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What changed in Fulcrum Therapeutics, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Fulcrum Therapeutics, 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.

+409 added−419 removedSource: 10-K (2026-02-24) vs 10-K (2024-12-31)

Top changes in Fulcrum Therapeutics, Inc.'s 2025 10-K

409 paragraphs added · 419 removed · 290 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

100 edited+58 added−77 removed284 unchanged
Biggest changeFDA regulations allow access to investigational drugs under an IND by the company or the treating physician for treatment purposes on a case-by-case basis for: individual patients (single-patient IND applications for treatment in emergency settings and non-emergency settings); intermediate-size patient populations; and larger populations for use of the drug under a treatment protocol or Treatment IND Application. 16 When considering an IND application for expanded access to an investigational product, the FDA will determine suitability when all of the following criteria apply: patient(s) have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; the potential patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to be treated; and the expanded use of the investigational drug for the requested treatment will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the potential development of the product.
Biggest changeWhen considering an IND application for expanded access to an investigational product, the FDA will determine suitability when all of the following criteria apply: patient(s) have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; the potential patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to be treated; and the expanded use of the investigational drug for the requested treatment will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the potential development of the product.
In addition, there may be additional federal, state and non-U.S. laws which govern the privacy and security of health and other personal information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; • the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for health care benefits, items or services; • the Foreign Corrupt Practices Act, or FCPA, which prohibits companies and their intermediaries from making, or offering or promising to make improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; • the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians, certain other licensed healthcare practitioners and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • 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 anti-kickback and false claims laws, which may apply to health care items or services that are reimbursed by non-government third-party payors, including private insurers.
In addition, there may be additional federal, state and non-U.S. laws which govern the privacy and 17 security of health and other personal information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; • the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for health care benefits, items or services; • the Foreign Corrupt Practices Act, or FCPA, which prohibits companies and their intermediaries from making, or offering or promising to make improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; • the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians, certain other licensed healthcare practitioners and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • 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 anti-kickback and false claims laws, which may apply to health care items or services that are reimbursed by non-government third-party payors, including private insurers.
An applicant seeking approval to market and distribute a new drug in the United States generally must satisfactorily complete each of the following steps before the product candidate will be approved by the FDA: • preclinical testing including laboratory tests, animal studies and formulation studies, which must be performed in accordance with the FDA’s GLP regulations and standards; • submission to the FDA of an IND for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled human clinical trials to establish the safety and effectiveness of the product candidate for each proposed indication, in accordance with current good clinical practices, or GCP; • preparation and submission to the FDA of a new drug application, or NDA, for a drug product which includes not only the results of the clinical trials, but also, detailed information on the chemistry, manufacture and quality controls for the product candidate and proposed labelling for one or more proposed indication(s); • review of the product candidate by an FDA advisory committee, where appropriate or if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities, including those of third parties, at which the product candidate or components thereof are manufactured to assess compliance with current good manufacturing practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GCP and the integrity of clinical data in support of the NDA; • payment of user fees and securing FDA approval of the NDA to allow marketing of the new drug product; and • compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct any post-approval studies required by the FDA.
An applicant seeking approval to market and distribute a new drug in the United States generally must satisfactorily complete each of the following steps before the product candidate will be approved by the FDA: • preclinical testing including laboratory tests, animal studies and formulation studies, which must be performed in accordance with the FDA’s GLP regulations and standards; • submission to the FDA of an IND for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled human clinical trials to establish the safety and effectiveness of the product candidate for each proposed indication, in accordance with current good clinical practices, or GCP; • preparation and submission to the FDA of a new drug application, or NDA, for a drug product which includes not only the results of the clinical trials, but also, detailed information on the chemistry, manufacture and quality controls for the product candidate and proposed labelling for one or more proposed indication(s); • review of the product candidate by an FDA advisory committee, where appropriate or if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities, including those of third parties, at which the product candidate or components thereof are manufactured to assess compliance with current 8 good manufacturing practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GCP and the integrity of clinical data in support of the NDA; • payment of user fees and securing FDA approval of the NDA to allow marketing of the new drug product; and • compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct any post-approval studies required by the FDA.
Under the statute, a generic drug is bioequivalent to a RLD if “the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed drug.” Upon approval of an ANDA, the FDA indicates whether the 21 generic product is “therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the “Orange Book.” Depending on state laws, generic drugs that are found to be therapeutically equivalent may be automatically substituted for prescriptions for the RLD by the dispensing pharmacist, without the intervention of the prescriber.
Under the statute, a generic drug is bioequivalent to a RLD if “the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed drug.” Upon approval of an ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the “Orange Book.” Depending on state laws, generic drugs that are found to be therapeutically equivalent may be automatically substituted for prescriptions for the RLD by the dispensing pharmacist, without the intervention of the prescriber.
We are the FULcrew united around these Pillars: • We take great pride in being Purposeful Patient Partners • We have a culture of Trust and Transparency 32 • We are Invested in our People • We have a Playful spirit and have fun together at work • We launched Fulcrum with a Bold Scientific Vision and remain committed to this journey Our Management of Human Capital To effectively leverage and manage our peoples, we ensure our hiring needs are directly aligned with our strategy, we invest in our people focused on their development and journey while at Fulcrum and most importantly we identify our key talent to ensure we are focused on their retention.
We are the FULcrew united around these Pillars: • We take great pride in being Purposeful Patient Partners • We have a culture of Trust and Transparency • We are Invested in our People • We have a Playful spirit and have fun together at work • We launched Fulcrum with a Bold Scientific Vision and remain committed to this journey Our Management of Human Capital To effectively leverage and manage our peoples, we ensure our hiring needs are directly aligned with our strategy, we invest in our people focused on their development and journey while at Fulcrum and most importantly we identify our key talent to ensure we are focused on their retention.
A person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation; 23 • the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent or knowingly making, using or causing to made or used a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal government.
A person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation; • the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent or knowingly making, using or causing to made or used a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal government.
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including 27 for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medicinal products (gene-therapy, somatic cell-therapy or tissue-engineered medicines), and products with a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions, and viral diseases.
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medicinal products (gene-therapy, somatic cell-therapy or tissue-engineered medicines), and products with a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions, and viral diseases.
In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs. These measures could reduce the 26 ultimate demand for our products, once approved, or put pressure on our product pricing.
In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.
These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU. • The marketing and promotion of authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU.
These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, or API, including the manufacture of API outside of the EU with the intention to import the API into the EU. • The marketing and promotion of authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU.
Our approach to drug discovery generates significant insights into disease biology and allows us to think creatively about the best way to modulate and balance gene expression. Our patient-focused product discovery approach is designed to systematically identify and validate cellular drug targets that can modulate gene expression to treat the known root cause of genetically defined diseases.
Our approach to drug discovery generates significant insights into disease biology and allows us to think creatively about the best way to modulate and balance gene expression. Our patient-focused product discovery 26 approach is designed to systematically identify and validate cellular drug targets that can modulate gene expression to treat the known root cause of genetically defined diseases.
In addition, the coverage claimed in a patent application may be significantly reduced before a patent is issued, and its scope can be reinterpreted and even challenged after issuance. As a result, we cannot guarantee that any of our products will be protected or remain protectable by enforceable patents.
In addition, the coverage claimed in a patent application may be significantly reduced before a patent is issued, and its scope can be reinterpreted and 5 even challenged after issuance. As a result, we cannot guarantee that any of our products will be protected or remain protectable by enforceable patents.
Clinical trials are conducted under written clinical trial protocols detailing, among other things, the objectives of the study, inclusion and exclusion criteria, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Human clinical trials are typically conducted in three sequential phases, but the phases may overlap or be combined.
Clinical trials are conducted under written clinical trial protocols detailing, among other things, the objectives of the study, inclusion and exclusion criteria, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. 10 Human clinical trials are typically conducted in three sequential phases, but the phases may overlap or be combined.
The FDA 15 requires a 30-day waiting period after the filing of each IND before clinical trials may begin. This waiting period is designed to allow the FDA to review the IND to determine, among other things, whether human research subjects will be exposed to unreasonable health risks.
The FDA requires a 30-day waiting period after the filing of each IND before clinical trials may begin. This waiting period is designed to allow the FDA to review the IND to determine, among other things, whether human research subjects will be exposed to unreasonable health risks.
The failure of an applicant to comply with the applicable regulatory requirements at any time during the product development process, including non-clinical testing, clinical testing, the approval 14 process or post-approval process, may result in delays to the conduct of a study, regulatory review and approval and/or administrative or judicial sanctions.
The failure of an applicant to comply with the applicable regulatory requirements at any time during the product development process, including non-clinical testing, clinical testing, the approval process or post-approval process, may result in delays to the conduct of a study, regulatory review and approval and/or administrative or judicial sanctions.
The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.
The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality 9 and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.
License Agreement with CAMP4 In July 2023, we entered into a license agreement with CAMP4 pursuant to which we received a worldwide exclusive license (including the right to sublicense) from CAMP4 to rights under its DBA program, which includes certain small molecule compounds, composition of matter and method of use patent rights, and know-how for us to research, develop, manufacture, use, commercialize or otherwise exploit therapeutic products in any indication, including the grant of a sublicense under certain intellectual property rights that CAMP4 has licensed under an agreement with Children’s Medical Center Corporation, or CMCC.
License Agreements and Collaborations License Agreement with CAMP4 In July 2023, we entered into a license agreement with CAMP4 pursuant to which we received a worldwide exclusive license (including the right to sublicense) from CAMP4 to rights under its DBA program, which includes certain small molecule compounds, composition of matter and method of use patent rights, and know-how for us to research, develop, manufacture, use, commercialize or otherwise exploit therapeutic products in any indication, including the grant of a sublicense under certain intellectual property rights that CAMP4 has licensed under an agreement with Children’s Medical Center Corporation, or CMCC.
Importantly, a dedicated EMA contact and rapporteur from the Committee for Medicinal Products for Human Use, or CHMP, or Committee for Advanced Therapies, are appointed early in the PRIME scheme; facilitating increased understanding of the product at the EMA’s committee level.
Importantly, a dedicated EMA contact and rapporteur from the Committee for Medicinal 21 Products for Human Use, or CHMP, or Committee for Advanced Therapies, are appointed early in the PRIME scheme; facilitating increased understanding of the product at the EMA’s committee level.
This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.
This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in 14 which a company promotes or distributes drug products.
Shortly after birth, the genes encoding the γ-subunits, the HBG1 and HBG2 genes, are silenced and the HBB gene is activated. As described above, SCD is caused by a mutation in the HBB gene that gives rise to mutated ß-subunits.
Shortly after birth, the genes encoding the γ-subunits, the HBG1 2 and HBG2 genes, are silenced and the HBB gene is activated. As described above, SCD is caused by a mutation in the HBB gene that gives rise to mutated ß-subunits.
We expect to continue to rely on third parties for the manufacture of pociredir for any future clinical trials and for the manufacture of any future product candidates for preclinical and clinical testing, as well as for commercial manufacture if our product candidates receive marketing approval.
We expect to continue to rely on third parties for the manufacture of pociredir for any future clinical trials and for the manufacture of any future product candidates for preclinical and clinical 6 testing, as well as for commercial manufacture if our product candidates receive marketing approval.
The American Taxpayer Relief Act of 2012 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 Taxpayer Relief Act of 2012 further reduced Medicare payments to 19 several types of providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
Novartis is evaluating ITU-512, a small molecule designed to increase production of HbF, in a Phase 1/2 clinical trial comprised of a Phase 1 trial in healthy volunteers and a Phase 2 trial in subjects with SCD.
Novartis AG is evaluating ITU-512, a small molecule designed to increase production of HbF, in a Phase 1/2 clinical trial comprised of a Phase 1 trial in healthy volunteers and a Phase 2 trial in subjects with SCD.
The PDCO may also grant waivers when 29 development of a medicine for children is not needed or is not appropriate, such as for diseases that only affect the elderly population.
The PDCO may also grant waivers when development of a medicine for children is not needed or is not appropriate, such as for diseases that only affect the elderly population.
These sickle shaped cells are much less flexible than healthy cells and can block blood vessels (vaso-occlusion) or rupture (lysis), leading to pain, anemia, irreversible organ damage or even death. During fetal development, the major form of hemoglobin is HbF. Similar to hemoglobin in adults, HbF is also a complex of four proteins, two α-subunits and two γ-subunits.
These sickle-shaped cells are much less flexible than healthy cells and can block blood vessels (vaso-occlusion) or rupture (hemolysis), leading to pain, anemia, irreversible organ damage or even death. During fetal development, the major form of hemoglobin is HbF. Similar to hemoglobin in adults, HbF is also a complex of four proteins, two α-subunits and two γ-subunits.
Corporate Information Our principal executive office is located at 26 Landsdowne Street, Cambridge, MA 02139, and our telephone number is 617-651-8851. Our internet website address is www.fulcrumtx.com. The information contained on, or that can be accessed through, our website is not a part of this Annual Report on Form 10-K. 33
Corporate Information Our principal executive office is located at 26 Landsdowne Street, Cambridge, MA 02139, and our telephone number is 617-651-8851. Our internet website address is www.fulcrumtx.com. The information contained on, or that can be accessed through, our website is not a part of this Annual Report on Form 10-K. 27
We have retained all rights to our lead product candidate, and we plan to commercialize any approved product for such rare genetically defined diseases using a targeted sales infrastructure. We may in the future pursue commercialization partnerships for certain product candidates and/or markets outside the United States.
We have retained all rights to our lead product candidate, and we plan to commercialize any approved product for such rare genetically defined diseases using a targeted commercial infrastructure. We may in the future pursue commercialization partnerships for certain product candidates and/or markets outside the United States.
We also own three U.S. non-provisional applications and related patent applications pending in Europe directed to solid forms and methods of using pociredir and one pending U.S. non-provisional application directed to pociredir methods of use and formulations, that, if resulting in issued patents, would be expected to expire between 2042 and 2043.
We also own three U.S. non-provisional applications and related patent applications pending in Europe directed to solid forms and methods of using pociredir, and one pending U.S. non-provisional application and three U.S. provisional applications directed to pociredir methods of use and formulations, that, if resulting in issued patents, would be expected to expire between 2042 and 2046.
The FDA may designate a product for Priority Review if it treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. The FDA determines, on a case-by-case basis, whether the proposed product represents a significant improvement when compared with other available therapies.
The FDA may designate a product for Priority Review if it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety or effectiveness. The FDA determines, on a case-by-case basis, whether the proposed product represents a significant improvement when compared with other available therapies.
CAMP4 has the right to terminate the license agreement in the event of our non-payment (subject to cure periods and tolling for bona fide disputes). CAMP4 may also terminate the license agreement if we challenge certain patents sublicensed to us by CAMP4.
CAMP4 has the right to terminate the license agreement in the event of our non-payment (subject to cure periods and tolling for bona fide disputes). CAMP4 may alsBo terminate the license agreement if we challenge certain patents sublicensed to us by CAMP4.
We also seek to explore opportunities to acquire or in-license complementary technologies or therapies, such as our exclusive global license agreement with CAMP4 Therapeutics Corp., or CAMP4. • Maximize the commercial potential of our product candidates.
We also seek to explore opportunities to acquire or in-license complementary technologies or therapies, such as our exclusive global license agreement with CAMP4. • Maximize the commercial potential of our product candidates.
The California Privacy Rights Act, or CPRA, which became effective on January 1, 2023, imposes additional obligations on companies covered by the legislation and significantly modifies the CCPA, including by expanding consumers’ rights with respect to certain 24 sensitive personal information, and establishes a state agency vested with the authority to enforce the CCPA.
