COGT 10-K & 10-Q changes, risk factors and insider trading
Cogent Biosciences, Inc. · Nasdaq · Pharmaceutical Preparations · CIK 1622229 · All filings on SEC.gov
At a glance
What changed in the latest 10-K
Risk Factors
New heading “The insurance coverage and reimbursement status of newly approved products is uncertain. Failure to obtain or maintain adequate coverage and reimbursement for bezuclastinib or any of our other product candidates could limit our ability to market those products and decrease our ability to generate revenue.”
New heading “If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of bezuclastinib or any of our other product candidates.”
New heading “Breakthrough Therapy Designation for bezuclastinib and our other product candidates or participation in the FDA’s Real-Time Oncology Review (“RTOR”) program may not lead to a faster development or review process.”
New heading “We may seek priority review designation for one or more of our product candidates, but we might not receive such designation, and even if we do, such designation may not lead to faster development or regulatory review or approval process.”
New heading “Evolving regulatory standards, including as a result of changes in government leadership, make it difficult to accurately predict the likelihood of marketing approval even when clinical trials meet their endpoints.”
New heading “Even if we receive regulatory approval for any investigational product, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense.”
New heading “Pharmaceutical and biological product marketing is subject to substantial regulation in the United States. and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.”
New heading “We may have difficulty building our sales, marketing and distribution infrastructure.”
New heading “We may require additional capital to finance our planned operations. If we fail to obtain additional financing when needed, or on attractive terms, we may be unable to complete the development and commercialization of our product candidates.”
New heading “Risks Related to our Convertible Notes”
New heading “Our indebtedness and liabilities could limit the cash flow available for our operations, expose us to risks that could adversely affect our business, financial condition and results of operations and impair our ability to satisfy our obligations under the notes.”
New heading “We may be unable to raise the funds necessary to repurchase the Notes for cash following a fundamental change or to pay any cash amounts due upon maturity or conversion of the Notes.”
New heading “The conditional conversion feature of the Notes, if triggered, may adversely affect our financial condition and results of operations.”
New heading “Transactions relating to the Notes may affect the value of our common stock.”
New heading “The accounting method for the Notes could adversely affect our reported financial condition and results.”
New heading “The conversion of the Notes could impair our financial position and liquidity.”
Removed heading “Our updated bezuclastinib formulation is unproven and may not work as intended in clinical trials.”
Removed heading “If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our product candidates.”
Removed heading “Pharmaceutical and biological product marketing is subject to substantial regulation in the U.S. and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.”
Removed heading “We will require substantial additional funding. If we fail to obtain additional financing when needed, or on attractive terms, we may be unable to complete the development and commercialization of our product candidates.”
Largest changes
“As of December 31, 2025, we had $230.0 million in aggregate principal of Convertible Notes (the “Notes”) outstanding, and we may incur additional indebtedness to meet future financing needs. The interest rate for the Notes is fixed at 1.625% per annum and is payable semi-annually in arrears on May 15 and November 15 of each year, beginning on May 15, 2026. …”see in full comparison
“We face an inherent risk of product liability as a result of the clinical testing of our product candidates and will face an even greater risk if we commercialize bezuclastinib or any of other product candidates. If we cannot successfully defend ourselves against claims that any of our product candidates caused injuries, we could incur substantial liabilities. We may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability, or losses may exceed the amount of insurance that we carry. …”see in full comparison
“Pharmaceutical and biological product marketing is subject to substantial regulation in the United States. and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.”see in full comparison
“Pharmaceutical and biological product marketing is subject to substantial regulation in the U.S. and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.”see in full comparison
“In addition, if any of our investigational products are approved, our product labeling, advertising and promotion will be subject to regulatory requirements and continuing regulatory review. The FDA strictly regulates the promotional claims that may be made about drug and biological products. In particular, a product may not be promoted for uses that are not approved by the FDA as reflected in the product’s approved labeling. …”see in full comparison
“Even if we receive regulatory approval for any investigational product, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense.”see in full comparison
Full comparison: every changed paragraph (95)
The following risk factors and other information included in this Annual Report on Form 10-K should be carefully considered. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not presently known to us or that we presently deem less significant may also impair our business operations. You should carefully consider the risks described below, as well as the other information in this Annual Report on Form 10-K, including our financial statements and the related notes and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” as well as our other filings with the Securities and Exchange Commission, before deciding whether to invest in our common stock. If any of the following risks occur, our business, financial condition, results of operations and future growth prospects could be materially and adversely affected. Moreover, some of the factors, events and contingencies discussed below may have occurred in the past, but the disclosures below are not representations as to whether or not the factors, events or contingencies have occurred in the past and instead reflect our beliefs and opinions as to the factors, events, or contingencies that could materially and adversely affect us in the future. References to past events are provided by way of example only and are not intended to be a complete listing or a representation as to whether or not such factors have occurred in the past.
Risks Related to theour Discovery and Development of Our Drug CandidatesBusiness
Our business and future success depend on our ability to develop, obtain regulatory approval for and then successfully commercialize bezuclastinib and any other product candidates that we may discover and develop. We are pursuing clinical development of bezuclastinib to target SM and GIST through our APEX, SUMMIT and PEAK clinical trials. We submitted the first New Drug Application (“NDA”) for NonAdvSM in 2025; we initiated our NDA submission for GIST in January 2026 and expect to complete the submission in April 2026; and we plan to submit an NDA in AdvSM in the first half of 2026. There is no guarantee that bezuclastinib will be approved for any or all of these trials will be successful.indications. Even if our trials are successful,approved, bezuclastinib will require regulatory review and approval, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we are able to generate any revenue from product sales, if ever.
The development and commercialization of new pharmaceutical and biotechnology products is highly competitive. We face competition with respect to bezuclastinib and our other product candidates and will face competition with respect to any drug candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology companies worldwide. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of the disease indications for which we are developing our drug candidates. Potential competitors also include academic institutions, government agencies, and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization.
From time to time, we publicly disclose preliminary or “top-line” data from our clinical trials, which is based on a preliminary analysis of then-available data in a summary or “top-line” format, and the results and related findings may change as more patient data become available, may be interpreted differently if additional data are disclosed at a later time and are subject to audit and verification procedures that could result in material changes in the final data. If additional results from our clinical trials are not viewed favorably, our ability to obtain approval for and commercialize bezuclastinib and our other drug candidates, our business, operating results, prospects, or financial condition may be harmed and our stock price may decrease.
The insurance coverage and reimbursement status of newly approved products is uncertain. Failure to obtain or maintain adequate coverage and reimbursement for bezuclastinib or any of our other product candidates could limit our ability to market those products and decrease our ability to generate revenue.
The pricing, coverage, and reimbursement of bezuclastinib and any other product candidates, if approved, must be adequate to support our commercial infrastructure. Our per-patient prices must be sufficient to recover our development and manufacturing costs and potentially achieve profitability. Accordingly, the availability and adequacy of coverage and reimbursement by governmental and private payors are essential for most patients to afford expensive treatments such as ours. Sales of bezuclastinib will depend substantially, both domestically and abroad, on the extent to which their costs will be paid for by health maintenance, managed care, pharmacy benefit, and similar healthcare management organizations, or reimbursed by government authorities, private health insurers, and other payors. If coverage and reimbursement are not available, are available only to limited levels, or are not available on a timely basis, we may not be able to successfully commercialize bezuclastinib. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish or maintain pricing sufficient to sustain our overall enterprise.
There is significant uncertainty related to the insurance coverage and reimbursement of newly approved products. In the United States, the Centers for Medicare & Medicaid Services (“CMS”), an agency within the U.S. Department of Health and Human Services (the “HHS”), decides whether and to what extent a new drug will be covered and reimbursed under Medicare. Private payors tend to follow the coverage reimbursement policies established by CMS to a substantial degree. It is difficult to predict what CMS or private payors will decide with respect to reimbursement for a product such as ours. In addition, an executive order issued by the White House on May 12, 2025, directs the HHS to implement a “Most Favored Nation” drug pricing policy. See also “The impact of healthcare legislation and other changes in the healthcare industry and in healthcare spending on us is currently unknown, and may adversely affect our business model.” And the One Big Beautiful Bill Act (the “OBBBA”) imposes new restrictions on funding for government health care programs and on individual eligibility for coverage under those programs, which may lead to lower reimbursement for drugs covered by those programs.
Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for new products and, as a result, they may not cover or provide adequate payment for bezuclastinib. We expect to experience pricing pressures in connection with the sales bezuclastinib due to the trend toward managed healthcare, the increasing influence of health maintenance organizations, additional legislative changes, and statements by elected officials. The downward pressure on healthcare costs in general, and with respect to prescription drugs, surgical procedures, and other treatments in particular, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products.
We plan to seek regulatory approval of bezuclastinib and our other product candidates outside of the United States (either ourselves or through a partner) and, accordingly, we expect that we or any future partner will be subject to additional risks and regulatory requirements related to operating in foreign countries if we or they obtain the necessary approvals. Risks associated with any international operations may materially adversely affect our ability to attain or maintain profitable operations.
If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of bezuclastinib or any of our other product candidates.
We face an inherent risk of product liability as a result of the clinical testing of our product candidates and will face an even greater risk if we commercialize bezuclastinib or any of other product candidates. If we cannot successfully defend ourselves against claims that any of our product candidates caused injuries, we could incur substantial liabilities. We may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability, or losses may exceed the amount of insurance that we carry. A product liability claim or series of claims brought against us could cause our stock price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and business. In addition, regardless of merit or eventual outcome, product liability claims may result in impairment of our business reputation, costs due to related litigation, distraction of management’s attention from our primary business, initiation of investigations by regulators, substantial monetary awards to patients or other claimants, and decreased demand for bezuclastinib or any of our other product candidates, if approved for commercial sale.
