights for the applicable product candidate will be shortened, and our competitors may obtain approval to market competing products sooner.
Further, others, including regulatory authorities, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product or product candidate, and our company in general.
Further, others, including regulatory authorities, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular drug candidate or product and our company in general.
In 2020, the SCNPC promulgated the Biosecurity Law of the PRC, which reaffirms the regulatory requirements stipulated by the HGR Regulation while potentially increasing the administrative sanctions where China’s human genetic resources are collected, preserved, exported or used in international cooperation in violation of applicable laws.
In 2020, 80 the SCNPC promulgated the Biosecurity Law of the PRC, which reaffirms the regulatory requirements stipulated by the HGR Regulation while potentially increasing the administrative sanctions where China’s human genetic resources are collected, preserved, exported or used in international cooperation in violation of applicable laws.
In addition, if certain events occur, including certain bankruptcy events, non-payment of Payments, a change of control, expiration or termination of certain intellectual property rights or marketing authorization, an out-license or sale of all of the rights in and to taletrectinib in the United States and (subject to applicable cure periods) non-compliance with the covenants in the RIF Agreement, we may be required to repurchase the synthetical royalty financing at a repurchase price ranging from 1.4 to 2.0 times of the Investment Amount, depending on the time of such event, less all royalty payments we made by then (the “Put/Call Payment”).
In addition, if certain events occur, including certain bankruptcy events, non-payment of Payments, a change of control, expiration or termination of certain intellectual property rights or marketing authorization, an out-license or sale of all of the rights in and to IBTROZI in the United States and (subject to applicable cure periods) non-compliance with the covenants in the RIF Agreement, we may be required to repurchase the synthetical royalty financing at a repurchase price ranging from 1.4 to 2.0 times of the Investment Amount, depending on the time of such event, less all royalty payments we made by then (the “Put/Call Payment”).
If our third-party CMOs are unable to successfully scale up the manufacture of any of our product candidates in sufficient quality and quantity and at commercially reasonable prices, and we are unable to find one or more replacement suppliers or manufacturers capable of production at a substantially equivalent cost in substantially equivalent volumes 52 and quality, and we are unable to successfully transfer the processes on a timely basis, the development of that product candidate and regulatory approval or commercial launch for any resulting products may be delayed, or there may be a shortage in supply, either of which could significantly harm our business, financial condition, results of operations and prospects.
If our third-party CMOs are unable to successfully scale up the manufacture of any of our product candidates in sufficient quality and quantity and at commercially reasonable prices, and we are unable to find one or more replacement suppliers or manufacturers capable of production at a substantially equivalent cost in substantially equivalent volumes and quality, and we are unable to successfully transfer the processes on a timely basis, the development of that product candidate 56 and regulatory approval or commercial launch for any resulting products may be delayed, or there may be a shortage in supply, either of which could significantly harm our business, financial condition, results of operations and prospects.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted and the terms of these securities may include liquidation or other preferences 32 that adversely affect your rights as a stockholder.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a stockholder.
In addition, under the RIF Agreement, if certain events occur, including certain bankruptcy events, non-payment of Payments, a change of control, expiration or termination of certain intellectual property rights or marketing authorization, an out-license or sale of all of the rights in and to taletrectinib in the United States and (subject to applicable cure periods) non-compliance with the covenants in the RIF Agreement, we may be required to repurchase the synthetical royalty financing at a repurchase price ranging from 1.4 to 2.0 times of the Investment Amount, depending on the time of such event, less all royalty payments we made by then.
In addition, under the RIF Agreement, if certain events occur, including certain bankruptcy events, non-payment of Payments, a change of control, expiration or termination of certain intellectual property rights or marketing authorization, an out-license or sale of all of the rights in and to IBTROZI in the United States and (subject to applicable cure periods) non-compliance with the covenants in the RIF Agreement, we may be required to repurchase the synthetical royalty financing at a repurchase price ranging from 1.4 to 2.0 times of the Investment Amount, depending on the time of such event, less all royalty payments we made by then.
These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. 66 Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
We face the risk of potential unauthorized disclosure, infringement, misappropriation or other violation of our intellectual 50 property by CROs, which may reduce our trade secret protection and allow our potential competitors, and other third parties, to access and exploit our proprietary technology.
We face the risk of potential unauthorized disclosure, infringement, misappropriation or other violation of our intellectual property by CROs, which may reduce our trade secret protection and allow our potential competitors, and other third parties, to access and exploit our proprietary technology.
We may also issue additional shares of Class A Common Stock or other equity securities of equal or senior rank in the future in connection with, among other things, future acquisitions or repayment of outstanding indebtedness, without stockholder approval, in a number of circumstances.
We may also issue additional shares of Class A Common Stock or other equity securities of equal or senior rank in the future in connection with, among other 88 things, future acquisitions or repayment of outstanding indebtedness, without stockholder approval, in a number of circumstances.
Even if we obtain Orphan Drug exclusivity for any of our product candidates, that exclusivity may not effectively protect the product candidates from competition because different therapies can be approved for the same condition and the same therapy could be approved for different conditions.
Even if we obtain Orphan Drug exclusivity for any of our product candidates, that exclusivity may not effectively protect the product candidates from 53 competition because different therapies can be approved for the same condition and the same therapy could be approved for different conditions.
If the NYSE delists our securities from trading on its exchange for failure to meet the listing standards, we and our stockholders could face significant negative consequences including: • limited availability of market quotations for our securities; • a determination that our common stock is a “penny stock” which will require brokers trading in our common stock to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for shares of our common stock; • a limited amount of analyst coverage; and 82 • a decreased ability to issue additional securities or obtain additional financing in the future.
If the NYSE delists our securities from trading on its exchange for failure to meet the listing standards, we and our stockholders could face significant negative consequences including: • limited availability of market quotations for our securities; • a determination that our Common Stock is a “penny stock” which will require brokers trading in our Common Stock to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for shares of our Common Stock; • a limited amount of analyst coverage; and 87 • a decreased ability to issue additional securities or obtain additional financing in the future.
Separately, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or the Internal Revenue Code, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which generally is defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes, such as research tax credits, to offset its post-change income or taxes may be limited.
Separately, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, (the “Internal Revenue Code”), and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which generally is defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes, such as research tax credits, to offset its post-change income or taxes may be limited.
This indebtedness may create additional financing risk for us, particularly if our business or prevailing financial market conditions are not conducive to paying off or refinancing 34 the outstanding debt obligations at maturity.
This indebtedness may create additional financing risk for us, particularly if our business or prevailing financial market conditions are not conducive to paying off or refinancing the outstanding debt obligations at maturity.
There can be no assurance that any development problems we may experience in the future related to our DDC platform will not cause significant delays or unanticipated costs, or that such development problems can be efficiently solved.
There can be no assurance that any development problems we may experience in the future related to our DDC platform will 46 not cause significant delays or unanticipated costs, or that such development problems can be efficiently solved.
Due to our operations in China, any future Chinese, U.S. or other rules and regulations that place restrictions on capital raising or other activities by companies with operations in China could affect our business and results of operations.
Due to our operations in China, any future Chinese, U.S. or other rules and regulations that place restrictions on capital raising or other activities by companies with operations in China could negatively affect our business and results of operations.
In addition, changing laws, regulations and standards relating to corporate governance and public disclosure, including regulations implemented by the SEC and the NYSE may increase legal and financial compliance costs and make some activities more time consuming.
In addition, changing laws, regulations and standards relating to corporate governance and public disclosure, 90 including regulations implemented by the SEC and the NYSE may increase legal and financial compliance costs and make some activities more time consuming.
In accordance with the Stock Option Rules and other relevant rules and regulations, Chinese citizens or non-Chinese citizens residing in China for a continuous period of not less than one year who participate in any 80 stock incentive plan of an overseas publicly listed company, subject to a few exceptions, are required to register with SAFE through a domestic qualified agent, which could be a Chinese subsidiary of such overseas listed company, and complete certain procedures.
In accordance with the Stock Option Rules and other relevant rules and regulations, Chinese citizens or non-Chinese citizens residing in China for a continuous period of not less than one year who participate in any 85 stock incentive plan of an overseas publicly listed company, subject to a few exceptions, are required to register with SAFE through a domestic qualified agent, which could be a Chinese subsidiary of such overseas listed company, and complete certain procedures.
The research, testing, manufacturing, safety, efficacy, labeling, approval, sale, marketing and distribution of product candidates is, and will remain, subject to comprehensive regulation by the FDA and similar foreign regulatory authorities.
The research, testing, manufacturing, safety, efficacy, labeling, approval, sale, marketing and distribution of product candidates is, and will remain, subject to comprehensive 44 regulation by the FDA and similar foreign regulatory authorities.
