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What changed in Biomea Fusion, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Biomea Fusion, 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.

+500 added−548 removedSource: 10-K (2026-03-24) vs 10-K (2025-03-31)

Top changes in Biomea Fusion, Inc.'s 2025 10-K

500 paragraphs added · 548 removed · 353 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

86 edited+54 added−100 removed149 unchanged
Biggest changeThe process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory studies, animal studies and formulation studies in accordance with the FDA’s good laboratory practice (GLP) requirements and other applicable regulations; • 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 site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (GCPs), to establish the safety and efficacy of the proposed drug for its intended use; • preparation of and submission to the FDA of an NDA after completion of all pivotal trials; • a determination by the FDA within 60 days of its receipt of an NDA to file the application for review • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facilities at which the drug is produced to assess compliance with current good manufacturing practice (cGMP) requirements to ensure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of selected clinical investigation sites to assess compliance with GCPs; and • FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States. 25 Prior to beginning the first clinical trial with a product candidate in the United States, a sponsor must submit an IND to the FDA.
Biggest changeThe process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory studies, animal studies and formulation studies in accordance with the FDA’s good laboratory practice (GLP) requirements and other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin and must be updated annually or when certain changes are made; • approval by an independent Institutional Review Board (IRB), or ethics committee at each clinical site before each trial may be initiated; 14 • performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, good clinical practices (GCPs), and other clinical-trial regulations, to establish the safety and efficacy of the proposed drug for its intended use; • preparation of and submission to the FDA of an NDA after completion of all pivotal trials; • a determination by the FDA within 60 days of its receipt of an NDA to file the application for review • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA audit of the preclinical and/or clinical trial sites that generated the data in support of the NDA; • satisfactory completion of an FDA inspection of the manufacturing facilities at which the drug is produced to assess compliance with current good manufacturing practice (cGMP) requirements to ensure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of selected clinical investigation sites to assess compliance with GCPs; and • FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.
Our competitors will also include companies that are or will be developing other targeted therapies, including small molecule, antibody, or protein degraders for the same indications that we are targeting.
Our competitors also include companies that are or will be developing other targeted therapies, including small molecule, antibody, or protein degraders for the same indications that we are targeting.
The term of a patent claiming a new drug product may also be eligible for a limited patent term extension when FDA approval is granted, provided statutory and regulatory requirements are met.
The term of a patent claiming a new drug product may also be eligible for a limited patent term extension when FDA approval of the new drug product is granted, provided statutory and regulatory requirements are met.
Only one patent applicable to an approved product is eligible for the extension, and only those claims covering the approved product, a method for using it, or a method for manufacturing it may be extended. A patent that covers multiple products for which extension is sought can only be extended in connection with one of the approvals.
Only one patent applicable to an approved product is eligible for the extension, and only those claims covering the approved product, a method for using it, or a method for manufacturing it may be extended. A patent that covers multiple products for which extension is sought can be extended only in connection with one of the approvals.
We cannot guarantee that we will have executed such agreements with all applicable employees and contractors, or that these agreements will afford us adequate protection of our intellectual property and proprietary information rights.
We cannot guarantee that we have, or that we will have executed such agreements with all applicable employees and contractors, or that these agreements will afford us adequate protection of our intellectual property and proprietary information rights.
Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty 31 of violating these statutes without actual knowledge of the statutes or specific intent to violate them in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), imposes requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization.
Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating these statutes without actual knowledge of the statutes or specific intent to violate them in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), imposes requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization.
American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. 33 • The American Rescue Plan Act of 2021 eliminates the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.
American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. • The American Rescue Plan Act of 2021 eliminates the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.
These studies are designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. • Phase II: The product candidate is administered to a limited participant population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.
These studies are designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. • Phase II: The product candidate is administered to a limited participant population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and 15 safety risks.
Individually identifiable health information is considered sensitive data that merits stronger safeguards; • the federal Physician Payment Sunshine Act, created under the Patient Protection and Affordable Care Act of 2010, as amended (ACA) and its implementing regulations, which requires manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to HHS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other licensed health care practitioners and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • California’s California Consumer Privacy Act (CCPA), which went into effect on January 1, 2020, which affords consumers expanded privacy protections.
Individually identifiable health information is considered sensitive data that merits stronger safeguards; • the federal Physician Payment Sunshine Act, created under the Patient Protection and Affordable Care Act of 2010, as amended (ACA) and its implementing regulations, which requires manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to HHS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other licensed health care practitioners and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; 21 • The California Consumer Privacy Act (CCPA), which went into effect on January 1, 2020, which affords consumers expanded privacy protections.
We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of therapies that target irreversible covalent binding against protein targets of interest to us. 22 To our knowledge, there are no clinical-stage programs that aim to specifically regenerate insulin-producing beta cells in the islets by targeting menin for diabetes.
We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of therapies that target irreversible covalent binding against protein targets of interest to us. To our knowledge, there are no clinical-stage programs that aim to specifically regenerate insulin-producing beta cells in the islets by targeting menin for diabetes.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market 29 studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program.
These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. As a result, our competitors may discover, develop, license or commercialize products before or more successfully than we do.
These competitors also compete with us in 11 recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. As a result, our competitors may discover, develop, license or commercialize products before or more successfully than we do.
However, our pending provisional and Patent Cooperation Treaty (PCT) applications, and any patent applications that we may in the future file or license from third parties, may not result in the issuance of patents and any issued patents we may obtain do not guarantee us the right to practice our technology or commercialize our product candidates.
However, our pending provisional and Patent Cooperation Treaty (PCT) applications, and any patent applications that we might in the future file or license from third parties, may not result in the issuance of patents and any issued patents we may obtain do not guarantee us the right to practice our technology or commercialize our product candidates.
Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.
Physicians may prescribe, in their 19 independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters, or untitled letters; • clinical holds on clinical studies; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product approvals; • product seizure or detention, or refusal to permit the import or export of products; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; • mandated modification of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, FDA Form 483s, warning letters, or untitled letters; • clinical holds on clinical studies; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product approvals; • product seizure or detention, or refusal to permit the import or export of products; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; • mandated modification of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
If we do not successfully obtain patent protection, or, even if we do obtain patent protection, if the scope of the patent protection we obtain our product candidates or technology is not sufficiently broad, we will be unable to prevent others from using our technology or from developing or commercializing technology and products similar or identical to ours or other competing products and technologies.
If we do not successfully obtain patent protection, or, even if we do obtain patent protection, if the scope of the patent protection we obtain for our product candidates or technology is not sufficiently broad, we will be unable to prevent others from using our technology or from developing or commercializing technology and products similar or identical to ours or other competing products and technologies.
Any marketing application for a drug submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as priority review and accelerated approval.
Any marketing application for a drug submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as rolling review, priority review and accelerated approval.
Over time, uncontrolled blood sugar can result in serious complications, including cardiovascular disease, kidney failure, nerve damage, and vision impairment. People with diabetes often have a reduced life expectancy compared to those without this disease.
Over time, uncontrolled blood sugar can result in serious complications, including cardiovascular disease, kidney failure, nerve damage, and vision impairment. People with diabetes often have a reduced life expectancy 5 compared to those without this disease.
Once filed, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.
Once filed, the FDA 16 reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.
As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality 28 or other clinical benefit.
As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit.
We are subject to the informational requirements of the Exchange Act and file or furnish reports, proxy statements and other information with the SEC. The SEC maintains an Internet site that contains 34 reports, proxy and information statements and other information regarding issuers that file electronically with the SEC at www.sec.gov.
We are subject to the informational requirements of the Exchange Act and file or furnish reports, proxy statements and other information with the SEC. The SEC maintains an Internet site that contains reports, proxy and information statements and other information regarding issuers that file electronically with the SEC at www.sec.gov.
A potential partnership could provide non-dilutive funding and access to additional capabilities and expertise that a partner could provide to enhance the overall probability of program success. 24 Manufacturing We do not have any manufacturing facilities or personnel.
A potential partnership could provide non-dilutive funding and access to additional capabilities and expertise that a partner could provide to enhance the overall probability of program success. Manufacturing We do not have any manufacturing facilities or personnel.
Prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the USPTO or other foreign jurisdiction are often significantly narrowed by the time they issue, if they issue at all.
Patent prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the USPTO or other foreign jurisdiction are often significantly narrowed by the time they issue, if they issue at all.
Decreases in third-party reimbursement for any product or a decision by a third-party payor not to cover a product could reduce physician usage and patient demand for the product and also have a material adverse effect on sales.
Decreases in third-party reimbursement for any 22 product or a decision by a third-party payor not to cover a product could reduce physician usage and patient demand for the product and also have a material adverse effect on sales.
We believe that such an organization will be able to address the community of oncologists who are the key specialists in treating the patient populations for which our product candidates are being developed. Outside the United States, we expect to enter into distribution and other marketing arrangements with third parties for any of our product candidates that obtain marketing approval.
We believe that such an organization will be able to address the community of endocrinologists who are the key specialists in treating the patient populations for which our product candidates are being developed. Outside the United States, we expect to enter into distribution and other marketing arrangements with third parties for any of our product candidates that obtain marketing approval.
Additionally, even if any of our patent applications issue as patents, the patents covering our proprietary technologies and our product candidates would be expected to expire between 2039 to 2042. In addition to patent applications, we rely on unpatented trade secrets, know-how and continuing technological innovation to develop and maintain our competitive position.
Additionally, even if any of our patent applications issue as patents, the patents covering our proprietary technologies and our product candidates would be expected to expire between 2039 and 2045. In addition to patent applications, we rely on unpatented trade secrets, know-how and continuing technological innovation to develop and maintain our competitive position.
Patent term may be inadequate to protect our competitive position on our products, if approved, for an adequate amount of time.
A patent term may be inadequate to protect our competitive position on our products, if approved, for an adequate amount of time.
More broadly, we define ourselves as targeted drug developers focused on irreversible covalent drugs and as such expect substantial competition from multiple sources, including major pharmaceutical, specialty pharmaceutical, and existing or emerging biotechnology companies, academic research institutions and governmental agencies and public and private research institutions worldwide.
We define ourselves as targeted drug developers focused on irreversible covalent drugs and as such expect substantial competition from multiple sources, including major pharmaceutical, specialty pharmaceutical, and existing or emerging biotechnology companies, academic research institutions and governmental agencies and public and private research institutions worldwide.
Our provisional patent applications may never result in issued patents and are not eligible to become issued patents until, among other things, we file a non-provisional and/or PCT patent application within 12 months of filing the related provisional patent application.
Our provisional patent applications might never result in issued patents and are not eligible to become issued patents until, among other things, we file a non-provisional and/or PCT patent application within 12 months of filing the related provisional patent application.
For example, the CCPA gives California residents expanded rights to access and require deletion of their personal information, opt-out of certain personal information sharing, and receive detailed information about how their personal information is used.
For example, the CCPA gives California residents expanded rights to access and request deletion of their personal information, opt-out of certain personal information sharing, and receive detailed information about how their personal information is used.
The primary treatment objective is to achieve glycemic control, typically measured by reductions in HbA1c ( glycated hemoglobin), a marker indicating average blood glucose over the past two to three months, to 6.5% or lower. Effective glycemic control is critical in preventing or delaying complications such as kidney disease, heart disease and nerve damage.
The primary treatment objective, based on the ADA guidelines, is to achieve glycemic control, typically measured by reductions in HbA1c ( glycated hemoglobin), a marker indicating average blood glucose over the past two to three months, to 6.5% or lower. Effective glycemic control is critical in preventing or delaying complications such as kidney disease, heart disease and nerve damage.
The extension period granted on a patent covering a product is typically one-half the time between the effective date of a clinical investigation involving human beings is begun and the submission date of a new drug application (NDA), plus the time between the submission date of a NDA and the ultimate approval date.
The extension period granted on a patent covering a product is typically one-half the time between the effective date of a 12 clinical investigation involving human beings began and the submission date of a new drug application (NDA), plus the time between the submission date of a NDA and the ultimate approval date.
The extension period cannot be longer than five years and the total patent term, including the extension period, must not exceed 14 years following FDA approval.
The extension period cannot be longer than five years and the total patent term, including the extension period, must not exceed 14 years following the date of FDA approval.
If a product that has orphan drug designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or in instances of drug supply issues.
If a product that has orphan drug designation subsequently receives the first FDA approval for the approved used or indication for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same approved used or 18 indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or in instances of drug supply issues.
The CPRA, among other things, gives California residents the ability to limit use of certain sensitive personal information, further restrict the use of cross-contextual advertising, establish restrictions on the retention of personal information, expand the types of data breaches subject to the CCPA’s private right of action, provide for increased penalties for CPRA violations concerning California residents under the age of 16, and establish a new California Privacy Protection Agency to implement and enforce the new law; • federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; and • analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales, and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws requiring the registration of pharmaceutical sales representatives.
The CPRA, among other things, gave California residents the ability to limit use of certain sensitive personal information, further restricted the use of cross-contextual advertising, established restrictions on the retention of personal information, expanded the types of data breaches subject to the CCPA’s private right of action, provided for increased penalties for CPRA violations concerning California residents under the age of 16, and established a new privacy protection agency, now known as CalPrivacy; • federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; and • analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales, and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws requiring the registration of pharmaceutical sales representatives.
Any of our pending PCT patent applications are not eligible to become issued patents until, among other things, we file national stage patent applications within 30 months in the countries in which we seek patent protection.
None of our pending PCT patent applications are eligible to become issued patents until, among other things, we file national stage patent applications within 30 months in the countries in which we seek patent protection.
The former clinical hold imposed in June 2024 and lifted in September 2024, had a more profound impact on the COVALENT-112 study in type 1 diabetes, where over 90% of the targeted patient population was not able to complete dosing due to the clinical hold.
The former clinical hold imposed in June 2024 and lifted in September 2024, had a profound impact on the COVALENT-112 trial in type 1 diabetes, where over 90% of the targeted patient population was not 9 able to complete dosing due to the clinical hold.
These so-called Phase IV studies may be conducted after initial marketing approval, and may be used to gain additional experience from the treatment of participants in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase IV clinical trials as a condition of approval of an NDA.
These so-called Phase IV studies may be conducted after initial marketing approval, and may be used to gain additional experience from the treatment of participants in the intended therapeutic indication. In certain instances, such as for drugs granted accelerated approval, the FDA may mandate the performance of Phase IV clinical trials as a condition of approval of an NDA.
For example, the Fast Track program is intended to expedite or facilitate the process for reviewing new products that are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.
For example, the Fast Track program is intended to expedite or facilitate the process for reviewing new products that are intended to treat a serious or life-threatening disease or condition and preclinical or clinical data demonstrate the potential to address unmet 17 medical needs for the disease or condition.
In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.
Further, our references to the URLs for these websites are intended to be inactive textual references only. 35
Further, our references to the URLs for these websites are intended to be inactive textual references only. 25
If we do not timely file any national stage patent applications, we may lose our priority date with respect to our PCT patent applications and any patent protection on the inventions disclosed in such PCT patent applications.
If we do not timely file a national stage patent applications, we may lose our priority date in that country with respect to that PCT patent application and any patent protection on the inventions disclosed in such PCT patent application.
Human Capital Resources As of December 31, 2024, we had 106 full-time employees, 79 of whom were engaged in research and development activities. We believe we have good relationships with our employees. None of our employees are represented by a labor union or covered under a collective bargaining agreement.
Human Capital Resources As of December 31, 2025, we had 41 full-time employees, 27 of whom were engaged in research and development activities. We believe we have good relationships with our employees. None of our employees are represented by a labor union or covered under a collective bargaining agreement.
Item 1. B usiness Overview We are a clinical-stage diabetes and obesity medicines company focused on the discovery and development of oral covalent small molecule drugs to treat patients with metabolic diseases. We aim to cure.
Item 1. B usiness Overview We are a clinical‑stage diabetes and obesity medicines company focused on the discovery and development of oral, small molecule drugs to treat and improve the lives of patients with diabetes, obesity, and other metabolic diseases.
In the future, if any of our product candidates receive approval by the FDA, we expect to apply for a patent term extension on an issued patents covering the product, depending upon the length of the 23 clinical studies for the product and other factors.
In the future, if any of our product candidates receive approval by the FDA, we expect to apply for a patent term extension on issued patents covering the product, method of using it, or method for manufacturing it, depending upon the length of the clinical studies for the product and other factors.
As of December 31, 2024, we owned four issued U.S. patents, more than sixty U.S. and outside U.S. pending patent applications, directed to compositions of matter, methods of treatment, and methods of making with respect to our product candidates, including icovamenib and BMF-500.
As of December 31, 2025, we owned seven issued U.S. patents, more than 100 U.S. and outside U.S. pending patent applications, directed to compositions of matter, methods of treatment, and methods of making with respect to our product candidates, including icovamenib, BMF-500 and BMF-650.
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.
Drugs are also 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.
The study’s primary endpoint assesses the mean change from baseline in stimulated C-peptide AUC at Week 12.
The trial’s primary endpoint assesses the mean change from baseline in stimulated C-peptide AUC at Week 26.
The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.
The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial or imposes a full or partial clinical hold on the IND within that 30-day time period.
