Cogent Biosciences, Inc.

Previous wording

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-AdvSM”), Advanced Systemic Mastocytosis (“AdvSM”) and GIST. We also have an ongoing Phase 1 study of our novel internally developed FGFR2/3 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.

Current wording

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-AdvSM”), Advanced Systemic Mastocytosis (“AdvSM”) and GIST. We also have an ongoing Phase 1 study of our novel internally developed FGFR2/3 inhibitor. In addition, 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, KRAS and JAK2.

Previous wording

SUMMIT is our registration-directed randomized, global, multicenter, double-blind, placebo-controlled, multi-part Phase 2 clinical trial for patients with Non-AdvSM. The study is designed to explore the safety and efficacy of bezuclastinib in patients with moderate to severe Non-AdvSM, which includes Indolent Systemic Mastocytosis, Smoldering Systemic Mastocytosis and Bone Marrow Mastocytosis. 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, the potentially registrational portion of the study, completed enrollment in the fourth quarter of 2024, including over enrollment at 179 patients.

Current wording

SUMMIT is our registration-directed randomized, global, multicenter, double-blind, placebo-controlled, multi-part Phase 2 clinical trial for patients with Non-AdvSM. The study is designed to explore the safety and efficacy of bezuclastinib in patients with moderate to severe Non-AdvSM, which includes Indolent Systemic Mastocytosis, Smoldering Systemic Mastocytosis (“SSM”) and Bone Marrow Mastocytosis. 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, the potentially registrational portion of the study, completed enrollment in the fourth quarter of 2024, including over enrollment at 179 patients.

Previous wording

In July 2025, we announced positive top-line results from SUMMIT Part 2 demonstrating clinically meaningful and highly statistically significant improvements across the primary and all key secondary endpoints, including patient-reported symptoms and objective measures of disease burden. Based on these data, we plan to submit our first NDA to the FDA for bezuclastinib in NonAdvSM by the end of 2025. In addition, we plan to present detailed results from the SUMMIT trial at an upcoming medical meeting later this year.

Current wording

In July 2025, we announced positive top-line results from SUMMIT Part 2 demonstrating clinically meaningful and highly statistically significant improvements across the primary and all key secondary endpoints, including patient-reported symptoms and objective measures of disease burden. We plan to present more detailed results from the SUMMIT trial in two oral presentations at the 2025 ASH meeting in December 2025. In October 2025, the FDA granted Breakthrough Therapy Designation for bezuclastinib in Non-AdvSM patients previously treated with avapritinib as well as in patients with SSM, both patient populations with no currently approved standard of care. Based on our top-line results from SUMMIT Part 2 and our interactions with the FDA, we remain on track to submit our first NDA for bezuclastinib by the end of 2025 to treat patients with Non-AdvSM.

Previous wording

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, the potentially registrational portion of the study. 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 systemic mastocytosis with associated hematologic neoplasm (“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.

Current wording

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, the potentially registrational portion of the study. 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 systemic mastocytosis with associated hematologic neoplasm (“SM-AHN”). We completed enrollment in APEX Part 2 in the first quarter of 2025 with 58 patients and plan to present top-line results in December 2025.

Previous wording

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. In 2024, we announced APEX Part 2 would be conducted at the 150mg QD dose, and patients were subsequently enrolled with the following sub-types: 7 patients with aggressive systemic mastocytosis, 23 patients with SM-AHN, and 2 patients with mast cell leukemia.

Current wording

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. In 2024, we announced APEX Part 2 would be conducted at the 150mg daily dose, and patients were subsequently enrolled with the following sub-types: 7 patients with aggressive systemic mastocytosis, 23 patients with SM-AHN, and 2 patients with mast cell leukemia.

Previous wording

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 the 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 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 in the second half of 2025.

Current wording

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 the 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 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. We plan to present top line results in November 2025.