The California Privacy Rights Act, or CPRA, which became effective in January 2023, imposes additional obligations on companies covered by the legislation and significantly modifies the CCPA, including by expanding consumers’ rights with respect to certain sensitive personal information, and establishes a state agency vested with the authority to enforce the CCPA.
Other potential consequences may include: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or holds on post-approval clinical trials; 20 • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences may include: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, FDA Form 483s, untitled letters, warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
During Phase 1 clinical trials, information about the investigational drug product’s PK and pharmacological effects may be obtained to permit the design of scientifically valid Phase 2 clinical trials.
During Phase 1 clinical trials, information about the investigational drug product’s pharmacokinetic and pharmacological effects may be obtained to permit the design of scientifically valid Phase 2 clinical trials.
Washington state’s My Health My Data Act, which entered into force on March 31, 2024, expands the definition of consumer health data, affords consumers with privacy rights and creates a private right of action, which could generate litigation.
Washington state’s My Health My Data Act, which entered into force in March 2024, expands the definition of consumer health data, affords consumers with privacy rights and creates a private right of action, which could generate litigation.
A Priority Review designation is intended to direct overall attention and resources to the evaluation of such applications and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months.
A Priority Review designation is intended to direct overall attention and resources to the evaluation of such applications and to shorten the FDA’s goal for taking action on a marketing application for a new molecular entity from ten months to six months.
Pociredir Currently, our patent portfolio related to pociredir includes three issued U.S. patents directed to composition of matter that is expected to expire in 2040, one U.S. non-provisional application and related granted patents and pending patent applications in Canada and Mexico, Europe, Africa, Australia and New Zealand, South America, and Asia that, if issued, are expected to expire between 2039 and 2040.
Pociredir Currently, our patent portfolio related to pociredir includes three issued U.S. patents directed to composition of matter and methods of using pociredir that are expected to expire in 2040, two U.S. non-provisional applications and related granted patents and pending patent applications in Canada and Mexico, Europe, Africa, Australia and New Zealand, South America, and Asia that, if issued, are expected to expire between 2039 and 2040.
Bristol-Myers Squibb is evaluating BMS-986470, a small molecule designed to increase production of HbF, in a Phase 1/2a clinical trial in healthy volunteers and subjects with SCD. GSK is evaluating GSK4172239D, a small molecule designed to increase production of HbF, in a Phase 1 clinical trial in subjects with SCD.
BMS is evaluating BMS-986470, a small molecule designed to increase production of HbF, in a Phase 1/2a clinical trial in healthy volunteers and subjects with SCD. GSK plc is evaluating GSK4172239D, a small molecule designed to increase production of HbF, in a Phase 1 clinical trial in subjects with SCD.
We have developed a discovery approach that we employ to systematically identify and validate cellular drug targets that can potentially modulate gene expression to treat known root causes of genetically defined rare diseases, with a primary focus on hematology diseases.
We have developed a discovery approach that we use to identify and validate cellular drug targets that may modulate gene expression to treat known root causes of genetically defined rare diseases, with a primary focus on hematology diseases.
However, trade secrets and confidential know-how are difficult to protect. We seek to protect our proprietary information, in part, using confidentiality agreements with any collaborators, scientific advisors, employees and consultants and invention assignment agreements with our employees. We also have agreements requiring assignment of inventions with selected consultants, scientific advisors and collaborators. These agreements may not provide meaningful protection.
We seek to protect our proprietary information, in part, using confidentiality agreements with any collaborators, scientific advisors, employees and consultants and invention assignment agreements with our employees. We also have agreements requiring assignment of inventions with selected consultants, scientific advisors and collaborators. These agreements may not provide meaningful protection.
Even if a product is considered to be an innovative medicinal product so that the innovator gains the prescribed period of data exclusivity, another company nevertheless could also market another version of the product if such company obtained marketing authorization based on an MAA with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.
Even if a product is considered to be an innovative medicinal product so that the innovator gains the prescribed period of data exclusivity, another company nevertheless could also market another version of the product if such company obtained marketing authorization based on an MAA with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials. 23 Periods of Authorization and Renewals A marketing authorization has an initial validity for five years in principle.
As of February 18, 2025, we had 45 full-time employees, including a total of 13 employees with M.D. or Ph.D. degrees. Of these full-time employees, 30 employees are engaged in research and development. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.
As of February 17, 2026, we had 55 full-time employees, including a total of 19 employees with M.D. or Ph.D. degrees. Of these full-time employees, 36 employees are engaged in research and development. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.
Orphan drug exclusivity means that the FDA may not approve another sponsor’s marketing application for the same drug for the same condition for seven years, except in certain limited circumstances.
Orphan drug exclusivity means that the FDA may not approve another sponsor’s marketing application for the same drug for the same approved use or indication for seven years, except in certain limited 16 circumstances.
In February 2023, the FDA placed the IND for pociredir for the potential treatment of SCD on full clinical hold. Accordingly, we suspended enrollment and dosing in the Phase 1b trial of pociredir and withdrew our separate IND for pociredir in ß- thalassemia.
Regulatory History In February 2023, the FDA placed the IND for pociredir in SCD on full clinical hold based on nonclinical toxicology findings. Accordingly, we suspended enrollment and dosing in the Phase 1b trial of pociredir and withdrew our separate IND for pociredir in ß- thalassemia.
Periods of Authorization and Renewals A marketing authorization has an initial validity for five years in principle. The marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the EU Member State for a nationally authorized product.
The marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the EU Member State for a nationally authorized product.
There have been a number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for drugs and biologics and other medical products, government control and other changes to the health care system in the United States. 25 In 2010, the United States Congress enacted the ACA, which, among other things, included changes to the coverage and payment for drug products under government health care programs.
There have been a number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for drugs and biologics and other medical products, government control and other changes to the health care system in the United States.
A product may be designated as a Breakthrough Therapy if it is intended, either alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
In addition, the Fast Track designation may be withdrawn if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process or for the other reasons. 12 A product may be designated as a Breakthrough Therapy if it is intended, either alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
As of February 18, 2025, we owned or in-licensed eight U.S. patents, nine U.S. pending non-provisional patent applications and related pending foreign patent applications, and one pending U.S. provisional patent application. The intellectual property portfolio for our most advanced programs as of February 18, 2025, is summarized below.
As of February 24, 2026, we owned or in-licensed 16 U.S. patents, 12 U.S. pending non-provisional patent applications and related pending foreign patent applications, and four pending U.S. provisional patent applications. The intellectual property portfolio for our most advanced programs as of February 24, 2026, is summarized below.
The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. 22 Orphan Drug Designation and Exclusivity Under the Orphan Drug Act, the FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or condition, generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a product available in the United States for treatment of the disease or condition will be recovered from sales of the product.
Orphan Drug Designation and Exclusivity Under the Orphan Drug Act, the FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or condition, generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a product available in the United States for treatment of the disease or condition will be recovered from sales of the product.
Our discovery approach led to the identification of pociredir for SCD, as well as other drug candidates. 1 Our Pipeline Using our discovery approach, we have generated a pipeline of potentially disease-modifying therapies that address the known root causes of rare genetic diseases. The following chart summarizes key information about our pipeline of clinical stage and pre-clinical programs.
Our Pipeline Using our discovery approach, we have generated a pipeline of potentially disease-modifying therapies that are designed to address the known root causes of rare genetic diseases. The following chart summarizes key information about our pipeline of clinical stage and pre-clinical programs.
If the FDA approves a new product, it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, or require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval.
Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. 13 If the FDA approves a new product, it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, or require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval.
The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.
Crizanlizumab, a fully-human monoclonal antibody p-selectin inhibitor marketed by Novartis as ADAKVEO, is approved for the reduction in the frequency of VOCs. L-glutamine, brand name ENDARI, marketed by Emmaus Life Sciences, Inc., is approved to reduce acute complications of the disorder. Lovo-cel and exa-cel are gene therapies approved for the treatment of severe SCD.
Crizanlizumab (ADAKVEO®) is a monoclonal antibody p-selectin inhibitor approved for the reduction in the frequency of VOCs and is marketed by Novartis AG. L-glutamine (ENDARI®), is approved to reduce acute complications of SCD and is marketed by Emmaus Life Sciences, Inc. Two gene therapies are approved for certain patients with severe SCD.
Pociredir We are developing pociredir, which is designed to elevate the level of fetal hemoglobin, or HbF, for the treatment of people with SCD. We also believe that people with some types of ß-thalassemia may benefit from treatment with pociredir. Overview of Sickle Cell Disease Sickle cell disease is a genetic disorder of RBCs.
Pociredir We are developing pociredir, which is designed to elevate the level of HbF for the treatment of people with SCD. We also believe that people with some types of ß-thalassemia may benefit from treatment with pociredir.
Item 1. Bu siness. Overview We are a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Our clinical-stage product candidate, pociredir, is being developed for the potential treatment of sickle cell disease, or SCD.
Item 1. Bu siness. Overview We are a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need.
We also intend to seek patent term extensions in any jurisdictions where available, however, there is no guarantee that the applicable authorities, including the FDA, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions. 12 In addition to patent protection, we rely upon unpatented trade secrets and confidential know-how and continuing technological innovation to develop and maintain our competitive position.
We also intend to seek patent term extensions in any jurisdictions where available, however, there is no guarantee that the applicable authorities, including the FDA, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions.
Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable deterioration over its shelf life. 17 Pediatric Studies Under the Pediatric Research Equity Act of 2003, or PREA, an NDA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Pediatric Studies Under the Pediatric Research Equity Act of 2003, or PREA, an NDA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Pharmaceutical Insurance Coverage and Health Care Reform In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated health care costs.
Actual or alleged violations of these regulations may be punishable by criminal and/or civil sanctions, and may result in exclusion from participation in federal and state programs. 18 Pharmaceutical Insurance Coverage and Health Care Reform In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated health care costs.
The benefit of accelerated approval derives from the potential to receive approval based on surrogate endpoints sooner than possible for trials with clinical or survival endpoints, rather than deriving from any explicit shortening of the FDA approval timeline, as is the case with Priority Review. 19 The accelerated approval pathway is contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the product’s clinical benefit.
The benefit of accelerated approval derives from the potential to receive approval based on surrogate endpoints sooner than possible for trials with clinical or survival endpoints, rather than deriving from any explicit shortening of the FDA approval timeline, as is the case with Priority Review.
The five drug treatments approved in the United States are hydroxyurea, crizanlizumab, L-glutamine, lovo-cel, and exa-cel. Hydroxyurea is approved for the treatment of SCD to reduce the frequency of painful crises and to reduce the need for blood transfusions. Hydroxyurea is available in both generic and brand name formulations including DROXIA manufactured by Bristol-Myers Squibb, and SIKLOS manufactured by Addmedica.
Hydroxyurea is approved for the treatment of SCD to reduce the frequency of painful crises and the need for blood transfusions and is available in both generic and brand name formulations including DROXIA® manufactured by Bristol-Myers Squibb Company, or BMS, and SIKLOS® manufactured by Norgine.
The FDA maintains a list of diseases that are exempt from the requirements of PREA, due to low prevalence of disease in the pediatric population, and product candidates that have received orphan drug designation are generally exempt from PREA requirements, although orphan-designated drugs intended for treatment of certain molecularly targeted cancer indications are not eligible for the exemption.
The FDA maintains a list of diseases that are exempt from the requirements of PREA, due to low prevalence of disease in the pediatric population, and product candidates that have received orphan drug designation are generally exempt from PREA requirements, although orphan-designated drugs intended for treatment of certain molecularly targeted cancer indications are not eligible for the exemption. 11 Review and Approval of an NDA In order to obtain approval to market a drug product in the United States, a marketing application must be submitted to the FDA that provides sufficient data establishing the safety and effectiveness of the proposed drug product for its intended indication.
Novo Nordisk A/S, or Novo, is evaluating NDec (decitabine-tetrahydrouridine), a combination of two small molecules designed to increase production of HbF, in a Phase 2 clinical trial.
Pociredir could face competition from a number of different therapeutic approaches in development for people with SCD. Novo Nordisk A/S, or Novo, is evaluating NDec (decitabine-tetrahydrouridine), a combination of two small molecules designed to increase production of HbF, in a Phase 2 clinical trial.
Pfizer, Inc. is evaluating osivelotor, an HbS polymerization inhibitor, in a Phase 2/3 clinical trial and inclacumab, a P-selectin inhibitor that is being evaluated in a Phase 3 clinical trial. Beam Therapeutics is evaluating BEAM-101, an autologous base edited CD34+ HSPC designed to increase production of HbF, in a Phase 1/2 clinical trial in subjects with severe SCD.
Sanofi is evaluating rilzabrutinib, a Bruton’s tyrosine kinase, or BTK, inhibitor, in a Phase 3 clinical trial in subjects with SCD. Beam Therapeutics Inc. is evaluating BEAM-101, an autologous base edited CD34+ HSPC designed to increase production of HbF, in a Phase 1/2 clinical trial in subjects with severe SCD.
General Data Protection Regulation The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the EU GDPR, which became effective on May 25, 2018.
In general, however, the healthcare budgetary constraints in most EU Member States have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. 25 General Data Protection Regulation The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the EU GDPR, which became effective in May 2018.
All of the aforementioned EU rules are generally applicable in the European Economic Area, or EEA, which consists of the EU Member States, plus Norway, Liechtenstein and Iceland. 30 Reform of the Regulatory Framework in the European Union The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children).
Reform of the Regulatory Framework in the European Union The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children).
In cases where such NCE exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its application four years following the original product approval.
In cases where such NCE exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its application four years following the original product approval. 15 Hatch-Waxman Patent Certification and the 30-Month Stay Upon approval of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with claims that cover the applicant’s product or an approved method of using the product.
Regulators and legislators in the U.S. are increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries.
Regulators and legislators in the United States are increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries. For example, the DOJ’s January 2025 Rule on Preventing Access to U.S.
See Note 10 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for a description of license agreements with Sanofi and GSK. 11 Intellectual Property We strive to protect and enhance our discovery approach, inventions and improvements that are commercially important to the development of our business, including by seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties.
Intellectual Property We strive to protect and enhance our discovery approach, inventions and improvements that are commercially important to the development of our business, including by seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties.
The period of market exclusivity may, in addition, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.
The period of market exclusivity may, in addition, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. 24 Regulatory Requirements After a Marketing Authorization has been Obtained If an authorization for a medicinal product in the EU is obtained, the holder of the marketing authorization is required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products.
National governments and health service providers have different priorities and approaches to the delivery of healthcare and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU Member States have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers.
National governments and health service providers have different priorities and approaches to the delivery of healthcare and the pricing and reimbursement of products in that context.
Compliance with the GDPR is a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance. 31 Brexit and the Regulatory Framework in the United Kingdom The United Kingdom formally left the EU on January 31, 2020, and the EU and the United Kingdom have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.
Brexit and the Regulatory Framework in the United Kingdom The United Kingdom formally left the EU on January 31, 2020, and the EU and the United Kingdom have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.
On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”.
In February 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”. The Windsor Framework was approved by the EU-UK Joint Committee in March 2023, and the medicines aspects of the Windsor Framework have applied since January 1, 2025.
We believe that pociredir may address the root cause of SCD through this mechanism of action. Identification of the Drug Target for SCD We conducted target identification and validation activities using human umbilical cord blood-derived erythroid progenitor 2, or HUDEP2, cells as a model to study HbF reactivation. HUDEP2 cells are immature RBCs.
Identification of the Drug Target for SCD We conducted target identification and validation activities using human umbilical cord blood-derived erythroid progenitor 2, or HUDEP2, cells as a model system to study HbF reactivation. HUDEP2 cells are immature RBCs. Screening of small molecule and CRISPR libraries identified polycomb repressive complex 2, or PRC2, as a regulator of HbF expression.