In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 26 While the IND is active and before approval, progress reports summarizing the results of the clinical trials and non-clinical studies performed since the last progress report must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.
While the IND is active and before approval, progress reports summarizing the results of the clinical trials and non-clinical studies performed since the last progress report must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.
Although we take steps to protect our product candidates or any future proprietary information, third parties may independently develop the same or similar proprietary information or may otherwise gain access to our proprietary information. As a result, we may be unable to meaningfully protect our trade secrets and proprietary information.
Although we take steps to protect our product candidates and any future proprietary information, third parties may independently develop the same or similar proprietary information or may otherwise gain access to our proprietary information.
Preclinical studies to evaluate the properties of BMF-650 in comparison to a leading oral GLP-1 RA showed that BMF-650 exhibited higher bioavailability and a less variable pharmacokinetic profile, which may translate to improved tolerability and support successful dose escalation in patients.
Comparative preclinical studies evaluating BMF-650 against a leading oral GLP-1 RA showed that BMF-650 exhibited higher oral bioavailability and a less variable pharmacokinetic profile, which may translate to improved tolerability and support successful dose escalation in clinical development.
The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity.
Regulatory exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications. The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity.
Corporate Information We were established in the state of Delaware in August 2017 as Biomea Fusion, LLC. In December 2020, all outstanding membership interests in Biomea Fusion, LLC were converted into equity interests in the Company. Our principal executive offices are located at 900 Middlefield Road, 4 th Floor, Redwood City, California 94063, and our telephone number is (650) 980-9099.
Corporate Information We were established in the state of Delaware in August 2017 as Biomea Fusion, LLC. In December 2020, all outstanding membership interests in Biomea Fusion, LLC were converted into equity interests in the Company. Our principal executive office is located at 1599 Industrial Road, San Carlos, California 94070, and our telephone number is (650) 980-9099.
For more information regarding the risks related to our intellectual property, please see “Risk Factors—Risks related to our intellectual property.” License and Partnership Agreements As of December 31, 2024, we did not have any license or partnership agreements related to any of our programs.
As a result, we might be unable to meaningfully protect our trade secrets and proprietary information. 13 For more information regarding the risks related to our intellectual property, please see “Risk Factors—Risks related to our intellectual property.” License and Partnership Agreements As of December 31, 2025, we did not have any license or partnership agreements related to any of our programs.
These third-party payors are increasingly reducing reimbursements for medical products, drugs and services. 32 Factors payors consider in determining reimbursement are based on whether the product is: • a covered benefit under its health plan; • safe, effective and medically necessary; • appropriate for the specific patient; • cost-effective; and • neither experimental nor investigational.
Factors payors consider in determining reimbursement are based on whether the product is: • a covered benefit under its health plan; • safe, effective and medically necessary; • appropriate for the specific patient; • cost-effective; and • neither experimental nor investigational. No uniform policy for coverage and reimbursement for products exists among third-party payors in the U.S.
We are prioritizing the development of icovamenib initially for two key patient populations: • Severe Insulin Deficient Diabetes Patients (SIDD): Representing approximately 14 million of type 2 diabetes in the United States and European Union (EU), and more than 50 million patients in Asian countries.
We are prioritizing the development of icovamenib initially in two key patient populations with significant unmet medical need: • Severe Insulin Deficient Diabetes Patients: This population is estimated to include approximately 14 million of type 2 diabetes patients across the United States and European Union (EU), and more than 50 million patients in Asian countries.
The FDA may delay or refuse approval of an NDA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product. 27 If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed.
The FDA may delay or refuse approval of an NDA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.
Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The U.S.
Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The U.S. Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.
Dual Potential Mechanism of Action Icovamenib has demonstrated a generally well-tolerated safety profile in preclinical and early-stage clinical studies. Mechanistic studies support two potential modes of action: (i) increasing beta cell mass and function, thereby enhancing insulin synthesis and secretion, and (ii) upregulating glucagon-like peptide-1 (GLP-1) receptor expression, which may contribute to improved glycemic control and metabolic benefits.
Mechanistic studies support two potential modes of action: (i) increasing beta cell mass and function, thereby enhancing insulin synthesis and secretion, and (ii) upregulating GLP-1 receptor expression, which may contribute to improved glycemic control and metabolic benefits.
Key Strategic Priorities • Advance Icovamenib as a Disease-Modifying Therapy for Diabetes and Obesity: Icovamenib, a potentially first-in-class covalent menin inhibitor, has demonstrated the potential to restore beta cell function, and mass to improve glycemic control.
Key Strategic Priorities • Execute Phase II Development of Icovamenib in Type 2 Diabetes: Icovamenib, a potentially first-in-class oral, selective, covalent inhibitor of menin, has demonstrated the potential to restore beta cell function and mass, to improve glycemic control.
Our lead clinical program’s drug candidate, icovamenib, is currently being developed as an orally bioavailable, and selective covalent inhibitor of menin in two clinical and multiple preclinical studies, investigating icovamenib’s potential in type 1 and type 2 diabetes, as well as its impact in obesity. After working closely together at Pharmacyclics, Inc.
Diabetes progression of type 1 and type 2 driven by beta cell loss Icovamenib – Our Oral Menin Inhibitor Icovamenib is an orally bioavailable, and selective, covalent inhibitor of menin being developed in two clinical and multiple preclinical studies, investigating icovamenib’s potential in type 1 and type 2 diabetes, as well as its impact in obesity.
An IND is a request for authorization from the FDA to administer an investigational new drug product to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies.
The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies.
Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.
Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis. These third-party payors are increasingly reducing reimbursements for medical products, drugs and services.
For example, the FDA may approve the NDA with a risk evaluation and mitigation strategy (REMS) to ensure the benefits of the product outweigh its risks.
If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the NDA with a risk evaluation and mitigation strategy (REMS) to ensure the benefits of the product outweigh its risks.
(i) Beta Cell Quantity and Function Icovamenib is designed to increase beta cell mass and function, addressing a fundamental deficiency in patients with diabetes. Through its proposed mechanism of action, icovamenib has been observed in non-clinical and early-stage clinical studies to promote glucose-regulated beta cell proliferation and enhance insulin synthesis and secretion.
(i) Restoration of Beta Cell Quantity and Function Icovamenib has been observed in preclinical and early-stage clinical studies to increase beta cell quantity and function, addressing a fundamental deficiency in patients with diabetes.
Non-clinical data suggest that this upregulation could contribute to metabolic benefits, including improved glycemic control and potential weight loss. Due to the long half-life of beta cells, icovamenib is not intended as a chronic therapy for insulin deficient diabetes, but rather as a 12-week treatment designed to produce lasting effects beyond the period of active administration.
Due to the long half-life of beta cells, icovamenib is not intended as a chronic therapy for insulin deficient diabetes, but rather as a 12-week treatment produced lasting effects beyond the active dosing period.
Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.
This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study. 20 Other Healthcare Laws Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations.
Our website address is www.biomeafusion.com . We do not incorporate the information on or accessible through our website into this Annual Report on Form 10-K, and you should not consider any information on, or that can be accessed through, our website a part of this Annual Report on Form 10-K.
We do not incorporate the information on or accessible through our website into this Annual Report on Form 10-K, and you should not consider any information on, or that can be accessed through, our website a part of this Annual Report on Form 10-K. 24 Biomea Fusion, Inc., the Biomea logo, FUSION ™ System and our other registered or common law trademarks, trade names or service marks appearing in this Annual Report on Form 10-K are owned by us.
We own full worldwide development and commercialization rights to each of our programs. In the future, we may selectively enter into collaborations where we believe there is an opportunity to speed up clinical development or enhance the commercialization potential of our product candidates.
In the future, we may selectively enter into collaborations where we believe there is an opportunity to accelerate clinical development or enhance the potential of our product candidates. We intend to commercialize our product candidates in key markets either alone or with partners to maximize the value of our assets.
We believe that our approach, strategy, scientific capabilities, know-how and experience provide us with competitive advantages. In addition, we believe we are currently the only company in the United States developing irreversible covalent binders specifically against menin.
In addition, we believe we are currently the only company in the United States clinically developing irreversible covalent binders specifically against menin.
Members of the team have held various positions at several renowned biotechnology companies including Gilead Sciences, Inc. (Nasdaq: GILD), Genentech, Inc., Pharmacyclics, AbbVie Inc. (NYSE: ABBV), Celera Genomics, Johnson and Johnson, Inc. (NYSE: JNJ), and others. The team includes the co-inventors of the covalent inhibitors Imbruvica, Remdesivir, and Harvoni.
Members of our leadership and scientific teams have held roles at leading biotechnology and pharmaceutical companies such as Gilead Sciences, Inc. (Nasdaq: GILD), Genentech, Inc., Pharmacyclics, AbbVie Inc. (NYSE: ABBV), Johnson and Johnson, Inc. (NYSE: JNJ), and others. The team includes individuals who contributed to the invention or advancement of several approved medicines including imbruvica, remdesivir, and Harvoni.
By inducing controlled beta cell regeneration, this approach aims to restore endogenous insulin production and provide a durable glycemic benefit. 6 (ii) GLP-1 Receptor Expression In addition to its effects on beta cell mass and function, icovamenib has been shown to upregulate GLP-1 receptor expression in preclinical studies, which may enhance incretin signaling and improve glucose metabolism.
(ii) GLP-1 Receptor Expression In addition to its observed effects on beta cell mass and function, icovamenib has been shown in preclinical studies to increase expression of the GLP-1 receptor, which may enhance incretin signaling and responsiveness to incretin-based therapies, thereby improving glucose metabolism.
We aim to leverage our capabilities and platform to establish ourselves as a leader in developing covalent small molecules in order to maximize the depth and durability of clinical benefit for patients with various metabolic diseases. 12 Our Initial Focus: Menin Menin and Beta Cell Biology in Diabetes Diabetes is a chronic metabolic disease that affects the body’s ability to regulate blood sugar levels, leading to elevated glucose in the bloodstream.
OUR PROGRAMS Our current pipeline OUR INITIAL FOCUS Menin and Beta Cell Biology in Diabetes and Other Metabolic Diseases Diabetes is a chronic metabolic disease that affects the body’s ability to regulate blood sugar levels, leading to elevated glucose in the bloodstream.
No uniform policy for coverage and reimbursement for products exists among third-party payors in the U.S. Therefore, coverage and reimbursement for products can differ significantly from payor to payor.
Therefore, coverage and reimbursement for products can differ significantly from payor to payor.
This population of patients exhibit the highest unmet medical need, experiencing high treatment failure rates, rapid progression to insulin-dependency, and poor cardiovascular outcomes. • Combination with GLP-1R Based Therapies: Icovamenib has been shown to enhance the activity of GLP-1 Rs in preclinical studies, leading to superior glucose control, weight loss, and muscle preservation.
This population of patients exhibit the highest unmet medical need, experiencing high treatment failure rates, rapid progression to insulin-dependency, and poor cardiovascular outcomes.
Loss of functional beta cell mass is a core component of the natural history in both types of diabetes – type 1 diabetes, which is mediated by autoimmune dysfunction leading to destruction of the beta cells, and type 2 diabetes, which is mediated by metabolic dysfunction.
Loss of functional beta cell mass is a core characteristic in both type 1 7 diabetes and type 2 diabetes. In type 1 diabetes, autoimmune destruction leads to nearly complete loss of insulin producing beta cells. In type 2 diabetes, progressive metabolic dysfunction and beta cell exhaustion results in declining insulin secretion over time.
We plan to conclude our studies exploring icovamenib’s potential in oncology and explore partnerships to further advance our oncology assets (i.e. BMF-500), while concentrating internal resources on metabolic disorders. As part of this transition, we have discontinued our oncology programs, including COVALENT-101 (hematologic malignancies) and COVALENT-102 (solid tumors), and are concluding our study COVALENT-103 (BMF-500 for acute leukemia).
With our strategic focus to become a diabetes and medicines company, as announced in January 2025, we are concluding our studies exploring icovamenib’s potential in oncology and plan to explore partnerships to further advance our oncology assets (i.e. BMF-500), while concentrating internal resources on metabolic disorders.
In cynomolgus monkey studies, BMF-650 showed significant improvements in glucose-stimulated insulin secretion, in line with findings from human donor islet experiments. BMF-650 also demonstrated superior glucose control. Appetite suppression studies demonstrated that daily oral BMF-650 dosing significantly reduced food intake during peak drug concentration, with sustained effects throughout the day for a six-day study period.
In cynomolgus monkey studies, BMF-650 showed robust effects on metabolic function, including significant improvements in glucose control and glucose-stimulated insulin secretion consistent with findings from human donor islet experiments. Appetite suppression studies demonstrated that once daily oral administration of BMF-650 resulted in a clear, dose-dependent reduction in daily food intake and continuous, progressive weight loss over a 28-day treatment period.
Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition. If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.
Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have at least one orphan designation and any approved indications are for rare diseases. The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeThe success of our product candidates will depend on several factors, including the following: 43 • our ability to continue our business operations and product candidate research and development, and adapt to any changes in the regulatory approval process, manufacturing supply or clinical trial requirements and timing due to a continued and prolonged public health emergencies, such as the COVID-19 pandemic; • successful completion of preclinical studies; • receipt of authorization to proceed under INDs for our planned clinical trials or future clinical trials; • successful initiation, patient enrollment in, and completion of clinical trials, including our ongoing Phase I clinical trial of icovamenib in various types of liquid tumors, our Phase I/Ib clinical trial of icovamenib in various types of solid tumors, our Phase I/II clinical trial of icovamenib in type 2 diabetes, our Phase II clinical trial of icovamenib in type 1 diabetes, and our Phase I clinical trial of BMF-500 in relapsed or refractory acute leukemia with FLT3 wild-type and FLT3 mutations, including those with MLL1r / NPM1 mutations; • whether icovamenib, BMF-500 or any other product candidates that we may identify and pursue will demonstrate safety, tolerability and efficacy profiles that are satisfactory to the FDA or any foreign regulatory authority for marketing approval; • receipt of marketing approvals for our product candidates from applicable regulatory authorities; • completion of any required post-marketing approval commitments to applicable regulatory authorities in order to maintain marketing authorization for any of our product candidates that receive regulatory approval; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; • making arrangements with third-party manufacturers, or establishing manufacturing capabilities, for both clinical and commercial supplies of our product candidates, if any product candidates are approved; • establishing sales, marketing, and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others; • acceptance of our products, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies for diabetes and obesity; • obtaining and maintaining third-party coverage and adequate reimbursement; and • maintaining a continued acceptable safety profile of our products following approval.
Biggest changeThe success of our product candidates will depend on several factors, including the following: • our ability to continue our business operations and product candidate research and development, and adapt to any changes in the regulatory approval process, manufacturing supply or clinical trial requirements, disruptions of staffing and operations at the FDA or other government agencies and timing due to any continued and prolonged public health emergencies; • successful completion of preclinical studies, regulatory submissions and clinical trials; • receipt of authorization to proceed under INDs for our planned clinical trials or future clinical trials; 32 • successful initiation, patient enrollment in, and completion of current and future clinical trials, including our ongoing Phase II clinical trial of icovamenib in type 2 diabetes and our Phase II clinical trial of icovamenib in insulin-deficient type 2 diabetes as well as our Phase I clinical trial for BMF-650; • successful partnerships to further advance our oncology assets; • whether icovamenib, BMF-650 or any other product candidates that we may identify and pursue will demonstrate safety, tolerability and efficacy profiles that are satisfactory to the FDA or any foreign regulatory authority for marketing approval; • receipt of marketing approvals for our product candidates from applicable regulatory authorities; • completion of any required post-marketing approval commitments to applicable regulatory authorities in order to maintain marketing authorization for any of our product candidates that receive regulatory approval; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; • making arrangements with third-party manufacturers, or establishing manufacturing capabilities, for both clinical and commercial supplies of our product candidates, if any product candidates are approved; • establishing sales, marketing, and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others; • acceptance of our products, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies for diabetes and obesity; • obtaining and maintaining third-party coverage and adequate reimbursement; and • maintaining a continued acceptable safety profile of our products following approval.
Even if we are able to limit off-target interaction, there can be no assurance that treatment with any of our novel covalent small molecule product candidates will demonstrate the deep inactivation of their targets or offer greater therapeutic windows than conventional non-covalent drugs.
Even if we are able to limit off-target interaction, there can be no assurance that treatment with any of our novel small molecule product candidates will demonstrate the deep inactivation of their targets or offer greater therapeutic windows than conventional non-covalent drugs.
For example, under Section 174 of the Code, in taxable years beginning after December 31, 2021, expenses that are incurred for research and development performed in the U.S. and outside the U.S. will be capitalized and amortized, which may have an adverse effect on our cash flow.
For example, under Section 174 of the Code, in taxable years beginning after December 31, 2021, expenses that are incurred for research and development performed outside the U.S. will be capitalized and amortized, which may have an adverse effect on our cash flow.