We have expanded access programs in the United States for patients with SM and GIST to receive investigational bezuclastinib after meeting certain eligibility criteria. These programs are uncontrolled, carried out by individual physicians and not typically conducted in strict compliance with GCPs, all of which can lead to a treatment effect that may differ from that in placebo-controlled trials. These programs provide only anecdotal evidence of efficacy and contain no control or comparator group for reference. This patient data is not designed to be aggregated or reported as study results. Moreover, expanded access programs provide supportive safety information for regulatory review, and many of the patients in our programs will have life-threatening illnesses where the risk for serious adverse events is high. If serious adverse events in these programs are determined to be bezuclastinib-related, they could have a negative impact on the safety profile of bezuclastinib, which could cause significant delays or an inability to successfully obtain regulatory approval with labeling that we consider desirable, if at all.
The development and commercialization of new pharmaceutical and biotechnology products is highly competitive. We face competition with respect to our current clinical-stage drug candidates and will face competition with respect to any drug candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology companies worldwide. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of the disease indications for which we are developing our drug candidates. Potential competitors also include academic institutions, government agencies, and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization.
Since the number of patients that we have dosed to date in some of our clinical trials is small, the results from such clinical trials may be less reliable than results achieved in larger clinical trials.
A study design that is considered appropriate for regulatory approval includes a sufficiently large sample size with appropriate statistical power, as well as proper control of bias, to allow a meaningful interpretation of the results. The preliminary results of trials with smaller sample sizes can be disproportionately influenced by the impact the treatment had on a few individuals, which limits the ability to generalize the results across a broader community, thus making the study results less reliable than studies with a larger number of patients. As a result, there may be less certainty that such product candidates would achieve a statistically significant effect in any future clinical trials. In some of our current and any future clinical trials, we may not achieve a statistically significant result or the same level of statistical significance, if any, that we may have seen in prior clinical trials or preclinical studies.
From time to time, we publicly disclose preliminary or “top-line” data from our clinical trials, which is based on a preliminary analysis of then-available data in a summary or “top-line” format, and the results and related findings may change as more patient data become available, may be interpreted differently if additional data are disclosed at a later time and are subject to audit and verification procedures that could result in material changes in the final data. If additional results from our clinical trials are not viewed favorably, our ability to obtain approval for and commercialize our drug candidates, our business, operating results, prospects, or financial condition may be harmed and our stock price may decrease.
Our updated bezuclastinib formulation is unproven and may not work as intended in clinical trials.
In November 2021, we announced an updated formulation of bezuclastinib which is intended to reduce the number of daily tablets required for patients with GIST, thereby potentially improving the overall GIST patient experience. This formulation has now been incorporated into all three of our ongoing clinical trials. The formulation is unproven to date, and there is no guarantee that it will be successful or perform as desired.
We plan to seek regulatory approval of our product candidates outside of the United States (either ourselves or through a partner) and, accordingly, we expect that we or any future partner will be subject to additional risks and regulatory requirements related to operating in foreign countries if we or they obtain the necessary approvals. Risks associated with any international operations may materially adversely affect our ability to attain or maintain profitable operations.
If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our product candidates.
We face an inherent risk of product liability as a result of the clinical testing of our product candidates and will face an even greater risk if we commercialize any products.
We are initiating expanded access programs in the United States for patients with SM and GIST to receive investigational bezuclastinib after meeting certain eligibility criteria. These programs are uncontrolled, carried out by individual physicians and not typically conducted in strict compliance with GCPs, all of which can lead to a treatment effect that may differ from that in placebo-controlled trials. These programs provide only anecdotal evidence of efficacy and contain no control or comparator group for reference. This patient data is not designed to be aggregated or reported as study results. Moreover, expanded access programs provide supportive safety information for regulatory review, and many of the patients in our programs will have life-threatening illnesses where the risk for serious adverse events is high. If serious adverse events in these programs are determined to be bezuclastinib-related, they could have a negative impact on the safety profile of bezuclastinib, which could cause significant delays or an inability to successfully obtain regulatory approval with labeling that we consider desirable, if at all.
Third-party manufacturers may not be able to comply with the FDA’s cGMP regulations or similar regulatory requirements outside of the U.S.United States Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, seizures or voluntary recalls of drug candidates or products, operating restrictions, and criminal prosecutions, any of which could significantly and adversely affect supplies of our products. Third-party manufacturers’ failure to achieve and maintain high manufacturing standards, in accordance with applicable regulatory requirements, or the incidence of manufacturing errors, also could result in patient injury or death, product shortages, delays or failures in product testing or delivery, cost overruns, or other problems that could seriously harm our business. Third-party manufacturers often encounter difficulties involving production yields, quality control, and quality assurance, as well as shortages of qualified personnel.
For bezuclastinib and any other product candidates, we intend to identify and qualify additional manufacturers to provide such API and drug product prior to submission of a New Drug Application (“NDA”) to the FDA and/or a Marketing Authorization Application (“MAA”) to the EMA. We are not certain, however, that our single-source suppliers will be able to meet our demand for their products, either because of the nature of our agreements with those suppliers, our limited experience with those suppliers or our relative importance as a customer to those suppliers. It may be difficult for us to assess their ability to timely meet our demand in the future based on past performance and they may subordinate our needs in the future to their other customers.
Breakthrough Therapy Designation for bezuclastinib and our other product candidates or participation in the FDA’s Real-Time Oncology Review (“RTOR”) program may not lead to a faster development or review process.
We have been granted a Breakthrough Therapy Designation for bezuclastinib in the United States in NonAdvSM patients previously treated with avapritinib as well as in patients with SSM, both patient populations with no currently approved standard of care. We have also been granted Breakthrough Therapy Designation for bezuclastinib in combination with sunitinib in the United States for patients with GIST who have received prior treatment with imatinib. We may seek Breakthrough Therapy Designation for other current or future product candidates. Breakthrough Therapy Designation is intended to facilitate the development and expedite the review of new therapies to treat serious conditions with unmet medical needs by providing sponsors with the opportunity for frequent interactions with and additional drug development guidance from the FDA and its senior managers. Breakthrough Therapy Designation applies to the combination of the product candidate and the specific indication for which it is being studied. Product candidates that receive Breakthrough Therapy Designation may receive more frequent interactions with the FDA regarding the product candidate’s development plan and clinical trials and may be eligible for the FDA’s rolling or priority review.
Despite receiving Breakthrough Therapy Designation, bezuclastinib or other product candidates may not actually benefit from faster clinical development or regulatory review or approval any sooner than other product candidates that do not have such designation, or at all. Furthermore, such a designation does not increase the likelihood that bezuclastinib will receive marketing approval in the United States. The FDA may also rescind Breakthrough Therapy Designation if it determines that bezuclastinib no longer meets the relevant criteria.
In January 2026, we announced that the FDA agreed to accept our NDA for bezuclastinib in combination with sunitinib for patients with GIST who have received prior treatment with imatinib under the RTOR program, and shortly thereafter we initiated our NDA submission to FDA under this program. Our acceptance into RTOR does not guarantee or influence approval of our application, which is subject to the same statutory and regulatory requirements for approval as applications that are not included in RTOR. Although early approvals have occurred with applications selected for RTOR, this may not be the case for our application. If at any time the FDA determines our participation in RTOR is no longer appropriate, the FDA may rescind our acceptance and instruct us to follow routine submission procedures for marketing approval.
We currently have one drug candidate in clinical development for three indications and its risk of failure is high.indications. We are unable to predict when or if any of our drug candidates will prove effective or safe in humans or will obtain marketing approval. Before obtaining marketing approval from regulatory authorities for the sale of any drug candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our drug candidates in humans.
While bezuclastinib is a highly potent and selective KIT D816V inhibitor that is being developed to treat SM and GIST patients, we may find that patients treated with bezuclastinib or our other drug candidates have or develop mutations that confer resistance to treatment. If patients have or develop resistance to treatment with bezuclastinib or our other drug candidates, we may be unable to successfully complete our clinical trials, and may not be able to obtain regulatory approval of, and commercialize, our drug candidates.
We may seek priority review designation for one or more of our product candidates, but we might not receive such designation, and even if we do, such designation may not lead to faster development or regulatory review or approval process.
If the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review designation means that the goal for the FDA to review an application is six months from the NDA filing date, rather than the standard review period of ten months. We may request priority review for bezuclastinib or any other product candidate. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does not necessarily guarantee a faster development or regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures and timelines. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all.
We are conducting clinical trials with our lead product candidate, bezuclastinib, in patients with GIST, AdvSM and Non-AdvSM.NonAdvSM. We submitted the first NDA for bezuclastinib in NonAdvSM in 2025 and initiated our NDA for patients with GIST under the RTOR program in January 2026 and plan to submit an NDA for bezuclastinib in GIST in April 2026 and in AdvSM in the first half of 2026. The FDA may not agree with some or all of our regulatory plans for initial registration of bezuclastinib in some or all of these indications and may require additional clinical trials to be conducted prior to approval. Our clinical trial results may also not support approval.
Evolving regulatory standards, including as a result of changes in government leadership, make it difficult to accurately predict the likelihood of marketing approval even when clinical trials meet their endpoints.
Regulatory standards are promulgated by various government entities and are subject to change based on factors such as scientific developments, public perceptions of risk, and political forces. Because clinical trials often take years to complete, it is sometimes possible for standards that exist during the conception and initiation of a clinical trial to change before the clinical trial is completed or ultimately reviewed by government regulators. For example, we may initiate clinical trials that are designed to show benefits on relatively short-term endpoints, but ultimately may be required to show benefits in longer-term outcome studies. While some government entities have safeguards intended to ensure standards agreed upon by sponsors and regulators at the outset of a clinical trial are applied during regulatory review processes, those safeguards generally permit regulators to apply more rigorous standards where regulators believe doing so is necessary. As such, there can be no assurance that regulatory standards that are appropriate at the outset of a clinical trial program will not become more rigorous during the regulatory approval process and could potentially result in a delayed approval or denial of marketing authorization.