The root cause of SCD is a mutant hemoglobin that polymerizes in low oxygen conditions. This polymerization creates the abnormal, elongated, or sickle, shape of the RBC and results in, ultimately, hemolysis and vascular injury that causes major morbidities and significantly limits lifespan in people with SCD.
This polymerization leads to the abnormal sickle shape of RBCs and ultimately results in hemolysis and vascular injury that causes major morbidities and significantly limits lifespan in people with SCD.
The protocol was amended to revise the inclusion and exclusion criteria to target patients with higher disease severity. Key inclusion criteria includes patients with certain frequencies of vaso-occlusive crises and/or other specified measures of severity, previous experience with hydroxyurea, and previous experience with a stable dose of voxelotor, crizanlizumab, or L-glutamine or lack of access to these advanced therapies.
Key inclusion criteria includes patients with certain frequencies of VOCs and/or other specified measures of severity, previous experience with hydroxyurea, and previous experience with a stable dose of voxelotor, crizanlizumab, or L-glutamine or lack of access to these advanced therapies. Key exclusion criteria excludes subjects currently on or having received hydroxyurea within 60 days prior to initiating pociredir.
In addition to our product candidates, we developed a discovery approach that we employ to systematically identify and validate cellular drug targets that can potentially modulate gene expression to treat known root causes of genetically defined rare diseases.
Pending feedback from the FDA, we plan to initiate a potential registration-enabling trial in the second half of 2026. In addition to our product candidates, we have developed a discovery approach that we use to identify and validate cellular drug targets that may modulate gene expression to treat the root causes of genetically defined rare diseases.
If our lead product candidates are approved for the indications for which we are currently undertaking clinical trials, they will compete with the therapies and currently marketed drugs discussed below. 13 SCD Several approved drug treatments for SCD focus primarily on the management and reduction of painful vaso-occlusive crises, and improvement of hemolytic anemia.
If our lead product candidates are approved for the indications for which we are currently undertaking clinical trials, they will compete with the therapies and currently marketed drugs discussed below. SCD Several approved therapies for SCD are intended to reduce VOCs or other complications of SCD.
People with SCD typically suffer from serious clinical consequences, which may include vaso-occlusive crises, anemia, pain, infections, stroke, heart disease, pulmonary hypertension, kidney failure, liver disease and reduced life expectancy. According to a study published by the American Medical Association, approximately 32.5% of adults with SCD were hospitalized three or more times per year due to pain crises.
People with SCD typically suffer from serious clinical consequences, which may include vaso-occlusive crises, or VOCs, anemia, pain, infections, stroke, heart disease, pulmonary hypertension, kidney failure, liver disease and reduced life expectancy.
A conditional marketing authorization can be converted into a standard centralized marketing authorization (no longer subject to specific obligations) once the marketing authorization holder fulfils the obligations imposed and the complete data confirm that the medicine’s benefits continue to outweigh its risks. 28 The EU medicines rules expressly permit the EU Member States to adopt national legislation prohibiting or restricting the sale, supply or use of any medicinal product containing, consisting of or derived from a specific type of human or animal cell, such as embryonic stem cells.
The EU medicines rules expressly permit the EU Member States to adopt national legislation prohibiting or restricting the sale, supply or use of any medicinal product containing, consisting of or derived from a specific type of human or animal cell, such as embryonic stem cells.
Similar requirements for posting clinical trial information are present in the European Union and other countries, as well.
Competitors may use this publicly available information to gain knowledge regarding the progress of development programs as well as clinical trial design. Similar requirements for posting clinical trial information are present in the European Union and other countries, as well.
Novo is also evaluating etavopivat, a pyruvate kinase activator, or PK activator, in a Phase 2/3 clinical trial. Agios Pharmaceuticals, Inc., or Agios, is evaluating mitapivat, a PK activator, in a Phase 2/3 clinical trial in subjects with SCD. Agios also anticipates initiating a Phase 2 clinical trial in mid-2025 to evaluate tebapivat, a PK activator, in subjects with SCD.
Agios is also evaluating tebapivat, a PK activator, in a Phase 2 clinical trial in subjects with SCD. Novo is also evaluating etavopivat, a PK activator, in a Phase 2/3 clinical trial. Pfizer, Inc. is evaluating osivelotor, an HbS polymerization inhibitor, in a Phase 2/3 clinical trial in subjects with SCD.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeFurthermore, the failure of any of our product candidates to demonstrate safety and efficacy in any clinical trial could negatively impact the perception of our other product candidates and/or cause the FDA or other regulatory authorities to require additional testing before approving any of our product candidates. 41 We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including: • regulators or institutional review boards, or IRBs, may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; • we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; • regulators may decide the design of our clinical trials is flawed, for example if our trial protocol does not evaluate treatment effects in trial subjects for a sufficient length of time; • clinical trials of our product candidates may produce negative or inconclusive results, such as with the recent Phase 3 REACH trial, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs; • we may be unable to establish clinical endpoints that applicable regulatory authorities would consider clinically meaningful, or, if we seek accelerated approval, biomarker efficacy endpoints that applicable regulatory authorities would consider likely to predict clinical benefit; • preclinical testing may produce results based on which we may decide, or regulators may require us, to conduct additional preclinical studies before we proceed with certain clinical trials, limit the scope of our clinical trials, halt ongoing clinical trial(s) or abandon product development programs; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate (for example, we initially experienced difficulty enrolling patients who met the updated inclusion and exclusion criteria for our trial of pociredir in SCD) or participants may drop out of these clinical trials at a higher rate than we anticipate; • our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • we may decide, or regulators or IRBs may require us, to suspend or terminate clinical trials of our product candidates for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; • regulators or IRBs may require us to perform additional or unanticipated clinical trials to obtain approval or we may be subject to additional post-marketing testing requirements to maintain regulatory approval; • regulators may revise the requirements for approving our product candidates, or such requirements may not be as we anticipate; • the cost of clinical trials of our product candidates may be greater than we anticipate; • the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; • our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs to suspend or terminate the trials; • unforeseen global instability, including political instability, such as the Russian invasion of Ukraine or hostilities in Israel, Lebanon and the Gaza Strip, changes in U.S. economic policy that adversely impact the U.S. economy and/or economies worldwide, or instability from an outbreak of pandemic or contagious disease in or around the countries in which we conduct our clinical trials (such as closure of clinical trial sites, like we experienced in our ReDUX4 clinical trial due to COVID-19), could delay the commencement or rate of completion of our clinical trials; and • regulators may withdraw their approval of a product or impose restrictions on its distribution, such as in the form of a risk evaluation and mitigation strategy, or REMS. 42 Further, in February 2023, the FDA imposed a clinical hold on our IND for pociredir in SCD, which halted our clinical trial until the FDA lifted the clinical hold in August 2023.
Biggest changeWe may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including: • regulators or institutional review boards, or IRBs, may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; • we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; 41 • regulators may decide the design of our clinical trials is flawed, for example if our trial protocol does not evaluate treatment effects in trial subjects for a sufficient length of time; • clinical trials of our product candidates may produce negative or inconclusive results, such as with the Phase 3 REACH trial, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs; • we may be unable to establish clinical endpoints that applicable regulatory authorities would consider clinically meaningful, or, if we seek accelerated approval, biomarker efficacy endpoints that applicable regulatory authorities would consider likely to predict clinical benefit; • preclinical testing may produce results based on which we may decide, or regulators may require us, to conduct additional preclinical studies before we proceed with certain clinical trials, limit the scope of our clinical trials, halt ongoing clinical trial(s) or abandon product development programs; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate (for example, we initially experienced difficulty enrolling patients who met the updated inclusion and exclusion criteria for our trial of pociredir in SCD) or participants may drop out of these clinical trials at a higher rate than we anticipate, or fail to complete follow-up periods; • our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • we may decide, or regulators or IRBs may require us, to suspend or terminate clinical trials of our product candidates for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; • regulators or IRBs may require us to perform additional or unanticipated clinical trials to obtain approval or we may be subject to additional post-marketing testing requirements to maintain regulatory approval; • regulators may revise the requirements for approving our product candidates, or such requirements may not be as we anticipate; • the cost of clinical trials of our product candidates may be greater than we anticipate; • the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; • our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs to suspend or terminate the trials; • unforeseen global instability, including political instability, both ex-U.S. and domestically, or changes in U.S. economic policy that adversely impact the U.S. economy and/or economies worldwide, or instability from an outbreak of pandemic or contagious disease in or around the countries in which we conduct our clinical trials (such as closure of clinical trial sites, as we previously experienced due to COVID-19), could delay the commencement or rate of completion of our clinical trials; and • regulators may withdraw their approval of a product or impose restrictions on its distribution, such as in the form of a risk evaluation and mitigation strategy, or REMS.
Factors that may inhibit our efforts to commercialize our products on our own include: • our inability to recruit, train and retain adequate numbers of effective sales, marketing, coverage or reimbursement, customer service, medical affairs and other support personnel; • the inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to prescribe any future products; • the inability of reimbursement professionals to negotiate arrangements for formulary access, reimbursement and other acceptance by payors; • the inability to price our products at a sufficient price point to ensure an adequate and attractive level of profitability; • restricted or closed distribution channels that make it difficult to distribute our products to segments of the patient population; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and • unforeseen costs and expenses associated with creating an independent sales and marketing organization.
Factors that may inhibit our efforts to commercialize our products on our own include: • our inability to recruit, train and retain adequate numbers of effective sales, marketing, coverage or reimbursement, customer service, medical affairs and other support personnel; • the inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to prescribe any future products; • the inability of reimbursement professionals to negotiate arrangements for formulary access, reimbursement and other acceptance by payors; • the inability to price our future products at a sufficient price point to ensure an adequate and attractive level of profitability; • restricted or closed distribution channels that make it difficult to distribute our products to segments of the patient population; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and • unforeseen costs and expenses associated with creating an independent sales and marketing organization.
We do not have any manufacturing facilities and rely, and expect to continue to rely, on third parties to manufacture clinical supplies of our product candidates and we expect to rely on third parties to manufacture commercial supplies of our products, if and when approved for marketing by applicable regulatory authorities, as well as for packaging, sterilization, storage, distribution and other production logistics.
We do not have any manufacturing facilities and rely, and expect to continue to rely, on third parties to manufacture clinical supplies of our product candidates and to manufacture commercial supplies of our products, if and when approved for marketing by applicable regulatory authorities, as well as for packaging, sterilization, storage, distribution and other production logistics.
The FDA granted fast track designation to pociredir for the treatment of SCD, and we may seek fast track designation for some of our other product candidates as well as breakthrough therapy designation.
The FDA granted fast track designation to pociredir for the treatment of SCD, and we may seek fast track designation as well as breakthrough therapy designation for some of our other product candidates.
As a public company we have incurred, and we will continue to incur significant legal, accounting and other expenses that we did not incur as a private company.
As a public company we have incurred and will continue to incur significant legal, accounting and other expenses that we did not incur as a private company.
The market price for our common stock may be influenced by many factors, including: • results of or developments in preclinical studies and clinical trials of our product candidates or those of our competitors or potential collaborators; • our success in commercializing our products, if and when approved; • the success of competitive products or technologies; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents or other intellectual property or proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to any of our product candidates or clinical development programs; • the results of our efforts to discover, develop, acquire or in-license products, product candidates, technologies or data referencing rights, the costs of commercializing any such products and the costs of development of any such product candidates or technologies; 74 • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or the financial results of companies that are perceived to be similar to us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; and • the other factors described in this “Risk Factors” section.
The market price for our common stock may be influenced by many factors, including: • results of or developments in preclinical studies and clinical trials of our product candidates or those of our competitors or potential collaborators; • our success in commercializing our products, if and when approved; • the success of competitive products or technologies; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents or other intellectual property or proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to any of our product candidates or clinical development programs; • the results of our efforts to discover, develop, acquire or in-license products, product candidates, technologies or data referencing rights, the costs of commercializing any such products and the costs of development of any such product candidates or technologies; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or the financial results of companies that are perceived to be similar to us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; and • the other factors described in this “Risk Factors” section.
Among other things, these provisions: • establish a classified board of directors such that only one of three classes of directors is elected each year; • allow the authorized number of our directors to be changed only by resolution of our board of directors; • limit the manner in which stockholders can remove directors from our board of directors; • establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board of directors; 73 • require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent; • limit who may call stockholder meetings; • authorize our board of directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our board of directors; and • require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repeal specified provisions of our certificate of incorporation or bylaws.
Among other things, these provisions: • establish a classified board of directors such that only one of three classes of directors is elected each year; • allow the authorized number of our directors to be changed only by resolution of our board of directors; • limit the manner in which stockholders can remove directors from our board of directors; • establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board of directors; • require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent; • limit who may call stockholder meetings; • authorize our board of directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our board of directors; and • require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repeal specified provisions of our certificate of incorporation or bylaws.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and potential advantages of our product candidates compared to the advantages and relative risks of alternative treatments; • the effectiveness of sales and marketing efforts; • the cost of treatment in relation to alternative treatments, including any similar generic treatments; • our ability to offer our products, if approved, for sale at competitive prices; • the clinical indications for which the product is approved; • the convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the strength of marketing and distribution support; • the timing of market introduction of competitive products; • the availability of third-party coverage and adequate reimbursement, and patients’ willingness to pay out of pocket for required co-payments or in the absence of third-party coverage or adequate reimbursement; • the prevalence and severity of any side effects; and • any restrictions on the use of our products, if approved, together with other medications.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and potential advantages of our product candidates compared to the advantages and relative risks of alternative treatments; • the effectiveness of sales and marketing efforts; • the cost of treatment in relation to alternative treatments, including any similar generic treatments; • our ability to offer our products, if approved, for sale at competitive prices; • the clinical indications for which the product is approved; • the convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the strength of marketing and distribution support; • the timing of market introduction of competitive products; • the availability of third-party coverage and adequate reimbursement, and patients’ willingness to pay out of pocket for required co-payments or in the absence of third-party coverage or adequate reimbursement; 45 • the prevalence and severity of any side effects; and • any restrictions on the use of our products, if approved, together with other medications.
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; 62 • 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 candidate; • 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; • portions of our discovery technology are protected by trade secrets, but much is not protected by intellectual property, including patents, trade secrets and know-how, and we may not be able to develop, acquire or in-license any patentable technologies or other intellectual property related to the unprotected portions of our discovery portfolio; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: • others may be able to make 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; 61 • 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 candidate; • 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; • portions of our discovery technology are protected by trade secrets, but much is not protected by intellectual property, including patents, trade secrets and know-how, and we may not be able to develop, acquire or in-license any patentable technologies or other intellectual property related to the unprotected portions of our discovery portfolio; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
If these third parties do not successfully carry out their contractual duties, meet expected deadlines or manufacture our product candidates in accordance with regulatory requirements, if there are disagreements between us and such parties or if such parties are unable to expand capacities to support commercialization of any of our product candidates for which we obtain marketing approval, we may not be able to fulfill, or may be delayed in producing sufficient product candidates to meet, our supply requirements, or we may be forced to manufacture the materials ourselves, for which we may not have the capabilities or resources, or enter into an agreement with a different manufacturer, which we may not be able to do on 48 reasonable terms, if at all.
If these third parties do not successfully carry out their contractual duties, meet expected deadlines or manufacture our product candidates in accordance with regulatory requirements, if there are disagreements between us and such parties or if such parties are unable to expand capacities to support commercialization of any of our product candidates for which we obtain marketing approval, we may not be able to fulfill, or may be delayed in producing sufficient product candidates to meet, our supply requirements, or we may be forced to manufacture the materials ourselves, for which we may not have the capabilities or resources, or enter into an agreement with a different manufacturer, which we may not be able to do on reasonable terms, if at all.