In addition, 74 online platform operators possessing personal information of more than one million users seeking to be listed on foreign stock markets must apply for a cybersecurity review.
In addition, online platform operators possessing personal information of more than one million users seeking to be listed on foreign stock markets must apply for a cybersecurity review.
Failure to satisfy our current and future debt obligations under the Loan Agreement, the RIF Agreement, or to comply with certain covenants in such agreements could result in an event of default, the occurrence and continuance of which provides Sagard with the right to demand immediate repayment of all outstanding obligations under such agreements (and in the case of certain insolvency, liquidation, bankruptcy or similar events, automatically requires 35 immediate repayment of all outstanding obligations under such agreements), and to exercise remedies against us and the collateral securing such agreements.
Failure to satisfy our current and future debt obligations under the Loan Agreement, the RIF Agreement, or to comply with certain covenants in such agreements could result in an event of default, the occurrence and continuance of which provides Sagard with the right to demand immediate repayment of all outstanding obligations under such agreements (and in the case of certain insolvency, liquidation, bankruptcy or similar events, automatically requires 43 immediate repayment of all outstanding obligations under such agreements), and to exercise remedies against us and the collateral securing such agreements.
The continuing efforts of the government, insurance companies, managed care organizations and other payors of health care services to contain or reduce costs of health care may adversely affect: • the demand for any products for which we may obtain regulatory approval; • our ability to set a price that we believe is fair for our products; • our ability to obtain coverage and reimbursement approval for a product; • our ability to generate revenues and achieve or maintain profitability; and • the level of taxes that we are required to pay.
The continuing efforts of the government, insurance companies, managed care organizations and other payors of health care services to contain or reduce costs of health care may adversely affect: • the demand for any products for which we may obtain regulatory approval; • our ability to set a price that we believe is fair for our products; • our ability to obtain coverage and reimbursement approval for a product; • our ability to generate revenues and achieve or maintain profitability; and • the amount of taxes that we are required to pay.
Innovative drugs similar to taletrectinb have historically been more limited on their inclusion in the NRDL due to the affordability of the government’s Basic Medical Insurance, although this has been changing in recent years. Obtaining and maintaining reimbursement status is time-consuming and costly. No uniform policy for coverage and reimbursement for products exists among third-party payors in the U.S.
Innovative drugs similar to taletrectinib have historically been more limited on their inclusion in the NRDL due to the affordability of the government’s Basic Medical Insurance, although this has been changing in recent years. Obtaining and maintaining reimbursement status is time-consuming and costly. No uniform policy for coverage and reimbursement for products exists among third-party payors in the U.S.
Additionally, certain data privacy and security obligations may require us to implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and sensitive data.
Additionally, certain data privacy and security obligations may require us to 76 implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and sensitive data.
Risks Related to our Indebtedness Our level of indebtedness and debt service obligations could adversely affect our financial condition and may make it more difficult for us to fund our operations. On March 3, 2025, the Company announced the closing of a non-dilutive financing of up to $250.0 million from entities affiliated with Sagard Healthcare Partners (collectively, “Sagard”).
Risks Related to our Indebtedness Our level of indebtedness and debt service obligations could adversely affect our financial condition and may make it more difficult for us to fund our operations. On March 3, 2025, we announced the closing of a non-dilutive financing of up to $250.0 million from entities affiliated with Sagard Healthcare Partners (collectively, “Sagard”).
Some of these competitive products and therapies are based on scientific approaches that 45 are the same as or similar to our approach, and others are based on entirely different approaches.
Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely different approaches.
Switching or adding additional suppliers or vendors involves 69 substantial cost and requires management time and focus. In addition, there is a natural transition period when a new supplier or vendor commences work. As a result, delays generally occur, which could adversely impact our ability to meet our desired clinical development and any future commercialization timelines.
Switching or adding additional suppliers or vendors involves 73 substantial cost and requires management time and focus. In addition, there is a natural transition period when a new supplier or vendor commences work. As a result, delays generally occur, which could adversely impact our ability to meet our desired clinical development and any future commercialization timelines.
In 2022, together with 12 other Chinese regulatory authorities, the CAC released the final version of the Revised Draft CAC Measures (the “Revised CAC Measures”), which came into effect in 2022.
In 2022, together with 12 other Chinese regulatory authorities, the CAC released the final version of the Revised Draft CAC Measures (the 79 “Revised CAC Measures”), which came into effect in 2022.
While we intend to closely monitor the evolving laws and regulations in this area and take all reasonable measures to mitigate compliance risks, we cannot guarantee that our business and operations will not be adversely affected by the potential impact of the Revised CAC Measures, the Draft Management Regulations or other laws and regulations related to privacy, data protection and information security.
While we intend to closely monitor the evolving laws and regulations in this area and take all reasonable measures to mitigate compliance risks, we cannot guarantee that our business and operations will not be adversely affected by the potential impact of the Revised CAC Measures, the Network Data Management Regulations or other laws and regulations related to privacy, data protection and information security.
These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with current Good Manufacturing Practice (“cGMP”), regulations and GCPs, for any clinical trials that we conduct post-approval, all of which may result in significant expense and limit our ability to commercialize such products.
These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with current Good Manufacturing Practice (“cGMP”), regulations and Good Clinical Practice (“GCP”), for any clinical trials that we conduct post-approval, all of which may result in significant expense and limit our ability to commercialize such products.
Collaborations are complex and time-consuming to negotiate 53 and document. In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. We may not be able to negotiate collaboration agreements on a timely basis, on acceptable terms, or at all.
Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. 57 We may not be able to negotiate collaboration agreements on a timely basis, on acceptable terms, or at all.
Even if our product candidates and any associated companion diagnostics are approved for marketing, the need for companion diagnostics may slow or limit adoption of our product candidates.
Even if our product candidates and any associated companion diagnostics are approved or certified for marketing, the need for companion diagnostics may slow or limit adoption of our product candidates.
We would continue to bear the risk that the FDA or similar foreign regulatory authorities such as the European Medicines Agency (“EMA”), the U.K. Medicines & Healthcare Products Regulatory Agency (“MHRA”) or the National Medical Product Administration of China (“NMPA”), could revoke approval, or that safety, efficacy, manufacturing or supply issues could arise that negatively impact product sales.
We would continue to bear the risk that the FDA or similar foreign regulatory authorities such as the European Commission, the U.K. Medicines & Healthcare Products Regulatory Agency (“MHRA”) or the National Medical Product Administration of China (“NMPA”), could revoke approval, or that safety, efficacy, manufacturing or supply issues could arise that negatively impact product sales.
Future guidance from the Internal Revenue Service and other tax authorities with respect to any such legislation may affect us, and certain aspects of such legislation could be repealed or modified in future legislation. In addition, it is uncertain if and to what extent various states will conform to federal tax laws.
Future guidance from the Internal Revenue Service and other tax authorities with respect to any such legislation may affect us, and certain aspects of such legislation could be repealed or modified in future legislation or sunset in future years. In addition, it is uncertain if and to what extent various states will conform to federal tax laws.
These include: • issuing warning or untitled letters; • seeking an injunction or imposing civil or criminal penalties or monetary fines; • suspension or imposition of restrictions on operations, including product manufacturing; • seizure or detention of products, refusal to permit the import or export of products or request that we initiate a product recall; • suspension, variation or withdrawal of our marketing authorizations; • suspension of any ongoing clinical trials; • refusal to approve pending applications or supplements to applications submitted by us; or • requiring us to conduct additional clinical trials, change our product labeling or submit additional applications for marketing authorization.
These include: • issuing warnings or untitled letters; 36 • seeking an injunction or imposing civil or criminal penalties or monetary fines; • suspension or imposition of restrictions on operations, including product manufacturing; • seizure or detention of products, refusal to permit the import or export of products or request that we initiate a product recall; • suspension, variation or withdrawal of our marketing authorizations; • suspension of any ongoing clinical trials; • refusal to approve pending applications or supplements to applications submitted by us; or • requiring us to conduct additional clinical trials, change our product labeling or submit additional applications for marketing authorization.