Furthermore, our operating results may fluctuate due to a variety of other factors, many of which are outside of our control and may be difficult to predict, including the following: • the timing and cost of, and level of investment in, research and development activities relating to our current product candidates and any future product candidates and research-stage programs, which will change from time to time; • our ability to enroll participants in clinical trials and the timing of enrollment; • the cost of manufacturing our current product candidates and any future product candidates, which may vary depending on FDA or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers; • expenditures that we will or may incur to acquire or develop additional product candidates and technologies or other assets; • the timing and outcomes of clinical trials for our current and future product candidates, or competing product candidates; • the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated; • competition from existing and potential future products that compete with our product candidates and any of our future product candidates, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • any delays in regulatory review or approval of our product candidates; • the level of demand for our future product candidates, if approved, which may fluctuate significantly and be difficult to predict; • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future products that compete with our product candidates; • our ability to commercialize our product candidates, if approved, inside and outside of the United States, either independently or working with third parties; • our ability to establish and maintain future collaborations, licensing or other arrangements; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; • tariffs (including tariffs that have been or may in the future be imposed by the United States or other countries), trade protection measures, import or export licensing requirements, trade embargoes, sanctions (including those administered by the Office of Foreign Assets Control of the U.S.
Furthermore, our operating results may fluctuate due to a variety of other factors, many of which are outside of our control and may be difficult to predict, including the following: • the timing and cost of, and level of investment in, research and development activities relating to our current product candidates and any future product candidates and research-stage programs, which will change from time to time; • our ability to enroll participants in clinical trials and the timing of enrollment; • the cost of manufacturing our current product candidates and any future product candidates, which may vary depending on FDA or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers; • expenditures that we will or may incur to acquire or develop additional product candidates and technologies or other assets; • the timing and outcomes of clinical trials for our current and future product candidates, or competing product candidates; • the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated; • competition from existing and potential future products that compete with our product candidates and any of our future product candidates, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • any delays in regulatory review or approval of our product candidates; • the level of demand for our future product candidates, if approved, which may fluctuate significantly and be difficult to predict; • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future products that compete with our product candidates; 75 • our ability to commercialize our product candidates, if approved, inside and outside of the United States, either independently or working with third parties; • our ability to establish and maintain future collaborations, licensing or other arrangements; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; • tariffs (including tariffs that have been or may in the future be imposed by the United States or other countries), trade protection measures, import or export licensing requirements, trade embargoes, sanctions (including those administered by the Office of Foreign Assets Control of the U.S.
Further, collaborations involving our product candidates are subject to numerous risks, which may include the following: • collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization of our product candidates based on clinical trial results, changes in their strategic focus due to the acquisition of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates; • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to their marketing and distribution; • collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; • disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our product candidates, or that result in costly litigation or arbitration that diverts management attention and resources; • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; and • collaborators may own or co-own intellectual property covering our product candidates that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property.
Further, collaborations involving our product candidates are subject to numerous risks, which may include the following: • collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization of our product candidates based on clinical trial results, changes in their strategic focus due to the acquisition of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates; • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to their marketing and distribution; • collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; 59 • disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our product candidates, or that result in costly litigation or arbitration that diverts management attention and resources; • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; and • collaborators may own or co-own intellectual property covering our product candidates that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property.
For example: 78 • others may be able to make product candidates that are similar to ours but that are not covered by the claims of the patents that we own; • we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent applications that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or in-licensed intellectual property rights; • it is possible that our owned and in-licensed pending patent applications or those we may own or in-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 our competitors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we cannot ensure that any of our patents, or any of our pending patent applications, if issued, or those of our licensors, will include claims having a scope sufficient to protect our product candidates; • we cannot ensure that any patents issued to us or our licensors will provide a basis for an exclusive market for our commercially viable product candidates or will provide us with any competitive advantages; • we cannot ensure that our commercial activities or product candidates will not infringe upon the patents of others; • we cannot ensure that we will be able to successfully commercialize our product candidates on a substantial scale, if approved, before the relevant patents that we own or license expire; • we may not develop additional proprietary technologies that are patentable; • the patents or intellectual property rights of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: • others may be able to make product candidates that are similar to ours but that are not covered by the claims of the patents that we own; • we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent applications that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or in-licensed intellectual property rights; • it is possible that our owned and in-licensed pending patent applications or those we may own or in-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 our competitors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we cannot ensure that any of our patents, or any of our pending patent applications, if issued, or those of our licensors, will include claims having a scope sufficient to protect our product candidates; • we cannot ensure that any patents issued to us or our licensors will provide a basis for an exclusive market for our commercially viable product candidates or will provide us with any competitive advantages; • we cannot ensure that our commercial activities or product candidates will not infringe upon the patents of others; • we cannot ensure that we will be able to successfully commercialize our product candidates on a substantial scale, if approved, before the relevant patents that we own or license expire; • we may not develop additional proprietary technologies that are patentable; • the patents or intellectual property rights of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
Delaware law provides that a corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of the registrant and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful; • we may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law; • we are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such directors or officers shall undertake to repay such advances if it is ultimately determined that such person is not entitled to indemnification; • we will not be obligated pursuant to our amended and restated bylaws to indemnify a person with respect to proceedings initiated by that person against us or our other indemnitees, except with respect to proceedings authorized by our board of directors or brought to enforce a right to indemnification; • the rights conferred in our amended and restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons; and • we may not retroactively amend our amended and restated bylaw provisions to reduce our indemnification obligations to directors, officers, employees and agents.
Delaware law provides that a corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of the registrant and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful; • we may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law; • we are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such directors or officers shall undertake to repay such advances if it is ultimately determined that such person is not entitled to indemnification; • we will not be obligated pursuant to our amended and restated bylaws to indemnify a person with respect to proceedings initiated by that person against us or our other indemnitees, except with respect to proceedings authorized by our Board or brought to enforce a right to indemnification; 74 • the rights conferred in our amended and restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons; and • we may not retroactively amend our amended and restated bylaw provisions to reduce our indemnification obligations to directors, officers, employees and agents.
If a third party claims that we infringe or misappropriate its intellectual property rights, we may face a number of issues, including, but not limited to: infringement, misappropriation and other intellectual property related claims, which, regardless of merit, may be expensive and time-consuming to litigate and may divert our management’s attention from our core business; substantial damages for infringement, which we may have to pay if a court decides that the product candidate or technology at issue infringes on or violates the third party’s rights, and, if the court finds that the infringement or 76 misappropriation was willful, we could be ordered to pay treble damages and the patent owner’s attorneys’ fees; a court prohibiting us from developing, manufacturing, marketing or selling our products or product candidates, or from using our proprietary technologies, unless the third party licenses its product rights to us; however, the third party is not required to grant the license; if a license is available from a third party, we may have to pay substantial royalties, upfront fees and other amounts, and/or grant cross-licenses to intellectual property rights for our products; and redesigning our technology, product candidates or products so they do not infringe such third party patents; redesign may not be possible or may require substantial monetary expenditures and time.
If a third party claims that we infringe or misappropriate its intellectual property rights, we may face a number of issues, including, but not limited to: infringement, misappropriation and other intellectual property related claims, which, regardless of merit, may be expensive and time-consuming to litigate and may divert our management’s attention from our core business; substantial damages for infringement, which we may have to pay if a court decides that the product candidate or technology at issue infringes on or violates the third party’s rights, and, if the court finds that the infringement or misappropriation was willful, we could be ordered to pay treble damages and the patent owner’s attorneys’ fees; a court prohibiting us from developing, manufacturing, marketing or selling our products or product candidates, or from using our proprietary technologies, unless the third party licenses its product rights to us; however, the third party is not required to grant the license; if a license is available from a third party, we may have to pay substantial royalties, upfront fees and other amounts, and/or grant cross-licenses to intellectual property rights for our products; and redesigning our technology, product candidates or products so they do not infringe such third party patents; redesign may not be possible or may require substantial monetary expenditures and time.
These provisions, among other things: • establish a classified board of directors so that not all members of our Board are elected at one time; 82 • permit only the Board to establish the number of directors and fill vacancies on the Board; • provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders; • authorize the issuance of “blank check” preferred stock that our Board could use to implement a stockholder rights plan (poison pill); • eliminate the ability of our stockholders to call special meetings of stockholders; • prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders; • prohibit cumulative voting; • authorize our Board to amend the bylaws; • establish advance notice requirements for nominations for election to our Board or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and • require a super-majority vote of stockholders to amend some provisions described above.
These provisions, among other things: • establish a classified Board so that not all members of our Board are elected at one time; • permit only the Board to establish the number of directors and fill vacancies on the Board; • provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders; • authorize the issuance of “blank check” preferred stock that our Board could use to implement a stockholder rights plan (poison pill); • eliminate the ability of our stockholders to call special meetings of stockholders; • prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders; • prohibit cumulative voting; • authorize our Board to amend the bylaws; • establish advance notice requirements for nominations for election to our Board or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and • require a super-majority vote of stockholders to amend some provisions described above.
Various factors will influence whether our product candidates, if approved, are accepted in the market, including: • the clinical indications for which our product candidates are approved; • physicians, hospitals, and patients considering our product candidates as a safe and effective treatment; • the potential and perceived advantages of our product candidates over alternative treatments; • our ability to demonstrate the advantages of our product candidates over other available medicines; • the prevalence and severity of any side effects; • the prevalence and severity of any side effects for other precision medicines and public perception of other precision medicines; • product labeling or product insert requirements of the FDA or other regulatory authorities; • limitations or warnings contained in the labeling approved by the FDA; • the timing of market introduction of our product candidates as well as competitive products; • the cost of treatment in relation to alternative treatments; • pricing and the availability of adequate coverage and reimbursement by third-party payors and government authorities; • the willingness of patients to pay out-of-pocket in the absence of coverage by third-party payors and government authorities; 52 • relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; and • the effectiveness of our sales and marketing efforts.
Various factors will influence whether our product candidates, if approved, are accepted in the market, including: • the clinical indications for which our product candidates are approved; • physicians, hospitals, and patients considering our product candidates as a safe and effective treatment; • the potential and perceived advantages of our product candidates over alternative treatments; • our ability to demonstrate the advantages of our product candidates over other available medicines; • the prevalence and severity of any side effects; • the prevalence and severity of any side effects for other precision medicines and public perception of other precision medicines; • product labeling or product insert requirements of the FDA or other regulatory authorities; • limitations or warnings contained in the labeling approved by the FDA; • the timing of market introduction of our product candidates as well as competitive products; • the cost of treatment in relation to alternative treatments; • pricing and the availability of adequate coverage and reimbursement by third-party payors and government authorities; • the willingness of patients to pay out-of-pocket in the absence of coverage by third-party payors and government authorities; • relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; and • the effectiveness of our sales and marketing efforts.
Disputes may arise between us and our future licensors regarding intellectual property subject to a license agreement, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; • our right to sublicense patents and other rights to third parties; • our diligence obligations with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates, and what activities satisfy those diligence obligations; • our right to transfer or assign the license; and • the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners.
Disputes may arise between us and our future licensors regarding intellectual property subject to a license agreement, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; • our right to sublicense patents and other rights to third parties; 68 • our diligence obligations with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates, and what activities satisfy those diligence obligations; • our right to transfer or assign the license; and • the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners.
Our future capital requirements depend on many factors, including but not limited to: 39 • the scope, timing, progress, duration, costs and results of our clinical trials, drug discovery, preclinical development activities, and laboratory testing for our product candidates; • the number and scope of clinical programs we decide to pursue; • the scope and costs of manufacturing development and commercial manufacturing activities; • the extent to which we discover and develop additional product candidates; • the cost, timing, and outcome of regulatory review of our product candidates; • the cost and timing of establishing sales and marketing capabilities, if any of our product candidates receive marketing approval; • the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property rights, and defending intellectual property-related claims; • our ability to establish and maintain collaborations on favorable terms, if at all; • licensing, or other arrangements into which we may enter in the future, including the timing of receipt of any milestone or royalty payments under these agreements; • the timing, receipt, and amount of sales from our potential products; • our need and ability to hire additional management, scientific, and medical personnel; • our need to implement additional internal systems and infrastructure, including financial and reporting systems; • our efforts to enhance operational systems and our ability to attract, hire, and retain qualified personnel, including personnel to support the development of our product candidates; • the costs associated with being a public company; • the cost associated with commercializing our product candidates, if they receive regulatory approval; • our ability to establish and maintain strategic collaborations and other similar partnerships for the development and commercialization of our product candidates; and • the impact of adverse global economic conditions on our business, which may exacerbate the magnitude of the factors discussed above.
Our future capital requirements depend on many factors, including but not limited to: • the scope, timing, progress, duration, costs and results of our clinical trials, drug discovery, preclinical development activities, and laboratory testing for our product candidates; 29 • the number and scope of clinical programs we decide to pursue; • the scope and costs of manufacturing development and commercial manufacturing activities; • the extent to which we discover and develop additional product candidates; • the cost, timing, and outcome of regulatory review of our product candidates; • the cost and timing of establishing sales and marketing capabilities, if any of our product candidates receive marketing approval; • the costs of preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property rights, and defending intellectual property-related claims; • our ability to establish and maintain collaborations on favorable terms, if at all; • licensing, or other arrangements into which we may enter in the future, including the timing of receipt of any milestone or royalty payments under these agreements; • the timing, receipt, and amount of sales from our potential products; • our need and ability to hire additional management, scientific, and medical personnel; • our need to implement additional internal systems and infrastructure, including financial and reporting systems; • our efforts to enhance operational systems and our ability to attract, hire, and retain qualified personnel, including personnel to support the development of our product candidates; • the costs associated with being a public company; • the cost associated with commercializing our product candidates, if they receive regulatory approval; • our ability to establish and maintain strategic collaborations and other similar partnerships for the development and commercialization of our product candidates; and • the impact of adverse global economic conditions on our business, which may exacerbate the magnitude of the factors discussed above.
In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (the Code), if a corporation undergoes an “ownership change” (generally defined as a cumulative change (by value) in the corporation’s ownership by “5-percent shareholders” that exceeds 50 percentage points over a rolling three-year period), the corporation’s ability to use its 64 pre-change NOLs and certain other pre-change tax attributes to offset its post-change taxable income or tax liabilities may be limited.
In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (the Code), if a corporation undergoes an “ownership change” (generally defined as a cumulative change (by value) in the corporation’s ownership by “5-percent shareholders” that exceeds 50 percentage points over a rolling three-year period), the corporation’s ability to use its pre-change NOLs and certain other pre-change tax attributes to offset its post-change taxable income or tax liabilities may be limited.
We commenced operations in August 2017, have not completed any clinical trials, have no products approved for commercial sale and have never generated any revenue, and our operations to date have been primarily limited to organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, filing patent applications, identifying potential product candidates, undertaking preclinical studies, preparing for and initiating our initial clinical trials, and establishing arrangements with third parties for the manufacture of initial quantities of product candidates.
We commenced operations in August 2017, have not completed the clinical development of any product candidates, have no products approved for commercial sale and have never generated any revenue, and our operations to date have been primarily limited to organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, filing patent applications, identifying potential product candidates, undertaking preclinical studies, preparing for and initiating our initial clinical trials, and establishing arrangements with third parties for the manufacture of initial quantities of product candidates.
The commencement and rate of completion of preclinical studies and clinical trials for a product candidate may be delayed by many factors, including, for example: • inability to generate sufficient preclinical or other in vivo or in vitro data to support the initiation of clinical trials; • timely completion of preclinical laboratory tests, animal studies and formulation studies in accordance with the FDA’s GLP requirements and other applicable regulations; • approval by an independent IRB ethics committee at each clinical site before each trial may be initiated; • delays in reaching a consensus with regulatory agencies on study design and obtaining regulatory authorization to commence clinical trials; • delays in reaching agreement on acceptable terms with prospective CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • delays in identifying, recruiting and training suitable clinical investigators; • delays in recruiting suitable participants to participate in our clinical trials; • delays in manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing; • insufficient or inadequate supply or quality of product candidates or other materials necessary for use in clinical trials, or delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for clinical trials; • imposition of a temporary or permanent clinical hold by regulatory authorities; • developments on trials conducted by competitors for related technology that raises FDA or foreign regulatory authority concerns about risk to patients of the technology broadly, or if the FDA or a foreign regulatory authority finds that the investigational protocol or plan is clearly deficient to meet its stated objectives; 45 • delays in recruiting, screening and enrolling participants and delays caused by participants withdrawing from clinical trials or failing to return for post-treatment follow-up; • difficulty collaborating with patient groups and investigators; • failure by our CROs, other third parties or us to adhere to clinical trial protocols; • failure to perform in accordance with the FDA’s or any other regulatory authority’s GCPs, or applicable regulatory guidelines in other countries; • occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits, or occurrence of adverse events in trial of the same class of agents conducted by other companies; • changes to the clinical trial protocols; • clinical sites deviating from trial protocol or dropping out of a trial; • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; • changes in the standard of care on which a clinical development plan was based, which may require new or additional trials; • selection of clinical endpoints that require prolonged periods of observation or analyses of resulting data; • the cost of clinical trials of our product candidates being greater than we anticipate; • clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of such product candidates; • transfer of manufacturing processes to larger-scale facilities operated by a contract manufacturing organization (CMO), and delays or failure by our CMOs or us to make any necessary changes to such manufacturing process; and • third parties being unwilling or unable to satisfy their contractual obligations to us.