In general, under Section 382 of the Code, and corresponding provisions of state law, a corporation that undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership by certain stockholders over a three-year period, is subject to limitations on its ability to utilize its pre-change net operating losses and research and development tax credit carryforwards to offset future taxable income.
In general, under Section 382 of the Code, or Section 382, and corresponding provisions of state law, a corporation that undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership by certain stockholders over a three-year period, is subject to limitations on its ability to utilize its pre-change net operating losses and research and development tax credit carryforwards to offset future taxable income.
If our operations, including anticipated activities that would be conducted by our sales team, are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations.
If our operations, including anticipated activities that would be conducted by our sales team, are found to be in violation of any of 66 these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations.
The success of any of our product candidates will depend on several factors, including the following: • successfully completing preclinical studies and clinical trials; • allowance by the FDA or other regulatory agencies of the INDs, clinical trial applications, or CTAs, or other regulatory filings; • expanding and maintaining a workforce of experienced scientists and others to continue development efforts; • applying for and receiving marketing approvals from applicable regulatory authorities; • obtaining and maintaining intellectual property protection and regulatory exclusivity; • making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities; • establishing sales, marketing and distribution capabilities and successfully launching commercial sales, if and when approved, whether alone or in collaboration with others; • acceptance, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies; • obtaining and maintaining coverage, adequate pricing and adequate reimbursement from third-party payors, including government payors; • maintaining, enforcing, defending and protecting our rights in our intellectual property portfolio; • not infringing, misappropriating or otherwise violating others’ intellectual property or proprietary rights; and • maintaining a continued acceptable safety profile following receipt of any regulatory approvals.
The success of any of our product candidates will depend on several factors, including the following: • successfully completing preclinical studies and clinical trials; • clearance by the FDA or other regulatory agencies of the INDs, clinical trial applications, or CTAs, or other regulatory filings; • expanding and maintaining a workforce of experienced scientists and others to continue development efforts; • applying for and receiving marketing approvals from applicable regulatory authorities; • obtaining and maintaining intellectual property protection and regulatory exclusivity; • making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities; • establishing sales, marketing and distribution capabilities and successfully launching commercial sales, if and when approved, whether alone or in collaboration with others; • acceptance, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies; • obtaining and maintaining coverage, adequate pricing and adequate reimbursement from third-party payors, including government payors; • maintaining, enforcing, defending and protecting our rights in our intellectual property portfolio; • not infringing, misappropriating or otherwise violating others’ intellectual property or proprietary rights; and • maintaining a continued acceptable safety profile following receipt of any regulatory approvals.
If one or more of our product candidates receives regulatory approval, and we, or others, later discover that they are less effective than previously believed, or cause undesirable side effects, a number of potentially significant negative consequences could result, including: • withdrawal or limitation by regulatory authorities of approvals of such product; • seizure of the product by regulatory authorities; • recall of the product; • restrictions on the marketing of the product or the manufacturing process for any component thereof; 44 • requirement by regulatory authorities of additional warnings on the label, such as a “black box” warning or contraindication; • requirement that we implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients; • commitment to expensive post-marketing studies as a prerequisite of approval by regulatory authorities of such product; • the product may become less competitive; • initiation of regulatory investigations and government enforcement actions; • initiation of legal action against us to hold us liable for harm caused to patients; and • harm to our reputation and resulting harm to physician or patient acceptance of our products.
If one or more of our product candidates receives regulatory approval, and we, or others, later discover that they are less effective than previously believed, or cause undesirable side effects, a number of potentially significant negative consequences could result, including: • suspension, withdrawal or limitation by regulatory authorities of approvals of such product; • seizure of the product by regulatory authorities; • recall of the product; • restrictions on the marketing of the product or the manufacturing process for any component thereof; • requirement by regulatory authorities of additional warnings on the label, such as a “black box” warning or contraindication; • requirement that we implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients; • commitment to expensive post-marketing studies as a prerequisite of approval by regulatory authorities of such product; • the product may become less competitive; • initiation of regulatory investigations and government enforcement actions; • initiation of legal action against us to hold us liable for harm caused to patients; and • harm to our reputation and resulting harm to physician or patient acceptance of our products.
A wide range of enforcement agencies at both the state and federal levels, such as the Federal Trade Commission and state Attorneys General have been increasingly aggressive in reviewing and enforcing privacy and data security-related consumer protection laws. Regulators and legislators in the U.S. are increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries.
A wide range of enforcement agencies at both the state and federal levels, such as the Federal Trade Commission and state Attorneys General have been increasingly aggressive in reviewing and enforcing privacy and data security-related consumer protection laws. 67 Regulators and legislators in the U.S. are increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries.
We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. Further, there can be no guarantee that we will be able to successfully enter into arrangements with third parties to perform sales, marketing or distribution services.
We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. Further, there can be no guarantee that we will be able to successfully enter into arrangements with third parties to perform 46 sales, marketing or distribution services.
The risks of being involved in such litigation 58 and proceedings may increase if and as our product candidates near commercialization and as we gain the greater visibility associated with being a public company. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future, regardless of merit.
The risks of being involved in such litigation and proceedings may increase if and as our product candidates near commercialization and as we gain the greater visibility associated with being a public company. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future, regardless of merit.
In addition, our supply chain may be adversely impacted if any of our third-party contract manufacturers become subject to injunctions or other sanctions as a result of their non-compliance with environmental, health and safety laws and regulations. 70 We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations.
In addition, our supply chain may be adversely impacted if any of our third-party contract manufacturers become subject to injunctions or other sanctions as a result of their non-compliance with environmental, health and safety laws and regulations. We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations.
Further, even if we obtain significant market share for our product candidates, because the potential target populations for many of the indications we are evaluating are very small, we may never achieve profitability despite obtaining such significant market share. Further, the pricing and reimbursement of our product candidates, if approved, is uncertain, but must be adequate to support commercial infrastructure.
Further, even if we obtain significant market share for our product candidates, because the potential target populations for many of the indications we are evaluating are very small, we may never achieve profitability despite obtaining such significant market share. 47 Further, the pricing and reimbursement of our product candidates, if approved, is uncertain, but must be adequate to support commercial infrastructure.
Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate.
Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from 62 preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidates for which we obtain marketing approval.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidates for which we obtain 68 marketing approval.
There is also the threat of consumer class actions related to these laws and the overall protection of personal data. Even if we are not determined to have violated these laws, 68 government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business.
There is also the threat of consumer class actions related to these laws and the overall protection of personal data. Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business.
Our management and other personnel will need to 75 devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations will increase our legal and financial compliance costs, particularly as we hire additional financial and accounting employees to meet public company internal control and financial reporting requirements, and will make some activities more time-consuming and costly.
Our management and other personnel will need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations will increase our legal and financial compliance costs, particularly as we hire additional financial and accounting employees to meet public company internal control and financial reporting requirements, and will make some activities more time-consuming and costly.
Moreover, if we pursue and obtain approval for the same product for another indication for which we are not entitled to or do not have orphan drug exclusivity, our period of orphan 64 exclusivity will not prevent third parties from obtaining approval for a competing drug containing the same active ingredient for use in this other, non-orphan indication.
Moreover, if we pursue and obtain approval for the same product for another indication for which we are not entitled to or do not have orphan drug exclusivity, our period of orphan exclusivity will not prevent third parties from obtaining approval for a competing drug containing the same active ingredient for use in this other, non-orphan indication.
There is also no assurance that any covering analyst will provide favorable coverage. Although we have obtained analyst coverage, if one or more of the analysts covering our business downgrade their evaluations of our stock or publish inaccurate or unfavorable research about our business, or provides more favorable relative recommendations about our competitors, the price of our stock could decline.
There is also no assurance that any covering analyst will provide favorable coverage. 73 Although we have obtained analyst coverage, if one or more of the analysts covering our business downgrade their evaluations of our stock or publish inaccurate or unfavorable research about our business, or provides more favorable relative recommendations about our competitors, the price of our stock could decline.
Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a 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.
Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a product is: • a covered benefit under its health plan; • safe, effective and medically necessary; • appropriate for the specific patient; • cost-effective; and 49 • neither experimental nor investigational.
If risks related to any of these uncertainties materializes, it could have a material adverse effect on our business. Clinical trial and product liability lawsuits against us could divert our resources and could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.
If risks related to any of these uncertainties materializes, it could have a material adverse effect on our business. 50 Clinical trial and product liability lawsuits against us could divert our resources and could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.
We and third-party manufacturers we engage now are, and any third-party manufacturers we may engage in the future will be, subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes.
We and third-party manufacturers we engage now are, and any third-party manufacturers we may engage in the future will be, subject to numerous environmental, health and safety laws and regulations, including those governing laboratory 69 procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes.
Risks Related to our Dependence on Third Parties We rely, and expect to continue to rely, on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials, which may harm our business. We currently rely on third-party contract CROs to conduct our clinical trials.
Risks Related to our Dependence on Third Parties We rely, and expect to continue to rely, on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials, which may harm our business. We currently rely on third-party CROs to conduct our clinical trials.
Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize the affected technology and product candidates, which could have a material adverse effect on our business, financial conditions, results of operations and prospects. 60 Our current or future licensors may have relied on third-party consultants or collaborators or on funds from third parties such that our licensors are not the sole and exclusive owners of the patents and patent applications we in-license.
Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize the affected technology and product candidates, which could have a material adverse effect on our business, financial conditions, results of operations and prospects. 59 Our current or future licensors may have relied on third-party consultants or collaborators or on funds from third parties such that our licensors are not the sole and exclusive owners of the patents and patent applications we in-license.
Our inability to locate and enroll a sufficient number of patients for our clinical trials would result in significant delays, could require us to abandon one or more clinical trials altogether and could delay or prevent our receipt of necessary regulatory approvals.
Our inability to locate and enroll a sufficient number of eligible patients for our clinical trials would result in significant delays, could require us to abandon one or more clinical trials altogether and could delay or prevent our receipt of necessary regulatory approvals.
We expect to devote substantial financial resources to our ongoing and planned activities, particularly as we continue our clinical development of pociredir, continue research and development and initiate additional clinical trials of, and seek regulatory approval for, this and any other product candidates.
We expect to devote substantial financial resources to our ongoing and planned activities, particularly as we continue our clinical development of pociredir, continue research and development and initiate additional clinical trials of, and seek regulatory approval for, pociredir and any other product candidates.
FDORA also requires sponsors to send updates to the FDA every 180 days on the status of such studies, including progress toward enrollment targets, and the FDA must promptly post this information publicly.
FDORA also requires sponsors to send updates to the FDA every 180 64 days on the status of such studies, including progress toward enrollment targets, and the FDA must promptly post this information publicly.
If we are unable to obtain or maintain patent protection with respect to any proprietary technology or product candidate, our business, financial condition, results of operations and prospects could be materially harmed. 54 The patent prosecution process is expensive, time-consuming and complex, and we may not be able to file, prosecute, maintain, defend or license all necessary or desirable patent applications at a reasonable cost or in a timely manner.
If we are unable to obtain or maintain patent protection with respect to any proprietary technology or product candidate, our business, financial condition, results of operations and prospects could be materially harmed. 53 The patent prosecution process is expensive, time-consuming and complex, and we may not be able to file, prosecute, maintain, defend or license all necessary or desirable patent applications at a reasonable cost or in a timely manner.
Litigation and contested proceedings can also be expensive and time-consuming, and our adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we can.
Litigation and contested proceedings can also be expensive and time-consuming, and our adversaries in these proceedings may have the ability to dedicate 57 substantially greater resources to prosecuting these legal actions than we can.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. 61 We may be subject to claims by third parties asserting that our employees, consultants or contractors have wrongfully used or disclosed confidential information of third parties, or we have wrongfully used or disclosed alleged trade secrets of their current or former employers or claims asserting we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. 60 We may be subject to claims by third parties asserting that our employees, consultants or contractors have wrongfully used or disclosed confidential information of third parties, or we have wrongfully used or disclosed alleged trade secrets of their current or former employers or claims asserting we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.
Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could have a material adverse effect on our patent rights and our ability to protect, defend and enforce our patent rights in the future. 57 Although we or our licensors are not currently involved in any litigation to protect or enforce our patent or other intellectual property rights, we may become involved in such lawsuits, which could be expensive, time-consuming and unsuccessful.
Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could have a material adverse effect on our patent rights and our ability to protect, defend and enforce our patent rights in the future. 56 Although we or our licensors are not currently involved in any litigation to protect or enforce our patent or other intellectual property rights, we may become involved in such lawsuits, which could be expensive, time-consuming and unsuccessful.
We have had recent executive transitions, including of our chief executive officer, chief financial officer, president of research and development, chief scientific officer, and chief medical officer. We cannot predict the likelihood, timing or effect of future transitions among our executive leadership.
We have had executive transitions, including of our chief executive officer, chief financial officer, president of research and development, chief scientific officer, and chief medical officer. We cannot predict the likelihood, timing or effect of future transitions among our executive leadership.
In addition, the FDA generally requires pre-approval of promotional materials for products under consideration for accelerated approval, which could adversely 65 impact the timing of the commercial launch of the product.
In addition, the FDA generally requires pre-approval of promotional materials for products under consideration for accelerated approval, which could adversely impact the timing of the commercial launch of the product.
Uncertainties resulting from the initiation and continuation of intellectual property litigation or other proceedings could compromise our ability to compete in the marketplace. 59 Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Uncertainties resulting from the initiation and continuation of intellectual property litigation or other proceedings could compromise our ability to compete in the marketplace. 58 Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Our future capital requirements will depend on many factors, including: • the progress, costs and results of our ongoing Phase 1b clinical trial of pociredir in SCD; • additional planned clinical trials; • the scope, progress, costs and results of discovery research, preclinical development, laboratory testing and clinical trials for any of our product candidates in additional indications or for any future product candidates that we may pursue; • the number of and development requirements for other product candidates that we pursue; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to enter into contract manufacturing arrangements for supply of API and manufacture of our product candidates and the terms of such arrangements; • the success of our collaboration with MyoKardia or under our license agreement with CAMP4; • our ability to establish and maintain additional strategic collaborations, licensing or other arrangements and the financial terms of such arrangements; • the payment or receipt of milestones, royalties and other collaboration-based revenues, if any; • the costs and timing of future commercialization activities, including product manufacturing, sales, marketing and distribution, for any of our product candidates for which we may receive marketing approval and that we do not out-license for commercialization; 36 • the amount and timing of revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights and defending any intellectual property-related claims; and • the extent to which we acquire or in-license other products, product candidates, technologies or data referencing rights.
Our future capital requirements will depend on many factors, including: • the progress, costs and results of our ongoing clinical development of pociredir in SCD; • additional planned clinical trials; • the scope, progress, costs and results of discovery research, preclinical development, laboratory testing and clinical trials for any of our product candidates in additional indications or for any future product candidates that we may pursue; • the number of and development requirements for other product candidates that we pursue; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to enter into contract manufacturing arrangements for supply of API and manufacture of our product candidates and the terms of such arrangements; • the success of our license agreement with CAMP4; • our ability to establish and maintain additional strategic collaborations, licensing or other arrangements and the financial terms of such arrangements; • the payment or receipt of milestones, royalties and other collaboration-based revenues, if any; 36 • the costs and timing of future commercialization activities, including product manufacturing, sales, marketing and distribution, for any of our product candidates for which we may receive marketing approval and that we do not out-license for commercialization; • the amount and timing of revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights and defending any intellectual property-related claims; and • the extent to which we acquire or in-license other products, product candidates, technologies or data referencing rights.