The market price for our securities may be influenced by many factors, including: • adverse regulatory decisions; • any delay in our regulatory filings for our product candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s review of such filings, including without limitation the FDA’s issuance of a “refusal to file” letter or a request for additional information; • the impact of health epidemics; • the commencement, enrollment or results of any future clinical trials we may conduct, or changes in the development status of our product candidates; • adverse results from, delays in or termination of clinical trials; • unanticipated serious safety concerns related to the use of our product candidates; • lower than expected market acceptance of our product candidates following approval for commercialization; • changes in financial estimates by us or by any securities analysts who might cover our securities; • conditions or trends in our industry; • changes in the market valuations of similar companies; • stock market price and volume fluctuations of comparable companies and, in particular, those that operate in the pharmaceutical industry; • publication of research reports about us or our industry or positive or negative recommendations or withdrawal of research coverage by securities analysts; • announcements by us or our competitors of significant acquisitions, strategic partnerships or divestitures; • announcements of investigations or regulatory scrutiny of our operations or lawsuits filed against us; • investors’ general perception of our company and our business; • recruitment or departure of key personnel; • overall performance of the equity markets; • trading volume of our securities; • disputes or other developments relating to intellectual property rights, including patents, litigation matters and our ability to obtain, maintain, defend, protect and enforce patent and other intellectual property rights for our technologies; 81 • significant lawsuits, including patent or stockholder litigation; • proposed changes to healthcare laws in the U.S., China or other foreign jurisdictions, or speculation regarding such changes including changes in the structure of healthcare payment systems; • general political and economic conditions; and • other events or factors, many of which are beyond our control.
The market price for our securities may be influenced by many factors, including: • lower than expected market acceptance of IBTROZI or our other product candidates if approved; • adverse regulatory decisions; • any delay in our regulatory filings for our product candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s review of such filings, including without limitation the FDA’s issuance of a “refusal to file” letter or a request for additional information; • the impact of health epidemics; • the commencement, enrollment or results of any future clinical trials we may conduct, or changes in the development status of our product candidates; • adverse results from, delays in or termination of clinical trials; • unanticipated serious safety concerns related to the use of our product candidates; • changes in financial estimates by us or by any securities analysts who might cover our securities; • conditions or trends in our industry; • changes in the market valuations of similar companies; • stock market price and volume fluctuations of comparable companies and, in particular, those that operate in the pharmaceutical industry; • publication of research reports about us or our industry or positive or negative recommendations or withdrawal of research coverage by securities analysts; • announcements by us or our competitors of significant acquisitions, strategic partnerships or divestitures; • announcements of investigations or regulatory scrutiny of our operations or lawsuits filed against us; • investors’ general perception of our company and our business; • recruitment or departure of key personnel; • overall performance of the equity markets; • trading volume of our securities; • disputes or other developments relating to intellectual property rights, including patents, litigation matters and our ability to obtain, maintain, defend, protect and enforce patent and other intellectual property rights for our technologies; 86 • significant lawsuits, including patent or stockholder litigation; • proposed changes to healthcare laws in the U.S., China or other foreign jurisdictions, or speculation regarding such changes including changes in the structure of healthcare payment systems; • general political and economic conditions; and • other events or factors, many of which are beyond our control.
Our product development programs and the potential commercialization of our product candidates will require substantial additional capital to fund expenses. The commercial rights to taletrectinib have been out-licensed in China and Japan, and we may enter into other collaboration agreements with pharmaceutical and biotechnology companies for the future development and potential commercialization of our product candidates.
Our product development programs and the commercialization of our product candidates will require substantial additional capital to fund expenses. The commercial rights to taletrectinib have been out-licensed in China, Japan, Europe and other territories, and we may enter into other collaboration agreements with pharmaceutical and biotechnology companies for the future development and potential commercialization of our product candidates.
These laws may impact, among other things, our current business operations, including our clinical research activities, and proposed sales, marketing and education programs and constrain the business of financial arrangements and relationships with healthcare providers and other parties through which we may market, sell and distribute our products for which we obtain marketing approval.
These laws may impact, among other things, our current business operations, including commercialization of IBTROZI, our clinical research activities, and proposed sales, marketing and education programs and constrain the business of financial arrangements and relationships with healthcare providers and other parties through which we may market, sell and distribute our products for which we obtain marketing approval.
During 71 times of war and other major conflicts, we and the third parties with whom we work may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our services.
During 75 times of war and other major conflicts, we and the third parties with whom we work may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our services.
In that case, we may be required to delay, limit, reduce or terminate our taletrectinib commercialization efforts, our research and development efforts, or grant to others rights to develop and market taletrectinib. Our business, financial condition and results of operations could be materially adversely affected as a result of any of these events.
In that case, we may be required to delay, limit, reduce or terminate our IBTROZI commercialization efforts, our research and development efforts, or grant to others rights to develop and market IBTROZI. Our business, financial condition and results of operations could be materially adversely affected as a result of any of these events.
The Chinese government has introduced various reforms to the Chinese healthcare system in recent years and may continue to do so, with an overall objective to expand basic medical insurance coverage and improve the quality and reliability of healthcare services. The specific regulatory changes under the various reform initiatives 76 remain uncertain.
The Chinese government has introduced various reforms to the Chinese healthcare system in recent years and may continue to do so, with an overall objective to expand basic medical insurance coverage and improve the quality and reliability of healthcare services. The specific regulatory changes under the various reform initiatives 81 remain uncertain.
Our ability to achieve acceptable levels of coverage and reimbursement for products by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize our product candidates and, if desired, attract collaboration partners to invest in the development of our product candidates.
Our ability to achieve acceptable levels of coverage and reimbursement for products by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize IBTROZI and our product candidates, if approved, and, if desired, attract collaboration partners to invest in the development of our product candidates.
Any such legal challenges, if successful, could have a material impact on our business. Additionally, the Loper decision may result in increased regulatory uncertainty, 48 inconsistent judicial interpretations, and other impacts to the agency rulemaking process, any of which could adversely impact our business and operations.
Any such legal challenges, if successful, could have a material impact on our business. Additionally, the Loper Bright decision may result in increased regulatory uncertainty, inconsistent judicial interpretations, and other impacts to the agency rulemaking process, any of which could adversely impact our business and operations.
In the future, we may choose to build a focused sales and marketing infrastructure to sell, or participate in sales activities with our collaborators for, taletretinib in territories outside of the U.S. and territories subject to existing partnerships, or for our other product candidates if and when they are approved.
In the future, we may choose to build a focused sales and marketing infrastructure to sell, or participate in sales activities with our collaborators for, taletrectinib in territories outside of the U.S. and territories subject to existing partnerships, or for our other product candidates if and when they are approved.
Moreover, failure to comply with the various foreign exchange registration requirements described above could result in liability under Chinese law for 79 circumventing applicable foreign exchange restrictions. As a result, our business operations and our ability to make distributions to you could be materially and adversely affected.
Moreover, failure to comply with the various foreign exchange registration requirements described above could result in liability under Chinese law for 84 circumventing applicable foreign exchange restrictions. As a result, our business operations and our ability to make distributions to you could be materially and adversely affected.
In addition, our tax obligations and effective tax rate could increase, including as a result of the base erosion and profit shifting (“BEPS”) project that is being led by the Organization for Economic Co-operation and Development (“OECD”), and other initiatives led by the OECD.
In addition, our tax obligations (including the cost of compliance) and effective tax rate could increase, including as a result of the base erosion and profit shifting (“BEPS”) project that is being led by the Organization for Economic Co-operation and Development (“OECD”), and other initiatives led by the OECD.
All obligations under the Loan Agreement are secured by substantially all of our assets, including our intellectual property, and all obligations under the RIF Agreement are secured by accounts receivable arising from U.S. net sales of taletrectinib and intellectual property, product registrations and regulatory approvals related to commercialization and development of taletrectinib in the United States.
All obligations under the Loan Agreement are secured by substantially all of our assets, including our intellectual property, and all obligations under the RIF Agreement are secured by accounts receivable arising from U.S. net sales of IBTROZI and intellectual property, product registrations and regulatory approvals related to commercialization and development of IBTROZI in the United States.
Under the RIF Agreement, in exchange for the Investment Amount, we have agreed to make tiered royalty payments to Sagard on U.S. net sales of taletrectinib equal to 5.5% of annual U.S. net sales up to $600 million and 3.0% of annual U.S. net sales between $600 million and $1 billion.
Under the RIF Agreement, in exchange for the Investment Amount, we have agreed to make tiered royalty payments to Sagard on U.S. net sales of IBTROZI equal to 5.5% of annual U.S. net sales up to $600 million and 3.0% of annual U.S. net sales between $600 million and $1 billion.
The completion of the 2021 merger of Nuvation 33 Bio Inc. and Panacea Acquisition Corp., together with private placements and other transactions that have occurred since our inception, may have triggered such an ownership change pursuant to Section 382.
The completion of the 2021 merger of Nuvation 41 Bio Inc. and Panacea Acquisition Corp., together with private placements and other transactions that have occurred since our inception, may have triggered such an ownership change pursuant to Section 382.
Remote work has become more common and has increased risks to our information technology systems and data, as more of our personnel utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit or in public locations.
Remote work has increased risks to our information technology systems and data, as more of our personnel utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit or in public locations.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeFor a description of the risks from cybersecurity threats that may materially affect the Company and how they may do so, see the section titled “Risk Factors” in Item 1A of this Annual Report on Form 10-K, including the risk factor titled “—Our internal computer systems, or those used by our CROs or other contractors or consultants, may fail or experience security breaches or other unauthorized or improper access.” Governance Our board of directors addresses the Company’s cybersecurity risk management as part of its general oversight function.