Previous wording

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. As of June 30, 2025, no other milestone payments have been made. Patents protecting bezuclastinib include composition of matter claims which have been issued in the US and other key territories and provide exclusivity through 2033 and potentially beyond through patent term extensions. In addition, we filed a patent application in 2023 seeking to protect our optimized formulation of bezuclastinib that is currently being used in all three of our ongoing bezuclastinib clinical trials, which could potentially provide exclusivity through at least 2043.

Current wording

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. As of September 30, 2025, no other milestone payments have been made. 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 filed a patent application in 2023 seeking to protect our optimized formulation of bezuclastinib that is currently being used in all three of our ongoing bezuclastinib clinical trials, which could potentially provide exclusivity through at least 2043.

Previous wording

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 FGFR2/3 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 FGFR2/3 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 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.

Current wording

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 FGFR2/3 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 nanomolar potency on WT FGFR2 and FGFR2/3 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 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.

Previous wording

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 December 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. In April of 2025 at the American Association of Cancer Research annual meeting (“AACR 2025”), we presented robust tumor growth inhibition in a mutant Her2-YVMA subcutaneous Patient Derived Xenograft model, supporting potential clinical development in HER2-YVMA lung cancer. 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.

Current wording

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 showed 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 December 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. In April of 2025 at the American Association of Cancer Research annual meeting (“AACR 2025”), we presented robust tumor growth inhibition in a mutant Her2-YVMA subcutaneous Patient Derived Xenograft model, supporting potential clinical development in HER2-YVMA lung cancer. These advances continue to highlight a favorable profile for optimal clinical efficacy. We recently received clearance from the FDA on our IND submission for CGT4255 and plan to initiate a Phase 1 clinical trial in November 2025.

Previous wording

Our research team is also 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. Preclinical data was presented at the October 2024 EORTC-NCI-AACR meeting as well as the December 2024 SABCS meeting, 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. At AACR 2025, we presented broad cellular panel profiling across multiple resistant and mutated cell lines, including, for the first time, efficacy against PI3K helical mutations. We also presented TGI data where CGT6297 was highly efficacious in both ST1056 (H1047R mutant) breast cancer and MCF-7 (E545K mutant) breast models. IND-enabling studies have been initiated and we expect to submit an IND application in 2025.

Current wording

Our research team is also 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. Preclinical data was presented at the October 2024 EORTC-NCI-AACR meeting as well as the December 2024 SABCS meeting, 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. At AACR 2025, we presented broad cellular panel profiling across multiple resistant and mutated cell lines, including, for the first time, efficacy against PI3K helical mutations. We also presented TGI data where CGT6297 was highly efficacious in both ST1056 (H1047R mutant) breast cancer and MCF-7 (E545K mutant) breast models. IND-enabling studies have been initiated and we expect to submit an IND application in the fourth quarter of 2025.

Previous wording

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. Preclinical data was presented at the 2024 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 other molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. At AACR 2025, we presented new and advanced lead data on CGT9109. In PK/PD assessment CGT9109 potently inhibited pERK (>90%) when dosed PO at 30 mg/kg in an AsPC-1 KRASG12Dtumor-bearing mouse model. In the same model, CGT9109 also demonstrated robust tumor regression when dosed PO BID at 30 mg/kg. Lead optimization of the CGT9109 series is ongoing.

Current wording

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. Preclinical data was presented at the 2024 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 other molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. At AACR 2025, we presented new and advanced lead data on CGT9109. In PK/PD assessment CGT9109 potently inhibited pERK (>90%) when dosed PO at 30 mg/kg in an AsPC-1 KRASG12Dtumor-bearing mouse model. In the same model, CGT9109 also demonstrated robust tumor regression when dosed PO BID at 30 mg/kg. Lead optimization of the CGT9109 series is ongoing. At the European Organization for Research and Treatment of Cancer meeting in October of 2025, our internally developed KRAS(ON/OFF) inhibitor CGT1263 was presented showing clear selectivity over HRAS and NRAS, with picomolar (pM) activity across a broad panel of KRAS mutant cell lines. In addition, the data presented also characterized CGT1815 (the prodrug of CGT1263), which is designed to optimize human pharmacokinetic performance, supported by pharmacokinetics data from both CGT1815 and CGT1263 across multiple species. Finally, the data presented highlighted that CGT1815 demonstrates superior efficacy in KRAS G12Dand KRAS G12V tumor growth inhibition studies when compared to RMC-6236. We plan submit an IND for this program in 2026.