Patient enrollment is affected by a variety of other factors, including: • the prevalence and severity of the disease under investigation; • the eligibility criteria for the trial in question (such as with our trial of pociredir for SCD); • the perceived risks and benefits of the product candidate under trial; • the requirements of the trial protocols, including invasive procedures; • the availability of existing treatments for the indications for which we are conducting clinical trials; • the ability to recruit clinical trial investigators with the appropriate competencies and experience; • the efforts to facilitate timely enrollment in clinical trials; • the patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; 43 • the proximity and availability of clinical trial sites for prospective patients; • the conduct of clinical trials by competitors for product candidates that treat the same indications as our current or future product candidates; • the ability to identify specific patient populations for biomarker-defined trial cohort(s); and • the cost to, or lack of adequate compensation for, prospective patients.
Patient enrollment is affected by a variety of other factors, including: • the prevalence and severity of the disease under investigation; • the eligibility criteria for the trial in question (such as with our trial of pociredir for SCD); • the perceived risks and benefits of the product candidate under trial; • the requirements of the trial protocols, including invasive procedures; • the availability of existing treatments for the indications for which we are conducting clinical trials; • the ability to recruit clinical trial investigators with the appropriate competencies and experience; • the efforts to facilitate timely enrollment in clinical trials; • the ability to obtain and maintain patient consents; • the patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • the proximity and availability of clinical trial sites for prospective patients; • the conduct of clinical trials by competitors for product candidates that treat the same indications as our current or future product candidates; • the ability to identify specific patient populations for biomarker-defined trial cohort(s); and • the cost to, or lack of adequate compensation for, prospective patients.
As a result, our owned and in-licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing technology and products similar or identical to any of our technology and product candidates. 55 Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time.
As a result, our owned and in-licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing technology and products similar or identical to any of our technology and product candidates. 54 Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time.
In September 2024 we suspended further development of losmapimod after topline data from the Phase 3 REACH trial indicated that it did not achieve its primary endpoint of change from baseline in relative surface area, a measure of reachable work space, compared to placebo.
For example, in September 2024 we suspended further development of losmapimod after topline data from the Phase 3 REACH trial indicated that it did not achieve its primary endpoint of change from baseline in relative surface area, a measure of reachable work space, compared to placebo.
If and when our 56 product candidate receives FDA approval, we expect to apply for patent term extensions where applicable, but there is no guarantee that the applicable governmental authorities will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions.
If and when our 55 product candidate receives FDA approval, we expect to apply for patent term extensions where applicable, but there is no guarantee that the applicable governmental authorities will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions.
See Item 1 “Business — Competition” for more information. 47 Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop.
See Item 1 “Business – Competition” for additional information. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may have various consequences, including: • suspension of or restrictions on such products, manufacturers or manufacturing processes; • restrictions and warnings on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to conduct post-marketing studies or clinical trials; • warning letters or untitled letters; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; 66 • recall of products; • fines, restitution or disgorgement of profits or revenues; • suspension of any ongoing clinical trials; • suspension or withdrawal of marketing approvals; • damage to relationships with any potential collaborators; • unfavorable press coverage and damage to our reputation; • refusal to permit the import or export of our products; • product seizure or detention; • injunctions or the imposition of civil or criminal penalties; or • litigation involving patients using our products.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may have various consequences, including: • suspension of or restrictions on such products, manufacturers or manufacturing processes; • restrictions and warnings on the labeling or marketing of a product; 65 • restrictions on product distribution or use; • requirements to conduct post-marketing studies or clinical trials; • FDA Form 483s, warning letters or untitled letters; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution or disgorgement of profits or revenues; • suspension of any ongoing clinical trials; • suspension or withdrawal of marketing approvals; • damage to relationships with any potential collaborators; • unfavorable press coverage and damage to our reputation; • refusal to permit the import or export of our products; • product seizure or detention; • injunctions or the imposition of civil or criminal penalties; or • litigation involving patients using our products.
Collaborations pose a number of risks, including the following: • collaborators have significant discretion in determining the amount and timing of efforts and resources that they will apply to these collaborations; • collaborators may not perform their obligations as expected; • collaborators may not pursue development of any of our product candidates or may elect not to continue or renew development programs based on results of clinical trials or other studies, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; 52 • collaborators may not pursue commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew commercialization programs based on results of clinical trials or other studies, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that may divert resources or create competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration and, consequently, may have limited ability to inform our stockholders about the status of such product candidates on a discretionary basis; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates and products if the collaborators believe that the competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; • a collaborator may fail to comply with applicable regulatory requirements regarding the development, manufacture, distribution or marketing of a product candidate or product; • a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; • disagreements with collaborators, including disagreements over intellectual property or proprietary rights, contract interpretation or the preferred course of development, might cause delays or terminations of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; • collaborators may not properly obtain, maintain, enforce, defend or protect our intellectual property or proprietary rights or may use our proprietary information in such a way as to potentially lead to disputes or legal proceedings that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; • disputes may arise with respect to the ownership of intellectual property developed pursuant to our collaborations; • collaborators may infringe, misappropriate or otherwise violate the intellectual property or proprietary rights of third parties, which may expose us to litigation and potential liability; and • collaborations may be terminated for the convenience of the collaborator (e.g., our former collaboration with Acceleron Pharma, Inc.), and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Collaborations pose a number of risks, including the following: • collaborators have significant discretion in determining the amount and timing of efforts and resources that they will apply to these collaborations; • collaborators may not perform their obligations as expected; • collaborators may not pursue development of any of our product candidates or may elect not to continue or renew development programs based on results of clinical trials or other studies, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; • collaborators may not pursue commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew commercialization programs based on results of clinical trials or other studies, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that may divert resources or create competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration and, consequently, may have limited ability to inform our stockholders about the status of such product candidates on a discretionary basis; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates and products if the collaborators believe that the competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; • a collaborator may fail to comply with applicable regulatory requirements regarding the development, manufacture, distribution or marketing of a product candidate or product; • a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; • disagreements with collaborators, including disagreements over intellectual property or proprietary rights, contract interpretation or the preferred course of development, might cause delays or terminations of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; • collaborators may not properly obtain, maintain, enforce, defend or protect our intellectual property or proprietary rights or may use our proprietary information in such a way as to potentially lead to disputes or legal proceedings that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; • disputes may arise with respect to the ownership of intellectual property developed pursuant to our collaborations; • collaborators may infringe, misappropriate or otherwise violate the intellectual property or proprietary rights of third parties, which may expose us to litigation and potential liability; and • collaborations may be terminated for the convenience of the collaborator (e.g., our former collaborations with Acceleron Pharma, Inc. and MyoKardia, Inc., the latter of which was terminated on June 26, 2025), and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates. 52 Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, or at all.
If reimbursement of our products is unavailable or limited in scope, our business could be materially harmed. See Item 1 “Business—Government Regulation and Product Approval—Pharmaceutical Insurance Coverage and Health Care Reform” for more information.
If reimbursement of our products is unavailable or limited in scope, our business could be materially harmed. See Item 1 “Business – Government Regulation and Product Approval – Pharmaceutical Insurance Coverage and Health Care Reform” for additional information.
Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation.
Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to grant such designation.
The ability of the FDA to review and clear or approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, shifting policy priorities as a result of changes in the Presidential administration and political appointees tasked to oversee the agency, and statutory, regulatory, and policy changes.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, shifting policy priorities as a result of changes in the presidential administration and political appointees tasked to oversee the agency, and statutory, regulatory, leadership, and policy changes.
For example, in September 2024, we announced that REACH, our Phase 3 trial evaluating losmapimod in patients with FSHD, did not successfully achieve its primary endpoint as compared to placebo, and we suspended further development of losmapimod. Additionally, pociredir, our clinical-stage candidate to treat SCD, is an embryonic ectoderm development, or EED, inhibitor.
For example, in September 2024, we announced that REACH, our Phase 3 trial evaluating losmapimod in patients with FSHD, did not successfully achieve its primary endpoint as compared to placebo, and we suspended further development of losmapimod. Additionally, pociredir, our clinical-stage candidate to treat SCD, is an EED inhibitor.
Any product candidate for which we obtain marketing approval could be subject to post-marketing restrictions or withdrawal from the market and we may be subject to substantial penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them are approved.
Any product candidate for which we obtain marketing approval could be subject to post-marketing restrictions or withdrawal from the market under certain circumstances, and we may be subject to substantial penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them are approved.
If our collaborator terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities could be adversely affected. 53 If we are not able to establish or maintain collaborations, we may have to alter our development and commercialization plans and our business could be adversely affected.
If our collaborator terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities could be adversely affected. If we are not able to establish collaborations, we may have to alter our development and commercialization plans and our business could be adversely affected.
If we experience a change of control, as defined by Section 382, subsequent to December 31, 2024, utilization of the net operating loss carryforwards or research and development tax credit carryforwards would be subject to an annual limitation under Section 382.
If we have experienced a change of control, as defined by Section 382, subsequent to December 31, 2024, utilization of the net operating loss carryforwards or research and development tax credit carryforwards would be subject to an annual limitation under Section 382.
If we commercialize our product candidates in foreign markets, we will be subject to additional risks and uncertainties, including: • economic weakness, including inflation, or political instability in particular economies and markets, which could include localized disputes that have a broader regional or global impact (such as the Russian invasion of Ukraine or recent hostilities in Israel, Lebanon, and the Gaza Strip); • the burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements, many of which vary between countries; • different medical practices and customs in foreign countries affecting acceptance in the marketplace; • tariffs and trade barriers, as well as other governmental controls and trade restrictions; • other trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or foreign governments (such as the recent announced tariffs by the current U.S. administration); • longer accounts receivable collection times; • longer lead times for shipping; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • workforce uncertainty in countries where labor unrest is common; • language barriers for technical training; • reduced protection of intellectual property rights in some foreign countries, and related prevalence of generic alternatives to therapeutics; • foreign currency exchange rate fluctuations and currency controls; • differing foreign reimbursement landscapes; • uncertain and potentially inadequate reimbursement of our products; and • the interpretation of contractual provisions governed by foreign laws in the event of a contract dispute.
If we commercialize our product candidates in foreign markets, we will be subject to additional risks and uncertainties, including: • economic weakness, including inflation, or political instability in particular economies and markets, which could include localized disputes that have a broader regional or global impact; • the burden of complying with complex and changing foreign regulatory, tax, accounting and legal requirements, many of which vary between countries; • different medical practices and customs in foreign countries affecting acceptance in the marketplace; • tariffs and trade barriers, as well as other governmental controls and trade restrictions; • other trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or foreign governments (such as the announced tariffs by the current U.S. administration, which have led to volatility in the market and uncertainty); • longer accounts receivable collection times; • longer lead times for shipping; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • workforce uncertainty in countries where labor unrest is common; • language barriers for technical training; • reduced protection of intellectual property rights in some foreign countries, and related prevalence of generic alternatives to therapeutics; • foreign currency exchange rate fluctuations and currency controls; • differing foreign reimbursement landscapes; • uncertain and potentially inadequate reimbursement of our products; and • the interpretation of contractual provisions governed by foreign laws in the event of a contract dispute.
We anticipate that our expenses will increase substantially as we: • continue our clinical development of pociredir and any future product candidates; • continue our ongoing preclinical studies; • pursue the discovery of drug targets for other genetically-defined rare diseases and the subsequent development of any resulting product candidates, including for the potential treatment of inherited aplastic anemias, such as DBA, Shwachman-Diamond syndrome, and Fanconi anemia under our license agreement with CAMP4; • seek regulatory approvals for any product candidates that successfully complete clinical trials; • acquire or in-license products, product candidates, technologies and/or data referencing rights, such as our agreement with CAMP4; • make any milestone payments to CAMP4 under our license agreement with CAMP4; • maintain, expand, enforce, defend and protect our intellectual property; • hire additional clinical, quality control and scientific personnel as needed; • scale up our manufacturing processes and capabilities, or arrange for a third party to do so on our behalf, to support our clinical trials of any product candidate and commercialization of any of product candidates for which we may obtain marketing approval; • establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval and that we have not out-licensed; and • add operational, financial and management information systems and personnel, including personnel to support our product development and any future commercialization efforts, as needed, and our operations as a public company. 35 To become and remain profitable, we must succeed in developing, and eventually commercializing, a product or products that generate significant revenue.
We anticipate that our expenses will increase substantially as we: • continue our clinical development of pociredir and any future product candidates; • continue our ongoing preclinical studies; • pursue the discovery of drug targets for other genetically-defined rare diseases and the subsequent development of any resulting product candidates; • seek regulatory approvals for any product candidates that successfully complete clinical trials; • acquire or in-license products, product candidates, technologies and/or data referencing rights, such as our agreement with CAMP4; • make any milestone payments to CAMP4 under our license agreement with CAMP4; • maintain, expand, enforce, defend and protect our intellectual property; • hire additional clinical, quality control and scientific personnel as needed; • scale up our manufacturing processes and capabilities, or arrange for a third party to do so on our behalf, to support our clinical trials of any product candidate and commercialization of any of product candidates for which we may obtain marketing approval; • establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval and that we have not out-licensed; and • add operational, financial and management information systems and personnel, including personnel to support our product development and any future commercialization efforts, as needed, and our operations as a public company. 35 To become and remain profitable, we must succeed in developing, and eventually commercializing, a product or products that generate significant revenue.
Our expenses will increase if, among other things: • we are required by the FDA, the EMA, or other regulatory authorities to perform trials or studies in addition to, or different than, those expected; • there are any further delays in completing our ongoing clinical trial or otherwise in the development of any of our current or future product candidates, such as due to any further clinical holds imposed by the FDA (similar to the hold on the IND application for pociredir in SCD that was lifted in August 2023), or due to enrollment challenges (such as for our ongoing clinical trial of pociredir in light of the more stringent inclusion and exclusion criteria); or • there are any third-party challenges to our intellectual property or we need to defend against any intellectual property-related claim.
Our expenses will increase if, among other things: • we are required by the FDA, the EMA, or other regulatory authorities to perform trials or studies in addition to, or different than, those expected; • there are any further delays in our clinical development of pociredir or otherwise in the development of any of our current or future product candidates, such as due to any further clinical holds imposed by the FDA (similar to the hold on the IND application for pociredir in SCD that was lifted in August 2023), or due to enrollment challenges (such as our initial experience with our Phase 1b clinical trial of pociredir in light of the more stringent inclusion and exclusion criteria); or • there are any third-party challenges to our intellectual property or we need to defend against any intellectual property-related claim.
If that were to occur, the protection we derive from orphan exclusivity may be adversely affected. Designation by the FDA, such as fast track or breakthrough therapy, may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
If that were to occur, the protection we derive from orphan exclusivity may be adversely affected. Designations by the FDA, such as fast track designation or breakthrough therapy designation, may not lead to a faster development or regulatory review or approval process, and do not increase the likelihood that our product candidates will receive marketing approval.
As of December 31, 2024, we also had federal and state research and development tax credit carryforwards of $2.5 million and $0.2 million, respectively, which begin to expire in 2039. These net operating loss and tax credit carryforwards could expire unused and be unavailable to offset future income tax liabilities.
As of December 31, 2025, we also had federal and state research and development tax credit carryforwards of $1.2 million and $0.2 million, respectively, which begin to expire in 2039. These net operating loss and tax credit carryforwards could expire unused and be unavailable to offset future income tax liabilities.
If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive, such as our recent topline data from the Phase 3 REACH trial, or are only modestly positive or if there are safety concerns, we may: • suspend further development (such as with losmapimod for FSHD); • be delayed in obtaining marketing approval for our product candidates; • not obtain marketing approval at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling or a REMS that includes significant use or distribution restrictions or safety warnings; • be subject to additional post-marketing testing requirements; or • have the product removed from the market after obtaining marketing approval.