The commencement and rate of completion of preclinical studies and clinical trials for a product candidate may be delayed by many factors, including, for example: • inability to generate sufficient preclinical or other in vivo or in vitro data to support the initiation of clinical trials; • timely completion of preclinical laboratory tests, animal studies and formulation studies in accordance with the FDA’s GLP requirements and other applicable regulations; • approval by an independent IRB ethics committee at each clinical site before each trial may be initiated; • delays in reaching a consensus with regulatory agencies on study design and obtaining regulatory authorization to commence clinical trials; • delays in reaching agreement on acceptable terms with prospective CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • delays in identifying, recruiting and training suitable clinical investigators; • delays in recruiting suitable participants to participate in our clinical trials; • delays in manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing; • insufficient or inadequate supply or quality of product candidates or other materials necessary for use in clinical trials, or delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for clinical trials; • imposition of a temporary or permanent clinical hold by regulatory authorities; • developments on trials conducted by competitors for related technology that raises FDA or foreign regulatory authority concerns about risk to patients of the technology broadly, or if the FDA or a foreign regulatory authority finds that the investigational protocol or plan is clearly deficient to meet its stated objectives; • delays in recruiting, screening and enrolling participants and delays caused by participants withdrawing from clinical trials or failing to return for post-treatment follow-up; • difficulty collaborating with patient groups and investigators; • failure by our CROs, other third parties or us to adhere to clinical trial protocols; • failure to perform in accordance with the FDA’s or any other regulatory authority’s Good Clinical Practices (GCPs), or applicable regulatory guidelines in other countries; • occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits, or occurrence of adverse events in trial of the same class of agents conducted by other companies; • changes to the clinical trial protocols; 34 • clinical sites deviating from trial protocol or dropping out of a trial; • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; • changes in the standard of care on which a clinical development plan was based, which may require new or additional trials; • selection of clinical endpoints that require prolonged periods of observation or analyses of resulting data; • the cost of clinical trials of our product candidates being greater than we anticipate; • clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of such product candidates; • transfer of manufacturing processes to larger-scale facilities operated by a contract manufacturing organization (CMO), and delays or failure by our CMOs or us to make any necessary changes to such manufacturing process; and • third parties being unwilling or unable to satisfy their contractual obligations to us.
These could include, but may not be limited to, the following: • Delayed access to deposits or other financial assets or the uninsured loss of deposits or other financial assets; • Delayed or lost access to working capital sources and/or delays, inability or reductions in our ability to enter into new credit facilities or access other working capital resources; • Potential or actual breach of contractual obligations that require us to maintain letters of credit or other credit support arrangements; or • Potential or actual breach of financial covenants in any credit agreements or credit arrangements.
These could include, but may not be limited to, the following: • Delayed access to deposits or other financial assets or the uninsured loss of deposits or other financial assets; • Delayed or lost access to working capital sources and/or delays, inability or reductions in our ability to enter into new credit facilities or access other working capital resources; 31 • Potential or actual breach of contractual obligations that require us to maintain letters of credit or other credit support arrangements; or • Potential or actual breach of financial covenants in any credit agreements or credit arrangements.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by third-party service providers is compromised for any reason, our preclinical studies and clinical trials may be extended, delayed or terminated, and we may not be able to obtain marketing approval of icovamenib, BMF-500 or any future product candidates or otherwise advance our business.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by third-party service providers is compromised for any reason, our preclinical studies and clinical trials may be extended, delayed or terminated, and we may not be able to obtain marketing approval of icovamenib, BMF-500, BMF-650 or any future product candidates or otherwise advance our business.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any approval in the future, we may need to find alternative manufacturing facilities, which would require the incurrence of significant additional costs and delays, and materially adversely affect our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would require the incurrence of significant additional costs and delays, and materially adversely affect our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
Our ability to generate revenue depends on a number of factors, including, but not limited to: • timely initiation and completion of our preclinical studies and clinical trials for icovamenib, BMF-500, BMF-650 and our future product candidates, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors; 37 • establishing and maintaining relationships with contract research organizations (CROs) and clinical sites for the ongoing clinical and preclinical development of icovamenib and BMF-650 and any future product candidates; • our ability to complete IND-enabling studies, and successfully submit and receive authorization to proceed under INDs or comparable regulatory applications; • whether we are required by the FDA or other comparable foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates; • our ability to demonstrate to the satisfaction of the FDA and comparable foreign regulatory authorities the safety, efficacy, consistent manufacturing quality, and acceptable risk-benefit profile of our small molecule product candidates or any future product candidates; • the prevalence, duration, and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any; • the timely receipt of necessary regulatory approvals from the FDA and comparable foreign regulatory authorities; • the willingness of physicians, operators of clinics, and patients to utilize or adopt any of our product candidates or future product candidates over alternative or more conventional therapies; • the actual and perceived availability, cost, risk profile and side effects and efficacy of our product candidates, if approved, relative to existing and future alternative therapies in our target indications, including diabetes and obesity, and competitive product candidates and technologies; • our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with cGMP; • our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others; • patient demand for our current product candidates and any future product candidates, if approved; • our ability to establish and enforce intellectual property rights in and to our product candidates or any future product candidates; • obtaining coverage and adequate reimbursement by third-party payors for our product candidates; • addressing any competing therapies and technological and market developments; and • attracting, hiring, and retaining qualified personnel.
Our ability to generate revenue depends on a number of factors, including, but not limited to: • timely initiation and completion of our preclinical studies and clinical trials for icovamenib, BMF-650 and our future product candidates, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors; • establishing and maintaining relationships with contract research organizations (CROs) and clinical sites for the ongoing clinical and preclinical development of icovamenib, BMF-650 and any future product candidates; 27 • our ability to complete IND-enabling studies and successfully submit and receive authorization to proceed under INDs or comparable regulatory applications; • whether we are required by the FDA or other comparable foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates; • our ability to demonstrate to the satisfaction of the FDA and comparable foreign regulatory authorities the safety, efficacy, consistent manufacturing quality, and acceptable risk-benefit profile of our novel small molecule product candidates or any future product candidates; • the prevalence, duration, and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any; • the timely receipt of necessary regulatory approvals from the FDA and comparable foreign regulatory authorities; • the willingness of physicians, operators of clinics, and patients to utilize or adopt any of our product candidates or future product candidates over alternative or more conventional therapies; • the actual and perceived availability, cost, risk profile and side effects and efficacy of our product candidates, if approved, relative to existing and future alternative therapies in our target indications, including diabetes and obesity, and competitive product candidates and technologies; • our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with cGMP; • our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others; • patient demand for our current product candidates and any future product candidates, if approved; • our ability to establish and enforce intellectual property rights in and to our product candidates or any future product candidates; • obtaining coverage and adequate reimbursement by third-party payors for our product candidates; • addressing any competing therapies and technological and market developments; and • attracting, hiring, and retaining qualified personnel.
Furthermore, significant disruptions of our internal information technology systems, data breaches, cybersecurity incidents, or other compromises could result in the loss, misappropriation and/or unauthorized access, use or disclosure of, or the prevention of access to, data (including trade secrets or other confidential information, intellectual property, proprietary business information and personal information and Sensitive Information), which could result in a material adverse impact including financial, legal, business and reputational harm.
Furthermore, significant disruptions of our internal information technology systems, data breaches, cybersecurity incidents, or other compromises could result in the loss, misappropriation and/or unauthorized access, use or disclosure or other compromise of, or the prevention of access to, data (including trade secrets or other confidential information, intellectual property, proprietary business information and personal information and Sensitive Information), which could result in a material adverse impact including financial, legal, business and reputational harm.
We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of therapies that target covalent binding against protein targets of interest to us. To our knowledge, there are no clinical-stage programs that aim to specifically regenerate insulin-producing beta cells in the islets by targeting menin for diabetes.
We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of therapies that target binding against protein targets of interest to us. To our knowledge, there are no clinical-stage programs that aim to specifically regenerate insulin-producing beta cells in the islets by targeting menin for diabetes.
In addition, if the breadth or strength of protection provided 73 by our patents and patent applications or those of our future licensors is threatened, it could dissuade other companies from collaborating with us to license, develop or commercialize current or future product candidates. Such a loss of patent protection would have a material adverse impact on our business.
In addition, if the breadth or strength of protection provided by our patents and patent applications or those of our future licensors is threatened, it could dissuade other companies from collaborating with us to license, develop or commercialize current or future product candidates. Such a loss of patent protection would have a material adverse impact on our business.
We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success. We are currently focused on the discovery and development of novel covalent small molecules to treat patients with diabetes and obesity.
We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success. We are currently focused on the discovery and development of novel small molecules to treat patients with diabetes and obesity.
Risks Related to Product Development Our discovery and development activities are focused on the development of novel covalent small molecule therapies, initially targeted at menin, to treat patients with diabetes and obesity, and the approach we are taking to discover and develop such product candidates is novel, may never lead to marketable products and may not ultimately represent a significant market.
Risks Related to Product Development Our discovery and development activities are focused on the development of novel small molecule therapies, initially targeted at menin, to treat patients with diabetes and obesity, and the approach we are taking to discover and develop such product candidates is novel, may never lead to marketable products and may not ultimately represent a significant market.
If the market opportunities for icovamenib, BMF-500 and BMF-650 or any future product candidate we may develop, if and when approved, are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the patient population, our revenue and ability to achieve profitability might be materially and adversely affected.
If the market opportunities for icovamenib and BMF-650 or any future product candidate we may develop, if and when approved, are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the patient population, our revenue and ability to achieve profitability might be materially and adversely affected.
The incidence and prevalence for target patient populations of icovamenib, BMF-500 and BMF-650 are based on estimates and third-party sources. These estimates may be inaccurate or based on imprecise data. For example, the total addressable market opportunity will depend on, among other things, acceptance of our drugs by the medical community and patient access, drug pricing and reimbursement.
The incidence and prevalence for target patient populations of icovamenib and BMF-650 are based on estimates and third-party sources. These estimates may be inaccurate or based on imprecise data. For example, the total addressable market opportunity will depend on, among other things, acceptance of our drugs by the medical community and patient access, drug pricing and reimbursement.
If the market opportunities for icovamenib, BMF-500, BMF-650 or any future product candidate we may develop, if and when approved, are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the patient population, our revenue and ability to achieve profitability might be materially and adversely affected.
If the market opportunities for icovamenib, BMF-650 or any future product candidate we may develop, if and when approved, are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the patient population, our revenue and ability to achieve profitability might be materially and adversely affected.
If we are not able to effectively expand our organization by hiring new employees and/or engaging additional third-party service providers, we may not be able to successfully implement the tasks necessary to further develop and commercialize icovamenib, BMF-500 or any future product candidates and, accordingly, may not achieve our research, development and commercialization goals.
If we are not able to effectively expand our organization by hiring new employees and/or engaging additional third-party service providers, we may not be able to successfully implement the tasks necessary to further develop and commercialize icovamenib, BMF-650, BMF-500 or any future product candidates and, accordingly, may not achieve our research, development and commercialization goals.
Such Trade Laws also govern export controls, as well as economic sanctions 62 and embargoes on certain countries and persons. We have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities and other organizations. We also expect our non-U.S. activities to increase in time.
Such Trade Laws also govern export controls, as well as economic sanctions and embargoes on certain countries and persons. We have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities and other organizations. We also expect our non-U.S. activities to increase in time.
Our ability to develop icovamenib, BMF-500 or any future product candidates we may develop could be disrupted if our operations or those of our suppliers are affected by man-made or natural disasters or other business interruptions. Our corporate headquarters are located in California near major earthquake faults and fire zones.
Our ability to develop icovamenib, BMF-500, BMF-650 or any future product candidates we may develop could be disrupted if our operations or those of our suppliers are affected by man-made or natural disasters or other business interruptions. Our corporate headquarters are located in California near major earthquake faults and fire zones.
Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign governmental patent agencies also require compliance with a number of procedural, documentary, fee payment (such as annuities) and other similar provisions during the patent 72 application process.
Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign governmental patent agencies also require compliance with a number of procedural, documentary, fee payment (such as annuities) and other similar provisions during the patent application process.
We have not previously submitted an NDA to the FDA or similar approval filings to a comparable foreign regulatory authority, for any product candidate. An NDA or other relevant regulatory filing must include extensive preclinical and 44 clinical data and supporting information to establish that the product candidate is safe and effective for each desired indication.
We have not previously submitted an NDA to the FDA or similar approval filings to a comparable foreign regulatory authority, for any product candidate. An NDA or other relevant regulatory filing must include extensive preclinical and clinical data and supporting information to establish that the product candidate is safe and effective for each desired indication.
Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable authorities in other countries.
Our product candidates and the activities associated with their development and potential commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable authorities in other countries.
As a result, our financial results and the commercial prospects for our product candidates would be adversely affected, our costs could increase and our ability to generate revenue could be delayed. 66 Switching or adding third parties to conduct our preclinical studies and clinical trials involves substantial cost and requires extensive management time and focus.
As a result, our financial results and the commercial prospects for our product candidates would be adversely affected, our costs could increase and our ability to generate revenue could be delayed. Switching or adding third parties to conduct our preclinical studies and clinical trials involves substantial cost and requires extensive management time and focus.
Changes in U.S. patent law, or laws in other countries, could diminish the value of patents in general, thereby impairing our ability to protect our technology, products and product candidates. As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents.
Changes in U.S. patent law, or laws in other countries, could diminish the value of patents in general, thereby impairing our ability to protect our technology, products and product candidates. 65 As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents.
Our business could be negatively impacted by corporate citizenship and environmental, social and corporate governance matters and/or our reporting of such matters. There is an increasing focus from certain investors, consumers, and other stakeholders concerning corporate citizenship and sustainability matters. We could be perceived as not acting responsibly in connection with these matters.
Our business could be negatively impacted by corporate citizenship and environmental, social and corporate governance (ESG) matters and/or our reporting of such matters. There is an increasing focus from certain investors, consumers, and other stakeholders concerning corporate citizenship and sustainability matters. We could be perceived as not acting responsibly in connection with these matters.
If we do not achieve regulatory approval in a timely manner or at all, we could experience significant delays or an inability to commercialize our current or future product candidates, which would materially adversely affect our business. If we do not receive regulatory approvals for our current or future product candidates, we will not be able to continue our operations.
If we do not achieve regulatory approval in a timely manner or at all, we could experience significant delays or an inability to commercialize our current or future product candidates, which could materially adversely affect our business. If we do not receive regulatory approvals for our current or future product candidates, we will not be able to continue our operations.
As a result, increasingly high barriers are being erected to the entry of new products. If product liability lawsuits are brought against us, we may incur substantial liabilities, which may not be sufficiently covered by insurance, and may be required to limit commercialization of our product candidates.
As a result, increasingly high barriers are being erected to the entry of new products. 42 If product liability lawsuits are brought against us, we may incur substantial liabilities, which may not be sufficiently covered by insurance, and may be required to limit commercialization of our product candidates.
The growth of our business may depend in part on our ability to acquire or in-license additional proprietary rights from third parties in the future. For example, our programs may involve additional product candidates that may require the use of 77 proprietary rights held by third parties. Our product candidates may also require specific formulations to work effectively and efficiently.
The growth of our business may depend in part on our ability to acquire or in-license additional proprietary rights from third parties in the future. For example, our programs may involve additional product candidates that may require the use of proprietary rights held by third parties. Our product candidates may also require specific formulations to work effectively and efficiently.
If our Board elects to increase the number of shares available for future grant under the 2021 Plan or the ESPP, our stockholders may experience additional dilution, and our stock price may fall. Our failure to meet the continued listing requirements of Nasdaq could result in a delisting of our securities.
If our Board elects to increase the number of shares available for future grant under the 2021 Plan, the ESPP or the Inducement Plan, our stockholders may experience additional dilution, and our stock price may fall. Our failure to meet the continued listing requirements of Nasdaq could result in a delisting of our securities.
Any drug candidates that we successfully develop and commercialize will likely compete with existing therapies and new therapies that may become available in the future. The incidence and prevalence for target patient populations of icovamenib, BMF-500 and BMF-650 are based on estimates and third-party sources.
Any drug candidates that we successfully develop and commercialize will likely compete with existing therapies and new therapies that may become available in the future. The incidence and prevalence for target patient populations of icovamenib and BMF-650 are based on estimates and third-party sources.
FDORA also gives the FDA increased authority to withdraw approval of a drug granted accelerated approval on an expedited basis if the sponsor fails to conduct such studies in 57 a timely manner, send the necessary updates to the FDA, or if such post-approval studies fail to verify the drug’s predicted clinical benefit.
FDORA also gives the FDA increased authority to withdraw approval of a drug granted accelerated approval on an expedited basis if the sponsor fails to conduct such studies in a timely manner, send the necessary updates to the FDA, or if such post-approval studies fail to verify the drug’s predicted clinical benefit.
If a competitor independently develops a technology that we protect as a trade secret and files a patent application on that technology, then we may not be able to patent that technology in the future, may require a license from the competitor to use our own know-how, and even then, the license may 71 not be available on commercially reasonable terms.