Biggest changeFor a description of the risks from cybersecurity threats that may materially affect the Company and how they may do so, see the section titled “Risk Factors” in Item 1A of this Annual Report on Form 10-K, including the risk factor titled “— If our information technology systems or those of third parties with whom we work, or our data are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions; litigation; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue or profits; and other adverse consequences .” Governance Our board of directors addresses the Company’s cybersecurity risk management as part of its general oversight function.
For example, (1) cybersecurity risk is addressed as a component of the Company’s enterprise risk management program; (2) security management works with management to prioritize our risk management processes and mitigate cybersecurity threats that are more likely to lead to a material impact to our business; (3) our management evaluates material risks from cybersecurity threats against our overall business objectives and reports to the audit committee of the board of directors, which evaluates our overall enterprise risk, and (4) we have a cybersecurity incident response plan to identify, assess, respond to, and inform escalating levels of management based on the nature and severity of such incidents.
For example, (1) cybersecurity risk is addressed as a component of the Company’s enterprise risk management program; (2) security management works with management to prioritize our risk management processes and mitigate cybersecurity threats that are more likely to lead to a material impact to our 91 business; (3) our management evaluates material risks from cybersecurity threats against our overall business objectives and reports to the audit committee of the board of directors, which evaluates our overall enterprise risk, and (4) we have a cybersecurity incident response plan to identify, assess, respond to, and inform escalating levels of management based on the nature and severity of such incidents.
We use third-party service providers to perform a variety of functions throughout our business, such as application providers, hosting companies, and contract research organizations. We have a vendor management program to manage cybersecurity risks associated with our use of these providers.
We use third-party service providers to perform a variety of functions throughout our business, such as application providers, hosting companies, and contract research organizations. We have a vendor management program designed to manage cybersecurity risks associated with our use of these providers.
In addition, the Company’s incident response 87 processes and policies include reporting to the audit committee of the board of directors for certain cybersecurity incidents. The board of directors and audit committee receive periodic reports concerning the Company’s significant cybersecurity threats and risk and the processes the Company has implemented to address them.
In addition, the Company’s incident response processes and policies include reporting to the audit committee of the board of directors for certain cybersecurity incidents. The board of directors and audit committee receive periodic reports concerning the Company’s significant cybersecurity threats and risk and the processes the Company has implemented to address them.
We use third-party service providers to assist us from time to time to identify, assess, and manage material risks from cybersecurity threats, including for example Professional services firms, including legal counsel, threat intelligence service providers, cybersecurity consultants, cybersecurity software providers, managed cybersecurity service providers (including SIEM tools and 24/7 managed detection and response), penetration testing firms, and dark web monitoring services.
We use third-party service providers to assist us from time to time in an effort to identify, assess, and manage material risks from cybersecurity threats, including for example professional services firms, including legal counsel, threat intelligence service providers, cybersecurity consultants, cybersecurity software providers, managed cybersecurity service providers (including SIEM tools and 24/7 managed detection and response), penetration testing firms, and dark web monitoring services.
Our Audit Committee, together with our information security function and third-party service providers help identify, assess, and manage the Company’s cybersecurity threats and risks.
Our audit committee of our board of directors, together with our information security function and third-party service providers help identify, assess, and manage the Company’s cybersecurity threats and risks.
Additionally they identify and assess risks from cybersecurity threats by monitoring and evaluating our threat environment and the Company’s risk profile using various methods including, for example using automated tools, subscribing to reports and services that identify cybersecurity threats, analyzing reports of threats and actors, conducting scans of the threat environment, evaluating our and our industry’s risk profile, evaluating threats reported to us, conducting internal and/or external audits, 86 conducting threat assessments for internal and external threats, third party threat assessments, conducting vulnerability assessments to identify vulnerabilities, and using external intelligence feeds.
We take steps designed to identify and assess risks from cybersecurity threats by monitoring and evaluating our threat environment and the Company’s risk profile using various methods including, for example using automated tools, subscribing to reports and services that identify cybersecurity threats, analyzing reports of threats and actors, conducting scans of the threat environment, evaluating our and our industry’s risk profile, evaluating threats reported to us, conducting internal and/or external audits, conducting threat assessments for internal and external threats, third party threat assessments, conducting vulnerability assessments to identify vulnerabilities, and using external intelligence feeds.
The program includes a risk assessment for each vendor, a security questionnaire, review of the vendor's written security program, review of security assessments and other reports.
The program includes the following elements such as a risk assessment, a security questionnaire, a review of the vendor's written security program, a review of security assessments and other reports.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeOur principal executive offices are located in New York, New York, where we lease approximately 7,900 square feet of office space under a lease that terminates in 2027, with an option for us to extend the lease for an additional five years which is not reasonably assured of exercise, and in San Francisco, where we lease approximately 19,418 square feet of office space that terminates in 2029.
Biggest changeItem 2. Prop erties. Our principal executive offices are located in New York, New York, where we lease approximately 7,900 square feet of office space under a lease that terminates in 2027, and in San Francisco, where we lease approximately 19,418 square feet of office space that terminates in 2029.
We also occupy office space located in Burlington, Massachusetts, where we lease approximately 2,235 square feet of office space under a lease that terminates in 2027, as well as a total of approximately 1,735 square meters of office space in the People’s Republic of China, in the cities of Beijing, Guangzhou, Hangzhou and Shanghai, under leases that terminate in 2026 through 2027.
We also occupy office space located in Burlington, Massachusetts, where we lease approximately 2,235 square feet of office space under a lease that terminates in 2027, as well as a total of approximately 1,799 square meters of office space in the People’s Republic of China, in the cities of Beijing, Guangzhou, Hangzhou and Shanghai, under leases that terminate in 2026 through 2029.
Added
In the second half of 2026, we plan to move our New York office to a new location in New York, New York with approximately 18,563 square feet of office space and a lease expiring 92 in 2037.
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We consider our current office spaces adequate to meet our ongoing needs. From time to time we may evaluate additional or substitute office spaces. We believe that we will be able to obtain additional facilities, as needed, on commercially reasonable terms.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Item 3. Legal Pro ceedings. From time to time, we may become involved in legal proceedings or be subject to claims arising in the ordinary course of our business. We are not currently a party to any material legal proceedings.
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Item 3. Legal Pro ceedings. On July 30, 2025, Tim Patterson filed a derivative complaint (Tim Patterson, derivatively on behalf of Nuvation Bio, Inc. v. David Hung, et al.
Removed
Regardless of outcome, such proceedings or claims can have an adverse impact on us because of defense and settlement costs, diversion of resources and other factors, and there can be no assurances that favorable outcomes will be obtained. Item 4. Mine Sa fety Disclosures. Not applicable. 88 PAR T II
Added
Index No. 654535/2025) (the “Action”) in the Supreme Court of the State of New York for the County of New York on behalf of Nuvation Bio against our seven current directors and one former director (the “Individual Defendants”).
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The Action asserts claims against the Individual Defendants for allegedly breaching their fiduciary duties to us by awarding our directors excessive compensation between 2021 and 2024 and seeks restitution from the Individual Defendants, changes to our director compensation policies and practices, and attorneys’ fees and other costs of suit.
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On November 12, 2025, the plaintiff voluntarily discontinued the Action without prejudice. Item 4. Mine Sa fety Disclosures. Not applicable. PAR T II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeHolders of Record As of February 14, 2025, there were approximately 55 holders of record of our Class A common stock and 20 holders of record of our warrants to purchase shares of our Class A common stock. Dividend Policy We have never declared or paid cash dividends on our capital stock.
Biggest changeOn February 10, 2026, the warrants to purchase Class A Common Stock expired and were delisted pursuant to a Form 25 filed by The New York Stock Exchange. Holders of Record As of February 26, 2026, there were approximately 36 holders of record of our Class A common stock.
We intend to retain all available funds and any future earnings, if any, to fund the development and expansion of our business and we do not anticipate paying any cash dividends in the foreseeable future. Any future determination related to dividend policy will be made at the discretion of our board of directors.
Dividend Policy We have never declared or paid cash dividends on our capital stock. We intend to retain all available funds and any future earnings, if any, to fund the development and expansion of our business and we do not anticipate paying any cash dividends in the foreseeable future.