In addition, the FDA, EMA and other regulatory authorities may change their policies, issue additional regulations or revise existing regulations, or take other actions, including as a result of changes in leadership at the FDA and other federal agencies under the current U.S. administration, which may prevent or delay approval of our product candidates on a timely basis. Such policy or regulatory changes could impose additional requirements upon us that could delay our ability to obtain approvals, increase the costs of compliance or restrict our ability to maintain any marketing authorizations we may have obtained. In June 2024, the Supreme Court overruled the Chevron doctrine, which had given deference to regulatory agencies’ statutory interpretations of ambiguous regulations in litigation against federal government agencies, such as the FDA. The overruling of the Chevron doctrine may significantly increase the number of challenges brought by companies and other stakeholders against federal agencies such as the FDA and its longstanding decisions and policies, including the FDA’s statutory interpretations of market exclusivities and the “substantial evidence” requirements for drug approvals, which could undermine the FDA’s authority, lead to uncertainties in the industry, and disrupt the FDA’s normal operations, any of which could delay the FDA’s review of our regulatory submissions. We cannot predict the full impact of this decision, future judicial challenges brought against the FDA, or the nature or extent of government regulation that may arise from future legislation or administrative action.
Further, under the new leadership at the HHS under the current administration, agency reorganization, mass layoffs due to the reduction in force initiative and other measures implemented by the Department of Government Efficiency may impact the normal operations of the FDA as well as other federal agencies. FDA may lack adequate staff and resources to meet current review, approval, and inspection schedules, which could delay our anticipated timelines and may have a material impact on the industry and our clinical development plans. For example, average review times at the FDA have fluctuated in recent years as a result. Our business depends upon the ability of the FDA to accept and review our potential regulatory filings. If a prolonged government shutdown occurs or if a significant number of federal employees are laid off or leave federal agencies, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our ability to advance clinical development of our product candidates.
In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. In January 2025, an executive order entitled “Unleashing Prosperity Through Deregulation”, was issued which calls for at least 10 existing regulations to be repealed whenever an executive department or agency publicly proposes for notice and comment or otherwise promulgates a new regulation. Recent developments at the FDA include announcement of a plan to phase out animal testing for monoclonal antibodies and certain other drugs, the proposed rare disease evidence principles (RDEP) program to facilitate approval of drugs to treat rare diseases with very small patient populations with significant unmet medical need and with a known genetic defect that is the major driver of the pathophysiology, and the announcement of a new Commissioner’s National Priority Voucher program for companies supporting certain U.S. national health priorities and interests. To the extent our competitors are selected for this new voucher pilot program, or are otherwise able to participate in any of these initiatives intended to accelerate drug development and application review, and obtain faster approval than us, our competitive position may be harmed. It is unclear how our industry and our clinical programs will be impacted by policies and regulations implemented under the current administration and FDA leadership, or other executive orders. There is significant uncertainty in the industry and how federal agencies like the FDA will change in the coming years under the current administration. To the extent the agency reorganization and other agency changes lead to disruptions in FDA’s operations, our correspondence and regulatory review processes with the FDA may be materially delayed.
Even if we receive regulatory approval for any investigational product, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense.
Following potential approval of any our investigational products, the FDA may impose significant restrictions on a product’s indicated uses or marketing or impose ongoing requirements for potentially costly and time-consuming post-approval studies, post-market surveillance or clinical trials to monitor the safety and efficacy of the product. The FDA may also require a REMS as a condition of approval of our investigational products, which could include requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA or a comparable foreign regulatory authority approves our investigational products, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for our products will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMPs and GCP requirements for any clinical trials that we conduct post-approval. Later discovery of previously unknown problems with our products, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things:
restrictions on the marketing or manufacturing of our products, withdrawal of the product from the market or voluntary or mandatory product recalls;
restrictions on product distribution or use, or requirements to conduct post-marketing studies or clinical trials;
fines, restitutions, disgorgement of profits or revenues, warning letters, untitled letters or holds on clinical trials;
refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of approvals;
product seizure or detention, or refusal to permit the import or export of our products; and injunctions or the imposition of civil or criminal penalties.
The occurrence of any event or penalty described above may inhibit our ability to commercialize our investigational products and generate revenue and could require us to expend significant time and resources in response and could generate negative publicity.
In addition, if any of our investigational products are approved, our product labeling, advertising and promotion will be subject to regulatory requirements and continuing regulatory review. The FDA strictly regulates the promotional claims that may be made about drug and biological products. In particular, a product may not be promoted for uses that are not approved by the FDA as reflected in the product’s approved labeling. If we receive marketing approval for an investigational product, physicians may nevertheless, in their independent medical judgment, prescribe it to their patients in a manner that is inconsistent with the approved label. The FDA does not regulate the behavior of physicians in their choice of treatments but the FDA does restrict manufacturer’s communications on the subject of off-label use of their products. If we are found to have promoted such off-label uses, we may become subject to liability. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant sanctions.
The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our investigational products. In addition, the FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our investigational products. We also cannot predict the likelihood, nature or extent of government If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may be subject to enforcement action and we may not achieve or sustain profitability.
Pharmaceutical and biological product marketing is subject to substantial regulation in the United States. and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.
Many federal and state legislatures have considered, and adopted, healthcare policies intended to curb rising healthcare costs, such as the Inflation Reduction Act of 2022. These cost-containment measures may include, among other measures: requirements for pharmaceutical companies to negotiate prescription drug prices with government healthcare programs; controls on government-funded reimbursement for drugs; new or increased requirements to pay prescription drug rebates to government healthcare programs, including if drug prices increase at a higher rate than inflation; controls on healthcare providers; challenges to or limits on the pricing of drugs, including pricing controls or limits or prohibitions on reimbursement for specific products through other means; requirements to try less expensive products or generics before a more expensive branded product; and public funding for cost effectiveness research, which may be used by government and private third-party payors to make coverage and payment decisions. In addition, in May 2025, the Trump administration issued an executive order entitled “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients,” which, among other things, directs the HHS and other agencies to communicate most-favored-nation (“MFN”) price targets to pharmaceutical manufacturers to bring prices for U.S. patients in line with comparably developed nations and to facilitate direct-to-consumer purchasing programs. The HHS subsequently issued guidance indicating the MFN target price is the lowest price paid in an Organization for Economic Co-operation and Development country with a gross domestic product (“GDP”) per capita of at least 60% of the U.S. GDP per capita. It is currently unclear whether and to what extent these measures will be implemented and what impact any such implementation would have on our business. Further, there can be no assurance that the current administration or future administrations will not pursue different or additional measures that could impact drug pricing in the United States. Political, economic and regulatory developments may further complicate developments in healthcare systems and pharmaceutical drug pricing. These developments could, for example, impact our potential licensing agreements as commercial and collaborative partners may also consider the impact of these pressures on their licensing strategies.
Pharmaceutical and biological product marketing is subject to substantial regulation in the U.S. and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.
We rely upon a combination of patents, confidentiality agreements, trade secret protection and license agreements to protect the intellectual property related to our technologies. Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly duplicate or surpass our technological achievements, thus eroding our competitive position in our market. While we undertake efforts to protect our trade secrets and other confidential information from disclosure, others may independently discover trade secrets and proprietary information, and in such cases, we may not be able to assert any trade secret rights against such party. Enforcing a claim that a party illegally obtained and is using our trade secrets is challenging and the outcome is unpredictable. In addition, courts outside of the U.S.United States may be less willing to protect trade secrets. Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive business position.
Currently, we have patents issued from our in-licensed portfolio under our licenseLicense agreementAgreement with Plexxikon. in multiple territories, including but not limited to, Australia, Brazil, Canada, China, Colombia, Europe (validated in Germany, Spain, France, Great Britain, Italy, the Netherlands, as well as various other EU countries), Hong Kong, India, Indonesia, Israel, Japan, Mexico, New Zealand, Peru, the Philippines, Republic of Korea, Russia, Singapore, South Africa, Taiwan, and the United States. We also have in-licensed patent applications pending in Australia, Brazil, Canada, China, Egypt, Europe, India, Indonesia, Israel, Japan, Korea, Mexico, Philippines, Singapore, South Africa, and the United States. In addition, we have our own USapplications pending in the United States, Europe, Australia, Brazil, Canada, China, Colombia, Egypt, Indonesia, Israel, India, Japan, Korea, Mexico, New Zealand, Peru, Philippines, Russia, Singapore, Thailand, Vietnam, and South Africa as well as our own international patent application and United States provisional applications. We anticipate additional patent applications will be filed both in the United States and in other countries, as appropriate. There is no guarantee that patent applications will provide meaningful protection or result in patents being issued and granted.
Further, a new court system recently became operational in the European Union. The Unified Patent Court,Court or UPC,(“UPC”), began accepting patent cases on June 1, 2023. The UPC is a common patent court with jurisdiction over patent infringement and revocation proceedings effective for multiple member states of the European Union. The broad geographic reach of the UPC could enable third parties to seek revocation of any of our European patents in a single proceeding at the UPC rather than through multiple proceedings in each of the individual European Union member states in which the European patent is validated. Under the UPC, a successful revocation proceeding for a European Patent under the UPC would result in loss of patent protection in those European Union countries. Accordingly, a single proceeding under the UPC could result in the partial or complete loss of patent protection in numerous European Union countries. Such a loss of patent protection could have a material adverse impact on our business and our ability to commercialize our technology and product candidates. Moreover, the controlling laws and regulations of the UPC will develop over time and we cannot predict what the outcomes of cases tried before the UPC will be. The case law of the UPC may adversely affect our ability to enforce or defend the validity of our or our licensors’ European patents. Patent owners have the option to opt-out their European Patents from the jurisdiction of the UPC, defaulting to pre-UPC enforcement mechanisms.
We have experienced significant growth and expect to continue to expand our company to support research, development and future commercial capabilities and may face challenges in managing our growth.
During the past two years we increased our headcount from 138164 to 205258 full time employees through the expansion of our research, development, manufacturing and G&A infrastructure. In addition, we are building an internal commercial organization as we prepare to launch bezuclastinib in the United States, and we expect our commercial organization to include up to 100 additional employees inclusive of both home office and field-based employees. We need to continue to recruit, train and retain qualified personnel to support our growth and we may be unable to do so effectively.