If a competitor independently develops a technology that we protect as a trade secret and files a patent application on that technology, then we may not be able to patent that technology in the future, may require a license from the competitor to use our own know-how, and even then, the license may not be available on commercially reasonable terms.
Any efforts to enforce our intellectual property rights are also likely to be costly and may divert the efforts of our scientific and management personnel. We may become involved in lawsuits or litigation at the USPTO to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful.
Any efforts to enforce our intellectual property rights are also likely to be costly and may divert the efforts of our scientific and management personnel. 63 We may become involved in lawsuits or litigation at the USPTO to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful.
These factors may make it difficult for us to enroll enough participants to complete our clinical trials in a timely and cost-effective manner. Our inability to enroll a sufficient number of participants for our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether.
These factors may make it difficult for us to enroll enough participants to complete our clinical trials in a timely and cost-effective manner. Our inability to enroll a sufficient number of eligible participants for our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether.
For additional information, see the section of this Annual Report on Form 10-K titled “Business—Government Regulation—Other Healthcare Laws.” The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform.
For additional information, see the section of this Annual Report on Form 10-K titled “Business—Government Regulation—Other Healthcare Laws.” 50 The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform.
There 88 can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions.
There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions.
Our anticipated reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following: • we may be unable to identify manufacturers on acceptable terms or at all because the number of potential manufacturers is limited and the FDA or other comparable foreign regulatory authority must inspect any manufacturers for cGMP compliance as part of our marketing application; • manufacturing processes and testing methods will need to be transferred to a new manufacturer, or develop substantially equivalent processes and testing methods for, the production of our product candidates; • our third-party manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; • contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our future contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our products, if any; • contract manufacturers are subject to ongoing periodic unannounced inspection by the FDA or other comparable foreign regulatory authority and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these changing and tightening regulations and standards; • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; • our third-party manufacturers could breach or terminate their agreements with us; 67 • our third-party manufacturers may experience change of control of their ownership including ownership by a competitor, • raw materials and components used in the manufacturing process, particularly those for which we have no other source or supplier, may not be available at acceptable prices, or at all, or may not be suitable or acceptable for use due to material or component defects; • our contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; and • our contract manufacturers may have unacceptable or inconsistent product quality success rates and yields, and we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance, qualified personnel, their equipment and facilities and any applicable licenses or approvals.
Our anticipated reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following: • we may be unable to identify manufacturers on acceptable terms or at all because the number of potential manufacturers is limited and the FDA or other comparable foreign regulatory authority must inspect any manufacturers for cGMP compliance as part of our marketing application; • manufacturing processes and testing methods may need to be transferred to a new manufacturer, or we or others on our behalf may need to develop substantially equivalent processes and testing methods for, the production of our product candidates; • our third-party manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; • contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; 57 • our future contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our products, if any; • contract manufacturers are subject to ongoing periodic unannounced inspection by the FDA or other comparable foreign regulatory authority and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these changing and tightening regulations and standards; • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; • our third-party manufacturers could breach or terminate their agreements with us; • our third-party manufacturers may experience change of control of their ownership including ownership by a competitor, • raw materials and components used in the manufacturing process, particularly those for which we have no other source or supplier, may not be available at acceptable prices, or at all, or may not be suitable or acceptable for use due to material or component defects; • our contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; and • our contract manufacturers may have unacceptable or inconsistent product quality success rates and yields, and we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance, qualified personnel, their equipment and facilities and any applicable licenses or approvals.
Even if our agreements with any future 54 corporate collaborators entitle us to indemnification against losses, such indemnification may not be available or adequate should any claim arise. Furthermore, clinical trial and product liability insurance is becoming increasingly expensive.
Even if our agreements with any future corporate collaborators entitle us to indemnification against losses, such indemnification may not be available or adequate should any claim arise. Furthermore, clinical trial and product liability insurance is becoming increasingly expensive.
There are numerous domestic and foreign laws, regulations, and other legal obligations regarding privacy, data protection, and information security, the scope of which is changing and subject to differing applications and interpretations, and which may be inconsistent among jurisdictions or conflict with each other.
There are numerous domestic and foreign laws, regulations, and other legal obligations regarding privacy, data protection, and information security, the scope of which are changing and subject to differing applications and interpretations, and which may be inconsistent among jurisdictions or conflict with each other.
Our manufacturers may use highly flammable reagents at high 68 reaction temperature, are subject to federal, state and local laws and regulations in the United States and their country governing the use, manufacture, storage, handling and disposal of medical and hazardous materials.
Our manufacturers may use highly flammable reagents at high reaction temperature, are subject to federal, state and local laws and regulations in the United States and their country governing the use, manufacture, storage, handling and disposal of medical and hazardous materials.
The actual or perceived failure by us or our partners, 61 customers, vendors, third-party payors or other related third parties to comply with such obligations could harm our reputation, subject us to significant fines and liability, or otherwise adversely affect our business.
The actual or perceived failure by us or our partners, customers, vendors, third-party payors or other related third parties to comply with such obligations could harm our reputation, subject us to significant fines and liability, or otherwise adversely affect our business.
Furthermore, the enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that a court could find these types of provisions to 83 be inapplicable or unenforceable.
Furthermore, the enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that a court could find these types of provisions to be inapplicable or unenforceable.
From time to time, we may enter into license or collaboration agreements or strategic partnerships with other companies that include development funding and significant upfront and milestone payments and/or 84 royalties, which may become an important source of our revenue.
From time to time, we may enter into license or collaboration agreements or strategic partnerships with other companies that include development funding and significant upfront and milestone payments and/or royalties, which may become an important source of our revenue.
Failure to remedy any material weakness or 86 significant deficiencies in our internal controls over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.
Failure to remedy any material weakness or significant deficiencies in our internal controls over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.
In addition to the factors discussed in this “Risk Factors” section and elsewhere herein, these factors include: • the timing, progress, costs and results of our ongoing, planned or any future preclinical studies, clinical trials or clinical development programs; • the commencement, enrollment, progress or results of clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates; • adverse results or delays in preclinical studies and clinical trials such as the recent clinical hold on our INDs for the Phase I/II clinical trials of icovamenib in type 2 and type 1 diabetes, from June 2024 to September 2024; • our decision to initiate a clinical trial, not to initiate a clinical trial, or to terminate an existing clinical trial, including due to the suspension of a clinical trial by the FDA or other regulatory authorities; • any delay in our regulatory filings or any adverse regulatory decisions, including failure to receive regulatory approval of our product candidates; 79 • changes in laws or regulations applicable to our product candidates and any future products, including but not limited to clinical trial requirements for approvals; • adverse developments concerning our manufacturers or our manufacturing plans; • our inability to obtain adequate supply for any of our product candidates or the components thereof, or inability to do so at acceptable prices; • our inability to establish collaborations if needed; • our failure to commercialize our product candidates; • additions or departures of key scientific or management personnel; • unanticipated serious safety concerns related to the use of our product candidates; • introduction of new products or services offered by us or our competitors; • announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; • our ability to effectively manage our growth; • our ability to develop our product candidates for the treatment of type 1 and type 2 diabetes or other metabolic diseases; • actual or anticipated variations in quarterly operating results; • our cash position; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • publication of research reports about us or our industry, or menin inhibitors in particular, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • changes in the market valuations of similar companies; • changes in the structure of healthcare payment systems; • overall performance of the equity markets; • sales of our common stock by us or our stockholders in the future; • trading volume of our common stock; • changes in accounting practices; • ineffectiveness of our internal controls; • disputes or other developments relating to intellectual property or proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; • significant lawsuits, including intellectual property or stockholder litigation; • the impact of any natural disasters or public health emergencies; • inflationary pressures and general economic, political, industry and market conditions; and • other events or factors, many of which are beyond our control.
In addition to the factors discussed in this “Risk Factors” section and elsewhere herein, these factors include: • the timing, progress, costs and results of our ongoing, planned or any future clinical trials, clinical development programs or preclinical studies; • the commencement, enrollment, progress or results of clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates; • adverse results or delays in preclinical studies and clinical trials such as the clinical hold on our INDs for the Phase I/II clinical trials of icovamenib in type 2 and type 1 diabetes, from June 2024 to September 2024; • our decision to initiate a clinical trial, not to initiate a clinical trial, or to terminate an existing clinical trial, including due to the suspension of a clinical trial by the FDA or other regulatory authorities; • any delay in our regulatory filings or any adverse regulatory decisions, including failure to receive regulatory approval of our product candidates; • changes in laws or regulations applicable to our product candidates and any future products, including but not limited to clinical trial requirements for approvals; • adverse developments concerning our manufacturers or our manufacturing plans; • our inability to obtain adequate supply for any of our product candidates or the components thereof, or inability to do so at acceptable prices; • our inability to establish collaborations if needed; • our failure to commercialize our product candidates; • additions or departures of key scientific or management personnel; • unanticipated serious safety concerns related to the use of our product candidates; • introduction of new products or services offered by us or our competitors; • announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; • our ability to effectively manage our growth; • our ability to develop our product candidates for the treatment of type 1 and type 2 diabetes or other metabolic diseases; • actual or anticipated variations in quarterly operating results; • our cash position; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • publication of research reports about us or our industry, or menin inhibitors in particular, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • changes in the market valuations of similar companies; • changes in the structure of healthcare payment systems; • overall performance of the equity markets; • sales of our common stock or securities exercisable for or convertible into shares of our common stock, by us or our stockholders in the future; • trading volume of our common stock; • changes in accounting practices; 70 • ineffectiveness of our internal controls; • disputes or other developments relating to intellectual property or proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; • significant lawsuits, including intellectual property or stockholder litigation; • the impact of any natural disasters or public health emergencies; • inflationary pressures and general economic, political, industry and market conditions; and • other events or factors, many of which are beyond our control.
In particular, a significant risk for toxicity is posed by these small-molecule covalent binders if they demonstrate a more promiscuous binding profile than intended, which can potentially cause unacceptable levels of off-target interactions.
In particular, a significant risk for toxicity is posed by these small molecule binders if they demonstrate a more promiscuous binding profile than intended, which can potentially cause unacceptable levels of off-target interactions.
Our business could be negatively impacted by such matters. Any such matters, or related corporate citizenship and sustainability matters, could have a material adverse effect on our business. 90 Geopolitical events and conditions could adversely affect our business, financial condition and operating results.
Our business could be negatively impacted by such matters. Any such matters, or related corporate citizenship and sustainability matters, could have a material adverse effect on our business. Geopolitical events and conditions could adversely affect our business, financial condition and operating results.
In order to successfully implement our development and commercialization plans and strategies, and as we continue to operate as a public company, we expect to need additional managerial clinical, regulatory, operational, sales, 63 marketing, financial and other personnel.
In order to successfully implement our development and commercialization plans and strategies, and as we continue to operate as a public company, we expect to need additional managerial clinical, regulatory, operational, sales, marketing, financial and other personnel.
If the market price of our common stock does not exceed the price at which you purchased shares of our common stock, you may not realize any return on your investment in us and may lose some or 80 all of your investment.
If the market price of our common stock does not exceed the price at which you purchased shares of our common stock, you may not realize any return on your investment in us and may lose some or all of your investment.
If icovamenib, BMF-500, BMF-650 or our future product candidates do not offer sustainable advantages over competing products, we may otherwise not be able to successfully compete against current and future competitors.
If icovamenib, BMF-650 or our future product candidates do not offer sustainable advantages over competing products, we may otherwise not be able to successfully compete against current and future competitors.
Our and their assignment agreements may not be self-executing or may be breached, and litigation may be necessary to defend against these and other claims challenging inventorship or our 75 ownership of our patents, trade secrets or other intellectual property.
Our and their assignment agreements may not be self-executing or may be breached, and litigation may be necessary to defend against these and other claims challenging inventorship or our ownership of our patents, trade secrets or other intellectual property.
Changes in funding or disruptions at the FDA, the SEC and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire and retain key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
Changes in funding or disruptions at the FDA, the SEC and other government agencies caused by reduction in staffing, funding shortages or global health concerns could hinder their ability to hire and retain key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
Further, if any of our product candidates obtains marketing approval, toxicities associated with such product candidates previously not seen during clinical testing may also develop after such approval and lead to a number of potentially significant negative consequences, including, but not limited to: • regulatory authorities may suspend, limit or withdraw approvals of such product, or seek an injunction against its manufacture or distribution; • regulatory authorities may require additional warnings on the label, including “boxed” warnings, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; • we may be required to change the way the product is administered or conduct additional clinical trials or post-approval studies; • we may be required to create a REMS, which could include a medication guide outlining the risks of such side effects for distribution to participants; • we may be subject to fines, injunctions or the imposition of criminal penalties; • we could be sued and held liable for harm caused to participants; and • our reputation may suffer.
Further, if any of our product candidates obtains marketing approval, toxicities associated with such product candidates previously not seen during clinical testing may also develop after such approval and lead to a number of potentially significant negative consequences, including, but not limited to: • regulatory authorities may suspend, limit or withdraw approvals of such product, or seek an injunction against its manufacture or distribution; • regulatory authorities may require additional warnings on the label, including “boxed” warnings, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; • we may be required to change the way the product is administered or conduct additional clinical trials or post-approval studies; • we may be required to create a risk evaluation and mitigation strategy (REMS), which could include a medication guide outlining the risks of such side effects for distribution to participants; • we may be subject to fines, injunctions or the imposition of criminal penalties; • we could be sued and held liable for harm caused to participants; and • our reputation may suffer.
Risks Related to Our Common Stock The price of our stock has been and is likely to continue to be volatile, and you may not be able to resell shares of our common stock at or above the price you paid.
Risks Related to Our Common Stock 69 The price of our stock has been and is likely to continue to be volatile, and you may not be able to resell shares of our common stock at or above the price you paid.
If our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our common stock 85 could decline substantially.
If our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our common stock could decline substantially.
If we or third parties related to us (such as our partners, CROs, and CMOs) have experienced or in the future experience any material cybersecurity incidents that result in any deletion or destruction of, unauthorized access to, loss of, unauthorized acquisition or disclosure of, or inadvertent exposure disclosure of, sensitive, confidential, or proprietary information, including trade secrets, other intellectual property, and personal information (Sensitive Information), or a compromise related to the security, confidentiality, integrity or availability of our (or their) information technology, software, services, communications, or data, it may result in a material adverse impact, including without limitation, regulatory investigations or enforcement actions, litigation, indemnity obligations, delays to the development and commercialization of our product candidates, disruption of our programs, negative publicity, and financial loss.
If we or third parties related to us (such as our partners, CROs, and CMOs) experience any material cybersecurity incidents that result in any deletion or destruction of, unauthorized access to, loss of, unauthorized acquisition or disclosure of, or inadvertent exposure or disclosure of, sensitive, confidential, or proprietary information, including trade secrets, other intellectual property, and personal information (Sensitive Information), or a compromise related to the security, confidentiality, integrity or availability of our (or their) information technology, software, services, communications, or data, it may result in a material adverse impact, including without limitation, regulatory investigations or enforcement actions, litigation, indemnity obligations, delays to the development and commercialization of our product candidates, disruption of our programs, negative publicity, and financial loss.
Based on our current operating plan, we believe that our existing cash and cash equivalents, and restricted cash as of December 31, 2024, without any future financing, will not be sufficient for us to continue as a going concern for at least one year from the issuance date of the financial statements appearing elsewhere in this Annual Report on Form 10-K.
Based on our current operating plan, we believe that our existing cash and cash equivalents, and restricted cash as of December 31, 2025, without any future financing, will not be sufficient for us to continue as a going concern for at least one year from the issuance date of the financial statements appearing elsewhere in this Annual Report on Form 10-K.
If our product candidates are associated with undesirable side effects or have unexpected characteristics in preclinical studies or clinical trials when used alone or in combination with other approved products or investigational new drugs we may need to interrupt, delay or abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective.
If our product candidates are associated with undesirable side effects or have unexpected characteristics in preclinical studies or clinical trials when used alone or in combination with other approved products or investigational product candidates, we may need to interrupt, delay or abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective.
Later discovery of previously unknown problems with our product candidates, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on the marketing or manufacturing of our product candidates, withdrawal of the product from the market or voluntary or mandatory product recalls; • manufacturing delays and supply disruptions where regulatory inspections identify observations of noncompliance requiring remediation; • revisions to the labeling, including limitation on approved uses or the addition of additional warnings, contraindications or other safety information, including boxed warnings; • imposition of a REMS, which may include distribution or use restrictions; • requirements to conduct additional post-market clinical trials to assess the safety of the product; • fines, warning or untitled letters or holds on clinical trials; • refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of approvals; • product seizure or detention, or refusal to permit the import or export of our product candidates; and 59 • injunctions or the imposition of civil or criminal penalties.
Later discovery of previously unknown problems with our product candidates, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on the marketing or manufacturing of our product candidates, withdrawal of the product from the market or voluntary or mandatory product recalls; • manufacturing delays and supply disruptions where regulatory inspections identify observations of noncompliance requiring remediation; • revisions to the labeling, including limitation on approved uses or the addition of additional warnings, contraindications or other safety information, including boxed warnings; • imposition of a REMS, which may include distribution or use restrictions; 48 • requirements to conduct additional post-market clinical trials to assess the safety of the product; • fines, FDA Form 483s, warning or untitled letters or holds on clinical trials; • refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of approvals; • product seizure or detention, or refusal to permit the import or export of our product candidates; and • injunctions or the imposition of civil or criminal penalties.
