Core Insights - Cogent Biosciences anticipates 2025 to be a transformational year, with plans to report top-line results from three registration-directed studies of bezuclastinib and submit its first New Drug Application (NDA) by the end of the year [2][9] Milestones for 2025 - The company plans to report top-line results from the SUMMIT trial for Non-Advanced Systemic Mastocytosis (NonAdvSM) in July 2025 [8][9] - Top-line results from the pivotal Phase 3 PEAK trial for gastrointestinal stromal tumors (GIST) are expected by the end of 2025 [4][9] - The APEX trial for Advanced Systemic Mastocytosis (AdvSM) will report results in the second half of 2025 [9] - An Expanded Access Program (EAP) for bezuclastinib will be initiated in Q1 2025 for eligible SM and GIST patients [5] Pipeline Development - The ongoing Phase 1 trial of CGT4859, a selective FGFR2 inhibitor, aims to explore safety and tolerability in patients with FGFR mutations [6] - The company plans to submit IND applications for CGT4255, a selective ErbB2 inhibitor, and CGT6737, a potent allosteric inhibitor of PI3Kα, during 2025 [7][10] Financial Position - Cogent Biosciences has a strong balance sheet, positioning the company well for its transition into a commercial-stage entity [2]

Core Points - Cogent Biosciences, Inc. is a biotechnology company focused on developing precision therapies for genetically defined diseases [3] - The company will present at the 43rd Annual J.P. Morgan Healthcare Conference on January 14, 2025 [1] - The most advanced clinical program is bezuclastinib, a selective tyrosine kinase inhibitor targeting the KIT D816V mutation [3] - Bezuclastinib is designed to treat systemic mastocytosis and advanced gastrointestinal stromal tumors (GIST) [3] - Cogent is also developing a portfolio of targeted therapies for mutations in FGFR2, ErbB2, PI3Kα, and KRAS [3] Company Information - Cogent Biosciences is headquartered in Waltham, MA, and Boulder, CO [3] - The company provides a live webcast of its presentations on its Investors & Media page [2] - A replay of the webcast will be available for 30 days after the event [2] Contact Information - Christi Waarich is the Senior Director of Investor Relations [4] - Contact details include email: christi.waarich@cogentbio.com and phone: 617-830-1653 [4]

Drug Development and Trials - Bezuclastinib is being developed for Advanced Systemic Mastocytosis (AdvSM) and Non-Advanced Systemic Mastocytosis (Non-AdvSM), with a median survival of less than 3.5 years for AdvSM patients[56]. - The SUMMIT trial for Non-AdvSM completed enrollment in Q3 2023 with 54 patients, and Part 2 is expected to enroll 159 patients, with top-line results anticipated in H2 2025[57]. - In SUMMIT Part 1b, 100% of patients with baseline tryptase ≥20ng/mL achieved <20ng/mL at week 12, compared to 0% in the placebo group[57]. - The APEX trial for AdvSM reported an objective response rate (ORR) of 52% as of September 25, 2023, with a 56% ORR for TKI-treatment-naïve patients[58]. - The PEAK trial for GIST enrolled 413 patients, with a median progression-free survival (mPFS) of 10.2 months and an ORR of 27.5%[60]. - Bezuclastinib has received orphan drug designation from the FDA and EMA for both Mastocytosis and GIST[59][60]. - The SUMMIT Part 1b showed a 51% mean improvement in overall symptom severity for bezuclastinib compared to 18% for placebo[57]. - The majority of treatment-emergent adverse events in clinical trials were low-grade and reversible, with no serious adverse events reported in the SUMMIT trial[57][60]. - The company initiated a Phase 1 study of CGT4859 in patients with FGFR2 mutations, with preliminary results expected in 2025[63]. - CGT4255 demonstrated low nM potency against ErbB2 wild-type and oncogenic mutations with over 100-fold selectivity over wild-type EGFR[64]. - CGT6297, a PI3Kα inhibitor, showed low nM potency in H1047R mutant PI3K cell lines and superior efficacy compared to Alpelisib in preclinical models[66]. - The company is developing a potent KRAS inhibitor, CGT6737, which demonstrated 90% PD inhibition in mouse xenograft models[67]. - The company plans to initiate IND-enabling studies for CGT4255 in mid-2024 and for CGT6297 in 2025[64][66]. Financial Performance - The company reported a net loss of $187.9 million for the nine months ended September 30, 2024, compared to a net loss of $138.0 million for the same period in 2023, with an accumulated deficit of $791.6 million as of September 30, 2024[68]. - The company expects to incur significant expenses and operating losses for at least the next several years, particularly related to ongoing clinical trials and product development[68]. - As of September 30, 2024, the company had cash, cash equivalents, and marketable securities of $345.5 million, expected to fund operations through late 2026[70]. - Total operating expenses for the three months ended September 30, 2024, were $75.4 million, an increase of $15.8 million (26.6%) compared to $59.6 million for the same period in 2023[75]. - Research and development expenses for the three months ended September 30, 2024, were $63.6 million, up $13.5 million (26.9%) from $50.1 million in 2023, driven by higher costs associated with bezuclastinib and increased personnel costs[76][77]. - Net loss for the three months ended September 30, 2024, was $70.6 million, compared to a net loss of $55.4 million for the same period in 2023, reflecting an increase of $15.2 million (27.5%) in losses[75]. - For the nine months ended September 30, 2024, total operating expenses were $202.2 million, an increase of $52.3 million (34.9%) from $149.9 million in 2023[81]. - Research and development expenses for the nine months ended September 30, 2024, totaled $170.6 million, up $45.6 million (36.5%) from $125.0 million in 2023, primarily due to increased costs for bezuclastinib and personnel[83][84]. - Interest income for the nine months ended September 30, 2024, was $14.2 million, compared to $9.2 million in 2023, reflecting an increase of $5.0 million (54.3%) due to higher invested balances[85]. - Other income, net for the nine months ended September 30, 2024, was less than $0.1 million, a decrease of $0.9 million compared to $1.0 million in 2023, primarily due to the expiration of a sublease[86]. - The change in fair value of the CVR liability for the nine months ended September 30, 2024, was nil, compared to a decrease of $1.7 million in 2023, as the CVRs expired on August 6, 2023[87]. - The company has incurred significant operating losses since inception and does not expect to generate revenue from product sales for several years[88]. Funding and Capital Raising - The company filed a shelf registration statement allowing the sale of up to $300.0 million in various securities, with a specific Sales Agreement for $75.0 million in common stock through Guggenheim Securities[89]. - The company completed a public offering of 17,899,698 shares at $8.25 per share, raising approximately $161.9 million in net proceeds[89]. - A subsequent public offering in June 2023 raised approximately $161.8 million from 14,375,000 shares sold at $12.00 per share[89]. - A private placement on February 16, 2024, generated net proceeds of approximately $213.4 million from the sale of 17,717,997 shares at $7.50 each and 12,280 shares of Series B Preferred Stock[89]. - The company expects expenses to increase as it advances clinical development and research activities, with funding requirements dependent on various operational factors[95]. - The company anticipates needing additional funding to support ongoing research and development programs, with potential dilution of existing ownership interests if equity is raised[97]. Operational Insights - The company has focused significant resources on establishing its intellectual property portfolio and conducting R&D since its inception in 2014[68]. - The company anticipates an increase in general and administrative expenses due to expansion of operations to support ongoing discovery and clinical activities[73]. - Operating activities used $147.2 million in cash during the nine months ended September 30, 2024, primarily due to a net loss of $187.9 million[91]. - Net cash provided by financing activities was $214.4 million for the nine months ended September 30, 2024, compared to $163.5 million in the same period of 2023[94]. - The company has no off-balance sheet arrangements and no material changes in critical accounting policies were reported[99][98].