If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive, such as our topline data from the Phase 3 REACH trial, or are only modestly positive or if there are safety concerns, we may: • suspend further development (such as with losmapimod for FSHD); • be delayed in obtaining marketing approval for our product candidates; • not obtain marketing approval at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling or a REMS that includes significant use or distribution restrictions or safety warnings; • be subject to additional post-marketing testing requirements; or • have the product removed from the market after obtaining marketing approval. 42 Our product development costs will also increase if we experience delays in testing or in obtaining marketing approvals.
This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.
Our reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or if approved, products at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.
As of December 31, 2024, we had federal net operating loss carryforwards of $5.0 million, which may be available to offset future taxable income and do not expire, but are limited in their usage to an annual deduction equal to 80% of annual taxable income.
As of December 31, 2025, we had federal net operating loss carryforwards of $102.8 million, which may be available to offset future taxable income and do not expire, but are limited in their usage to an annual deduction equal to 80% of annual taxable income.
As a result, the carryfowards before the ownership change date of September 12, 2024 are not available for utilization and have been written off. The carryfowards as of December 31, 2024 were generated after the ownership change on September 12, 2024.
As a result, the carryforwards before the deemed ownership change date of September 12, 2024 are not available for utilization and have been written off. The carryforwards as of December 31, 2025 were generated after the deemed ownership change.
Disruptions at the FDA, the SEC and other government agencies caused by the change in presidential administration, funding shortages or potential funding shortages could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner, or otherwise prevent those agencies from performing normal business functions, which could negatively impact our business and our timelines.
Disruptions at the FDA, the SEC and other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner, or otherwise prevent those agencies from performing normal business functions, which could negatively impact our business and our timelines.
We expect our expenses to increase substantially in connection with our ongoing activities, particularly as we advance our preclinical activities and Phase 1b clinical trial of pociredir in SCD.
We expect our expenses to increase substantially in connection with our ongoing activities, particularly as we advance our preclinical activities and clinical trials of pociredir in SCD.
Commercial revenues, if any, will not be derived unless and until we can achieve sales of products, which we do not anticipate for several years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives.
In addition, our product candidates, if approved, may not achieve commercial success. Commercial revenues, if any, will not be derived unless and until we can achieve sales of products, which we do not anticipate for several years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives.
We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates. We currently only have one product candidate in active clinical development following our recent decision to suspend further development of losmapimod.
We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates. We currently have only one product candidate in active clinical development.
Regulatory authorities in some jurisdictions, including the United States and European Union, may designate drugs for relatively small patient populations as orphan drugs. We may seek orphan drug designation for our other current and future product candidates.
Regulatory authorities in some jurisdictions, including the United States and European Union, may designate drugs for relatively small patient populations as orphan drugs. We have received orphan drug designation for pociredir for the treatment of SCD and may seek orphan drug designation, as appropriate, for our other current and future product candidates.
If we are unable to commercialize directly or out-license to a third party any of our product candidates or experience significant delays in doing so, our business will be materially harmed. We are early in our development efforts, and we have advanced only two product candidates into clinical trials.
If we are unable to commercialize directly or out-license to a third party any of our product candidates or experience significant delays in doing so, our business will be materially harmed. We are early in our development efforts, and we have advanced only two product candidates into clinical trials (the first of which did not meet its primary endpoint).
In addition, we have filed or intend to file universal shelf registration statements (which allows us to offer and sell securities from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale) subject to an aggregate offering amount stated therein, as well as registration statements registering all shares of common stock that we may issue under our equity compensation plans or pursuant to equity awards made to newly hired employees outside of equity compensation plans.
If such persons sell, or indicate an intention to sell, substantial amounts of our common stock in the public market, the trading price of our common stock could decline. 74 In addition, we have filed or intend to file universal shelf registration statements (which allows us to offer and sell securities from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale) subject to an aggregate offering amount stated therein, as well as registration statements registering all shares of common stock that we may issue under our equity compensation plans or pursuant to equity awards made to newly hired employees outside of equity compensation plans.
Collaborations that we enter into, including our collaboration with MyoKardia, may not be successful, and any success will depend heavily on the efforts and activities of such collaborators.
Collaborations that we enter into may not be successful, and any success will depend heavily on the efforts and activities of such collaborators.
We expect to rely on third parties for the manufacture of pociredir for any future clinical trials and for the manufacture of any future product candidates for preclinical and clinical testing.
We do not have any manufacturing facilities and expect to rely on third parties for the manufacture of pociredir for any future clinical trials and for the manufacture of any future product candidates for preclinical and clinical testing.
We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future.
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future.
Failure by our third-party manufacturers to pass such inspections and otherwise satisfactorily complete the FDA approval regimen with respect to our product candidates may result in regulatory actions such as the issuance of FDA Form 483 notices of observations, warning letters or injunctions or the loss of operating licenses.
Failure by our third-party manufacturers to pass such inspections or otherwise satisfactorily complete applicable regulatory approval requirements with respect to our product candidates may result in regulatory actions, including the issuance of inspectional observations (such as FDA Form 483s), warning letters, or injunctions or the loss of operating licenses.
For example, we recently suspended further development of losmapimod after devoting significant time, effort and capital on the program but it did not meet its primary endpoint in the Phase 3 REACH trial.
For example, we devoted significant time, effort and capital on our losmapimod program but suspended further development when it did not meet its primary endpoint in the Phase 3 REACH trial.
Moreover, we or our licensors may be subject to a third-party preissuance submission of prior art to the United States Patent and Trademark Office, or USPTO, or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others.
For information relating to our patent portfolio, see Item 1 “Business – Intellectual Property.” Moreover, we or our licensors may be subject to a third-party preissuance submission of prior art to the United States Patent and Trademark Office, or USPTO, or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others.
In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that the products no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
In addition, even if one or more of our product candidates is granted breakthrough therapy designation, the FDA may later decide that the such product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
See Item 1 “Business — Government Regulation and Product Approval — Pharmaceutical Insurance Coverage and Health Care Reform.” Our ability to commercialize any product candidates successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
Our ability to commercialize any product candidates successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
These agreements might terminate for a variety of reasons, including a failure to perform by the third parties. If we need to enter into alternative arrangements, our product development activities might be delayed. Our reliance on these third parties for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities.
If we need to enter into alternative arrangements, our product development activities might be delayed. Our reliance on these third parties for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeFor more information about these risks, please refer to the section entitled “Risk Factors” in this Annual Report on Form 10-K. Governance Related to Cybersecurity Risks Our Executive Director, IT & Operations, or Executive Director, who reports to the Chief Financial Officer, is responsible for the strategic leadership and direction of our cybersecurity program.
Biggest changeFor more information about these risks, please refer to the section entitled “Risk Factors” in this Annual Report on Form 10-K. Governance Related to Cybersecurity Risks Our Vice President, IT & Operations, or Vice President, who reports to the Chief Financial Officer, is responsible for the strategic leadership and direction of our cybersecurity program.
The Executive Director and our Chief Legal Officer participate in periodic discussions with other members of our management, including executive leadership, regarding implementation of our cybersecurity program, program enhancements, and relevant cyber risks or threats. Our Chief Legal Officer has received the National Association of Corporate Directors CERT Certificate in Cyber-Risk Oversight.
The Vice President and our Chief Legal Officer participate in periodic discussions with other members of our management, including executive leadership, regarding implementation of our cybersecurity program, program enhancements, and relevant cyber risks or threats. Our Chief Legal Officer has received the National Association of Corporate Directors CERT Certificate in Cyber-Risk Oversight.
Our audit committee has oversight over cybersecurity risks . With the input of the executive team, the Executive Director provides annual presentations to the audit committee on our cyber program, including updates on security testing and assessments, cyber risks, and related cyber strategy as applicable.
Our audit committee has oversight over cybersecurity risks . With the input of the executive team, the Vice President provides annual presentations to the audit committee on our cyber program, including updates on security testing and assessments, cyber risks, and related cyber strategy as applicable.
With over 15 years of experience in information technology, the Executive Director works alongside individuals across other functions, such as legal and engineering, to establish and implement our cybersecurity strategy.
With over 15 years of experience in information technology, the Vice President works alongside individuals across other functions, such as legal and engineering, to establish and implement our cybersecurity strategy.

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures 78 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 79 Item 6. Reserved 79 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 80 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 91 Item 8.
Biggest changeItem 4. Mine Safety Disclosures 77 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 78 Item 6. Reserved 78 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 79 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 89 Item 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeAny future determination to declare dividends will be made at the discretion of our board of directors and will depend on our financial condition, operating results, capital requirements, general business conditions and other factors that our board of directors may deem relevant. Unregistered Sales of Equity Securities None.
Biggest changeAny future determination to declare dividends will be made at the discretion of our board of directors and will depend on our financial condition, operating results, capital requirements, general business conditions and other factors that our board of directors may deem relevant. Unregistered Sales of Equity Securities None. Issuer Purchases of Equity Securities None.
Holders of Our Common Stock As of February 18, 2025, there were approximately 11 holders of record of shares of our common stock. This number does not include stockholders for whom shares are held in “nominee” or “street” name. Dividends We have never declared or paid any cash dividends on our capital stock.
Holders of Our Common Stock As of February 17, 2026, there were approximately 11 holders of record of shares of our common stock. This number does not include stockholders for whom shares are held in “nominee” or “street” name. Dividends We have never declared or paid any cash dividends on our capital stock.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe decrease in research and development expense was primarily attributable to the following: • $4.9 million of decreased external research and development costs, primarily due to $8.1 million of reimbursement from the global development cost sharing under our collaboration with Sanofi for losmapimod, partially offset by increased development costs associated with the advancement of REACH, as we completed enrollment in September 2023, as well as increased costs associated with pociredir; • $2.0 million of decreased laboratory costs; • $0.8 million of decreased employee compensation costs due to decreased headcount, which reflects a partial offset of $0.9 million in increased stock-based compensation expense; • $0.4 million of decreased facilities costs; and • $0.5 million of decreased other costs. 85 General and Administrative Expenses The following table summarizes our general and administrative expenses for the years ended December 31, 2024 and 2023: Year Ended December 31, Change (in thousands) 2024 2023 $ Employee compensation $ 19,754 $ 24,809 $ (5,055 ) Professional services 11,999 11,023 976 Facility costs 1,483 2,516 (1,033 ) Other 3,212 3,320 (108 ) Total general and administrative expenses $ 36,448 $ 41,668 $ (5,220 ) General and administrative expenses decreased by $5.3 million from $41.7 million for the year ended December 31, 2023 to $36.4 million for the year ended December 31, 2024.
Biggest changeThe decrease in research and development expense was primarily attributable to the following: • $4.6 million of decreased external research and development costs, primarily due to the suspension of the losmapimod program, including decreased development cost sharing reimbursement under our former collaboration with Sanofi for losmapimod, partially offset by increased development costs associated with the advancement of the Phase 1b PIONEER trial of pociredir; • $3.9 million of decreased employee compensation costs due to decreased headcount, including a $1.2 million decrease in stock-based compensation expense; • partially offset by $0.8 million of increased laboratory supplies costs and $0.4 million of increased other costs.
This process involves reviewing open contracts and purchase orders, communicating 89 with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual cost.
This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual cost.
Our funding requirements and timing and amount of our operating expenditures will depend largely on: • the progress, costs and results of our clinical trials of pociredir; • the scope, progress, costs and results of discovery research, preclinical development, laboratory testing and clinical trials for our current product candidates in additional indications or for any future product candidates that we may pursue, including under our license agreement with CAMP4; • the number of and development requirements for other product candidates that we pursue; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to enter into contract manufacturing arrangements for supply of API and manufacture of our product candidates and the terms of such arrangements; 87 • the success of our collaboration with MyoKardia; • our ability to establish and maintain additional strategic collaborations, licensing or other arrangements and the financial terms of such arrangements; • the payment or receipt of milestones, royalties and other collaboration-based revenues, if any; • the costs and timing of future commercialization activities, including product manufacturing, sales, marketing and distribution, for any of our product candidates for which we may receive marketing approval and that we do not out-license to a third party; • the amount and timing of revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights and defending any intellectual property-related claims; and • the extent to which we acquire or in-license other products, product candidates, technologies or data referencing rights.
Our funding requirements and timing and amount of our operating expenditures will depend largely on: • the progress, costs and results of our clinical trials of pociredir; • the scope, progress, costs and results of discovery research, preclinical development, laboratory testing and clinical trials for our current product candidates in additional indications or for any future product candidates that we may pursue, including under our license agreement with CAMP4; • the number of and development requirements for other product candidates that we pursue; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to enter into contract manufacturing arrangements for supply of API and manufacture of our product candidates and the terms of such arrangements; • our ability to establish and maintain additional strategic collaborations, licensing or other arrangements and the financial terms of such arrangements; • the payment or receipt of milestones, royalties and other collaboration-based revenues, if any; • the costs and timing of future commercialization activities, including product manufacturing, sales, marketing and distribution, for any of our product candidates for which we may receive marketing approval and that we do not out-license to a third party; • the amount and timing of revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property and proprietary rights and defending any intellectual property-related claims; and • the extent to which we acquire or in-license other products, product candidates, technologies or data referencing rights.
Payments for these activities are based on the terms of the individual agreements, which may differ from the pattern of expenses incurred. Non-refundable advance payments for goods or services to be received in the future for use in research and development activities are recorded as 82 prepaid expenses.
Payments for these activities are based on the terms of the individual agreements, which may differ from the pattern of expenses incurred. Non-refundable advance payments for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses.
Given the lack of public market for our common stock prior to the closing of our IPO and a lack of company-specific historical and implied volatility data, we based the estimate of expected volatility on the historical volatility of a representative group of publicly traded companies for which historical information is available.
Given the lack of public market for our common stock prior to the closing of our IPO and a lack of company-specific historical and implied volatility data, we based the 88 estimate of expected volatility on the historical volatility of a representative group of publicly traded companies for which historical information is available.
See “—Liquidity and Capital Resources.” Components of Results of Operations Revenue We have not generated any revenue from product sales and do not expect to generate revenue from the sale of products for several years, if at all.
See “—Liquidity and Capital Resources.” 80 Components of Results of Operations Revenue We have not generated any revenue from product sales and do not expect to generate revenue from the sale of products for several years, if at all.
Changes to the constraint of variable consideration can have a material effect on the amount of revenue recognized in the period. If the contract contains a single performance obligation, the entire transaction price is allocated to the single performance obligation.
Changes to the constraint of variable consideration can have a material effect on the amount of revenue recognized in the period. 87 If the contract contains a single performance obligation, the entire transaction price is allocated to the single performance obligation.
A valuation allowance against deferred tax assets is recorded if, based on the weight of the available evidence, it is more likely than not that some or all of the deferred tax assets 90 will not be realized.
A valuation allowance against deferred tax assets is recorded if, based on the weight of the available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.
We may also in the future enter into additional license or collaboration agreements for our product candidates or intellectual property, and we may generate revenue in the future from payments as a result of such license or collaboration agreements.
In the future, we may enter into additional license or collaboration agreements for our product candidates or intellectual property, and we may generate revenue in the future from payments as a result of such license or collaboration agreements.
We do not track our internal research and development expenses on a program-by-program basis as the resources are deployed across multiple projects. The following table summarizes our external research and development expenses by program for the years ended December 31, 2024 and 2023. Pre-development candidate expenses, unallocated expenses and internal research and development expenses are classified separately.
We do not track our internal research and development expenses on a program-by-program basis as the resources are deployed across multiple projects. 81 The following table summarizes our external research and development expenses by program for the years ended December 31, 2025 and 2024. Pre-development candidate expenses, unallocated expenses and internal research and development expenses are classified separately.