Further, as we launch bezuclastinib or as demand for bezuclastinib changes, our initial estimate of the size of the required field force may be materially more or less than the size of the field force actually required to effectively commercialize bezuclastinib. As such, we may be required to hire larger teams to adequately support the commercialization of our products and product candidates or we may incur excess costs in an effort to optimize the hiring of commercial personnel. With respect to certain geographical markets, we may enter into collaborations with other entities to utilize their local marketing and distribution capabilities, but we may be unable to enter into such agreements on favorable terms, if at all. See also “We currently rely and for the foreseeable future will continue to rely on third parties to conduct our clinical trials and to assist with various research, discovery, manufacturing and supply activities. If these third parties do not properly and successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval of or commercialize our product candidates or discover new product candidates on our intended timelines, if at all.” If our future collaborators do not commit sufficient resources to commercialize our future products, if any, and we are unable to develop the necessary marketing capabilities on our own, we will be unable to generate sufficient product sales to sustain our business. We face competition from companies that currently have extensive and well-funded marketing and sales operations. Without a large internal team or the support of a third party to perform key commercial functions, we may be unable to compete successfully against these more established companies.
We may have difficulty building our sales, marketing and distribution infrastructure.
To market bezuclastinib or any approved product candidate in the future, we must continue building our sales, marketing, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, as we do not presently have all of these capabilities.
Management's Discussion & Analysis (MD&A)
New heading “Other Bezuclastinib Information”
New heading “CGT4255 (ErbB2)”
New heading “CGT6297 (PI3Kα)”
New heading “Interest Expense”
New heading “Loss on Debt Extinguishment”
New heading “Interest Expense”
New heading “Loss on Debt Extinguishment”
Removed heading “SUMMIT (Non-AdvSM)”
Removed heading “Change in Fair Value of the CVR liability”
Largest changes
“Our research team is building a pipeline of small molecule inhibitors, with our first efforts aimed toward targeting currently undrugged mutations in fibroblast growth factor receptor (“FGFR”). FGFR mutations are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. …”see in full comparison
“We are also advancing a novel, ErbB2 mutant program, which is focused on actionable and underserved mutations in a variety of solid tumor systemic and CNS involved indications. HER2 alterations such as amplification, overexpression, insertions, and point mutations, are established oncogenic drivers in many solid tumors. Activating HER2 mutations are found in 2-4% of advanced lung cancers and have emerged as mechanisms of acquired resistance to targeted therapies. …”see in full comparison
“As of the data cutoff, August 29, 2024, the median duration of bezuclastinib treatment was 56 weeks for patients in the active arm and 40 weeks for placebo patients who crossed over to the OLE. The majority of treatment emergent adverse events were low grade and reversible with no treatment-related bleeding or cognitive impairment events reported. The most common treatment-emergent adverse events were hair color changes and transaminase elevations. …”see in full comparison
“Fibroblast growth factor receptor (“FGFR”) mutations are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. We are actively enrolling our Phase 1 study of CGT4859 in patients with tumors bearing FGFR2/3 mutations, including advanced cholangiocarcinoma. …”see in full comparison
Full comparison: every changed paragraph (108)
We are a clinical-stage biotechnology company focused on developing precision therapies for genetically defined diseases. Our approach is to design rational precision therapies that treat the underlying cause of disease and improve the lives of patients. Our most advanced program is bezuclastinib, also known as CGT9486, a highly selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. In the vast majority of cases, KIT D816V is responsible for driving Systemic Mastocytosis (“SM”), a serious and rare disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (“GIST”), a type of cancer with strong dependence on oncogenic KIT signaling. Bezuclastinib is a highly selective and potent KIT inhibitor with the potential to provide a new treatment option for these patient populations. We are developing bezuclastinib to treat patients living with Non-Advanced Systemic Mastocytosis (“Non-AdvSMNonAdvSM”), Advanced Systemic Mastocytosis (“AdvSM”) and GIST.GIST, Weand alsoin have2025 anwe ongoingreported Phasepositive 1top-line studyresults from registrational trials in each of ourthese novel internally developed FGFR2 inhibitor. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in ErbB2, PI3Kα and KRAS.indications.
We believe bezuclastinib represents a significant commercial opportunity across each of these indications. Based on internal analyses and external market research, we estimate a global annual market opportunity of over $4 billion for bezuclastinib in combination with sunitinib as a potential second-line treatment for patients with GIST, approximately $3.5 billion for the treatment of patients with NonAdvSM, and approximately $500 million for the treatment of patients with AdvSM. We are building an internal commercial organization and expect to launch bezuclastinib commercially in the United States in the second half of 2026, pending regulatory approval.
We also have an ongoing Phase 1 study of our novel internally developed FGFR2/3 inhibitor and have initiated a Phase 1 study of our CNS-penetrant, selective mutant ErbB2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in PI3Kα, KRAS and JAK2.
The following is an illustration of the status of our current clinical and preclinical programs:
Our Pipeline
SM is driven by KIT D816V mutations causing a perpetual ‘on’ state within mast cells, a type of white blood cell, leading to proliferation and accumulation in various internal organs and bone marrow. Key biomarkers of SM include but are not limited to, elevated serum tryptase, high mast cell burden in bone marrow and the KIT D816V variant allele frequency. As a highly selective and potent KIT inhibitor, bezuclastinib has the potential to provide a new treatment option for patients with SM. SM occurs when mast cells inappropriately accumulate in various internal organs in the body. Approximately 90% of SM patients present with NonAdvSM and 10% of patients present with AdvSM, a rare and very aggressive form of SM. There are three subtypes of AdvSM: aggressive SM (“ASM”), SM with associated hematologic neoplasm (“SM-AHN”) and mast cell leukemia (“MCL”).
The vast majority of AdvSM and Non-AdvSM patients have a KIT D816V mutation. Patients with AdvSM have a significantly diminished lifespan with a median survival of less than 3.5 years. For patients with Non-AdvSM, while their lifespan is not impacted by the disease, these patients suffer from a poor quality of life and new treatment options are badly needed. The FDA has granted orphan drug designation to bezuclastinib for the treatment of Mastocytosis.
We expect to report top-line results from our SUMMIT trial in July 2025 and from our APEX trial in the second half of 2025, and we plan to submit the first bezuclastinib New Drug Application (“NDA”) by the end of 2025 for patients with SM.
In the first quarter of 2025, we expect to initiate an expanded access program in the United States for SM patients to receive investigational bezuclastinib after meeting certain eligibility criteria.
SUMMIT (Non-AdvSM)
SUMMIT is our registration-directed randomized, global, multicenter, double-blind, placebo-controlled, multi-part Phase 2 clinical trial for patients with Non-AdvSM.NonAdvSM. The study is designed to explore the safety and efficacy of bezuclastinib in patients with moderate to severe Non-AdvSM,NonAdvSM, which includes Indolent Systemic Mastocytosis (“ISM”), Smoldering Systemic Mastocytosis (“SSM”) and Bone Marrow Mastocytosis. BasedAPEX onis our registration-directed global, open-label, multi-center, Phase 2 clinical trial in patients with AdvSM evaluating the performancesafety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib’sbezuclastinib. optimizedWe formulationreported top-line results from our SUMMIT trial in theJuly PEAK2025 lead-inand trial,full results in December 2025, as well as in a healthy normal volunteer study, the SUMMIT trial protocol was amended to allow for the optimized formulation to be introduced during the Phase 1b dose optimization phase. SUMMIT Part 1 completed enrollment in the third quarter of 2023, including over enrollment at 54 patients across Part 1a and Part 1b. SUMMIT Part 2 completed enrollment in the fourth quarter of 2024, including over enrollment at 179 patients. We expect to report top-line results from our APEX trial in JulyDecember 2025.2025, all of which were positive and achieved all primary and key secondary endpoints.
We submitted the first New Drug Application (“NDA”) for bezuclastinib in patients with NonAdvSM in December 2025 and expect to submit an NDA in the first half of 2026 for patients with AdvSM. In October 2025, the FDA granted Breakthrough Therapy Designation for bezuclastinib in NonAdvSM patients previously treated with avapritinib as well as in patients with SSM, both patient populations with no currently approved standard of care. The U.S. Food and Drug Administration (“FDA”) and European Medicines Agency (“EMA”) have granted orphan drug designation to bezuclastinib for the treatment of Mastocytosis.
In addition, in 2025, we initiated an expanded access program in the United States to allow eligible SM patients to receive investigational bezuclastinib prior to potential regulatory approval.
From the data collected in Part 1 of SUMMIT and in accordance with FDA guidelines, we have developed a novel patient reported outcomes measure (“PROM”) called Mastocytosis Symptom Severity Daily Diary (“MS2D2”). Based on literature review, patient and physician interviews, data from SUMMIT Part 1, and our interactions with the FDA, we believe our MS2D2 is a reliable, valid and fit-for-purpose PROM. The MS2D2 Total Symptom Score (“TSS”) is comprised of 11 items, and scored on a 0-110 scale. The primary endpoint of SUMMIT Part 2 is a comparison of week 24 mean absolute change from baseline in MS2D2 TSS between bezuclastinib and placebo. In June 2024, we announced a positive discussion with the FDA and that we reached alignment with the FDA on the use of MS2D2 in Part 2 of SUMMIT.
In February 2024, we presented data from SUMMIT Part 1b at the 2024 American Academy of Allergy, Asthma and Immunology. Thirty-four patients were enrolled in Part 1b and were treated with either bezuclastinib or placebo plus best supportive care. These patients were evaluated for signs of clinical activity over 12 weeks, including well-accepted biomarkers of disease burden. Based on the totality of the results from SUMMIT Part 1, the data support 100 mg QD as the optimal dose of bezuclastinib in Part 2 of SUMMIT for patients with Non-AdvSM. After the initial 12-week period, all patients were given the opportunity to receive bezuclastinib in the SUMMIT Open Label Extension (“OLE”). In December 2024 at the 2024 American Society of Hematology (“ASH”) Annual Meeting, we presented updated data on the 27 patients who were randomized in either Part 1 or the OLE to receive the 100 mg QD dose.