Previous wording

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 ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $145.5 million for the six months ended June 30, 2025 compared to net losses of $117.3 million for the six months ended June 30, 2024. As of June 30, 2025, we had an accumulated deficit of $1,005.0 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:

Current wording

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 ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $226.4 million for the nine months ended September 30, 2025 compared to net losses of $187.9 million for the nine months ended September 30, 2024. As of September 30, 2025, we had an accumulated deficit of $1,085.9 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:

Previous wording

Total research and development expense increased by $7.9 million for the three months ended June 30, 2025 compared to the three months ended June 30, 2024, driven by the continued development of bezuclastinib and progression of our early stage, preclinical and discovery programs. There was also an increase in unallocated expenses driven by higher personnel costs due to an increase in headcount, including stock-based compensation expense which increased by $0.2 million for the three months ended June 30, 2025 compared to the three months ended June 30, 2024.

Current wording

Total research and development expense increased by $5.4 million for the three months ended September 30, 2025 compared to the three months ended September 30, 2024, driven by the continued development of bezuclastinib including our on-going SUMMIT, PEAK and APEX clinical trials, and the continued progression of our early stage, preclinical and discovery programs. There was also an increase in unallocated expenses driven by higher personnel costs due to an increase in headcount, including stock-based compensation expense which increased by $0.6 million for the three months ended September 30, 2025 compared to the three months ended September 30, 2024.

Previous wording

General and administrative expenses for the three months ended June 30, 2025 were $13.4 million, compared to $10.1 million for the three months ended June 30, 2024. The increase in general and administrative expenses was primarily due to higher personnel and support costs due to the growth of the organization including certain commercial readiness activities initiated in the second quarter of 2025.

Current wording

General and administrative expenses for the three months ended September 30, 2025 were $14.4 million, compared to $11.8 million for the three months ended September 30, 2024. The increase in general and administrative expenses was primarily due to higher personnel and support costs due to the growth of the organization, including commercial readiness activities initiated in 2025.

Previous wording

Interest income for the three months ended June 30, 2025 was $2.4 million, compared to $5.4 million for the three months ended June 30, 2024. The decrease is due to lower invested balances in cash equivalents and marketable securities.

Current wording

Interest income for the three months ended September 30, 2025 was $3.9 million, compared to $4.8 million for the three months ended September 30, 2024. The decrease is due to lower interest rates and lower invested balances in cash equivalents and marketable securities.

Previous wording

Interest expense for the three 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. Interest expense for the three months ended June 30, 2024 was nil.

Current wording

Interest expense for the three months ended September 30, 2025 was $1.5 million related to the Credit Facility and associated amortization of financing costs and the accretion of debt discount. Interest expense for the three months ended September 30, 2024 was nil.

Previous wording

The following table summarizes our results of operations for the six months ended June 30, 2025 and 2024:

Current wording

The following table summarizes our results of operations for the nine months ended September 30, 2025 and 2024:

Previous wording

The following table summarizes our research and development expenses for the six months ended June 30, 2025 and 2024:

Current wording

The following table summarizes our research and development expenses for the nine months ended September 30, 2025 and 2024:

Previous wording

Total research and development expense increased by $18.2 million for the six months ended June 30, 2025 compared to the six months ended June 30, 2024, driven by the continued development of bezuclastinib and progression of our early stage, preclinical and discovery programs. There was also an increase in unallocated expenses driven by higher personnel costs due to an increase in headcount, including stock-based compensation expense which increased by $1.1 million for the six months ended June 30, 2025 compared to the six months ended June 30, 2024.