Recent Sales of Unregistered Equity Securities None Issuer Purchases of Equity Securities None Item 6. R eserved 89
Any future determination related to dividend policy will be made at the discretion of our board of directors. Recent Sales of Unregistered Equity Securities None Issuer Purchases of Equity Securities None 93 Item 6. R eserved

Item 7. Management's Discussion & Analysis

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

47 edited+24 added−36 removed54 unchanged
Biggest changeOperating Expenses The following table presents a breakdown of our operating expenses by functional category: Years Ended December 31, Increase / 2024 2023 (Decrease) (In thousands) Operating expenses: Research and development $ 99,119 $ 71,289 $ 27,830 Acquired in-process research and development 425,070 — 425,070 General and administrative 69,233 28,533 40,700 Total operating expenses 593,422 99,822 493,600 Research and Development Expenses Research and development expenses increased by $27.8 million for the year ended December 31, 2024 compared to 2023.
Biggest changeThe increase is primarily due to a $19.1 million increase in license revenue and a $6.3 million increase in research and development service revenue as a result of the milestone payment from Nippon Kayaku for the establishment of the reimbursement price in Japan in December 2025, a $1.3 million increase in royalty revenue, and a $3.6 million increase in product supply. 97 Costs and Expenses The following table presents a breakdown of our costs and expenses by functional category: Years Ended December 31, Increase / 2025 2024 (Decrease) (In thousands) Costs and expenses: Cost of sales $ 856 $ — $ 856 Cost of collaboration and license agreements revenue 8,442 7,078 1,364 Research and development 115,106 99,119 15,987 Acquired in-process research and development — 425,070 (425,070 ) Selling, general and administrative 151,562 69,233 82,329 Total costs and expenses $ 275,966 $ 600,500 $ (324,534 ) Cost of Sales Cost of sales increased by $0.9 million for the year ended December 31, 2025 was primarily due to amortization of our licensed market approval.
Financing Activities In 2024, cash provided by financing activities of $0.3 million was related to the $4.5 million proceeds from exercise of options and $0.4 million of proceeds from issuance of Common Stock under the Employee Stock Purchase Plan and $12.6 million of proceeds from borrowings offset by $17.2 million of debt repayments.
In 2024, cash provided by financing activities of $0.3 million was related to the $4.5 million proceeds from exercise of options and $0.4 million of proceeds from issuance of Common Stock under the Employee Stock Purchase Plan and $12.6 million of proceeds from borrowings offset by $17.2 million of debt repayments.
In general, the consideration allocated to each performance obligation is recognized when the respective obligation is satisfied either by delivering a good or providing a service, limited to the consideration that is not constrained. Non-refundable 97 payments received before all of the relevant criteria for revenue recognition are satisfied are recorded as contract liabilities.
In general, the consideration allocated to each performance obligation is recognized when the respective obligation is satisfied either by delivering a good or providing a service, limited to the consideration that is not constrained. Non-refundable payments received before all of the relevant criteria for revenue recognition are satisfied are recorded as contract liabilities.
In addition, if certain events occur, including certain bankruptcy events, non-payment of Payments, a change of control, expiration or termination of certain intellectual property rights or marketing authorization, an out-license or sale of all of the rights in and to taletrectinib in the United States and (subject to applicable cure periods) non-compliance with the covenants in the RIF Agreement, we may be required to repurchase the synthetical royalty financing at a repurchase price ranging from 1.4 to 2.0 times of the Investment Amount, depending on the time of such event, less all royalty payments we made by then under the Loan Agreement, the term loan will bear interest at the secured overnight financing rate ("SOFR") plus a margin of 6.00%, subject to a 4.00% SOFR floor.
In addition, if certain events occur, including certain bankruptcy events, non-payment of Payments, a change of control, expiration or termination of certain intellectual property rights or marketing authorization, an out-license or sale of all of the rights in and to IBTROZI in the United States and (subject to applicable cure periods) non-compliance with the covenants in the RIF Agreement, we may be required to repurchase the synthetical royalty financing at a repurchase price ranging from 1.4 to 2.0 times of the Investment Amount, depending on the time of such event, less all royalty payments we made by then under the Loan Agreement, the term loan will bear interest at the secured overnight financing rate ("SOFR") plus a margin of 6.00%, subject to a 4.00% SOFR floor.
Research and Development Expenses Research and development expenses include: • expenses incurred under agreements with third-party contract organizations, and consultants; • costs related to production of drug substance, including fees paid to contract manufacturers; 92 • laboratory and vendor expenses related to the execution of preclinical trials; and • employee-related expenses, which include salaries, benefits and stock-based compensation.
Research and Development Expenses Research and development expenses include: • expenses incurred under agreements with third-party contract organizations, and consultants; • costs related to production of drug substance, including fees paid to contract manufacturers; • laboratory and vendor expenses related to the execution of preclinical trials; and • employee-related expenses, which include salaries, benefits and stock-based compensation.
Investing Activities In 2024, cash provided by investing activities of $122.7 million was related to the $450.1 million of proceeds from the sale of marketable securities, $19.9 million cash acquired from the acquisition of AnHeart offset by purchase of marketable securities of $339.7 million, $7.4 million of transaction costs related to the acquisition of AnHeart and purchase of property and equipment of $0.2 million.
In 2024, cash provided by investing activities of $122.7 million was related to the $450.1 million of proceeds from the sale of marketable securities, $19.9 million cash acquired from the acquisition of AnHeart offset by purchase 100 of marketable securities of $339.7 million, $7.4 million of transaction costs related to the acquisition of AnHeart and purchase of property and equipment of $0.2 million.
We expect to incur substantial expenses in the foreseeable future for the development and potential commercialization of our product candidates and ongoing internal research and development programs. At this time, we cannot reasonably estimate the nature, timing or aggregate amount of costs for our development, potential commercialization, and internal research and development programs.
We expect to incur substantial expenses in the foreseeable future for the development and commercialization of our product candidates and ongoing internal research and development programs. At this time, we cannot reasonably estimate the nature, timing or aggregate amount of costs for our development, commercialization, and internal research and development programs.
As a result, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of any of our product candidates.
As a result, we are unable to determine the duration and completion costs of 96 our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of any of our product candidates.
Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and disruptions to and volatility in the credit and financial markets in the United States and worldwide.
Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and disruptions to and volatility in the credit and financial markets in the United States and 95 worldwide.
General and Administrative Expenses General and administrative expenses consist of personnel-related costs, facilities costs, depreciation and amortization expenses and professional services expenses, including legal, human resources, audit and accounting services. Personnel-related costs consist of salaries, benefits and stock-based compensation. Facilities costs consist of rent and maintenance of facilities.
Selling, General and Administrative Expenses Selling, general and administrative expenses consist of personnel-related costs, facilities costs, depreciation and amortization expenses and professional services expenses, including legal, human resources, audit and accounting services. Personnel-related costs consist of salaries, benefits and stock-based compensation. Facilities costs consist of rent and maintenance of facilities.
We expect to continue to incur 91 significant expenses and increasing operating losses over at least the next several years.
We expect to continue to incur significant expenses and increasing operating losses over at least the next several years.
Under the RIF Agreement, in exchange for the Investment Amount, we have agreed to make tiered royalty payments to Sagard on U.S. net sales of taletrectinib equal to 5.5% of annual U.S. net sales up to $600 million and 3.0% of annual U.S. net sales between $600 million and $1 billion.
Under the RIF Agreement, in exchange for the Investment Amount, we have agreed to make tiered royalty payments to Sagard on U.S. net sales of IBTROZI equal to 5.5% of annual U.S. net sales up to $600 million and 3.0% of annual U.S. net sales between $600 million and $1 billion.
Based upon our current operating plan, we believe that our existing cash, cash equivalents and marketable securities as of December 31, 2024, will enable us to fund our operating expenses and capital expenditure requirements through at least the next 12 months.
Based upon our current operating plan, we believe that our existing cash, cash equivalents and marketable securities as of December 31, 2025, will enable us to fund our operating expenses and capital expenditure requirements through at least the next 12 months.
Collaborative Arrangement In November 2018, the FASB issued Topic 808, "Collaborative Arrangements" ("ASC 808"): Clarifying the Interaction between ASC 808 and ASC 606.
Collaborative Arrangements In November 2018, the FASB issued Topic 808, "Collaborative Arrangements" ("ASC 808"): Clarifying the Interaction between ASC 808 and ASC 606.
The optional future services do not include a material right to be accounted for as performance obligations. Milestone payments Our collaboration agreements include development and regulatory milestones. We evaluate whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method.
The optional future services do not include a material right to be accounted for as performance obligations. Milestone payments Our collaboration agreements include development and regulatory milestones. We evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the transaction price 102 using the most likely amount method.
There are no scheduled amortization payments associated with the term loan, with all outstanding principal due at maturity. The transaction will support the U.S. commercial launch of taletrectinib and general corporate purposes.
There are no scheduled amortization 99 payments associated with the term loan, with all outstanding principal due at maturity. The transaction will support the U.S. commercial launch of IBTROZI and general corporate purposes.