At the 100 mg QD dose and as of the cut-off date of August 29, 2024, 89% of patients had >50% decrease in serum tryptase by four weeks of treatment with bezuclastinib and 95% of patients with elevated baseline tryptase achieved serum tryptase levels <20 ng/ml by week 24. Additionally, 84% of patients with baseline serum tryptase >11.4ng/ml achieved <11.4ng/mL by week 24.
After 24 weeks of active treatment, the 27 patients randomized to receive 100 mg QD were evaluated for signs of clinical activity using multiple PRO measures, including the Mastocytosis Symptom Severity Daily Diary (“MS2D2”) and the Mastocytosis Quality-of-Life (“MC-QoL”) scale. These patients reported at 56% mean improvement in TSS from baseline. Additionally, 76% of patients demonstrated >50% reduction from baseline in MS2D2 TSS with 88% of patients exceeding 30% reduction from baseline after 24 weeks. At 24 weeks of treatment, 31% of patients have already reduced or discontinued best supportive care (“BSC”) medications. These same patients saw a 49% mean improvement in MC-QOL Total Score at 24 weeks.
As of the data cutoff, August 29, 2024, the median duration of bezuclastinib treatment was 56 weeks for patients in the active arm and 40 weeks for placebo patients who crossed over to the OLE. The majority of treatment emergent adverse events were low grade and reversible with no treatment-related bleeding or cognitive impairment events reported. The most common treatment-emergent adverse events were hair color changes and transaminase elevations. All patients experiencing elevated transaminases were asymptomatic and reversible: five patients resolved without any dose modifications and remained on study; two patients resolved with dose reduction and remained on study, one of whom re-escalated to the original dose; and two patients resolved following discontinuation. All of the safety data were previously reported at ASH 2024. There were no other discontinuations due to adverse events.
APEX (AdvSM)
APEX is our registration-directed global, open-label, multi-center, Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. In April 2023, we initiated Part 2 of the APEX trial using the optimized formulation of bezuclastinib at 150 mg daily dose. An additional APEX cohort was initiated in the third quarter of 2023 and is designed to allow concomitant administration of bezuclastinib with azacitadine in patients with SM-AHN. We completed enrollment in APEX Part 2 in the first quarter of 2025 with 58 patients and expect to present top-line results in the second half of 2025.
In December 2024, at the 2024 ASH meeting, we reported updated positive clinical data from Part 1 of the APEX trial. Thirty-two patients were treated in Part 1 at one of four dose levels (50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). In 2024, we announced APEX Part 2 would be conducted at the optimized 150mg QD dose, which closely matches the exposure from 100 mg BID dose in APEX Part 1. Patients were enrolled with the following sub-types: seven patients with aggressive systemic mastocytosis (“ASM”), 23 patients with systemic mastocytosis with associated hematologic neoplasm (“SM-AHN”), and two patients with mast cell leukemia (“MCL”).
As of the cutoff date of October 11, 2024, 32 patients enrolled were evaluated for signs of clinical activity, 27 of whom were mIWG-MRT-ECNM evaluable. An objective response rate (“ORR”) of 52% (including complete remission (“CR”), CR with partial hematologic remission (“CRh”), partial remission (“PR”), and clinical improvement (“CI”)) was achieved, including 61% ORR for TKI-treatment-naïve patients. An ORR of 88% was achieved by pure pathological response (“PPR”) criteria. The median time to achieve response was 2.2 months and median duration of response has not yet been reached. Median progression-free survival (“PFS”) was not yet reached at median follow-up of 20 months and the PFS rate at 24 months was 82%.
As of the cutoff date, 94% of patients achieved a ≥ 50% reduction in serum tryptase levels, with 100% of patients receiving at least two cycles of treatment achieving a ≥ 50% reduction and 66% of patients achieved a reduction of serum tryptase below 20 ng/ml. Additionally, 93% of KIT D9816V-positive patients achieved a ≥ 50% reduction in KIT D816V VAF and 100% of evaluable patients achieved ≥ 50% reduction in bone marrow mast cell burden, with 83% of patients achieving a complete clearance of mast cell aggregates.
As of the data cutoff date, bezuclastinib continues to demonstrate a differentiated safety and tolerability profile across doses. The majority of hematological adverse events were low grade and reversible. There have been no new treatment-related serious adverse events or discontinuations reported since ASH 2023. Twelve patients required dose reduction, eight of whom were treated at a 400 mg daily dose.
PEAK is our randomized open-label, global Phase 3 clinical trial designed to evaluate the safety, tolerability, and efficacy of bezuclastinib in combination with sunitinib compared to sunitinib alone in patients with locally advanced, unresectable or metastatic GIST who have received prior treatment with imatinib. We announced positive top-line results from PEAK in November 2025, which demonstrated a substantial and highly statistically significant clinical benefit on the primary endpoint of progression free survival (“PFS”). Median PFS was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy, and the bezuclastinib combination reduced the risk of disease progression or death by 50% compared to sunitinib monotherapy. In January 2026, we announced that the FDA agreed to accept our NDA for bezuclastinib in combination with sunitinib for patients with GIST who have received prior treatment with imatinib under the Real-Time Oncology Review (“RTOR”) program, and shortly thereafter we initiated our NDA submission to FDA under this program. We expect to complete the GIST NDA submission in April 2026. In January 2026, the FDA also granted Breakthrough Therapy Designation (“BTD”) for bezuclastinib in combination with sunitinib for patients with GIST who have received prior treatment with imatinib. Bezuclastinib has been granted orphan drug designation for the treatment of GIST by the FDA and under the Orphan Drug Act and the European Medicines Agency (“EMA”).
In mid-2026, we expect to initiate a Phase 2 trial investigating the benefit of the bezuclastinib plus sunitinib combination for first-line GIST patients with exon 9 mutations who are naive to, or recently initiated treatment with, imatinib.
PEAK (GIST)
PEAK is our randomized open-label, global Phase 3 clinical trial designed to evaluate the safety, tolerability, and efficacy of bezuclastinib in combination with sunitinib compared to sunitinib alone in patients with locally advanced, unresectable or metastatic GIST who have received prior treatment with imatinib. The FDA and EMA have granted orphan drug designation to bezuclastinib for the treatment of GIST. Patient enrollment for the pivotal portion of the PEAK trial was completed in the third quarter of 2024. Based on strong global patient interest, a total of 413 patients were enrolled in the trial. In addition, we completed a pre-planned interim futility analysis, and the Independent Data Monitoring Committee (“IDMC”) recommended continuing the PEAK study without modification. This pre-specified analysis was based on an assessment of PFS as determined by independent central review and did not include the option for early stopping due to efficacy. Top-line results are expected by the end of 2025.
In June 2024, we presented updated positive clinical data from the lead-in portion of the PEAK trial at the 2024 American Society of Clinical Oncology meeting. As of the cutoff date, April 1, 2024, the 42 patients in Part 1 have been on study for a median of 15.3 months. The median progression-free survival (“mPFS”) on the combination of bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of second-line GIST patients with only prior imatinib, a population that most closely resembles patients currently enrolling in the Phase 3 pivotal PEAK study, the data demonstrate a mPFS of 19.4 months. In addition, the ORR in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in second-line patients with prior imatinib only. As of the data cutoff, the combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated. The majority of treatment-emergent adverse events (“TEAEs”) were low-grade and reversible and discontinuations due to TEAEs remain limited.
In May 2024, we also announced the initiation of a new advanced Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients that is being sponsored by the Sarcoma Alliance for Research through Collaboration and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute. The open label, single arm Phase 2 trial is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib. This trial is focused on later line patients that are not eligible for PEAK and have limited treatment options.
In in the first quarter of 2025, we initiated an expanded access program in the United States for patients affected with advanced, metastatic, and/or unresectable GIST, intolerant to imatinib or received prior imatinib therapy for treatment that resulted in disease progression, and who meet other inclusion and exclusion criteria.
Other Bezuclastinib Information
Worldwide rights to develop and commercialize bezuclastinib are exclusively licensed from Plexxikon Inc., a member of the Daiichi Sankyo Group (“Plexxikon”). Under the terms of the license agreement, Plexxikon received an upfront payment and is eligible for additional development milestones of up to $7.5 million upon the satisfaction of certain clinical milestones and up to $25.0 million upon the satisfaction of certain regulatory milestones. During the second quarter of 2022, as a result of the progression of the PEAK study, the first clinical milestone was achieved, resulting in payment of $2.5 million to Plexxikon in June 2022. AsIn the fourth quarter of December2025, 31,$5.0 2024,million nobecame otherpayable milestoneon payments have been made. Patents protecting bezuclastinib include compositionachievement of matterregulatory claimsmilestones whichand haveanother been$15.0 issuedmillion may become payable in the USnext andtwelve othermonths key territories and provide exclusivity through 2033 and potentially beyond through patent term extensions. In addition, we filedas a patent application in 2023 seeking to protect our optimized formulationresult of bezuclastinib that is currently being used in all threeachievement of ouradditional ongoingregulatory clinical trials, which could potentially provide exclusivity through at least 2043.milestones.
Patents protecting bezuclastinib include composition of matter claims which have been issued in the United States and other key territories and provide exclusivity through 2033 and potentially beyond through patent term extensions. In addition, we have pending patent applications in the United States and other key territories that seeks to protect our optimized formulation of bezuclastinib, which could potentially provide exclusivity through at least 2043, as well as a pending U.S. provisional patent application directed to methods of administering bezuclastinib, which could potentially provide exclusivity through at least 2046.
CGT4859 (FGFR2/3)
Fibroblast growth factor receptor (“FGFR”) mutations are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. We are actively enrolling our Phase 1 study of CGT4859 in patients with tumors bearing FGFR2/3 mutations, including advanced cholangiocarcinoma. The trial will explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well tolerated dose for further clinical investigation. We expect to share clinical data from our Phase 1 study in 2026.