Current wording

Total research and development expense increased by $23.6 million for the nine months ended September 30, 2025 compared to the nine months ended September 30, 2024, driven by the continued development of bezuclastinib including our on-going SUMMIT, PEAK and APEX clinical trials, and the continued progression of our early stage, preclinical and discovery programs. There was also an increase in unallocated expenses driven by higher personnel costs due to an increase in headcount, including stock-based compensation expense which increased by $1.6 million for the nine months ended September 30, 2025 compared to the nine months ended September 30, 2024.

Previous wording

General and administrative expenses for the six months ended June 30, 2025 were $25.3 million, compared to $19.8 million for the six months ended June 30, 2024. The increase in general and administrative expenses was primarily due to higher personnel and support costs due to the growth of the organization including certain commercial readiness activities initiated in the first and second quarter of 2025.

Current wording

General and administrative expenses for the nine months ended September 30, 2025 were $39.6 million, compared to $31.6 million for the nine months ended September 30, 2024. The increase in general and administrative expenses was primarily due to higher personnel and support costs due to the growth of the organization, including commercial readiness activities initiated in 2025.

Previous wording

Interest income for the six months ended June 30, 2025 was $5.3 million, compared to $9.5 million for the six months ended June 30, 2024. The decrease is due to lower invested balances in cash equivalents and marketable securities.

Current wording

Interest income for the nine months ended September 30, 2025 was $9.2 million, compared to $14.2 million for the nine months ended September 30, 2024. The decrease is due to lower interest rates and lower invested balances in cash equivalents and marketable securities.

Previous wording

Interest expense for the six months ended June 30, 2025 was $0.3 million related to the Credit Facility and associated amortization of issuance costs and the accretion of debt discount. Interest expense for the six months ended June 30, 2024 was nil.

Current wording

Interest expense for the nine months ended September 30, 2025 was $1.8 million related to the Credit Facility and associated amortization of issuance costs and the accretion of debt discount. Interest expense for the nine months ended September 30, 2024 was nil.

Previous wording

Other income (expense), net for the six months ended June 30, 2025 and 2024 was less than $0.1 million and represented miscellaneous expense.

Current wording

Other income (expense), net for the nine months ended September 30, 2025 and 2024 was less than $0.1 million and represented miscellaneous expense.

Previous wording

As of June 30, 2025, we have 138,256,052 shares outstanding on an as-converted basis, which consists of (i) 113,928,492 shares of common stock outstanding, (ii) pre-funded warrants that are exercisable for 606,060 shares of common stock, (iii) 67,414 shares of Series A Non-Voting Convertible Preferred Stock (“Series A Preferred Stock”) that are convertible into 16,853,500 shares of common stock and (iv) 6,868 shares of Series B Preferred Stock that are convertible into 6,868,000 shares of common stock.

Current wording

As of September 30, 2025, we have 164,155,222 shares outstanding on an as-converted basis, which consists of (i) 139,827,662 shares of common stock outstanding, (ii) pre-funded warrants that are exercisable for 606,060 shares of common stock, (iii) 67,414 shares of Series A Non-Voting Convertible Preferred Stock (“Series A Preferred Stock”) that are convertible into 16,853,500 shares of common stock and (iv) 6,868 shares of Series B Preferred Stock that are convertible into 6,868,000 shares of common stock.

Previous wording

During the six months ended June 30, 2024, operating activities used $95.2 million of cash, primarily resulting from our net loss of $117.3 million and net cash used in changes in our operating assets and liabilities of $0.7 million, partially offset by net noncash charges of $22.7 million. Changes in our operating assets and liabilities for the six months ended June 30, 2024 consisted primarily of a $1.7 million increase in prepaid expenses and other current assets, and a $0.7 million decrease in the operating lease liability, partially offset by a $1.7 million increase in accounts payable and accrued expenses and other current liabilities.

Current wording

During the nine months ended September 30, 2025, operating activities used $185.3 million of cash, primarily resulting from our net loss of $226.4 million, partially offset by net non-cash charges of $33.2 million and by net cash provided by changes in our operating assets and liabilities of $7.9 million. Changes in our operating assets and liabilities for the nine months ended September 30, 2025 consisted primarily of a $3.0 million decrease in prepaid expenses and other current assets, a $5.6 million increase in accounts payable and accrued expenses and other current liabilities, and a $0.4 million decrease in other assets, partially offset by a $1.2 million decrease in the operating lease liability.