We leverage our team’s extensive expertise in medicinal chemistry, preclinical development, drug development, business development, manufacturing, and commercialization to pursue oncology targets validated by strong clinical or preclinical data and develop novel small molecules that improve the activity and overcome the liabilities of currently marketed drugs. As a result of our April 2024 acquisition of AnHeart Therapeutics Ltd.
We leverage our team’s extensive expertise in medicinal chemistry, preclinical development, drug development, business development, manufacturing, and commercialization to pursue oncology targets validated by strong clinical or preclinical data and develop novel small molecules that improve the activity and overcome the liabilities of currently marketed drugs.
As of December 31, 2024, we had $502.7 million in cash, cash equivalents and marketable securities and an accumulated deficit of $910.7 million. Our primary use of cash is to fund operating expenses, which consist of research and development expenses related to our clinical-stage product candidates and preclinical programs, and to a lesser extent, general and administrative expenses.
As of December 31, 2025, we had $529.2 million in cash, cash equivalents and marketable securities and an accumulated deficit of $1,115.4 million. Our primary use of cash is to fund operating expenses, which consist of research and development expenses related to our clinical-stage product candidates and preclinical programs, and to a lesser extent, general and administrative expenses.
We base our estimates on historical experience and on various other assumptions that we believe to be reasonable in the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions and conditions.
On an on-going basis, we evaluate our critical accounting policies and estimates. We base our estimates on historical experience and on various other assumptions that we believe to be reasonable in the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources.
The change in operating assets and liabilities was primarily due to a $2.3 million decrease in prepaid expenses and $0.1 million increase in accounts payable offset by $1.2 million increase in interest receivable on marketable securities and $0.6 million increase in other non-current assets.
The change in operating assets and liabilities was primarily due to a $3.4 million increase in accounts receivable, $11.4 million increase in inventory, $7.9 million decrease in contract liabilities, $4.3 million increase in prepaid expenses and other current assets, $0.8 million increase in other non-current assets offset by $3.1 million increase in accounts payable, $12.4 million increase in accrued expenses, and $0.3 million decrease in interest receivable on marketable securities.
While our significant accounting policies are described in the notes to our consolidated financial statements, we believe that the following critical accounting policies are most important to understanding and evaluating our reported financial results.
Actual results may differ from these estimates under different assumptions and conditions. While our significant accounting policies are described in the notes to our consolidated financial statements, we believe that the following critical accounting policies are most important to understanding and evaluating our reported financial results.
However, in order to complete our current and future preclinical studies and clinical trials, and to complete the process of obtaining regulatory approval for our product candidates, as well as to build the sales, marketing and distribution infrastructure that we believe will be necessary to commercialize our product candidates, if approved, we may require substantial additional funding in the future.
However, in order to complete our current and future preclinical studies and clinical trials, and to complete the process of obtaining regulatory approval for our product candidates, as well as to commercialize our product candidates, we may require substantial additional funding in the future.
General and Administrative Expenses General and administrative expenses increased by $40.7 million for the year ended December 31, 2024, compared to 2023.
Selling, General and Administrative Expenses Selling, general and administrative expenses increased by $82.3 million for the year ended December 31, 2025, compared to 2024.
Cash Flows The following table summarizes our cash flows for the periods indicated: 95 Years Ended December 31, 2024 2023 (In thousands) Cash used in operating activities $ (130,413 ) $ (67,999 ) Cash provided by investing activities 122,703 8,921 Cash provided by financing activities 331 628 Effect of foreign exchange rate changes on cash and cash equivalents 453 — Net decrease in cash and cash equivalents $ (6,926 ) $ (58,450 ) Operating Activities In 2024, cash used in operating activities of $130.4 million was attributable to a net loss of $567.9 million, a net change of $12.5 million in our net operating assets and liabilities offset by non-cash charges of $450.0 million.
Cash Flows The following table summarizes our cash flows for the periods indicated: Years Ended December 31, 2025 2024 (In thousands) Cash used in operating activities $ (173,427 ) $ (130,413 ) Cash provided by investing activities 99,520 122,703 Cash provided by financing activities 202,535 331 Effect of foreign exchange rate changes on cash and cash equivalents (265 ) 453 Net increase (decrease) in cash and cash equivalents $ 128,363 $ (6,926 ) Operating Activities In 2025, cash used in operating activities of $173.4 million was attributable to a net loss of $204.6 million, net change of $12.0 million in our net operating assets and liabilities offset by non-cash charges of $43.2 million.
The financing is comprised of a $150.0 million synthetic royalty financing and a $100.0 million senior secured term loan. The $150 million from the synthetic royalty financing and the first $50.0 million tranche of the term loan will be funded conditioned upon FDA’s approval of taletrectinib on or prior to September 30, 2025.
The financing is comprised of a $150.0 million synthetic royalty financing and a $100.0 million senior secured term loan. The $150 million from the synthetic royalty financing and the first $50.0 million tranche of the term loan was funded on June 25, 2025 upon FDA’s approval of IBTROZI.
Overview We are a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel product candidates.
Overview We are a commercial-stage, global biopharmaceutical company focused on tackling some of the greatest challenges in cancer treatment by developing differentiated and novel product candidates.
The non-cash charges consisted primarily of stock-based compensation of $19.5 million, realized loss on marketable securities of $0.1 million, depreciation and amortization of $0.2 million offset by changes in fair value of warrant liability of $0.5 million and amortization of premium on marketable securities of $12.1 million.
The non-cash charges consisted primarily of stock-based compensation of $35.9 million, $1.8 million of depreciation and amortization, $0.3 million of lease expense, $10.1 million in interest expense, $0.7 million of amortization of debt issuance costs, changes in fair value of warrant liability of $0.8 million offset by amortization of premium on marketable securities of $5.3 million, and $1.1 million of foreign currency transaction loss.
In 2023, cash used in operating activities of $68.0 million was attributable to a net loss of $75.8 million offset by a net change of $0.6 million in our net operating assets and liabilities and non-cash charges of $7.2 million.
In 2024, cash used in operating activities of $130.4 million was attributable to a net loss of $567.9 million, a net change of $12.5 million in our net operating assets and liabilities offset by non-cash charges of $450.0 million.
Other Income (Expense), Net The following table presents a breakdown of our other income (expense): Years Ended December 31, 2024 2023 Change (In thousands) Other income (expense): Interest income $ 27,062 $ 24,611 $ 2,451 Interest expense (341 ) — (341 ) Investment advisory fees (976 ) (949 ) (27 ) Change in fair value of warrant liability (936 ) 497 (1,433 ) Realized loss on marketable securities (12 ) (139 ) 127 Other expense (109 ) — (109 ) Total other income (expense), net $ 24,688 $ 24,020 $ 668 94 Other income (expense), net increased by $0.7 million for the year ended December 31, 2024 compared to 2023 primarily related to an increase in interest income from investments of $2.5 million primarily due to higher treasury yield offset by a $1.4 million increase in the change in fair value of warrant liability, a $0.3 million increase in interest expense, and a $0.1 million increase in other expense.
Other Income (Expense), Net The following table presents a breakdown of our other income (expense): 98 Years Ended December 31, 2025 2024 Change (In thousands) Other income (expense): Interest income $ 21,430 $ 27,062 $ (5,632 ) Interest expense (13,682 ) (341 ) (13,341 ) Investment advisory fees (722 ) (976 ) 254 Change in fair value of warrant liability (812 ) (936 ) 124 Realized gain (loss) on marketable securities 5 (12 ) 17 Net loss on fixed asset disposal (33 ) — (33 ) Other income (expense) 2,251 (109 ) 2,360 Total other income, net $ 8,437 $ 24,688 $ (16,251 ) Other income (expense), net decreased by $16.3 million for the year ended December 31, 2025 compared to 2024 primarily related to a decrease in interest income from investments of $5.6 million primarily due to lower treasury yield, a $13.3 million increase in interest expense offset by a $0.1 million decrease in the change in fair value of warrant liability, $2.3 million increase in other income due to government subsidy income and a $0.2 million decrease in investment advisory fees.
The second tranche of $50 million of the term loan will be available at our option until June 30, 2026, as long as we have achieved first U.S. commercial sale of taletrectinib.
The Investment Amount and a $50.0 million tranche of the term loan was funded on June 25, 2025, following FDA’s approval of IBTROZI. The second tranche of $50.0 million of the term loan will be available at our option until June 30, 2026, because we have achieved first U.S. commercial sale of IBTROZI.
In the event of an early termination of a collaboration agreement, any contract liabilities would be recognized in the period in which all our obligations under the agreement have been fulfilled. For a complete discussion of accounting for revenue, see the section titled "Collaboration and License Agreements" in Note 5 to our consolidated financial statements appearing elsewhere in this report.