CGT4255 (ErbB2)
We are also advancing a novel, ErbB2 mutant program, which is focused on actionable and underserved mutations in a variety of solid tumor systemic and CNS involved indications. HER2 alterations such as amplification, overexpression, insertions, and point mutations, are established oncogenic drivers in many solid tumors. Activating HER2 mutations are found in 2-4% of advanced lung cancers and have emerged as mechanisms of acquired resistance to targeted therapies. Patients with HER2 mutant lung tumors develop more brain metastasis during treatment than patients with any other oncogenic drivers in lung cancer. Addressing brain metastasis in this group of patients remains a clinical challenge with limited therapeutic options. Approved HER2 tyrosine kinase inhibitors have inferior potency against key mutations and lack sufficient brain penetration to be an impactful treatment option for patients with brain metastasis. We received clearance from the FDA on our investigational new drug application (“IND”) submission for CGT4255 and initiated a Phase 1 dose escalation study in the fourth quarter of 2025.
CGT6297 (PI3Kα)
Our research team is developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage of both the H1047R mutation as well as E542K and E545K helical mutants, which affects >30,000 cancer patients each year. The phosphoinositide 3-kinase (“PI3K”) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. PI3Kα mutations are highly prevalent in many solid tumors and are present in 36% of all breast cancer patients. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα. IND-enabling studies have been completed for CGT6297 and we submitted an IND application for this program in the fourth quarter of 2025. We expect to initiate a Phase 1 dose escalation in the first quarter of 2026.
Our research team is building a pipeline of small molecule inhibitors, with our first efforts aimed toward targeting currently undrugged mutations in fibroblast growth factor receptor (“FGFR”). FGFR mutations are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. In April 2023, we reported preclinical data at the American Association for Cancer Research (“AACR”) 2023 Annual Meeting providing the first published evidence of CGT4859 a reversible, selective FGFR2 inhibitor with coverage of activating and emerging resistance mutations that spares inhibition of FGFR1. Preclinical data demonstrate a profile that delivers equipotent coverage across both key gatekeeper and molecular brake mutations (V564X, N549X) in FGFR2, while avoiding any evidence of FGFR1-linked hyperphosphatemia at efficacious plasma concentrations. In October 2023, we presented updated preclinical data at the 2023 EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics (“EORTC-NCI-AACR”). Preclinical data demonstrate a profile that exhibits low namomolar potency on WT FGFR2 and FGFR2 mutations and is selective against the kinome, as well as a panel of ion channels and receptors. Exploratory pharmacokinetics studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in a mutant-driven mouse model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at 5 mg/kg PO and was well-tolerated. In addition, as a reversible inhibitor, the Cogent program retains enzymatic potency against potential cysteine 491 mutations. We are actively enrolling our Phase 1 study of CGT4859 in patients with FGFR2 mutations, including advanced cholangiocarcinoma. The trial will explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well tolerated dose for further clinical investigation.
The Cogent Research Team, based in Boulder, Colorado, is focused on pioneering best-in-class, small molecule therapeutics to expand our pipeline and deliver novel precision therapies for patients living with unmet medical needs. For ErbB2, PI3K and KRAS we see opportunities to provide a more robust molecular response compared to existing therapies.
ErbB2
Our research team is also advancing a novel, ErbB2 mutant program, which is focused on actionable and underserved mutations in a variety of solid tumor indications. In April 2023, we reported preclinical data at AACR describing a series of novel compounds which potently inhibit several key ErbB2 mutations, including YVMA insertions, while sparing inhibition of EGFR. An exemplar compound from these series demonstrates advantages versus tucatinib, an approved benchmark compound, on tumor growth inhibition in a peripheral ErbB2 L755S driven mutant model, as well as in an ErbB2 driven intracranial model. Recent program advances with a novel chemotype have further improved ErbB2 mutational potency and selectivity and improved human whole blood stability to nearly 24 hours, suggesting a favorable profile for optimal clinical efficacy. Updated data was presented in December 2024 at the San Antonio Breast Cancer Symposium (“SABCS”). The updated data presented shows that CGT4255 demonstrated low nM potency against ErbB2 wild-type and oncogenic ErbB2 mutations with greater than 100-fold selectivity over wild-type-EGFR. In addition to impressive selectivity across a broad range of kinases, receptors and ion channels, CGT4255 has exceptional half-life in human whole blood and liver cytosol fractions. Dose ascending PK data in mice showed low clearance and high oral bioavailability at all doses, with best-in-class 80% brain penetrance at 100 mg/kg. Maximum inhibition of ErbB2 was observed at a 30 mg/kg PO dose in both NIH/3T3 ErbB2-YVMA and ErbB2-L755S tumor models, with complete regressions at 100 mg/kg PO BID in the NIH3T3 ErbB2-L755S TGI model and was well tolerated. In addition, at the 2024 SABCS meeting, CGT4255 demonstrated robust efficacy in combination with T-DXd in an NCI-N87-luc Intracranial Her2+ Model, highlighting the ability to treat challenging intercranial tumors. These advances continue to highlight a favorable profile for optimal clinical efficacy. We selected our ErbB2 clinical candidate in 2024 and plan to submit an IND application in 2025.
PI3Kα
Our research team is also developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the H1047R mutation, which affects >30,000 cancer patients each year. The phosphoinositide 3-kinase (“PI3K”) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. PI3Kα mutations are highly prevalent in many solid tumors and are present in 36% of all breast cancer patients. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα. Preclinical data was presented at the 2024 EORTC-NCI-AACR meeting in October 2024 as well as the December 2024 SABCS, which highlighted that CGT6297 is an allosteric inhibitor of PI3K, was well-tolerated in the tumor growth inhibition efficacy models and has been profiled based on its selectivity for H1047R over WT PI3K. CGT6297 demonstrated low nM potency in H1047R mutant PI3K cell lines, differentiated dose ascending PK in mice with high bioavailability and low clearance. CGT6297 also showed >95% inhibition of pAKT in a H1047R PD model, without increases in insulin or C-peptide. Its efficacy profile was superior to a clinically-relevant dose of Alpelisib in the NCI H1048 mouse tumor growth inhibition model. CGT6297 has been selected as our clinical candidate for the PI3K 1047 mutation focused project. IND-enabling studies have been initiated and we expect to submit an IND application in 2025.
Our research team is also developing a potent and selective KRAS inhibitor. Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. PreclinicalWe dataplan wassubmit presentedan atIND thefor 2024this EORTC-NCI-AACR meeting and highlighted our internally-developed pan KRAS(ON) inhibitor with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations without the potential liabilities of moleculesprogram in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. Lead optimization of CGT6737 is ongoing.2026.
JAK2
Our research team is developing a novel, wild-type-sparing, JAK2 V617F mutant-selective inhibitor. The JAK2 V617F mutation is the most prevalent molecular abnormality in BCR-ABL-negative myeloproliferative neoplasms, occurring in approximately 95% of patients with polycythemia vera, and 50% of patients with essential thrombocythemia or primary myelofibrosis. We plan to submit an IND for this program in 2026.
Since our inception in 2014, we have focused significant efforts and financial resources on establishing and protecting our intellectual property portfolio, conducting research and development of our product candidates, manufacturing drug product material for use in preclinical studies and clinical trials, staffing our company, and raising capital. We do not have any products approved for sale and have not generated any revenue from product sales. Our abilitynet toloss generatewas product$328.9 revenuemillion sufficient to achieve profitability will depend heavily onfor the successfulyear developmentended andDecember eventual31, commercialization2025 ofcompared one or more of our product candidates. Ourto net loss wasof $255.9 million for the year ended December 31, 2024 compared to net loss of $192.4 million for the year ended December 31, 2023.2024. As of December 31, 2024,2025, we had an accumulated deficit of $859.5$1,188.4 million. We expect to continue to incur significant expenses and operating losses for at least the next several years. We expect that our expenses and capital requirements will increase substantially in connection with our ongoing activities, particularly if and as we:
establish a sales, marketing, and distribution infrastructure to commercialize any products for which we may obtain regulatory approval;
add operational, financial, and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts.
acquire or in-license other product candidates and technologies;
acquire or in-license other product candidates and technologies; and hire additional research, clinical, scientific, and commercial personnel;personnel.
establish a sales, marketing, and distribution infrastructure to commercialize any products for which we may obtain regulatory approval; and add operational, financial, and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts.
We will not generate revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for our product candidates. If we obtain regulatory approval for any of our product candidates and do not enter into a commercialization partnership, we expect to incur significant expenses related to developing our internal commercialization capability to support product sales, marketing, and distribution.
As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances, and marketing, distribution, or licensing arrangements. We may be unable to raise additional funds or enter into such other agreements or arrangements when needed on favorable terms, or at all. If we fail to raise capital or enter into such agreements as, and when, needed, we may have to significantly delay, scale back, or discontinue the development and commercialization of one or more of our product candidates.
As of December 31, 2024,2025, we had cash, cash equivalents and marketable securities of $287.1$900.8 million. BasedWe on our current plans, we expectbelieve that our current cash, cash equivalents and marketable securities will be sufficient to fund our operating expenses and capital expenditure requirements into 2028, including through clinicalpotential readoutsFDA fromapproval ongoingof SUMMIT, PEAK,bezuclastinib and APEXcommercial registration-directedlaunch trialsfor SM and into late 2026.GIST.
expenses incurred in connection with the discovery, preclinical and clinical development of our product candidates, including under agreements with third parties, such as consultants, contractorscontractors, and contract research organizations (“CROs”);
the cost of developing and manufacturing drug productsmaterial for use in our preclinical studies and clinical trials, including under agreements with consultants and third parties, such as consultants,party contractors and contract manufacturing organizations (“CMOs”);
What changed in the latest 10-Q
Risk Factors
There have been no material changes from our risk factors described in our Annual Report on Form 10-K for the year ended December 31, 2025, as filed with the SEC on February 17, 2026. The risks described in our Form 10-K are not the only risks facing our Company. Additional risk and uncertainties not currently known to us or that we currently deem to be immaterial also may materially adversely affect our business, financial condition and/or operating results.
No wording changes found in this section.