Many of our competitors, either alone or through 49 collaborations, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
Many of our competitors, either alone or through collaborations, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. 38 Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
Our lead product candidate, icovamenib, is in clinical development in type 1 and type 2 diabetes, and we cannot be sure that we will be able to submit INDs or similar applications with respect to additional indications or other product candidates on the timelines we expect, if at all, and we cannot be sure that submission of IND or similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin.
Our lead product candidate, icovamenib, is in clinical development for type 2 diabetes, and we cannot be sure that we will be able to submit INDs or similar applications with respect to additional indications or other product candidates on the timelines we expect, if at all, and we cannot be sure that submission of IND or similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin.
Currently, we plan to register any increase in the number of shares available for issuance under the 2021 Plan and the ESPP promptly following the effectiveness of any such increase.
Currently, we plan to register any increase in the number of shares available for issuance under the 2021 Plan, the ESPP and the Inducement Plan promptly following the effectiveness of any such increase.
The discovery and development of covalent small molecule therapies for patients with diabetes and obesity, with a particular focus on menin, is an emerging field.
The discovery and development of small molecule therapies for patients with diabetes and obesity, with a particular focus on menin, is an emerging field.
We may in the future receive inquiries or be subject to investigations, proceedings, or actions by governmental entities, or litigation by private parties, regarding our privacy, data protection, and information security practices, which could result in a cause a material adverse impact to our business operations or financial results, or otherwise result in material harm to our business, including without limitation, interruptions of or require changes to our business practices, the diversion of resources and the attention of management from our business, regulatory oversights and audits, discontinuance of necessary data processing, or other remedies that adversely affect our business.
We may in the future receive inquiries or be subject to investigations, proceedings, or actions by governmental entities, or litigation by private parties, regarding our privacy, data protection, and information security practices, which could result in a cause a material adverse impact to our business operations or financial results, or otherwise result in material harm to our business, including without limitation, interruptions of or requirements to make changes to our business practices, the diversion of resources and the attention of management from our business, regulatory oversights and audits, discontinuance of necessary data processing, or other remedies that adversely affect our business.
If we are unable to advance icovamenib, BMF-500 or any other product candidates through clinical development, obtain regulatory approval and ultimately commercialize icovamenib, BMF-500 or any other product candidates, or experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected. We are early in our development efforts.
If we are unable to advance icovamenib, BMF-650 or any other product candidates through clinical development, obtain regulatory approval and ultimately commercialize icovamenib, BMF-650 or any other product candidates, or experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected. We are early in our development efforts.
We also cannot 69 be certain that, following a strategic transaction or license, we will achieve the revenue or specific net income that justifies such transaction.
We also cannot be certain that, following a strategic transaction or license, we will achieve the revenue or specific net income that justifies such transaction.
In connection with the preparation of this Annual Report on Form 10-K for the year ended December 31, 2024, our management has concluded that there is substantial doubt as to whether we can continue as a going concern for the twelve months following the issuance of this Annual Report on Form 10-K.
In connection with the preparation of this Annual Report on Form 10-K for the year ended December 31, 2025, our management has concluded that there is substantial doubt as to whether we can continue as a going concern for the twelve months following the issuance of this Annual Report on Form 10-K.
In order to obtain FDA approval to market a new small molecule product, we must demonstrate the safety and efficacy of our product candidates in humans to meet the FDA requirements. To meet these requirements, we will have to conduct adequate and well-controlled clinical trials. Clinical testing is expensive, time-consuming, and subject to uncertainty.
In order to obtain FDA approval to market a novel small molecule product, we must demonstrate the safety and efficacy of our product candidates in humans to meet the FDA requirements. To meet these requirements, we will have to conduct adequate and well-controlled clinical trials. Clinical testing is expensive, time-consuming, and subject to uncertainty.
As a result of any future global health emergency such as a pandemic, epidemic, or outbreak of an infectious disease, we have experienced, and may in the future experience disruptions that could severely impact our business, preclinical studies and clinical trials, including: • interruptions in preclinical studies due to restricted or limited operations at our laboratory facility; • delays or difficulties in clinical site initiation, including difficulties in recruiting CROs for our preclinical studies and clinical site investigators and clinical site staff for our ongoing and planned clinical trials; • delays or difficulties in enrolling and retaining participants in our ongoing and planned clinical trials; • diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; • interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial participant visits and study procedures (such as endoscopies that are deemed non-essential), which may impact the integrity of participant data and clinical study endpoints; • interruption or delays in the operations of the FDA or other regulatory authorities, which may impact review and approval timelines; • interruption of, or delays in receiving, supplies of our product candidates from our CMOs due to staffing shortages, production slowdowns or stoppages and disruptions in delivery systems; • limitations on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; • interruptions or delays to our sourced discovery and clinical activities; and 47 • changes in clinical site procedures and requirements as well as regulatory requirements for conducting clinical trials during the pandemic.
Any global health emergency such as a pandemic, epidemic, or outbreak of an infectious disease, we have experienced, and may in the future experience disruptions that could severely impact our business, preclinical studies and clinical trials, including: • delays or difficulties in clinical site initiation, including difficulties in recruiting CROs for our preclinical studies and clinical site investigators and clinical site staff for our ongoing and planned clinical trials; • delays or difficulties in enrolling and retaining participants in our ongoing and planned clinical trials; • diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; • interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial participant visits and study procedures (such as endoscopies that are deemed non-essential), which may impact the integrity of participant data and clinical study endpoints; • interruption or delays in the operations of the FDA or other regulatory authorities, which may impact review and approval timelines; • interruption of, or delays in receiving, supplies of our product candidates from our CMOs due to staffing shortages, production slowdowns or stoppages and disruptions in delivery systems; • limitations on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; • interruptions or delays to our sourced discovery and clinical activities; and • changes in clinical site procedures and requirements as well as regulatory requirements for conducting clinical trials during any global health emergency.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeThe Head of Information Technology provides periodic updates on our information technology environment risk , which is inclusive of our cybersecurity risk profile, to the Board of Directors, which includes the Audit Committee members. 93
Biggest changeThe Head of Information Technology provides periodic updates on our information technology environment risk , which is inclusive of our cybersecurity risk profile, to the Board, which includes the Audit Committee members.
We take a risk-based approach to cybersecurity and have implemented cybersecurity policies throughout our operations that are designed to address cybersecurity threats and incidents. Our Head of Information Technology, and the Cybersecurity Committee, is responsible for the establishment and maintenance of our cybersecurity program, as well as the assessment and management of cybersecurity risks .
We take a risk-based approach to cybersecurity and have implemented cybersecurity policies throughout our operations that are designed to address cybersecurity threats and incidents. Our Head of Information Technology and the Cybersecurity Committee are responsible for the establishment and maintenance of our cybersecurity program, as well as the assessment and management of cybersecurity risks .
“Risk Factors” for additional description of cybersecurity risks and potential related impacts on our Company. Governance Our board of directors oversees our risk management process, including as it pertains to cybersecurity risks, directly and through its committees.
“Risk Factors” for additional description of cybersecurity risks and potential related impacts on our Company. Governance Our Board oversees our risk management process, including as it pertains to cybersecurity risks, directly and through its committees.
Audit Committee meetings include discussions of specific risk areas throughout the year, including, among others, those relating to cybersecurity threats, when applicable, and reports from the Chief Financial Officer on our enterprise risk profile on an annual basis.
Audit Committee meetings include discussions of specific risk areas throughout the year, including, among others, those relating to cybersecurity threats, when applicable, and reports from management on our enterprise risk profile on an annual basis.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeWe believe these facilities are sufficient to meet our near-term needs and that any additional space we may require will be available on commercially reasonable terms.
Biggest changeItem 2. Pr operties We currently lease approximately 18,796 square feet of office space in San Carlos, California under two leases which expire in January 2027. We believe these facilities are sufficient to meet our near-term needs and that any additional space we may require will be available on commercially reasonable terms. 83
Removed
Item 2. Pr operties We currently lease approximately 45,799 square feet of office, laboratory and manufacturing space in Redwood City and San Carlos, California under three leases which expire in July 2025 and January 2032.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeRegardless of outcome, litigation can have an adverse impact on us due to defense and settlement costs, diversion of management resources, negative publicity, reputational harm and other factors. Item 4. Mine Saf ety Disclosures Not Applicable. 94 PAR T II
Biggest changeRegardless of outcome, litigation can have an adverse impact on us due to defense and settlement costs, diversion of management resources, negative publicity, reputational harm and other factors. Item 4. Mine Saf ety Disclosures Not Applicable. 84 PAR T II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeOur future ability to pay cash dividends on our capital stock may be limited by the terms of any future debt or preferred securities. Unregistered Sales of Equity Securities Since January 1, 2022, we have not issued any unregistered securities. Purchases of Equity Securities by Issuers and Affiliated Purchasers None. Item 6. Selected Financial Data Not Applicable.
Biggest changeOur future ability to pay cash dividends on our capital stock may be limited by the terms of any future debt or preferred securities. Unregistered Sales of Equity Securities Since January 1, 2022, we have not issued any unregistered securities. Purchases of Equity Securities by Issuers and Affiliated Purchasers None. Item 6. R eserved
Holders of Record As of March 24, 2025, there were 40 holders of record of our common stock. The actual number of stockholders is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees.
Holders of Record As of March 18, 2026, there were 29 holders of record of our common stock. The actual number of stockholders is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe decrease of $3.2 million was primarily due to the decrease in cash, cash equivalents, and restricted cash balance. 99 Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended December 31, 2023 2022 $ Change Operating expenses: Research and development $ 102,546 $ 62,713 $ 39,833 General and administrative 23,589 20,921 2,668 Total operating expenses 126,135 83,634 42,501 Loss from operations (126,135 ) (83,634 ) (42,501 ) Interest and other income, net 8,880 1,806 7,074 Net loss $ (117,255 ) $ (81,828 ) $ (35,427 ) Research and Development Expenses The following table summarizes our research and development expenses incurred during the periods indicated (in thousands): Year Ended December 31, 2023 2022 $ Change External costs Clinical activities related expenses $ 36,098 $ 9,439 $ 26,659 Preclinical activities related expenses 10,165 13,095 (2,930 ) Expenses related to manufacturing of clinical and research material 13,237 12,619 618 Other external costs 5,528 2,693 2,835 Internal costs: Personnel-related expenses (including stock-based compensation) 28,838 19,361 9,477 Facilities and other allocated expenses 8,680 5,506 3,174 Total research and development expenses $ 102,546 $ 62,713 $ 39,833 Research and development expenses increased by $39.8 million during the year ended December 31, 2023 compared to the year ended December 31, 2022.
Biggest changeResults of Operations Comparison of the Years Ended December 31, 2025 and 2024 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended December 31, 2025 2024 $ Change Operating expenses: Research and development $ 61,979 $ 118,085 $ (56,106 ) General and administrative 19,328 25,985 (6,657 ) Impairment of long-lived assets 2,205 — 2,205 Total operating expenses 83,512 144,070 (60,558 ) Loss from operations (83,512 ) (144,070 ) 60,558 Change in fair value of common warrant liability 19,857 — 19,857 Interest and other income, net 1,858 5,644 (3,786 ) Net loss $ (61,797 ) $ (138,426 ) $ 76,629 Research and Development Expenses The following table summarizes our research and development expenses incurred during the periods indicated (in thousands): Year Ended December 31, 2025 2024 $ Change External costs Clinical activities related expenses $ 19,598 $ 48,100 $ (28,502 ) Preclinical activities related expenses 6,037 11,815 (5,778 ) Expenses related to manufacturing of clinical and research material 2,848 7,262 (4,414 ) Other external costs 6,935 10,948 (4,013 ) Internal costs: Personnel-related expenses (including stock-based compensation) 20,563 31,856 (11,293 ) Facilities and other allocated expenses 5,998 8,104 (2,106 ) Total research and development expenses $ 61,979 $ 118,085 $ (56,106 ) Research and development expenses decreased by $56.1 million during the year ended December 31, 2025 compared to the year ended December 31, 2024.
We anticipate that we will need to raise substantial additional capital, the requirements of which will depend on many factors, including: • the scope, timing, progress, duration, costs and results of our drug discovery, preclinical development activities, laboratory testing and clinical trials for our product candidates; • the number and scope of clinical programs we decide to pursue; • the scope and costs of manufacturing development and commercial manufacturing activities; • the extent to which we discover and develop additional product candidates; • the cost, timing and outcome of regulatory review of our product candidates; • the cost and timing of establishing sales and marketing capabilities, if any of our product candidates receive marketing approval; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; • our ability to establish and maintain collaborations on favorable terms, if at all; • licensing, or other arrangements into which we may enter in the future, including the timing of receipt of any milestone or royalty payments under these agreements; • the timing, receipt and amount of sales from our potential products; • our need and ability to hire additional management, scientific and medical personnel; • our need to implement additional internal systems and infrastructure, including financial and reporting systems; 101 • our efforts to enhance operational systems and our ability to attract, hire and retain qualified personnel, including personnel to support the development of our product candidates; • the costs associated with being a public company; • the cost associated with commercializing our product candidates, if they receive regulatory approval; • our ability to establish and maintain strategic collaborations and other similar partnerships for the development and commercialization of our product candidates; and • the impact of any global health emergency and adverse global economic conditions on our business, which may exacerbate the magnitude of the factors discussed above.
We anticipate that we will need to raise substantial additional capital, the requirements of which will depend on many factors, including: • the scope, timing, progress, duration, costs and results of our clinical trials, drug discovery, preclinical development activities and laboratory testing for our product candidates; • the number and scope of clinical programs we decide to pursue; • the scope and costs of manufacturing development and commercial manufacturing activities; • the extent to which we discover and develop additional product candidates; • the cost, timing and outcome of regulatory review of our product candidates; • the cost and timing of establishing sales and marketing capabilities, if any of our product candidates receive marketing approval; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; • our ability to establish and maintain collaborations on favorable terms, if at all; • licensing, or other arrangements into which we may enter in the future, including the timing of receipt of any milestone or royalty payments under these agreements; • the timing, receipt and amount of sales from our potential products; • our need and ability to hire additional management, scientific and medical personnel; • our need to implement additional internal systems and infrastructure, including financial and reporting systems; • our efforts to enhance operational systems and our ability to attract, hire and retain qualified personnel, including personnel to support the development of our product candidates; • the costs associated with being a public company; • the cost associated with commercializing our product candidates, if they receive regulatory approval; • our ability to establish and maintain strategic collaborations and other similar partnerships for the development and commercialization of our product candidates; and • the impact of any global health emergency and adverse global economic conditions on our business, which may exacerbate the magnitude of the factors discussed above.
We may also be required to sell or license to others rights to our product candidates in certain territories or indications that we would prefer to develop and commercialize ourselves. See the section of this Annual Report on Form 10-K titled “Risk Factors” for additional risks associated with our substantial capital requirements.
We may also be required to sell or license to others rights to our product candidates in certain territories or indications that we would prefer to develop and commercialize ourselves. 92 See the section of this Annual Report on Form 10-K titled “Risk Factors” for additional risks associated with our substantial capital requirements.
All of our product candidates are small molecules and are manufactured in synthetic processes from available or custom synthesized starting materials. The chemistry is scalable and uses commonly available pharmaceutical equipment in the manufacturing process. We expect to continue to develop product candidates that can be produced cost-effectively at contract manufacturing facilities.
All of our product candidates are novel small molecules and are manufactured in synthetic processes from available or custom synthesized starting materials. The chemistry is scalable and uses commonly available pharmaceutical equipment in the manufacturing process. We expect to continue to develop product candidates that can be produced cost-effectively at contract manufacturing facilities.
If sufficient funds on acceptable terms are not available when needed, we could be required to 96 significantly reduce our operating expenses and delay, reduce the scope of, or eliminate one or more of our development programs. We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates.
If sufficient funds on acceptable terms are not available when needed, we could be required to significantly reduce our operating expenses and delay, reduce the scope of, or eliminate one or more of our development programs. We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates.
We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future, and our net losses may fluctuate significantly from period to period, depending on the timing of and expenditures on our planned research and development activities.
We expect to continue to incur significant expenses and operating losses for the foreseeable future, and our net losses may fluctuate significantly from period to period, depending on the timing of and expenditures on our planned research and development activities.
In April 2023, pursuant to the Shelf Registration Statement, we sold an aggregate of 5,750,000 shares of common stock at a price of $30.00 per share in an underwritten public offering for gross proceeds of $172.5 million, resulting in net proceeds of $161.8 million after deducting underwriting discounts, commissions, and offering costs.
In April 2023, pursuant to the 2022 Registration Statement, we sold an aggregate of 5,750,000 shares of common stock at a price of $30.00 per share in an underwritten public offering for gross proceeds of $172.5 million, resulting in net proceeds of $161.8 million after deducting underwriting discounts and commissions, and offering costs.