Previous wording

During the six months ended June 30, 2025, operating activities used $121.1 million of cash, primarily resulting from our net loss of $145.5 million, partially offset by net non-cash charges of $21.3 million and net cash provided by changes in our operating assets and liabilities of $3.1 million. Changes in our operating assets and liabilities for the six months ended June 30, 2025 consisted primarily of a $2.2 million decrease in prepaid expenses and other current assets and a $1.6 million increase in accounts payable and accrued expenses and other current liabilities, partially offset by a $0.7 million decrease in the operating lease liability.

Current wording

During the nine months ended September 30, 2024, operating activities used $147.2 million of cash, primarily resulting from our net loss of $187.9 million, partially offset by net non-cash charges of $28.0 million and by net cash provided by changes in our operating assets and liabilities of $12.7 million. Changes in our operating assets and liabilities for the nine months ended September 30, 2024 consisted primarily of a $14.7 million increase in accounts payable and accrued expenses and other current liabilities, partially offset by a $0.9 million increase in prepaid expenses and other current assets, and a $1.0 million decrease in the operating lease liability.

Previous wording

During the six months ended June 30, 2024, net cash used in investing activities was $83.6 million which consisted of purchases of property and equipment and marketable securities, partially offset by maturities and sales of marketable securities.

Current wording

During the nine months ended September 30, 2025, net cash used in investing activities was $76.8 million which consisted of purchases of property and equipment and marketable securities, partially offset by maturities and sales of marketable securities.

Previous wording

During the six months ended June 30, 2025, net cash provided by investing activities was $78.3 million which consisted of maturities and sales of marketable securities, partially offset by purchases of property and equipment and marketable securities.

Current wording

During the nine months ended September 30, 2024, net cash used in investing activities was $23.4 million which consisted of purchases of property and equipment and marketable securities, partially offset by maturities and sales of marketable securities.

Previous wording

During the six months ended June 30, 2025, net cash provided by financing activities was $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 issuance 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.

Current wording

During the nine months ended September 30, 2025, net cash provided by financing activities was $289.6 million, which consisted of $215.8 million in proceeds from the issuance of common stock in a public offering, net of paid offering costs, $47.0 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 issuance costs, proceeds from the issuance of common stock under the ESPP and proceeds from the issuance of common stock upon stock option exercises.

Previous wording

During the six months ended June 30, 2024, net cash provided by financing activities was $213.8 million, which consisted of $213.3 million in proceeds from the issuance of common stock and Series B Preferred Stock in the Private Placement, net of paid offering costs and proceeds from the issuance of common stock under the 2018 Employee Stock Purchase Plan.

Current wording

During the nine months ended September 30, 2024, net cash provided by financing activities was $214.4 million, which consisted of $213.3 million in proceeds from the issuance of common stock and Series B Preferred Stock in the Private Placement, net of paid offering costs, proceeds from the issuance of common stock under the ESPP and proceeds from the issuance of common stock upon stock option exercises.

Previous wording

Based on our current plans, we believe that our existing cash, cash equivalents and marketable securities of $237.8 million, combined with the net proceeds of $215.8 million from the underwritten public offering in July 2025, will be sufficient to fund our operating expenses and capital expenditure requirements into 2027, including through potential FDA approval of bezuclastinib for Non-AdvSM and early commercial launch activities. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. We will require additional funding to complete the critical activities planned to support ongoing research and development programs.

Current wording

As of September 30, 2025, we had cash, cash equivalents and marketable securities of $390.9 million. We believe that our cash, cash equivalents and marketable securities, together with the $37.8 million net proceeds from shares sold under our at-the-market facility, will be sufficient to fund our operating expenses and capital expenditure requirements into 2027, including through potential FDA approval of bezuclastinib for Non-AdvSM and early commercial launch activities. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. We will require additional funding to complete the critical activities planned to support ongoing research and development programs.