Full comparison: every changed paragraph (0)
Management's Discussion & Analysis (MD&A)
New heading “Comparison of the Six Months Ended June 30, 2026 and 2025”
New heading “Research and Development Expenses”
New heading “General and Administrative Expenses”
New heading “Interest Income”
New heading “Interest Expense”
New heading “Other Income (Expense), Net”
Largest changes
Full comparison: every changed paragraph (46)
We are a clinical-stage biotechnology company focused on developing precision therapies for genetically defined diseases. Our approach is to design rational precision therapies that treat the underlying cause of disease and improve the lives of patients. Our most advanced program is bezuclastinib, also known as CGT9486, a highly selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. In the vast majority of cases, KIT D816V is responsible for driving Systemic Mastocytosis (“SM”), a serious and rare disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (“GIST”), a type of cancer with strong dependence on oncogenic KIT signaling. Bezuclastinib is a highly selective and potent KIT inhibitor with the potential to provide a new treatment option for these patient populations. We are developing bezuclastinib to treat patients living with Non-Advanced Systemic Mastocytosis (“NonAdvSM”), Advanced Systemic Mastocytosis (“AdvSM”) and GIST,GIST. and inIn 2025 we reported positive top-line results from registrational trials in each of these indications.indications, and we subsequently filed three New Drug Applications (each, an “NDA”) that are all currently pending review with the U.S. Food and Drug Administration (“FDA”).
In addition to bezuclastinib, we have a growing portfolio of novel targeted therapy candidates. We initiatedhave aan ongoing Phase 1 dose escalation study of our CNS-penetrant, selective mutant ErbB2 inhibitor in the fourth quarter of 2025, and we initiated a Phase 1 dose escalation study of our potential best-in-class, wild-type-sparing, PI3Kα inhibitor in the first quarter of 2026.inhibitor. The Cogent Research Team is also developing additional targeted therapies to help patients fighting serious, genetically driven diseases, including programs targeting mutations in KRAS and JAK2.
SUMMIT is our registration-directed randomized, global, multicenter, double-blind, placebo-controlled, multi-part Phase 2 clinical trial for patients with NonAdvSM. The study is designed to explore the safety and efficacy of bezuclastinib in patients with moderate to severe NonAdvSM, which includes Indolent Systemic Mastocytosis (“ISM”), Smoldering Systemic Mastocytosis (“SSM”) and Bone Marrow Mastocytosis. APEX is our registration-directed global, open-label, multi-center, Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. We reported top-line results from our SUMMIT trial in July 2025 and full results in December 2025, as well as top-line results from our APEX trial in December 2025,2025 and full results in June 2026, all of which were positive and achieved all primary and key secondary endpoints.
We submitted the first New Drug Application (“NDA”) for bezuclastinib in patients with NonAdvSM in December 2025, which was accepted by the U.S. Food and Drug Administration ("FDA") in March 2026. The FDA assigned a Prescription Drug User Fee Act ("PDUFA") target action date of December 30, 2026. We expect to submitsubmitted an NDA in the first half ofJune 2026 for patients with AdvSM. In October 2025, the FDA granted Breakthrough Therapy Designation for bezuclastinib in NonAdvSM patients previously treated with avapritinib as well as in patients with SSM, both patient populations with no currently approved standard of care. The FDA and European Medicines Agency (“EMA”) have granted orphan drug designation to bezuclastinib for the treatment of Mastocytosis.
PEAK is our randomized open-label, global Phase 3 clinical trial designed to evaluate the safety, tolerability, and efficacy of bezuclastinib in combination with sunitinib compared to sunitinib alone in patients with locally advanced, unresectable or metastatic GIST who have received prior treatment with imatinib. We announced positivereported top-line results from our PEAK trial in November 2025,2025 and full results in May 2026, which demonstrated a substantial and highly statistically significant clinical benefit on the primary endpoint of progression free survival (“PFS”). Median PFS was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy, and the bezuclastinib combination reduced the risk of disease progression or death by 50% compared to sunitinib monotherapy. In January 2026, we announced that the FDA agreed to accept our NDA for bezuclastinib in combination with sunitinib for patients with GIST who have received prior treatment with imatinib under the Real-Time Oncology Review (“RTOR”) program and we submitted our GIST NDA in March 2026 under this program.program, which was accepted by the FDA with Priority Review in May 2026. The FDA assigned a PDUFA target action date of November 30, 2026. In January 2026, the FDA also granted Breakthrough Therapy Designation (“BTD”) for bezuclastinib in combination with sunitinib for patients with GIST who have received prior treatment with imatinib. Bezuclastinib has been granted orphan drug designation for the treatment of GIST by the FDA and under the Orphan Drug Act and by the EMA. We plan to present detailed clinical data from PEAK at the 2026 American Society of Clinical Oncology meeting in May 2026.
InDuring mid-2026,the second quarter of 2026, we expect to initiateinitiated a Phase 2 trial investigating the benefit of the bezuclastinib plus sunitinib combination for first-line GIST patients with exon 9 mutations who are naive to, or recently initiated treatment with, imatinib.
Worldwide rights to develop and commercialize bezuclastinib are exclusively licensed from Plexxikon Inc., a member of the Daiichi Sankyo Group (“Plexxikon”). Under the terms of the license agreement, Plexxikon received an upfront payment and is eligible for additional development milestones of up to $7.5 million upon the satisfaction of certain clinical milestones and up to $25.0 million upon the satisfaction of certain regulatory milestones. During the second quarter of 2022, as a result of the progression of the PEAK study, the first clinical milestone was achieved, resulting in payment of $2.5 million to Plexxikon in June 2022. In the fourth quarter of 2025, $5.0 million became payable upon the achievement of certain regulatory milestones and was paid in the first quarter of 2026. An additional $15.0 million may become payable in the next twelve months as a result of the achievement of additional regulatory milestones. Plexxikon is also eligible to receive tiered royalties ranging from a low-single digit percentage to a high-single digit percentage on annual net sales of products, on a product-by-product and country-by-country basis until the later of the expiration of the last valid claim of a licensed Plexxikon patent covering the applicable product in a country or the tenth anniversary of the first commercial sale of the product in that country.
Patents protecting bezuclastinib include composition of matter claims which have been issued in the United States and other key territories and provide exclusivity through 2033 and potentially beyond through patent term extensions. In addition, we have pending patent applications in the United States and other key territories that seeksseek to protect our optimized formulation of bezuclastinib, which could potentially provide exclusivity through at least 2043, as well as a pending U.S. provisional patent application directed to methods of administering bezuclastinib, which could potentially provide exclusivity through at least 2046.
We are also advancing a novel, ErbB2 mutant program, which is focused on actionable and underserved mutations in a variety of solid tumor systemic and CNS involved indications. HER2 alterations such as amplification, overexpression, insertions, and point mutations, are established oncogenic drivers in many solid tumors. Activating HER2 mutations are found in 2-4% of advanced lung cancers and have emerged as mechanisms of acquired resistance to targeted therapies. Patients with HER2 mutant lung tumors develop more brain metastasis during treatment than patients with any other oncogenic drivers in lung cancer. Addressing brain metastasis in this group of patients remains a clinical challenge with limited therapeutic options. Approved HER2 tyrosine kinase inhibitors have inferior potency against key mutations and lack sufficient brain penetration to be an impactful treatment option for patients with brain metastasis. We received clearance from the FDA on our investigational new drug application (“IND”) submission for CGT4255 and initiatedhave aan ongoing Phase 1 dose escalation study in the fourth quarter of 2025.study.
Our research team is developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage of both the H1047R mutation as well as E542K and E545K helical mutants, which affects >30,000 cancer patients each year. The phosphoinositide 3-kinase (“PI3K”) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. PI3Kα mutations are highly prevalent in many solid tumors and are present in 36% of all breast cancer patients. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα. IND-enabling studies have been completed for CGT6297 and we submitted an IND application for this program in the fourth quarter of 2025. We initiatedhave aan ongoing Phase 1 dose escalation study in the first quarter of 2026.study.
Our research team is developing a potent and selective KRAS inhibitor. Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. We plan to submit an IND for this program in 2026.
Since our inception in 2014, we have focused significant efforts and financial resources on establishing and protecting our intellectual property portfolio, conducting research and development of our product candidates, manufacturing drug product material for use in preclinical studies and clinical trials, staffing our company, and raising capital. We do not have any products approved for sale and have not generated any revenue from product sales. Our net loss was $97.4$193.8 million for the threesix months ended MarchJune 31,30, 2026 compared to net loss of $72.0$145.5 million for the threesix months ended MarchJune 31,30, 2025. As of MarchJune 31,30, 2026, we had an accumulated deficit of $1,285.8$1,382.2 million. We expect to continue to incur significant expenses and operating losses for at least the next several years. We expect that our expenses and capital requirements will increase substantially in connection with our ongoing activities, particularly if and as we:
As of MarchJune 31,30, 2026, we had cash, cash equivalents and marketable securities of $866.4$792.3 million. We believe that our cash, cash equivalents and marketable securitiessecurities, with the $71.4 million net proceeds from shares sold under our ATM after the end of the quarter, will be sufficient to fund our operating expenses and capital expenditure requirements into late 2028, including through potential FDA approval of bezuclastinib and commercial launch for SM and GIST.
Interest expense consists of interest incurred on the Notes and the Credit Facility (as defined below) and associated amortization of issuance costs and the accretion of debt discount.
Comparison of the Three Months Ended MarchJune 31,30, 2026 and 2025
The following table summarizes our results of operations for the three months ended MarchJune 31,30, 2026 and 2025:
The following table summarizes our research and development expenses for the three months ended MarchJune 31,30, 2026 and 2025:
Total research and development expense increased by $12.3$8.6 million for the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025,2025. The increase was primarily driven by increasedcosts early-stage,to preclinicalsupport the SUMMIT, PEAK and discovery programs as we advance our pipeline of programs into Phase 1APEX clinical trialsprograms, andregulatory IND-enabling studies, and includes one-time costsactivities associated with thepotential wind downapprovals of bezuclastinib, continued investment in the FGFRcompany's 2/3early-stage clinicalresearch program.pipeline, and pre-approval manufacturing costs that would otherwise be capitalized following anticipated FDA approval. The increase ischange also driven by higher personnel costs resulting fromincludes an increase in headcount and includes stock-based compensation expense,expense whichof increased by $3.7$3.6 million for the three months ended MarchJune 31,30, 2026 as compared to the three months ended MarchJune 31,30, 2025.