For a complete discussion of accounting for revenue, see the section titled "Collaboration and License Agreements" in Note 5 to our consolidated financial statements appearing elsewhere in this report.
In 2023, cash provided by investing activities of $8.9 million was related to the purchase of marketable securities of $703.4 million and purchases of property and equipment of $0.1 million offset by $712.4 million of proceeds from the sale of marketable securities.
Investing Activities In 2025, cash provided by investing activities of $99.5 million was related to the $462.3 million of proceeds from the sale of marketable securities offset by purchase of marketable securities of $354.4 million, $8.0 million payment for capitalized market approval intangibles and $0.4 million purchase of property and equipment.
Recent Accounting Pronouncements For information about recent accounting pronouncements, see the sections titled “Significant Accounting Policies—Recent Accounting Pronouncements” in Note 2 to our consolidated financial statements for the year ended December 31, 2024 appearing elsewhere in this report.
We accounted for the transaction as an asset acquisition since the lead asset represented substantially all of the fair value of the gross assets acquired. 103 Recent Accounting Pronouncements For information about recent accounting pronouncements, see the sections titled “Significant Accounting Policies—Recent Accounting Pronouncements” in Note 2 to our consolidated financial statements for the year ended December 31, 2025 appearing elsewhere in this report.
Taletrectinib has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (“FDA”) for the treatment of patients with ROS1+ NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration ("NMPA") for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC.
FDA for the treatment of patients with ROS1+ NSCLC and other NSCLC indications, and was previously granted Breakthrough Therapy Designations by both the U.S. FDA and China’s NMPA for the treatment of both TKI-naïve and TKI-pretreated disease patients with locally advanced or metastatic ROS1+ NSCLC.
Any such adjustments are recorded on a cumulative catch-up basis, which would affect revenue and net loss in the period of adjustment. Royalties For sales-based royalties, including milestone payments based on the level of sales, we determine whether the sole or predominant item to which the royalties relate is a license.
Royalties For sales-based royalties, including milestone payments based on the level of sales, we determine whether the sole or predominant item to which the royalties relate is a license.
The financing is comprised of a $150.0 million synthetic royalty financing and a $100.0 million senior secured term loan.
The financing is comprised of a $150.0 million (the "Investment Amount") synthetic royalty financing agreement with Sagard Healthcare Partners (Delaware) II LP (the “RIF Agreement”) and a $100.0 million senior secured term loan with Sagard Holdings Manager LP (the “Loan Agreement”).
Results of Operations for the Years Ended December 31, 2024 and 2023 Revenues Our revenue related to its out-licensing collaborative agreements consist of upfront license fees and research and development services revenue from its collaboration agreements.
Our revenue related to its out-licensing collaborative agreements consists of product revenue, upfront license fees and milestone payments, royalty revenue and research and development services revenue from its collaboration agreements.
To date, we have not recognized any sales-based royalty revenue resulting from our collaboration agreements. We receive payments from our customers based on billing terms established in the contract. Up-front payments and fees are recorded as contract liabilities (e.g., deferred revenue) upon receipt or when due until we perform our obligations under the arrangement.
Up-front payments and fees are recorded as contract liabilities (e.g., deferred revenue) upon receipt or when due until we perform our obligations under the arrangement. In the event of an early termination of a collaboration agreement, any contract liabilities would be recognized in the period in which all our obligations under the agreement have been fulfilled.
In 2023, cash provided by financing activities of $0.6 million was related to the $0.4 million of proceeds from exercise of options and $0.2 million of proceeds from issuance of common stock under the Employee Stock Purchase Plan.
Financing Activities In 2025, cash provided by financing activities of $202.5 million was related to the $150.0 million proceeds from the RIF Agreement, $60.1 million proceeds from borrowings, $10.1 million proceeds from exercise of options and $1.3 million of proceeds from issuance of Common Stock under the Employee Stock Purchase Plan offset by $6.6 million payment of debt issuance costs, $11.9 million of debt repayments, and $0.5 million payment for revenue interest financing agreement.
The preparation of these consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenues and expenses. On an on-going basis, we evaluate our critical accounting policies and estimates.
Critical Accounting Policies and Significant Judgments and Estimates Our management’s discussion and analysis of financial condition and results of operations is based upon our consolidated financial statements, which have been prepared in accordance with GAAP. The preparation of these consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenues and expenses.
We recognize as revenue the amount of the transaction price that is allocated to each performance obligation when that performance obligation is satisfied or as it is satisfied. Accounts receivable represent amounts invoiced and revenues recognized prior to invoicing when we have satisfied our performance obligation and have the unconditional right to payment.
Accounts receivable represent amounts invoiced and revenues recognized prior to invoicing when we have satisfied our performance obligation and have the unconditional right to payment. Product revenue, net We recognize product revenue, net of variable consideration related to certain allowances and accruals, when the customer takes control of the product, which is typically upon delivery to the customer.
Acquisition of assets and businesses 98 Our consolidated financial statements include the operations of acquired businesses after the completion of the acquisitions.
Such costs are recognized under Interest expense in the Consolidated Statements of Operations and Comprehensive Loss and under Accrued expenses on the Consolidated Balance Sheets. Acquisition of assets and businesses Our consolidated financial statements include the operations of acquired businesses after the completion of the acquisitions.
Our revenue related to its out-licensing collaborative agreements consists of upfront license fees and research and development services revenue from its collaboration agreements. We have funded our operations to date primarily from the issuance and sale of our common and preferred stock, including through the Merger and a Private Investment in Public Equity ("PIPE") financing in connection with the Merger.
We have funded our operations to date primarily from the issuance and sale of our common and preferred stock, including through the Merger and a Private Investment in Public Equity ("PIPE") financing in connection with the Merger. We have incurred net losses in each year since inception. As of December 31, 2025, we had an accumulated deficit of $1,115.4 million.
The increase was due to a $18.3 million increase in personnel-related costs as a result of the acquisition of AnHeart, $13.2 million increase in sales and marketing expenses, $3.6 million increase in professional fees, $0.5 million increase in occupancy expenses, $1.5 million increase in legal fees, $0.1 million increase in amortization of assembled workforce, $0.1 million increase in taxes, $0.4 million increase in foreign currency impact and $3.9 million increase in other expenses as a result of the integration of AnHeart offset by $0.9 million decrease in insurance expense.
FDA approval of taletrectinib, $41.0 million increase in sales and marketing expenses, a $3.1 million increase in legal fees, a $0.1 million increase in professional fees and $0.2 million increase in other expenses offset by $1.5 million decrease in foreign currency impact.
These arrangements may include non-refundable upfront payments, contingent obligations for potential development, regulatory and commercial performance milestone payments, cost reimbursement arrangements and royalty payments. We receive payments from our customers based on billing terms established in the contract.
To date, these collaborative arrangements have included out-licenses of and options to out-licensing in-licensed compounds to other parties. These arrangements may include non-refundable upfront payments, contingent obligations for potential development, regulatory and commercial performance milestone payments, cost reimbursement arrangements and royalty payments.
("AnHeart"), our most advanced clinical-stage product candidate, taletrectinib, is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with ROS1+ non-small cell lung cancer ("NSCLC"). Taletrectinib is being evaluated in patients with advanced ROS1+ NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I in China, and TRUST-II, a global study.
Taletrectinib continues to be evaluated for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I in China, and TRUST-II, a global study, as well as in a confirmatory randomized Phase 3 study versus crizotinib in China known as TRUST-III.
The increase was primarily due to a $25.0 million increase in personnel-related costs driven by the acquisition of AnHeart as well as stock-based compensation and other benefits and $0.4 million increase in amortization of assembled workforce and $2.4 million increase in third-party costs related to clinical trial expense for taletrectinib offset by decrease in research services and drug manufacturing as a result of completing the Phase 1 monotherapy study of NUV-868.
FDA approval of taletrectinib, a $12.1 million increase in third-party costs related to clinical studies, and a $0.1 million increase in amortization of assembled workforce offset by a $4.0 million decrease in regulatory milestone payments to Daiichi.
Removed
Based on pooled results of the TRUST-I and TRUST-II studies, the Company submitted a New Drug Application (“NDA”) for taletrectinib to the U.S. FDA in October 2024 for the treatment of patients with advanced ROS1+ NSCLC who either have or have not previously been treated with a ROS1 tyrosine kinase inhibitor (“TKI”).
Added
We commercially launched IBTROZI in the U.S. in June 2025, following its approval by the FDA on June 11, 2025 for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC. Taletrectinib has also been approved by Japan’s MHLW and by China’s NMPA for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC.
Removed
Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not previously been treated with ROS1 TKIs.
Added
Taletrectinib is being commercialized in Japan by our partner NK under the brand name IBTROZI and in China by our partner Innovent under the brand name DOVBLERON®. Taletrectinib has been granted Orphan Drug Designation by the U.S.