Our lead clinical program’s drug candidate, icovamenib, is an orally bioavailable, and selective covalent inhibitor of menin currently in two clinical and multiple preclinical studies, investigating icovamenib’s potential in type 1 and type 2 diabetes, as well as its impact in obesity. Menin serves as a checkpoint to prevent beta cell proliferation.
Our lead clinical program’s drug candidate, icovamenib, is currently being developed as an orally bioavailable, and selective, covalent inhibitor of menin in two clinical and multiple preclinical studies, investigating icovamenib’s potential in type 1 and type 2 diabetes, as well as its impact in obesity. Menin serves as a checkpoint to prevent beta cell proliferation.
Nonrefundable advance payments for goods or services to be received in future periods for use in research and development activities are deferred and capitalized. The capitalized amounts are then expensed as the related goods are delivered and as services are performed. We track direct costs by stage of program, clinical or preclinical.
Non-refundable advance payments for goods or services to be received in future periods for use in research and development activities are deferred and capitalized. The capitalized amounts are then expensed as the related goods are delivered and as services are performed. We track direct costs by stage of program, clinical or preclinical.
We may need to raise additional capital in the future to fund our operations, including to conduct and complete clinical trials for any product candidates.
We will need to raise additional capital in the future to fund our operations, including to conduct and complete clinical trials for any product candidates.
We expect our research and development expenses to increase substantially during the next few years as we seek to initiate and complete clinical trials, pursue regulatory approval of icovamenib and BMF-500, and advance our other programs, through preclinical and clinical development.
We expect our research and development expenses to increase substantially during the next few years as we seek to initiate and complete clinical trials, pursue regulatory approval of icovamenib and advance BMF-650 and our other programs 87 through preclinical and clinical development.
Interest and Other Income, Net Interest and other income, net consists primarily of interest earned on our investments and non-cash interest income (loss) related to accretion (amortization) of the discount (premium) on marketable securities. 98 Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended December 31, 2024 2023 $ Change Operating expenses: Research and development $ 118,085 $ 102,546 $ 15,539 General and administrative 25,985 23,589 2,396 Total operating expenses 144,070 126,135 17,935 Loss from operations (144,070 ) (126,135 ) (17,935 ) Interest and other income, net 5,644 8,880 (3,236 ) Net loss $ (138,426 ) $ (117,255 ) $ (21,171 ) Research and Development Expenses The following table summarizes our research and development expenses incurred during the periods indicated (in thousands): Year Ended December 31, 2024 2023 $ Change External costs Clinical activities related expenses $ 48,100 $ 36,098 $ 12,002 Preclinical activities related expenses 11,815 10,165 1,650 Expenses related to manufacturing of clinical and research material 7,262 13,237 (5,975 ) Other external costs 10,948 5,528 5,420 Internal costs: Personnel-related expenses (including stock-based compensation) 31,856 28,838 3,018 Facilities and other allocated expenses 8,104 8,680 (576 ) Total research and development expenses $ 118,085 $ 102,546 $ 15,539 Research and development expenses increased by $15.5 million during the year ended December 31, 2024 compared to the year ended December 31, 2023.
Comparison of the Years Ended December 31, 2024 and 2023 The following table summarizes our results of operations for the periods indicated (in thousands): Year Ended December 31, 2024 2023 $ Change Operating expenses: Research and development $ 118,085 $ 102,546 $ 15,539 General and administrative 25,985 23,589 2,396 Total operating expenses 144,070 126,135 17,935 Loss from operations (144,070 ) (126,135 ) (17,935 ) Interest and other income, net 5,644 8,880 (3,236 ) Net loss $ (138,426 ) $ (117,255 ) $ (21,171 ) Research and Development Expenses The following table summarizes our research and development expenses incurred during the periods indicated (in thousands): Year Ended December 31, 2024 2023 $ Change External costs Clinical activities related expenses $ 48,100 $ 36,098 $ 12,002 Preclinical activities related expenses 11,815 10,165 1,650 Expenses related to manufacturing of clinical and research material 7,262 13,237 (5,975 ) Other external costs 10,948 5,528 5,420 Internal costs: Personnel-related expenses (including stock-based compensation) 31,856 28,838 3,018 Facilities and other allocated expenses 8,104 8,680 (576 ) Total research and development expenses $ 118,085 $ 102,546 $ 15,539 Research and development expenses increased by $15.5 million during the year ended December 31, 2024 compared to the year ended December 31, 2023.
With its strategic focus to become a diabetes and obesity medicines company, we plan to conclude our studies exploring icovamenib’s potential in oncology and explore partnerships to further advance our oncology assets (BMF-500, a covalent inhibitor of FLT3, currently in a Phase I study), while concentrating internal resources on metabolic disorders.
With our strategic focus to become a diabetes and obesity medicines company, we are concluding our studies exploring icovamenib’s potential in oncology and plan to explore partnerships to further advance our oncology assets (BMF-500, a covalent inhibitor of FLT3, currently in a Phase I trial), while concentrating internal resources on metabolic disorders.
To the extent that our product candidates continue to advance into clinical trials, as well as advance into larger and later stage clinical trials, our expenses will increase substantially and may become more variable. 97 Our future research and development costs may vary significantly based on a wide variety of factors, such as: • the scope, rate of progress, expense and results of our ongoing clinical trials, including our ongoing Phase I/II clinical trial of icovamenib in type 2 diabetes and Phase II clinical trial of icovamenib in type 1 diabetes, our preclinical development activities, as well as any future preclinical development and clinical trials of our product candidates, and other research and development activities we may conduct; • uncertainties in clinical trial design and the interpretation of clinical trial data; • per patient trial costs; • the duration, scope and number of trials required for approval; • the number of sites included in the trials; • the number of patients who participate in the trials; • the countries in which the trials are conducted; • the length of time required to enroll eligible patients; • the drop-out or discontinuation rates of patients; • the safety and efficacy profiles of our product candidates; • the timing receipt, and terms of any approvals from applicable regulatory authorities including the FDA and non-U.S. regulators; • maintaining a continued acceptable safety profile of our product candidates following approval, if any, of any of our product candidates; • significant and changing government regulation and regulatory guidance; • establishing clinical and commercial manufacturing capabilities or making arrangements with third-party manufacturers in order to ensure that we or our third-party manufacturers are able to make product successfully; • the impact of any business interruptions to our operations or to those of the third parties with whom we work in light of adverse global market conditions; and • the extent to which we establish additional strategic collaborations or other arrangements.
Our future research and development costs may vary significantly based on a wide variety of factors, such as: • the scope, rate of progress, expense and results of our ongoing clinical trials, including our ongoing Phase II clinical trial of icovamenib in type 2 diabetes and Phase II clinical trial of icovamenib in type 1 diabetes, enrollment in our Phase I clinical trial for BMF-650, as well as any future preclinical development and clinical trials of our product candidates, and other research and development activities we may conduct; • uncertainties in clinical trial design and the interpretation of clinical trial data; • per participant trial costs; • the duration, scope and number of trials required for approval; • the number of sites included in the trials; • the number of participants who participate in the trials; • the countries in which the trials are conducted; • the length of time required to enroll eligible participants; • the drop-out or discontinuation rates of participants; • the safety and efficacy profiles of our product candidates; • the timing, receipt, and terms of any approvals from applicable regulatory authorities including the FDA and non-U.S. regulators; • our ability to maintain a continued acceptable safety profile of our product candidates following approval, if any, of any of our product candidates; • significant and changing government regulation and regulatory guidance; • establishing clinical and commercial manufacturing capabilities or making arrangements with third-party manufacturers in order to ensure that we or our third-party manufacturers are able to make product successfully; • the impact of any business interruptions to our operations or to those of the third parties with whom we work in light of adverse global market conditions; and • the extent to which we establish additional strategic collaborations or other arrangements.
We have not generated any revenue from product sales and, as a result, we have never been profitable and have incurred net losses since commencement of our operations. As of December 31, 2024, we had an accumulated deficit of $387.3 million.
We have not generated any revenue from product sales and, as a result, we have never been profitable and have incurred net losses since commencement of our operations. As of December 31, 2025, we had an accumulated deficit of $449.0 million.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase substantially if and as we: • continue our research and development efforts and submit additional INDs; • conduct our ongoing preclinical studies and Phase I clinical trial of icovamenib in various types of liquid tumors, our planned Phase I/Ib clinical trial of icovamenib in solid tumors with kirsten rat sarcoma viral oncogene homolog gene mutations, our Phase I/II clinical trial of icovamenib in type 2 diabetes and our Phase II clinical trial of icovamenib in type 1 diabetes; • conduct preclinical studies and initiate and conduct clinical trials; • seek marketing approvals for any product candidates that successfully complete clinical trials; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues or other regulatory challenges; • establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities, whether alone or with third parties, to commercialize any product candidates for which we may obtain regulatory approval, if any; • obtain, expand, maintain, enforce and protect our intellectual property portfolio; • hire additional clinical, regulatory and scientific personnel; and • operate as a public company.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase substantially if and as we: • conduct our ongoing preclinical studies and our two Phase II clinical trials of icovamenib in type 2 and type 1 diabetes; • seek marketing approvals for any product candidates that successfully complete clinical trials; • continue our research and development efforts and submit additional INDs; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues or other regulatory challenges; • establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities, whether alone or with third parties, to commercialize any product candidates for which we may obtain regulatory approval, if any; • obtain, expand, maintain, enforce and protect our intellectual property portfolio; • hire additional clinical, regulatory and scientific personnel; and • operate as a public company.
Cash provided by financing activities was mainly related to net proceeds received from stock option exercises and purchases under the ESPP. Net cash provided by financing activities was $163.8 million for the year ended December 31, 2023. Cash provided by financing activities was mainly related to net proceeds received from the issuance of common stock from our public offering.
Cash provided by financing activities was mainly related to net proceeds received from stock option exercises and purchases under the ESPP. Net cash provided by financing activities was $163.8 million for the year ended December 31, 2023.
Net cash used in investing activities was $2.2 million for the year ended December 31, 2023. Cash used in investing activities was mainly related to purchases of property and equipment offset by maturities of investments. 102 Net cash provided by investing activities was $27.3 million for the year ended December 31, 2022.
Net cash used in investing activities was $2.2 million for the year ended December 31, 2023. Cash used in investing activities was mainly related to purchases of property and equipment offset by maturities of investments. Net Cash Provided by Financing Activities Net cash provided by financing activities was $67.9 million for the year ended December 31, 2025.
On October 14, 2022, we filed a shelf registration statement on Form S-3 (the Shelf Registration Statement) with the SEC relating to the registration of up to an aggregate of $350.0 million in shares of our common stock, preferred stock, debt securities, warrants and units or any combination thereof.
On October 14, 2022, we filed the 2022 Registration Statement with the SEC relating to the registration of up to an aggregate of $350.0 million in shares of our common stock, preferred stock, debt securities, warrants and units or any combination thereof. The 2022 Registration Statement was declared effective by the SEC on October 24, 2022.
Summary Statement of Cash Flows The following table sets forth the primary sources and uses of cash, cash equivalents and restricted cash for each of the periods presented below (in thousands): Year Ended December 31, 2024 2023 2022 Net cash (used in) provided by: Operating activities $ (119,894 ) $ (96,592 ) $ (62,417 ) Investing activities (362 ) (2,220 ) 27,341 Financing activities 1,668 163,798 1,239 Net (decrease) increase in cash, cash equivalents, and restricted cash $ (118,588 ) $ 64,986 $ (33,837 ) Net Cash Used in Operating Activities Net cash used in operating activities was $119.9 million for the year ended December 31, 2024 and consisted of a net loss of $138.4 million offset by increase in net assets of $5.1 million and non-cash adjustments of $23.7 million.
Summary Statement of Cash Flows The following table sets forth the primary sources and uses of cash, cash equivalents and restricted cash for each of the periods presented below (in thousands): Year Ended December 31, 2025 2024 2023 Net cash (used in) provided by: Operating activities $ (70,371 ) $ (119,894 ) $ (96,592 ) Investing activities — (362 ) (2,220 ) Financing activities 67,904 1,668 163,798 Net (decrease) increase in cash, cash equivalents, and restricted cash $ (2,467 ) $ (118,588 ) $ 64,986 Net Cash Used in Operating Activities Net cash used in operating activities was $70.4 million for the year ended December 31, 2025 and consisted of a net loss of $61.8 million offset by increase in net assets of $3.7 million and non-cash adjustments of $4.9 million.
We incurred net losses of $138.4 million and $117.3 million for the years ended December 31, 2024 and 2023, respectively.
We incurred net losses of $61.8 million and $138.4 million for the years ended December 31, 2025 and 2024, respectively.
(Piper Sandler) with respect to an at-the-market offering program, under which we may offer and sell, from time to time at our sole discretion, shares of our common stock having an aggregate offering price of up to $100.0 million (which is included in the $350.0 million originally registered under the Shelf Registration Statement) through Piper Sandler as the sales agent.
Additionally, we are party to an equity distribution agreement, dated November 25, 2022, with Piper Sandler with respect to the 2022 ATM Program, under which we may offer and sell, from time to time at our sole discretion, shares of our common stock having an aggregate offering price of up to $100.0 million (which was included in the $350.0 million originally registered under the 2022 Registration Statement and is now included in the $300.0 million originally registered under the 2025 Registration Statement) through Piper Sandler as the sales agent.
Manufacturing related costs decreased by $6.0 million primarily driven by timing of services performed by our contract manufacturers. Personnel-related expenses, including stock-based compensation, increased by $3.0 million due to an increase in headcount. General and Administrative Expenses General and administrative expenses increased by $2.4 million during the year ended December 31, 2024 compared to the year ended December 31, 2023.
Personnel-related expenses, including stock-based compensation, increased by $3.0 million due to an increase in headcount. 90 General and Administrative Expenses General and administrative expenses increased by $2.4 million during the year ended December 31, 2024 compared to the year ended December 31, 2023.
Interest and Other Income, Net Interest and other income, net was $5.6 million for the year ended December 31, 2024 compared to $8.9 million for the year ended December 31, 2023.
Interest and Other Income, Net Interest and other income, net was $5.6 million for the year ended December 31, 2024 compared to $8.9 million for the year ended December 31, 2023. The decrease of $3.2 million was primarily due to the decrease in cash, cash equivalents, and restricted cash balance.
Our net proceeds from the offering were $161.8 million, after deducting underwriting discounts and commissions and offering costs of $10.7 million. Components of Operating Results Revenue To date, we have not generated any revenue and do not expect to generate any revenue from the sale of products in the near future.
The aggregate gross proceeds from the offering, including the proceeds from the underwriters' over-allotment option, were approximately $25.0 million, before deducting underwriting discounts and commissions and offering costs. Components of Operating Results Revenue To date, we have not generated any revenue and do not expect to generate any revenue from the sale of products in the near future.
Overview We are a clinical-stage diabetes and obesity medicines company focused on the discovery and development of oral covalent small molecule drugs to treat patients with metabolic diseases.
Overview We are a clinical-stage diabetes and obesity medicines company dedicated to developing novel small molecule therapies to treat and improve the lives of patients with metabolic diseases.
Cash provided by investing activities was mainly related to maturities of investments offset by purchases of property and equipment. Net Cash Provided by Financing Activities Net cash provided by financing activities was $1.7 million for the year ended December 31, 2024.
Net Cash Used in Investing Activities Net cash used in investing activities was $0.0 million for the year ended December 31, 2025. Net cash used in investing activities was $0.4 million for the year ended December 31, 2024. Cash used in investing activities was mainly related to purchases of property and equipment.
Net cash provided by financing activities was $1.2 million for the year ended December 31, 2022. Cash provided by financing activities was mainly related to proceeds received from stock option exercises and purchases under the ESPP. Critical Accounting Estimates Our financial statements have been prepared in accordance with U.S. generally accepted accounting principles (GAAP).
Cash provided by financing activities was mainly related to net proceeds received from the issuance of common stock from our public offering. 93 Critical Accounting Estimates Our financial statements have been prepared in accordance with U.S. generally accepted accounting principles (GAAP).
Liquidity and Capital Resources Liquidity We have funded our operations primarily through the sale and issuance of shares of our common and convertible preferred stock and the issuance of unsecured promissory notes from inception through December 2020.
Liquidity and Capital Resources Liquidity We have funded our operations primarily through the sale and issuance of shares of our common and convertible preferred stock, pre-funded and common warrants and the issuance of unsecured promissory notes from inception through December 2020, issuance of our common stock through our IPO in April 2021, our public offerings in March 2023, June 2025 and October 2025 and through sales under our 2022 ATM Program.
We also expect that our future intellectual property expenses may increase as we expand our product portfolio of product candidates due to advances in our research and development programs.
We also expect that our future intellectual property expenses may increase as we expand our product portfolio of product candidates due to advances in our research and development programs. 88 Impairment of long-lived assets Impairment of long-lived assets consists of a one-time impairment charge, primarily for laboratory equipment and leasehold improvements (see Note 4).
Thus, we believe inhibiting menin via icovamenib has the potential to enable the proliferation, preservation, and reactivation of healthy, function beta 95 cells capable of producing insulin, thereby leading to long-term glycemic control in patients with type 1 and type 2 diabetes.