General and administrative expenses for the three months ended MarchJune 31,30, 2026 were $28.2$31.8 million, compared to $11.9$13.4 million for the three months ended MarchJune 31,30, 2025. The increase in general and administrative expenses was primarilydriven dueby tocontinued higherinvestments in commercial readiness, including personnel and relatedinfrastructure coststo associated withsupport the build-outpotential launch of ourbezuclastinib, commercialas organizationwell andas otheroverall supportingorganizational functions in preparation for our planned commercial launch..growth.
Interest income for the three months ended MarchJune 31,30, 2026 was $7.6$7.5 million, compared to $3.0$2.4 million for the three months ended MarchJune 31,30, 2025. The increase is due to higher invested balances in cash equivalents and marketable securities.
Interest expense for the three months ended MarchJune 31,30, 2026 was $1.2 million related to the Notes and associated amortization of financing costs and the accretion of debt discount. Interest expense for the three months ended MarchJune 31,30, 2025 was nil.$0.3 million related to the Credit Facility and associated amortization of financing costs and the accretion of debt discount.
Other income (expense), net for the three months ended MarchJune 31,30, 2026 and 2025 was not material and represented miscellaneous expense.
Comparison of the Six Months Ended June 30, 2026 and 2025
The following table summarizes our results of operations for the six months ended June 30, 2026 and 2025:
Research and Development Expenses
The following table summarizes our research and development expenses for the six months ended June 30, 2026 and 2025:
Total research and development expense increased by $20.9 million for the six months ended June 30, 2026 compared to the six months ended June 30, 2025. The increase was primarily driven by costs to support the SUMMIT, PEAK and APEX clinical programs, regulatory activities associated with potential approvals of bezuclastinib, continued investment in the company's early-stage research pipeline, and pre-approval manufacturing costs that would otherwise be capitalized following anticipated FDA approval. The change also includes an increase in stock-based compensation expense of $7.3 million for the six months ended June 30, 2026 as compared to the six months ended June 30, 2025.
General and Administrative Expenses
General and administrative expenses for the six months ended June 30, 2026 were $60.1 million, compared to $25.3 million for the six months ended June 30, 2025. The increase in general and administrative expenses was driven by continued investments in commercial readiness, including personnel and infrastructure to support the potential launch of bezuclastinib, as well as overall organizational growth.
Interest Income
Interest income for the six months ended June 30, 2026 was $15.1 million, compared to $5.3 million for the six months ended June 30, 2025. The increase is due to higher invested balances in cash equivalents and marketable securities.
Interest Expense
Interest expense for the six months ended June 30, 2026 was $2.4 million related to the Notes and associated amortization of issuance costs and the accretion of debt discount. Interest expense for the six months ended June 30, 2025 was $0.3 million related to the Credit Facility and associated amortization of financing costs and the accretion of debt discount.
Other Income (Expense), Net
Other income (expense), net for the six months ended June 30, 2026 and 2025 was not material and represented miscellaneous expense.
On May 6, 2022, we entered into a Sales Agreement (the “Sales Agreement”) with Guggenheim Securities, LLC (“Guggenheim Securities”), pursuant to which we may issue and sell, from time to time, shares of our common stock having an aggregate offering price of up to $75.0 million through Guggenheim Securities, as the sales agent, in an at the market offering (“ATM”) registered under a shelf registration statement on Form S-3. On November 7, 2025, we amended the Sales Agreement to increase the aggregate offering price to up to $300.0 million. DuringNo shares were sold under the Sales Agreement during the three months ended MarchJune 31,30, 2026. During the six months ended June 30, 2026, 1,340,699 shares were sold under the Sales Agreement for net proceeds of approximately $45.7 million. As of MarchJune 31,30, 2026, $88.6 million remained unsold and available for sale under the Sales Agreement. Subsequent to June 30, 2026, 1,743,528 shares of common stock were sold under the Sales Agreement for net proceeds of approximately $71.4 million.
As of MarchJune 31,30, 2026, we have 185,143,303185,967,909 shares outstanding on an as-converted basis, which consists of (i) 170,773,803171,598,409 shares of common stock outstanding, (ii) 39,414 shares of Series A Non-Voting Convertible Preferred Stock that are convertible into 9,853,500 shares of common stock and (iii) 4,516 shares of Series B Non-Voting Convertible Preferred Stock that are convertible into 4,516,000 shares of common stock.
As of MarchJune 31,30, 2026, we had cash, cash equivalents and marketable securities of $866.4$792.3 million. We believe that our cash, cash equivalents and marketable securitiessecurities, with the $71.4 million net proceeds from shares sold under our ATM after the end of the quarter, will be sufficient to fund our operating expenses and capital expenditure requirements into late 2028, including through potential FDA approval of bezuclastinib and commercial launch for SM and GIST.
Net cash used in operating activities was $86.9$164.2 million during the threesix months ended MarchJune 31,30, 2026 and primarily consisted of a net loss of $97.4$193.8 million, adjusted for changes in our net working capital and other non-cash items, including stock-based compensation of $16.9$34.0 million.
Net cash used in operating activities was $66.5$121.1 million during the threesix months ended MarchJune 31,30, 2025 and primarily consistedresulted offrom aour net loss of $72.0$145.5 million, adjusted for changes in our net working capital and other non-cash items, including stock-based compensation of $10.0$19.7 million.
During the threesix months ended MarchJune 31,30, 2026, net cash used in investing activities was $36.5$22.2 million, which consisted of purchases of marketable securities and property and equipment, partially offset by maturities and sales of marketable securities.
During the threesix months ended MarchJune 31,30, 2025, net cash provided by investing activities was $69.4$78.3 million,million which consisted of maturities and sales of marketable securities, partially offset by purchases of property and equipment.equipment and marketable securities.
During the threesix months ended MarchJune 31,30, 2026, net cash provided by financing activities was $52.5$55.5 million, which consisted of $45.7 million in proceeds from the issuance of common stock under the ATM, net of paid issuance costs, proceeds from the issuance of common stock upon stock option exercises, and proceeds from the issuance of common stock under the Employee Stock Purchase Plan.
During the threesix months ended MarchJune 31,30, 2025, net cash provided by financing activities was $25.0$72.2 million, which consisted of $47.2 million in proceeds from the Credit Facility, net of paid issuance costs, $24.3 million in proceeds from the issuance of common stock under the ATM, net of paid offeringissuance costs, proceeds from the issuance of common stock under the 2018 Employee Stock Purchase Plan and proceeds from the issuance of common stock upon stock option exercises.
As of MarchJune 31,30, 2026, we had cash, cash equivalents and marketable securities of $866.4$792.3 million. We believe that our cash, cash equivalents and marketable securitiessecurities, with the $71.4 million net proceeds from shares sold under our ATM after the end of the quarter, will be sufficient to fund our operating expenses and capital expenditure requirements into late 2028, including through potential FDA approval of bezuclastinib and commercial launch for SM and GIST. 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.
There have been no material changes in our critical accounting policies during the threesix months ended MarchJune 31,30, 2026, as compared to those described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Significant Judgments and Estimates” in our Annual Report on Form 10-K.
COGT insider buying and selling (Form 4)
Since 2026-04-11, insiders reported open-market purchases in 0 Form 4 filings and open-market sales in 1 filing (1 insider, 1 trade date, 45,510 shares, about $1.7M; 1 of these filings say the sales were made under a Rule 10b5-1 trading plan). Net open-market shares: -45,510 (purchases minus sales); net value about -$1.7M.Totals add up every open-market (code P and S) line in those filings, using the prices reported in the filings. Awards, option exercises, tax withholding and gifts are listed below but not counted.
| Trade date | Insider | Transaction | Shares | Price | Value |
|---|---|---|---|---|---|
| 2026-08-27 | Morris Arlene |
Option exercise |
41,927 | $5.64 | $236.5K |
| 2026-08-27 | Morris Arlene |
Open-market sale |
3,161 | $37.54 | $118.7K |
| 2026-08-27 | Morris Arlene |
Open-market sale |
42,349 | $37.09 | $1.6M |
| 2026-08-27 | Morris Arlene |
Option exercise |
3,583 | $2.52 | $9.0K |
| 2026-05-19 | Robbins Andrew R |
Gift | 160,000 | — | — |
| 2026-05-19 | Robbins Andrew R |
Gift | 160,000 | — | — |
Well-known investors holding COGT (13F)
| Investor | Quarter | Shares | Reported value | % of their 13F | Change vs prior quarter |
|---|---|---|---|---|---|
| Renaissance Technologies | 2026-06-30 | 996,168 | $38.6M | 0.05% | Added 41% |
| D. E. Shaw & Co. | 2026-06-30 | 922,479 | $35.7M | 0.02% | Reduced 51% |
| Millennium Management (Israel Englander) | 2026-06-30 | 907,712 | $35.1M | 0.02% | Reduced 24% |
| Citadel Advisors (Ken Griffin) | 2026-06-30 | 849,694 | $32.9M | 0.02% | Reduced 50% |
| Point72 Asset Management (Steve Cohen) | 2026-06-30 | 744,195 | $28.8M | 0.04% | Reduced 47% |
| Oaktree Capital Management (Howard Marks) | 2026-06-30 | 0 | $14.8M | 0.28% | No change |
| AQR Capital Management (Cliff Asness) | 2026-06-30 | 294,913 | $11.4M | 0.0% | Added 55% |
| Millennium Management (Israel Englander) | 2026-06-30 | 0 | $2.4M | 0.0% | No change |
| Two Sigma Investments | 2026-06-30 | 37,637 | $1.5M | 0.0% | Reduced 29% |