This is due to the numerous risks and uncertainties associated with developing our product candidates, including the uncertainty related to: • the timing and progress of preclinical and clinical development activities; • the number and scope of preclinical and clinical programs we decide to pursue; • our ability to raise additional funds necessary to complete clinical development of and, if applicable, commercialize our product candidates if and when approved; • our ability to maintain our current research and development programs and to establish new ones; • our ability to establish new licensing or collaboration arrangements; • the progress of the development efforts of parties with whom we may enter into collaboration arrangements; • the successful initiation and completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to the FDA or any comparable foreign regulatory authority; • the receipt and related terms of regulatory approvals from applicable regulatory authorities; • the availability of raw materials and active pharmaceutical ingredient, or API, for use in production of our product candidates; • our ability to establish and operate a manufacturing facility, or secure manufacturing supply through relationships with third parties; • our ability to consistently manufacture our product candidates in quantities sufficient for use in clinical trials; • our ability to obtain and maintain intellectual property protection and regulatory exclusivity, both in the United States and internationally (including defending and enforcing our rights); • our ability to obtain and maintain third-party coverage and adequate reimbursement for our product candidates, if approved; • the acceptance of our product candidates, if approved, by patients, the medical community and third-party payors; • competition with other products; and • a continued acceptable safety profile of our products following receipt of any regulatory approvals. 83 A change in the outcome of any of these variables with respect to the development of any of our product candidates would significantly change the costs and timing associated with the development of that product candidate, and potentially other candidates.
This is due to the numerous risks and uncertainties associated with developing our product candidates, including the uncertainty related to: • the timing and progress of preclinical and clinical development activities; • the number and scope of preclinical and clinical programs we decide to pursue; • our ability to raise additional funds necessary to complete clinical development of and, if applicable, commercialize our product candidates if and when approved; • our ability to maintain our current research and development programs and to establish new ones; • our ability to establish new licensing or collaboration arrangements; • the progress of the development efforts of parties with whom we may enter into collaboration arrangements; • the successful initiation and completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to the FDA or any comparable foreign regulatory authority; • the receipt and related terms of regulatory approvals from applicable regulatory authorities; • the availability of raw materials and API for use in production of our product candidates; • our ability to establish and operate a manufacturing facility, or secure manufacturing supply through relationships with third parties; • our ability to consistently manufacture our product candidates in quantities sufficient for use in clinical trials; • our ability to obtain and maintain intellectual property protection and regulatory exclusivity, both in the United States and internationally (including defending and enforcing our rights); • our ability to obtain and maintain third-party coverage and adequate reimbursement for our product candidates, if approved; • the acceptance of our product candidates, if approved, by patients, the medical community and third-party payors; • competition with other products; and • a continued acceptable safety profile of our products following receipt of any regulatory approvals.
We expect our expenses and operating losses will increase substantially over the next several years in connection with our ongoing activities, as we: • continue our clinical development of pociredir; • continue our ongoing preclinical studies; • advance clinical-stage product candidates into later stage trials; 80 • pursue the discovery of drug targets for other genetically-defined rare diseases and the subsequent development of any resulting product candidates, including for the potential treatment of inherited aplastic anemias, such as DBA, Shwachman-Diamond syndrome, and Fanconi anemia under our license agreement with CAMP4; • seek regulatory approvals for any product candidates that successfully complete clinical trials; • scale up our manufacturing processes and capabilities, or arrange for a third party to do so on our behalf, to support our clinical trials of our product candidates and commercialization of any of our product candidates for which we obtain marketing approval; • establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval and that we have not out-licensed; • acquire or in-license products, product candidates, technologies and/or data referencing rights, such as our agreement with CAMP4; • make any milestone payments to CAMP4 under our license agreement; • maintain, expand, enforce, defend and protect our intellectual property; • hire additional clinical, quality control and scientific personnel; and • add operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts and our operations as a public company.
We expect our expenses and operating losses will increase over the next several years in connection with our ongoing activities, as we: • continue our clinical development of pociredir and advance the program into a later stage trial; • continue our ongoing preclinical studies; • pursue the discovery of drug targets for other genetically-defined rare diseases and the subsequent development of any resulting product candidates; • seek regulatory approvals for any product candidates that successfully complete clinical trials; • scale up our manufacturing processes and capabilities, or arrange for a third party to do so on our behalf, to support our clinical trials of our product candidates and commercialization of any of our product candidates for which we obtain marketing approval; • establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval and that we have not out-licensed; • acquire or in-license products, product candidates, technologies and/or data referencing rights, such as our agreement with CAMP4; • make any milestone payments to CAMP4 under our license agreement; • maintain, expand, enforce, defend and protect our intellectual property; • hire additional clinical, quality control and scientific personnel; and • add operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts and our operations as a public company.
Our ability to generate product revenue sufficient to achieve profitability, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $9.7 million and $97.3 million for the years ended December 31, 2024 and 2023, respectively.
Our ability to generate product revenue sufficient to achieve profitability, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $74.9 million and $9.7 million for the years ended December 31, 2025 and 2024, respectively.
We believe that our existing cash, cash equivalents, and marketable securities as of December 31, 2024 will enable us to fund our operating expenses and capital expenditure requirements into at least 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
We believe that our existing cash, cash equivalents, and marketable securities as of December 31, 2025 will enable us to fund our operating expenses and capital expenditure requirements into 2029. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. As of December 31, 2024, we had $241.0 million in cash, cash equivalents, and marketable securities.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. As of December 31, 2025, we had $352.3 million in cash, cash equivalents, and marketable securities.
Overview We are a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Our clinical-stage product candidate, pociredir, is being developed for the potential treatment of sickle cell disease, or SCD.
Overview We are a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Our lead product candidate, pociredir, is in clinical development for the potential treatment of SCD.
Based on our current operating plan, we believe that our existing cash, cash equivalents, and marketable securities as of December 31, 2024 will enable us to fund our operating expenses and capital expenditure requirements into at least 2027.
Based on our current operating plan, we believe that our existing cash, cash equivalents, and marketable securities as of December 31, 2025 will enable us to fund our operating expenses and capital expenditure requirements into 2029.
The decrease in general and administrative expenses was primarily attributable to the following: • $5.1 million of decreased employee compensation costs due to decreased headcount, including a $1.1 million decrease in stock-based compensation expense; • $1.0 million of decreased facility costs primarily as a result of the expiration of our lease agreement for office space at 125 Sidney Street; and • $0.1 million in decreased other costs; • partially offset by $1.0 million in increased professional services costs, primarily due to increased legal and commercial costs.
The decrease in general and administrative expenses was primarily attributable to the following: • $4.4 million of decreased professional services costs, primarily due to decreased commercial and legal costs; • $2.4 million of decreased employee compensation costs due to decreased headcount, including a $0.9 million decrease in stock-based compensation expense; • $0.3 million of decreased facility costs primarily as a result of the expiration of our lease agreement for office space at 125 Sidney Street; and • $0.7 million of decreased other costs.
Net Cash Provided by Financing Activities Net cash provided by financing activities was $2.7 million during the year ended December 31, 2024 compared to $118.1 million during the year ended December 31, 2023.
Net Cash Provided by Financing Activities Net cash provided by financing activities was $168.7 million during the year ended December 31, 2025 compared to $2.7 million during the year ended December 31, 2024.
As of December 31, 2024, we have funded our operations primarily with aggregate gross proceeds of $792.5 million from the sale of shares of our capital stock and from upfront payments received under our collaboration and license agreements. As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $241.0 million.
As of December 31, 2025, we have funded our operations primarily with aggregate gross proceeds of $967.5 million from the sale of shares of our capital stock and pre-funded warrants and from upfront payments received under our collaboration and license agreements. As of December 31, 2025, we had cash, cash equivalents, and marketable securities of $352.3 million.
See Note 2 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for a description of our other significant accounting policies. 88 Collaborative Arrangements At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and are exposed to significant risks and rewards dependent on the commercial success of such activities, and therefore within the scope of the Financial Accounting Standards Board Accounting Standards Codification, or ASC, Topic 808, Collaborative Arrangements , or ASC 808.
Collaborative Arrangements At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and are exposed to significant risks and rewards dependent on the commercial success of such activities, and therefore within the scope of the Financial Accounting Standards Board Accounting Standards Codification, or ASC, Topic 808, Collaborative Arrangements , or ASC 808.
The increase in net cash provided by investing activities of $68.9 million was primarily due to net maturities of marketable securities during the year ended December 31, 2024, as compared to net purchases of marketable securities during the year ended December 31, 2023.
The decrease in net cash provided by investing activities of $1.5 million was primarily due to a decrease in net maturities of marketable securities during the year ended December 31, 2025, as compared to the year ended December 31, 2024.
Year Ended December 31, (in thousands) 2024 2023 Losmapimod external expenses $ 20,801 $ 29,069 Pociredir external expenses 8,577 7,442 Pre-development candidate expenses and unallocated expenses 14,008 14,536 Internal research and development expenses 20,000 20,754 Total research and development expenses $ 63,386 $ 71,801 The successful development of our product candidates is highly uncertain.
Year Ended December 31, (in thousands) 2025 2024 Pociredir external expenses $ 19,994 $ 8,577 Losmapimod external expenses 941 20,801 Pre-development candidate expenses and unallocated expenses 19,061 14,008 Internal research and development expenses 16,107 20,000 Total research and development expenses $ 56,103 $ 63,386 The successful development of our product candidates is highly uncertain.
Net cash provided by financing activities during the year ended December 31, 2023 primarily consisted of net proceeds of $117.3 million from the January 2023 public offering of our common stock.
Net cash provided by financing activities during the year ended December 31, 2025 primarily consisted of net proceeds of $164.2 million from the December 2025 public offering of our common stock and pre-funded warrants.
These increases will likely include increased costs related to the hiring of additional personnel, legal, audit, filing fees, and general compliance and consulting expenses, among other expenses.
These increases will likely include increased costs related to the hiring of additional personnel, legal, audit, filing fees, and general compliance and consulting expenses, among other expenses. Other Income, Net Other income, net consists primarily of interest income related to our investments in cash equivalents and marketable securities.
During the year ended December 31, 2024, we recognized $80.0 million of revenue associated with the upfront license payment. During the year ended December 31, 2024, we recorded a $8.1 million reduction in research and development expenses in connection with global development activities for losmapimod.
During the year ended December 31, 2025, we recorded a $1.0 million reduction in research and development expenses in connection with global development activities for losmapimod. During the year ended December 31, 2025, we recognized no revenue associated with the Sanofi territory-specific manufacturing activities for losmapimod.
We may never succeed in obtaining regulatory approval for any of our product candidates. In May 2024, we entered into a collaboration and license agreement with Sanofi, pursuant to which we granted Sanofi an exclusive license under certain intellectual property rights to commercialize losmapimod, an oral small molecule for the treatment of FSHD outside of the United States.
In May 2024, we entered into a collaboration and license agreement with Sanofi, pursuant to which we granted Sanofi an exclusive license under certain intellectual property rights to commercialize losmapimod, an oral small molecule that we were developing for the treatment of FSHD outside of the United States and received an upfront payment of $80.0 million.
Net Cash Provided by (Used in) Investing Activities Net cash provided by investing activities was $32.2 million during the year ended December 31, 2024 compared to net cash used in investing activities of $36.7 million during the year ended December 31, 2023.
The increase in net cash used in operating activities of $57.9 million was primarily due to an increase in net loss. Net Cash Provided by Investing Activities Net cash provided by investing activities was $30.7 million during the year ended December 31, 2025 compared to $32.2 million during the year ended December 31, 2024.
As of December 31, 2024, we had an accumulated deficit of $519.4 million.
As of December 31, 2025, we had an accumulated deficit of $594.3 million.
Funding Requirements We expect our expenses to increase substantially in connection with our ongoing research and development activities, particularly as we continue the research and development of, initiate clinical trials of, and seek marketing approval for, our product candidates, some of which are in the discovery stage of development.
Net cash provided by financing activities during the year ended December 31, 2024 consisted of net proceeds of $2.7 million from the issuance of common stock under our benefit plans. 85 Funding Requirements We expect our expenses to increase substantially in connection with our ongoing research and development activities, particularly as we continue the research and development of, initiate clinical trials of, and seek marketing approval for, our product candidates, some of which are in the discovery stage of development.
In addition to our product candidates, we developed a discovery approach that we employ to systematically identify and validate cellular drug targets that can potentially modulate gene expression to treat known root causes of genetically defined rare diseases. Our discovery approach led to the identification of pociredir for SCD, as well as other drug candidates.
We also plan to engage with the EMA in mid-2026 to obtain protocol assistance and feedback on the design of the next trial. 79 In addition to our product candidates, we developed a discovery approach that we employ to systematically identify and validate cellular drug targets that can potentially modulate gene expression to treat known root causes of genetically defined rare diseases.
Liquidity and Capital Resources Sources of Liquidity We have incurred significant operating losses since our inception and expect to continue to incur significant operating losses for the foreseeable future and may never become profitable.
The decrease was primarily due to a decrease in our average cash, cash equivalents, and marketable securities balance, and a decreased rate of return due to declining interest rates. 84 Liquidity and Capital Resources Sources of Liquidity We have incurred significant operating losses since our inception and expect to continue to incur significant operating losses for the foreseeable future and may never become profitable.
We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the most significant areas involving management’s judgments and estimates.
We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the most significant areas involving management’s judgments and estimates. See Note 2 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for a description of our other significant accounting policies.
If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. 86 Critical Accounting Policies and Estimates Our management’s discussion and analysis of our financial condition and results of operations are based on our consolidated financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States.
Other Income, Net Other income, net consists primarily of interest income related to our investments in cash equivalents and marketable securities. 84 Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following summarizes our results of operations for the years ended December 31, 2024 and 2023, along with the changes in those items in dollars: Year Ended December 31, Change (in thousands) 2024 2023 $ Collaboration revenue $ 80,000 $ 2,805 $ 77,195 Operating expenses: Research and development 63,386 71,801 (8,415 ) General and administrative 36,448 41,668 (5,220 ) Restructuring expense 2,063 — 2,063 Total operating expenses 101,897 113,469 (11,572 ) Loss from operations (21,897 ) (110,664 ) 88,767 Other income, net 12,172 13,329 (1,157 ) Net income (loss) $ (9,725 ) $ (97,335 ) $ 87,610 Collaboration Revenue Collaboration revenue increased by $77.2 million from $2.8 million for the year ended December 31, 2023 to $80.0 million for the year ended December 31, 2024.
Results of Operations Comparison of the Years Ended December 31, 2025 and 2024 The following summarizes our results of operations for the years ended December 31, 2025 and 2024, along with the changes in those items in dollars: Year Ended December 31, Change (in thousands) 2025 2024 $ Collaboration revenue — 80,000 (80,000 ) Operating expenses: Research and development 56,103 63,386 (7,283 ) General and administrative 28,666 36,448 (7,782 ) Restructuring expenses — 2,063 (2,063 ) Total operating expenses 84,769 101,897 (17,128 ) Loss from operations (84,769 ) (21,897 ) (62,872 ) Other income, net 9,889 12,172 (2,283 ) Net loss $ (74,880 ) $ (9,725 ) $ (65,155 ) Collaboration Revenue Collaboration revenue decreased by $80.0 million from the year ended December 31, 2024 to the year ended December 31, 2025.