Thus, the data support that inhibiting menin via icovamenib has the potential to enable the proliferation, preservation, and reactivation of healthy, functional beta cells capable of producing insulin, thereby leading to long-term glycemic control in patients with type 1 and type 2 diabetes. 85 In preclinical studies, the administration of icovamenib has produced a pronounced effect in preclinical models of diabetes, normalizing glucose levels during treatment and even after drug washout.
The Shelf Registration Statement was declared effective by the SEC on October 24, 2022.
The 2025 Registration Statement was declared effective by the SEC on August 15, 2025.
We have incurred substantial operating losses and have used cash in our operating activities since inception.
As of December 31, 2025, we had an accumulated deficit of $449.0 million. We have incurred substantial operating losses and have used cash in our operating activities since inception.
With its unique pharmacokinetic profile and enhanced bioavailability, we believe BMF-650 has the potential to provide a best-in-class therapeutic option for diabetes and obesity. Our goal is to utilize our capabilities and our FUSION™ System platform to become the leader in developing covalent small molecules to maximize the depth and durability of clinical benefit when treating various diseases.
With its unique pharmacokinetic profile and enhanced bioavailability, we believe BMF-650 has the potential to provide a best-in-class therapeutic option for diabetes and obesity.
In addition, we do not yet have a marketing or sales organization or commercial infrastructure. Accordingly, we will incur significant expenses to develop a marketing and sales organization and commercial infrastructure in advance of generating any product sales.
In addition, we do not yet have a marketing or sales organization or commercial infrastructure.
Without any future financing, the current operating plan under the existing cash and cash equivalents, and restricted cash as of December 31, 2024, will not be sufficient for us to fund our operating expenses and capital expenditure requirements for at least twelve months following the issuance date of the financial statements.
Without any future financing, the current operating plan under the existing cash and cash equivalents, and restricted cash as of December 31, 2025, will only be sufficient to fund our operations into the first quarter of 2027.
In April 2021, we completed our IPO and issued an aggregate of 9,000,000 shares of our common stock at a price of $17.00 per share. Subsequent to the close, an additional 823,532 shares were issued in connection with the partial exercise by the underwriters of their option to purchase additional shares of common stock.
Subsequent to the close, an additional 823,532 shares were issued in connection with the partial exercise by the underwriters of their option to purchase additional shares of common stock. In addition, immediately prior to the closing of the IPO, all outstanding shares of our convertible preferred stock automatically converted into 7,064,925 shares of common stock.
As of December 31, 2024 icovamenib is being evaluated in type 1 and type 2 diabetes across two ongoing clinical trials.
In October 2025, we reported 52-week results from our Phase II COVALENT-111 trial of icovamenib in type 2 diabetes. Results from our type 1 diabetes trial (COVALENT-112) are still outstanding. As of December 31, 2025 icovamenib is now being evaluated across two ongoing Phase II clinical trials (COVALENT-211 and COVALENT-212) in type 2 diabetes.
Interest and Other Income, Net Interest and other income, net was $8.9 million for the year ended December 31, 2023 compared to $1.8 million for the year ended December 31, 2022. The increase of $7.1 million was primarily due to interest earned from cash and investment balances.
The common warrants are re-measured at each balance sheet date. Interest and Other Income, Net Interest and other income, net was $1.9 million for the year ended December 31, 2025 compared to $5.6 million for the year ended December 31, 2024. The decrease of $3.7 million was primarily due to the decrease in cash and cash equivalents balance.
Net cash used in operating activities was $62.4 million for the year ended December 31, 2022. Cash used in operating activities in 2022 was mainly the result of the net loss of $81.8 million and increase in prepaid expenses and other assets of $3.6 million.
Net cash used in operating activities was $119.9 million for the year ended December 31, 2024 and consisted of a net loss of $138.4 million offset by increase in net assets of $5.1 million and non-cash adjustments of $23.7 million.
Based on our current operating plan, we believe that our existing cash and cash equivalents, and restricted cash as of December 31, 2024, without any future financing, will not be sufficient for us to continue as a going concern for at least one year from the issuance date of the financial statements appearing elsewhere in this Annual Report on Form 10-K.
Based on our current operating plan, we believe that our existing cash and cash equivalents, and restricted cash as of December 31, 2025, without any future financing, will only be sufficient to fund our operations into the first quarter of 2027.
The increase was primarily due to increased personnel-related expenses, including stock-based compensation, of $2.3 million due to an increase in headcount. Professional services and administrative expenses increased by $1.0 million due to legal, accounting, consulting and other services incurred as a public company offset by a decrease in insurance expense of $0.6 million.
Personnel-related expenses, including stock-based compensation, decreased by $11.3 million due to a decrease in headcount. Facilities and other allocated expenses decreased by $2.1 million due to a decrease in rent and facilities-related costs.
In April 2021, we completed 100 our IPO and issued an aggregate of 9,000,000 shares of our common stock at a price of $17.00 per share. Following the close of the IPO, an additional 823,532 shares were issued in connection with the partial exercise by the underwriters of their option to purchase additional shares of common stock.
Accordingly, we will incur significant expenses to develop a marketing and sales organization and commercial infrastructure in advance of generating any product sales. 86 In April 2021, we completed our initial public offering (IPO) and issued an aggregate of 9,000,000 shares of our common stock at a price of $17.00 per share.
In the event we make advance payments, the payments are recorded as a prepaid expense and recognized as the services are performed.
In the event we make advance payments, the payments are recorded as a prepaid expense and recognized as the services are performed. Warrant Liability We account for our warrants in accordance with ASC 815, Derivatives and Hedging - Contracts in Entity's Own Equity, as either liabilities or as equity instruments depending on the specific terms of the warrant agreement.
Other external costs increased by $2.8 million primarily driven by external consultants and professional services to support clinical and preclinical activities. Manufacturing related costs increased by $0.6 million primarily driven by timing of services performed by our contract manufacturers. Personnel-related expenses, including stock-based compensation, increased by $9.5 million due to an increase in headcount.
Manufacturing related costs decreased by $6.0 million primarily driven by timing of services performed by our contract manufacturers.
This was offset by an increase in accounts payable and accrued liabilities of $11.9 million and stock-based compensation expense of $10.3 million. Net Cash Provided by (Used in) Investing Activities Net cash used in investing activities was $0.4 million for the year ended December 31, 2024. Cash used in investing activities was mainly related to purchases of property and equipment.
Cash provided by financing activities was mainly related to net proceeds of $67.7 million from issuance of common stock and pre-funded warrants under the public offerings and the 2022 ATM Program, and $0.2 million of proceeds from purchases under the ESPP. Net cash provided by financing activities was $1.7 million for the year ended December 31, 2024.
Removed
Leveraging our extensive expertise in covalent binding chemistry and development, we built our proprietary FUSION™ System discovery platform to advance a pipeline of novel small molecule product candidates.
Added
In September 2025, we announced that BMF-650, our investigational, next-generation, oral small molecule GLP-1 RA, received IND-clearance from the FDA. Initiation of our Phase I GLP-131 trial for BMF-650 in obese, otherwise healthy volunteers is ongoing, and data is anticipated in the second quarter of 2026.
Removed
Menin is also an important transcriptional regulator known to play a direct role in oncogenic signaling in multiple cancers and in beta cell homeostasis . In preclinical studies, the administration of icovamenib has produced a pronounced effect in preclinical models of diabetes, normalizing glucose levels during treatment and even after drug washout.
Added
Our net proceeds from the offering were $161.8 million, after deducting underwriting discounts and commissions and offering costs of $10.7 million. During the twelve months ended December 31, 2025, we issued 2,271,122 shares of our common stock for aggregate proceeds of $4.9 million, net of commissions and offering costs from our 2022 ATM Program.
Removed
Beyond icovamenib, we are utilizing our novel FUSION™ System to pioneer covalent treatments against other high-value genetic drivers of disease. In October 2024, we announced the nomination of BMF-650 our investigational, next-generation, oral small molecule GLP-1 RA, which is currently advancing through IND-enabling studies.
Added
In June 2025, we issued and sold 19,450,000 shares of common stock at an offering price of $2.00 per share and, to a certain investor in lieu of common stock, pre-funded warrants to purchase up to 550,000 shares of common stock at an offering price of $1.9999 per share, and accompanying common warrants to purchase up to 23,000,000 shares of common stock at a per share exercise price of $2.50.
Removed
In addition, immediately prior to the closing of the IPO, all outstanding shares of our convertible preferred stock automatically converted into 7,064,925 shares of common stock. Proceeds from the IPO, net of underwriting discounts and commissions and offering costs were $152.8 million.
Added
In July 2025, in connection with the June 2025 underwritten public offering, the underwriters partially exercised their over-allotment option to purchase an additional 1,381,262 shares of common stock at an offering price of $2.00 per share.
Removed
The increase of $27.2 million in external costs was primarily driven by an increase of $26.7 million related to clinical activities due to increased enrollment of our diabetes and oncology trials. Preclinical activities related expenses decreased by $2.9 million primarily driven by timing of our exploratory programs.
Added
The aggregate gross proceeds from the offering, including the proceeds from the underwriters' over-allotment option, were approximately $42.8 million, before deducting underwriting discounts and commissions and offering costs.
Removed
Facilities and other allocated expenses increased by $3.2 million primarily due to new lease agreements for additional office and laboratory space in Redwood City and San Carlos which commenced in 2023. General and Administrative Expenses General and administrative expenses increased by $2.7 million during the year ended December 31, 2023 compared to the year ended December 31, 2022.
Added
In October 2025, we issued and sold 11,195,121 shares of common stock at an offering price of $2.05 per share and, to a certain investor in lieu of common stock, pre-funded warrants to purchase up to 1,000,000 shares of common stock at an offering price of $2.0499 per share and accompanying common warrants to purchase up to 14,024,389 shares of common stock at a per share exercise price of $2.50, which included the underwriters' partial exercise of their over-allotment option to purchase additional common warrants.
Removed
Additionally, we are party to an equity distribution agreement, dated November 25, 2022, with Piper Sandler & Co.
Added
To the extent that our product candidates continue to advance into clinical trials, as well as advance into larger and later stage clinical trials, our expenses will increase substantially and may become more variable.
Removed
In the year ended December 31, 2024, we did not sell any shares of common stock pursuant to the sales agreement with Piper Sandler. As of December 31, 2024, we had cash, cash equivalents and restricted cash of $58.6 million. As of December 31, 2024, we had an accumulated deficit of $387.3 million.
Added
Change in fair value of common warrant liability Change in fair value of common warrant liability consists of revaluation of the common warrants issued in connection with the June and October 2025 underwritten public offerings (see Note 5). The common warrants are re-measured at each balance sheet date.
Added
Interest and Other Income, Net Interest and other income, net consists primarily of interest income earned on our cash and cash equivalents.
Added
The decrease of $42.7 million in external costs was primarily driven by a decrease of $28.5 million related to clinical activities due to our strategic realignment to focus on our core assets and ceasing internal development of our oncology programs, a decrease of $4.4 million in manufacturing costs, a decrease of $4.0 million related to consultants, advisors and other professional services to support our clinical studies, discovery research and overall research and development program, and a decrease of $5.8 million related to preclinical and exploratory programs.
Added
General and Administrative Expenses 89 General and administrative expenses decreased by $6.7 million during the year ended December 31, 2025 compared to the year ended December 31, 2024. The decrease was primarily driven by a decrease of $5.9 million related to personnel-related expenses, including stock-based compensation, due to a decrease in headcount.
Added
Consulting and professional expenses decreased by $0.7 million due to legal, accounting, consulting and other services. Facilities and other allocated expenses decreased by $0.1 million due to a decrease in rent and facilities-related costs.
Added
Impairment of long-lived assets Impairment of long-lived assets was $2.2 million for the year ended December 31, 2025 and $0 for the year ended December 31, 2024, attributable to a one-time impairment charge (see Note 4).
Added
Change in fair value of common warrant liability Change in fair value of common warrant liability was $19.9 million for the year ended December 31, 2025 and $0 for the year ended December 31, 2024, attributable to revaluation of the common warrants issued in connection with the June and October 2025 underwritten public offerings (see Note 5).
Added
On August 5, 2025, we filed the 2025 Registration Statement with the SEC relating to the registration of up to an aggregate of $300.0 million in shares of our common stock, preferred stock, debt securities, warrants and units or any combination thereof to replace the 2022 Registration Statement.
Added
In June 2025, we completed an underwritten public offering, in which we issued and sold 19,450,000 shares of common stock at an offering price of $2.00 per share and to a certain investor in lieu of common stock, pre-funded warrants to purchase up to 550,000 shares of common stock at an offering price of $1.9999 per share, and accompanying common warrants to purchase up to 23,000,000 shares of common stock at a per share exercise price of $2.50.
Added
Our net proceeds from the offering were approximately $37.2 million, after deducting underwriting discounts and commissions and offering costs of approximately $2.8 million. In July 2025, in connection with the June 2025 underwritten public offering, the underwriters partially exercised their over-allotment option to purchase an additional 1,381,262 shares of common stock at an offering price of $2.00 per share.
Added
The net proceeds from the offering pursuant to the over-allotment option were approximately $2.6 million, after deducting underwriting discounts and commissions and offering costs of approximately $0.2 million.
Added
Through December 31, 2025, we have received aggregate proceeds from our 2022 ATM Program of $4.9 million, net of commissions and offering costs, pursuant to the issuance of 2,271,122 shares. As of December 31, 2025, we have $94.8 million available under the 2022 ATM Program.
Added
In October 2025, we completed an underwritten public offering in which we issued and sold 11,195,121 shares of common stock at an offering price of $2.05 per share and, to a certain investor in lieu of common stock, pre-funded warrants to purchase up to 1,000,000 shares of common stock at an offering price of $2.0499 per share and accompanying common warrants to purchase up to 12,195,121 shares of common stock at a per share exercise price of $2.50.
Added
Our net proceeds from the offering, including the proceeds from the underwriter’s over-allotment option, were approximately $23.1 million, after deducting underwriting discounts and commissions and offering costs of approximately $1.9 million. 91 As of December 31, 2025, we had cash, cash equivalents and restricted cash of $56.2 million.
Added
The increase in net assets consisted primarily of a decrease in prepaid expenses and other current assets of $7.8 million, a decrease in other assets of $0.6 million, a decrease in accounts payable of $9.7 million, a decrease in accrued expenses and other current liabilities of $0.3 million and a decrease in operating lease liabilities of $2.2 million.
Added
Non-cash adjustments consisted primarily of a non-cash gain on the change in fair value of warrant liability of $19.9 million, stock-based compensation expense of $9.5 million, impairment of property and equipment of $2.2 million, operating lease expense of $1.8 million and depreciation expense of $1.4 million.
Added
The common warrants issued in connection with the June and October 2025 underwritten public offerings (see Note 5) are classified as liabilities and are recorded at fair value.
Added
The warrants are subject to re-measurement at each settlement date and at each balance sheet date and any change in fair value is recognized in Change in fair value of common warrant liability in the statements of operations and comprehensive loss. We estimate the fair value of the warrant liability using a Black-Scholes pricing model.
Added
We are required to make assumptions and estimates in determining an appropriate expected term, risk-free interest rate, volatility factor, dividend yield, and the fair value of common stock. Any significant adjustments to the unobservable inputs would have a direct impact on the fair value of the warrant liability. 94

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

3 edited+2 added−0 removed0 unchanged
Biggest changeWe held $58.6 million in cash, cash equivalents, and restricted cash as of December 31, 2024. Cash equivalents consisted of money market funds. Restricted cash consisted of two stand-by letter of credits issued to our landlord in connection with the laboratory leases. We held no interest-bearing liabilities as of December 31, 2024.
Biggest changeThere was no material foreign currency risk for the year ended December 31, 2025. We held $56.2 million in cash, cash equivalents, and restricted cash as of December 31, 2025. Cash equivalents consisted of money market funds. Restricted cash consisted of two stand-by letter of credits issued to our landlord in connection with the laboratory leases.
Historical fluctuations in interest rates have not been significant for us. Due to the short-term maturities of our cash equivalents, an immediate 10% relative change in interest rates would not have a material effect on the fair market value of our cash equivalents.
We held no interest-bearing liabilities as of December 31, 2025. Historical fluctuations in interest rates have not been significant for us. Due to the short-term maturities of our cash equivalents, an immediate 10% relative change in interest rates would not have a material effect on the fair market value of our cash equivalents.
Item 7A. Quantitative and Qualitat ive Disclosures About Market Risk The primary objectives of our investment activities are to ensure liquidity and to preserve capital. We are exposed to market risks in the ordinary course of our business. These risks primarily include interest rate sensitivities. There was no material foreign currency risk for the year ended December 31, 2024.
Item 7A. Quantitative and Qualitat ive Disclosures About Market Risk Interest Rate Risk The primary objectives of our investment activities are to ensure liquidity and to preserve capital. We are exposed to market risks in the ordinary course of our business. These risks primarily include interest rate sensitivities.
Added
Effect of Inflation Inflation generally affects us by increasing our cost of labor and research and development costs.
Added
Although we do not believe that inflation has had a material impact on our financial position or results of operations to date, we may experience some effect in the future due to an impact on the costs to conduct research and development, labor costs we incur to attract and retain qualified personnel, and other operational costs. 95