Removed
Worldwide development and commercial rights to taletrectinib have been in-licensed from Daiichi Sankyo. Commercial rights to taletrectinib have been out-licensed in China and Japan.
Added
Taletrectinib is also being evaluated for the adjuvant treatment of patients with resected ROS1+ early-stage NSCLC in a global Phase 3, placebo-controlled study known as TRUST-IV. In addition to taletrectinib, our clinical stage pipeline includes safusidenib, a novel, oral, potent, brain penetrant, targeted inhibitor of mutant isocitrate dehydrogenase 1 (“mIDH1”).
Removed
In addition to taletrectinib, our clinical-stage pipeline includes differentiated, novel oncology product candidates that have been generated from our proprietary drug discovery and development programs or acquired through business development activities: • Safusidenib is a novel, oral, potent, brain penetrant, targeted inhibitor of mutant isocitrate dehydrogenase 1 ("mIDH1").
Added
Safusidenib is being evaluated in the SIGMA study, which is currently a randomized registration-enabling phase 3 study evaluating the efficacy and safety of safusidenib versus placebo for the maintenance treatment of patients with high-risk or high-grade IDH1-mutant astrocytoma following standard-of-care. 94 Recent Developments • On November 8, 2025, positive results from a Phase 2 study of safusidenib in Japanese patients with chemotherapy- and radiotherapy-naïve grade 2 IDH1-mutant gliomas were published in the online journal of Neuro-Oncology. • In January 2026, we announced entry into an exclusive license agreement for taletrectinib in Europe and additional countries with Eisai. • On February 10, 2026, the outstanding warrants to purchase Class A Common stock expired and were delisted pursuant to a Form 25 filed by The New York Stock Exchange.
Removed
Safusidenib is being evaluated in a Phase 2 study in patients with diffuse IDH1-mutant 90 glioma.
Added
The transaction will support the U.S. launch of IBTROZI and general corporate purposes. Components of Results of Operations Revenues Prior to our commercialization of IBTROZI, substantially all of our revenues were generated from payments under prior collaboration agreements, and milestones, royalties and other revenues from our licensing arrangements.
Removed
The Company is advancing its clinical development strategy for safusidenib with registrational intent based on clinical data generated to date, including two complete responses in high-grade glioma. • NUV-1511 is our first clinical-stage drug-drug conjugate ("DDC"), which fuses a targeting agent to a widely used chemotherapy agent.
Added
Our revenue related to our out-licensing collaborative agreements consists of product revenue, upfront license fees, milestone payments, royalty revenue and research and development services revenue from its collaboration agreements. We receive payments from our customers based on billing terms established in the contract.
Removed
NUV-1511 is being evaluated in a Phase 1/2 study in patients with advanced solid tumors who previously received and progressed on or after treatment with Enhertu® and/or Trodelvy® per approved U.S.
Added
Cost of Sales Cost of sales includes primarily of all product related costs, third-party manufacturing, distribution, employee personnel costs and amortization of our licensed market approval for IBTROZI.
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FDA labeling, human epidermal growth factor receptor 2-negative ("HER2-") metastatic breast cancer, metastatic castration-resistant prostate cancer (“mCRPC”), advanced pancreatic cancer, and platinum-resistant ovarian cancer ("PROC"). • NUV-868 is a BD2-selective, oral, small molecule bromodomain and extra-terminal ("BET") inhibitor that inhibits BRD4.
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Cost of Collaboration and License Agreements Revenue Cost of collaboration and license agreements revenue includes royalties on net sales of IBTROZI owed to our licensing partner and the proportion of expense recognized under the terms of our collaboration agreements.
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As previously announced, we are evaluating next steps for the NUV-868 program, including further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients.
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Results of Operations for the Years Ended December 31, 2025 and 2024 Revenues The following table summarizes total revenue recognized for the years ended December 31, 2025 and 2024: For the Years Ended December 31, 2025 2024 Revenues: Product revenue, net $ 24,663 $ — Collaboration and license agreements revenue 38,239 7,873 Total revenues $ 62,902 $ 7,873 Product Revenue, Net On June 11, 2025, we announced that the FDA approved IBTROZI for the treatment of adult patients with locally advanced or metastatic ROS1+ non-small cell lung cancer (“NSCLC”).
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Recent Developments • In September 2024, we announced pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies of taletrectinib in patients with advanced ROS1+ NSCLC, which was presented at the European Society of Medical Oncology Congress 2024. • In September 2024, David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio, was appointed as Chairman of the Board of Directors.
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To date, our only source of product revenue has been from the U.S. sales of IBTROZI. We began shipping IBTROZI to our U.S. customers in June 2025. Net product revenue from U.S. sales of IBTROZI was approximately $24.7 million for the year ended December 31, 2025.
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Additionally, Robert Bazemore was appointed as the lead independent director. • In October 2024, we announced the appointment of Philippe Sauvage as the Company’s Chief Financial Officer. • In October 2024, we announced submission of a NDA to the FDA for the full approval of taletrectinib for the treatment of patients with advanced ROS1+ NSCLC (line agnostic).
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Collaboration and License Agreements Revenue Collaboration and license agreements revenue increased by $30.3 million for the year ended December 31, 2025 compared to 2024.
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In December 2024, the FDA accepted the NDA with Priority Review designation and assigned a Prescription Drug User Fee Action (“PDUFA”) target action date of June 23, 2025. • In January 2025, China’s NMPA approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not been previously treated with ROS1 TKIs. • In March 2025, we announced that we had entered into a non-dilutive financing of up to $250.0 million from Sagard.
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During the year ended December 31, 2024, there were no cost of sales recognized. Cost of Collaboration and License Agreements Revenue Cost of collaboration and license agreements revenue increased by $1.4 million for the year ended December 31, 2025 compared to 2024.
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We have incurred net losses in each year since inception. As of December 31, 2024, we had an accumulated deficit of $910.7 million.
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The increase was primarily due to a $2.7 million increase in royalty payment for Daiichi Sankyo offset by $1.3 million decrease in research and development service costs under the term of our collaboration agreement with Innovent. Research and Development Expenses Research and development expenses increased by $16.0 million for the year ended December 31, 2025 compared to 2024.
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The transaction will support the U.S. launch of taletrectinib and general corporate purposes. Components of Results of Operations Revenues We enter into collaborative arrangements for the research and development, and commercialization of drug products and drug candidates. To date, these collaborative arrangements have included out-licenses of and options to out-license in-licensed compound to other parties.
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The increase was primarily due to a $7.8 million increase in salaries and other benefits driven by the increase in headcount and stock-based compensation primarily related to one-time charge for the vesting of performance-based awards upon receiving U.S.
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The following table summarizes total revenue recognized for the year ended December 31, 2024: Year Ended December 31, 2024 Revenue License revenue 2,086 Research and development service revenue 5,787 Total $ 7,873 93 There was no revenue in 2023 since the acquisition of AnHeart completed in the second quarter of 2024.
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The increase was due to a $39.4 million increase in personnel-related costs as a result of the increase in headcount and stock-based compensation primarily related to one-time charge for the vesting of performance-based awards upon receiving U.S.
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The financing is comprised of a $150.0 million (the "Investment Amount") synthetic royalty financing under the RIF Agreement and a $100.0 million of senior secured term loan under the Loan Agreement. The Investment Amount and a $50.0 million tranche of the term loan will be funded conditioned upon FDA’s approval of taletrectinib on or prior to September 30, 2025.
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We recognize as revenue the amount of the transaction price that is allocated to each performance obligation when that performance obligation is satisfied or as it is satisfied. The Company recognizes shipping and handling costs as an expense in cost of revenue.
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Off-Balance Sheet Financing Arrangements As of December 31, 2024, we did not have any off-balance sheet arrangements, as defined in Regulation S-K, Item 303(a)(4)(ii). 96 Critical Accounting Policies and Significant Judgments and Estimates Our management’s discussion and analysis of financial condition and results of operations is based upon our consolidated financial statements, which have been prepared in accordance with GAAP.

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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 changeItem 7A. Quantitative and Qualitativ e Disclosures about Market Risk Interest Rate Risk We had cash and investments of $502.7 million as of December 31, 2024, consisting of cash, money market funds, municipal bonds, certificate of deposits, exchange traded fund, government securities, commercial paper, and corporate bonds. To date, fluctuations in interest income have not been significant.
Biggest changeItem 7A. Quantitative and Qualitativ e Disclosures about Market Risk Interest Rate Risk We had cash and investments of $529.2 million as of December 31, 2025, consisting of cash, money market funds, municipal bonds, certificate of deposits, exchange traded fund, government securities, commercial paper, and corporate bonds. To date, fluctuations in interest income have not been significant.

Other NUVB 10-K year-over-year comparisons