As of December 31, 2024, we have not issued or sold any shares of common stock under the at-the-market offering program. 86 Cash Flows The following table provides information regarding our cash flows for the years ended December 31, 2024 and 2023: Year Ended December 31, (in thousands) 2024 2023 Net cash used in operating activities $ (2,218 ) $ (90,965 ) Net cash provided by (used in) investing activities 32,230 (36,692 ) Net cash provided by financing activities 2,746 118,122 Net increase (decrease) in cash, cash equivalents, and restricted cash $ 32,758 $ (9,535 ) Net Cash Used in Operating Activities Net cash used in operating activities was $2.2 million during the year ended December 31, 2024 compared to $91.0 million during the year ended December 31, 2023.
Cash Flows The following table provides information regarding our cash flows for the years ended December 31, 2025 and 2024: Year Ended December 31, (in thousands) 2025 2024 Net cash used in operating activities $ (60,065 ) $ (2,218 ) Net cash provided by investing activities 30,719 32,230 Net cash provided by financing activities 168,667 2,746 Net increase in cash, cash equivalents, and restricted cash $ 139,321 $ 32,758 Net Cash Used in Operating Activities Net cash used in operating activities was $60.1 million during the year ended December 31, 2025 compared to $2.2 million during the year ended December 31, 2024.
Other Income, Net Other income, net decreased by $1.1 million from $13.3 million for the year ended December 31, 2023 to $12.2 million for the year ended December 31, 2024. The decrease in other income, net was primarily attributable to a decrease in our average cash, cash equivalents, and marketable securities balance.
Other Income, Net Other income, net decreased by $2.3 million from $12.2 million for the year ended December 31, 2024 to $9.9 million for the year ended December 31, 2025.
Research and Development Expenses The following table summarizes our research and development expenses for the years ended December 31, 2024 and 2023: Year Ended December 31, Change (in thousands) 2024 2023 $ External research and development $ 36,327 $ 41,179 $ (4,852 ) Employee compensation 20,000 20,754 (754 ) Laboratory supplies 1,528 3,501 (1,973 ) Facility costs 4,483 4,834 (351 ) Other 1,048 1,533 (485 ) Total research and development expenses $ 63,386 $ 71,801 $ (8,415 ) Research and development expense decreased by $8.4 million from $71.8 million for the year ended December 31, 2023 to $63.4 million for the year ended December 31, 2024.
The decrease was attributable to the recognition of $80.0 million of revenue associated with the upfront license payment received during the year ended December 31, 2024 under the now terminated Sanofi collaboration agreement. 83 Research and Development Expenses The following table summarizes our research and development expenses for the years ended December 31, 2025 and 2024: Year Ended December 31, Change (in thousands) 2025 2024 $ External research and development $ 31,744 $ 36,327 $ (4,583 ) Employee compensation 16,108 20,000 (3,892 ) Laboratory supplies 2,361 1,528 833 Facility costs 4,449 4,483 (34 ) Other 1,441 1,048 393 Total research and development expenses $ 56,103 $ 63,386 $ (7,283 ) Research and development expense decreased by $7.3 million from $63.4 million for the year ended December 31, 2024 to $56.1 million for the year ended December 31, 2025.
Research and development activities account for a significant portion of our operating expenses.
A change in the outcome of any of these variables with respect to the development of any of our product candidates would significantly change the costs and timing associated with the development of that product candidate, and potentially other candidates. 82 Research and development activities account for a significant portion of our operating expenses.
Removed
In January 2023, we announced interim data from our Phase 1b clinical trial of pociredir in SCD. We completed enrollment in the 6 mg and 2 mg dose cohorts, and do not plan to enroll additional subjects in these cohorts.
Added
In February 2026, we announced updated 20 mg cohort results from the PIONEER trial as of the December 23, 2025 data cut off date showing: • Mean absolute HbF increased by 12.2% at 12 weeks of treatment with pociredir (vs. 8.6% at Week 12 in the 12 mg cohort), increasing from a baseline of 7.1% to 19.3%.
Removed
Although we commenced enrollment in the 12 mg dose cohort, in February 2023 the FDA placed a full clinical hold on the investigational new drug, or IND, application for pociredir for SCD, which was lifted in August 2023.
Added
Seven of 12 patients (58%) achieved absolute HbF levels ≥20% at Week 12, and all patients demonstrated a clinically relevant HbF increase.
Removed
Following the clinical hold, we amended the protocol to revise the inclusion and exclusion criteria for the Phase 1b clinical trial to target subjects with higher disease severity.
Added
HbF levels of 20% are associated with ~90% of patients experiencing zero VOCs per year, based on real-world data that we presented at the 20th Annual Sickle Cell & Thalassemia Conference in October 2025. • The proportion of HbF-containing red blood cells, or F-cells, increased from a mean of 31% at baseline to 63% at Week 12 (n=10), indicating progression toward pan-cellular HbF induction (HbF distributed across a substantial proportion of RBCs).
Removed
We reinitiated the Phase 1b clinical trial at the 12 mg once daily dose level in the fourth quarter of 2023, with that cohort expected to enroll approximately 10 subjects, to be followed by an additional cohort of approximately 10 subjects at the 20 mg once daily dose level. Subjects are evaluated over a 12-week treatment period.
Added
F-cells are more resistant to sickling and hemolysis because of HbF-mediated inhibition of HbS polymerization.
Removed
We have enrolled 10 patients in the 12 mg dose cohort, and we expect to provide clinical data from the 12 mg dose cohort in mid-2025 and from the 20 mg dose cohort by the end of 2025. In September 2024, we announced topline results from our Phase 3 REACH clinical trial of losmapimod in facioscapulohumeral muscular dystrophy, or FSHD.
Added
Higher proportions of F-cells are associated with improved RBC health. • Mean changes in markers of hemolysis and erythropoiesis improved during the 12-week treatment period: o Indirect bilirubin decreased by 40% (vs. 37% at Week 12 in the 12 mg cohort) o Lactate dehydrogenase decreased by 34% (vs. 28% at Week 12 in the 12 mg cohort) o RBC distribution width decreased by 26% (vs. 27% at Week 12 in the 12 mg cohort) o Reticulocyte counts decreased by 42% (vs. 31% at Week 12 in the 12 mg cohort) • Mean hemoglobin increased by 1.1 g/dL at Week 12 (vs. 0.9 g/dL at Week 12 in the 12 mg cohort), increasing from a baseline of 7.3 g/dL to 8.4 g/dL. • Based on treating physician-documented medical records from the 6-12 months prior to enrollment, approximately 16 VOCs would have been expected during the 12-week treatment period.
Removed
The Phase 3 REACH trial did not achieve its primary endpoint of change from baseline in relative surface area with losmapimod compared to placebo. In addition, secondary endpoints did not achieve nominal statistical significance. The safety and tolerability profile of losmapimod was consistent with previously reported studies. We plan to share the results at an upcoming medical meeting.
Added
During the 12-week treatment period, six VOCs were reported.
Removed
Based on the results of the REACH trial, we have suspended future development of losmapimod.
Added
Seven of 12 patients (58%) reported no VOCs during the treatment period. • Through the completion of the 20 mg dose cohort, pociredir has been dosed in 148 adults, including 89 subjects in multiple dose cohorts up to 12 weeks. o 103 healthy subjects, including 44 who received pociredir for 10 to 14 days treatment duration o 45 SCD patients who received pociredir for up to 12 weeks treatment duration • The safety profile observed in the 20 mg dose cohort as of the December 23, 2025 data cut off date remained consistent with previously reported safety data.
Removed
In September 2024, we also announced a strategic plan to reprioritize research and development activities and are now focused on advancing pociredir for the treatment of SCD, novel therapeutic agents for the potential treatment of inherited aplastic anemias, such as DBA, Shwachman-Diamond syndrome, and Fanconi anemia, and our other discovery programs.
Added
Pociredir was generally well-tolerated, with no treatment-related serious adverse events and no discontinuations due to treatment-related adverse events through the December 23, 2025 data cut off date. We are currently activating sites in an open-label extension trial to evaluate longer-term safety and PD durability in patients who completed the PIONEER trial.
Removed
The plan reduced our workforce from 80 to 51 full-time employees, including a reduction of positions across both research and development and general and administrative functions. We estimate that this restructuring will result in annual operating expense savings of approximately $10.0 million beginning in the first quarter of 2025.
Added
We plan to provide details regarding the design of the next trial in the second quarter of 2026 following receipt of meeting minutes from our End-of-Phase meeting with the FDA. Pending feedback from the FDA, we plan to initiate a potential registration-enabling trial in the second half of 2026.
Removed
We continue to advance our program for the potential treatment of inherited aplastic anemias, such as DBA, Shwachman-Diamond syndrome, and Fanconi anemia, and we plan to submit an IND for DBA during the fourth quarter of 2025.
Added
Our discovery approach led to the identification of pociredir for SCD, as well as other drug candidates. We are applying our discovery capabilities to explore additional mechanisms that may complement pociredir’s mechanism of action to induce HbF for the potential treatment of SCD.
Removed
Since inception, our operations have focused on organizing and staffing our company, business planning, raising capital, establishing our intellectual property, building our discovery platform, including our proprietary compound library and technologies, identifying drug targets and potential product candidates, in-licensing assets, producing drug substance and drug product material for use in clinical trials and conducting preclinical studies and clinical trials.
Added
We also presented preclinical data for FTX-6274, an oral EED inhibitor candidate, at the European Society for Medical Oncology (ESMO) Congress 2025, demonstrating tumor growth inhibition in castration resistant prostate cancer models.
Removed
To date, we have funded our operations primarily from the sale of shares of our capital stock and from upfront payments received under our collaboration and license agreements. We have incurred significant operating losses since our inception and we expect to continue to incur significant operating losses for the foreseeable future.
Added
Based on results from IND-enabling studies, we have decided not to advance our program for bone marrow failure syndromes into clinical development and will focus our resources on advancing pociredir and our core benign hematology programs. We have incurred significant operating losses since our inception and we expect to continue to incur significant operating losses for the foreseeable future.
Removed
During the year ended December 31, 2024, we recognized no revenue associated with the Sanofi territory-specific manufacturing activities for losmapimod.
Added
We may never succeed in obtaining regulatory approval for any of our product candidates.
Removed
As a result of the suspension of future development of losmapimod, and Sanofi’s recent notification of termination for convenience, we do not expect to recognize additional revenues under the Sanofi collaboration agreement. 81 In July 2020, we entered into a collaboration and license agreement with MyoKardia, which we amended in April 2023 and again in July 2024, pursuant to which we granted to MyoKardia an exclusive worldwide license under certain intellectual property rights to research, develop, make, have made, use, have used, sell, have sold, offer for sale, have offered for sale, import, have imported, export, have exported, distribute, have distributed, market, have marketed, promote, have promoted, or otherwise exploit products directed against certain biological targets identified by us that are capable of modulating up to a certain number of genes of interest with relevance to certain genetically defined cardiomyopathies.
Added
As a result of the suspension of future development of losmapimod following our September 2024 announcement that there was no statistically significant difference between losmapimod and placebo on the primary endpoint in the Phase 3 REACH trial, Sanofi terminated the license. Accordingly, we will not recognize additional revenues under the Sanofi collaboration agreement.
Removed
MyoKardia was subsequently acquired by Bristol-Myers Squibb Company in November 2020. The primary goal of the collaboration is to identify and validate potential biological targets for further research, in order to support the development, manufacture and commercialization of product candidates by MyoKardia for the potential treatment of certain genetically defined cardiomyopathies.
Added
General and Administrative Expenses The following table summarizes our general and administrative expenses for the years ended December 31, 2025 and 2024: Year Ended December 31, Change (in thousands) 2025 2024 $ Employee compensation $ 17,328 $ 19,754 $ (2,426 ) Professional services 7,621 11,999 (4,378 ) Facility costs 1,194 1,483 (289 ) Other 2,523 3,212 (689 ) Total general and administrative expenses $ 28,666 $ 36,448 $ (7,782 ) General and administrative expenses decreased by $7.7 million from $36.4 million for the year ended December 31, 2024 to $28.7 million for the year ended December 31, 2025.
Removed
We satisfied our obligation to perform research services as of December 31, 2023. Under the terms of the MyoKardia collaboration agreement, we received a $10.0 million upfront payment and a $2.5 million payment as prepaid research funding in July 2020.
Added
As of December 31, 2025, we have not issued or sold any shares of common stock under the at-the-market offering program. In December 2025, pursuant to an underwriting agreement with J.P.
Removed
MyoKardia agreed to reimburse us for the costs of the research activities not covered by the prepaid research funding, up to a maximum amount of total research funding (including the prepaid research funding).
Added
Morgan Securities LLC, Leerink Partners LLC, and Cantor Fitzgerald & Co., we and issued and sold (i) 11,851,853 shares of our common stock at a public offering price of $13.50 per share and (ii) pre-funded warrants to purchase up to 1,111,193 shares of our common stock at a public offering price of $13.499 per pre-funded warrant.
Removed
Upon the achievement of specified preclinical, development and sales milestones, we will be entitled to preclinical milestone payments, development milestone payments and sales milestone payments of up to $298.5 million in the aggregate per target for certain potential cardiomyopathy gene targets, and of up to $150.0 million in the aggregate per target for certain other potential cardiomyopathy gene targets.
Added
The net proceeds of the offering were $164.2 million, after deducting underwriting discounts and commissions and offering expenses.
Removed
To date, we have achieved a $2.5 million specified preclinical milestone. MyoKardia will also pay us tiered royalties ranging from a mid single-digit percentage to a low double-digit percentage based on MyoKardia’s, and any of its affiliates’ and sublicensees’, annual worldwide net sales of products under the MyoKardia collaboration agreement directed against any identified target.
Removed
The royalties are payable on a product-by-product basis during a specified royalty term, and may be reduced in specified circumstances. For the year ended December 31, 2024 we recognized no collaboration revenue under the MyoKardia collaboration agreement. For the year ended December 31, 2023 we recognized $2.8 million of collaboration revenue under the MyoKardia collaboration agreement.
Removed
As of December 31, 2024 and December 31, 2023, we have recorded no deferred revenue associated with the MyoKardia collaboration agreement. As of December 31, 2024, we had received $7.7 million of cost reimbursement payments and $2.5 million of milestone payments under the MyoKardia collaboration agreement.
Removed
As of December 31, 2024, we recorded no unbilled accounts receivable related to reimbursable research and development costs under the MyoKardia collaboration agreement for activities performed during the three months ended December 31, 2024. In the future, we may generate revenue from milestones and royalty payments under the MyoKardia collaboration agreement.
Removed
We expect that our revenue may fluctuate from quarter-to-quarter and year-to-year as a result of the timing, amount, and achievement of milestones under the MyoKardia collaboration agreement.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeInflation generally affects us by increasing our cost of labor and clinical trial costs. We do not believe that inflation had a material effect on our business, financial condition or results of operations during the years ended December 31, 2024 and 2023.
Biggest changeInflation generally affects us by increasing our cost of labor and clinical trial costs. We do not believe that inflation had a material effect on our business, financial condition or results of operations during the years ended December 31, 2025 and 2024.
We contract with vendors that are located outside of the United States and certain invoices are denominated in foreign currencies. We are subject to fluctuations in foreign currency rates in connection with these arrangements. We do not currently hedge our foreign currency exchange rate risk. As of December 31, 2024, we had minimal or no liabilities denominated in foreign currencies.
We contract with vendors that are located outside of the United States and certain invoices are denominated in foreign currencies. We are subject to fluctuations in foreign currency rates in connection with these arrangements. We do not currently hedge our foreign currency exchange rate risk. As of December 31, 2025, we had minimal or no liabilities denominated in foreign currencies.
Treasury securities and our investments are in short-term marketable securities, such as corporate bonds and commercial paper. As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $241.0 million.
Treasury securities and our investments are in short-term marketable securities, such as corporate bonds and commercial paper. As of December 31, 2025, we had cash, cash equivalents, and marketable securities of $352.3 million.

Other FULC 10-K year-over-year comparisons