Clinical Trials - Top-line results from the registration-directed SUMMIT, PEAK, and APEX trials are expected in 2025[1] - Enrollment in the Phase 3 PEAK trial for GIST patients was completed with a total of 413 patients, focusing on median progression-free survival (mPFS) as the primary endpoint[3] - A Phase 1 trial for CGT-4859, a reversible FGFR2 inhibitor, was initiated, with preliminary results expected in 2025[6] - The company plans to present updated clinical data from SUMMIT and APEX at the ASH annual meeting in December 2024[5] - Anticipated milestones include completing enrollment in SUMMIT Part 2 in Q1 2025 and delivering top-line results from PEAK by the end of 2025[10] Financial Performance - Research and development expenses for Q3 2024 were $63.6 million, up from $50.1 million in Q3 2023, reflecting increased costs associated with trial enrollments[14] - General and administrative expenses for Q3 2024 were $11.8 million, compared to $9.5 million in Q3 2023, primarily due to organizational growth[15] - Net loss for Q3 2024 was $70.6 million, compared to a net loss of $55.4 million for the same period in 2023[16] - Cash position as of September 30, 2024, was $345.5 million, down from $389.9 million as of June 30, 2024, sufficient to fund operations into late 2026[13] - Total assets as of September 30, 2024, were $384.0 million, compared to $313.4 million as of December 31, 2023[21]

Drug Development and Trials - Bezuclastinib is a highly selective tyrosine kinase inhibitor targeting the KIT D816V mutation, primarily responsible for Systemic Mastocytosis (SM) and advanced gastrointestinal stromal tumors (GIST) [49]. - The median survival for patients with Advanced Systemic Mastocytosis (AdvSM) is less than 3.5 years, highlighting the urgent need for new treatment options [52]. - The SUMMIT trial for Non-AdvSM has enrolled 54 patients in Part 1, with Part 2 expected to include 159 patients and top-line results anticipated by the end of 2025 [53]. - In the SUMMIT Part 1b, 100% of patients with baseline tryptase ≥20ng/mL achieved <20ng/mL at week 12, compared to 0% in the placebo group [53]. - The APEX trial for AdvSM reported an objective response rate (ORR) of 52%, with a 56% ORR for TKI-treatment-naïve patients [54]. - The PEAK trial for GIST patients demonstrated a median progression-free survival (mPFS) of 19.4 months in second-line patients previously treated with imatinib [56]. - Bezuclastinib has received orphan drug designation from the FDA and EMA for both SM and GIST treatments [56]. - The company is advancing CGT4859, a reversible, selective FGFR2 inhibitor, with plans to initiate a clinical trial by the end of 2024 [59]. - CGT4255, a novel ErbB2 mutant program, demonstrated low nM potency against ErbB2 mutations with over 100-fold selectivity over wild-type EGFR, and IND-enabling studies are set to begin in mid-2024 [60]. - The company is developing CGT4824, a PI3Kα inhibitor targeting the H1047R mutation, which affects over 30,000 cancer patients annually, showing over 95% inhibition of pAKT in preclinical models [61]. Financial Performance and Projections - The company reported a net loss of $117.3 million for the six months ended June 30, 2024, compared to a net loss of $82.7 million for the same period in 2023, resulting in an accumulated deficit of $720.9 million as of June 30, 2024 [62]. - The company expects to incur significant expenses and operating losses for at least the next several years, particularly as it initiates and increases enrollment for clinical trials and continues to develop additional product candidates [62]. - As of June 30, 2024, the company had cash, cash equivalents, and marketable securities totaling $389.9 million, which is expected to fund operations into 2027 [63]. - The company has not generated any revenue from product sales and will need substantial additional funding to support ongoing operations and growth strategy [62]. - General and administrative expenses are anticipated to increase due to the expansion of operations to support ongoing discovery and clinical activities [66]. - Total operating expenses for the three months ended June 30, 2024, were $64.4 million, an increase of $17.3 million (36.7%) compared to $47.1 million for the same period in 2023 [68]. - Research and development expenses increased by $15.4 million (39.6%) to $54.3 million for the three months ended June 30, 2024, driven by higher costs associated with bezuclastinib and increased personnel costs [70]. - General and administrative expenses rose to $10.1 million, up $1.9 million (23.1%) from $8.2 million for the same period in 2023, primarily due to higher personnel costs [71]. - Net loss for the three months ended June 30, 2024, was $58.9 million, compared to a net loss of $44.1 million for the same period in 2023, reflecting an increase of $14.9 million (33.8%) [68]. - For the six months ended June 30, 2024, total operating expenses were $126.8 million, an increase of $36.5 million (40.4%) from $90.3 million in the same period in 2023 [74]. - Research and development expenses for the six months ended June 30, 2024, totaled $107.0 million, up $32.1 million (42.8%) from $74.9 million in 2023, driven by costs related to bezuclastinib and ongoing trials [76]. - The company completed a public offering in June 2023, raising approximately $161.8 million in net proceeds [81]. - For the six months ended June 30, 2024, cash used in operating activities was $95.2 million, compared to $71.6 million for the same period in 2023, reflecting an increase of approximately 33% [83]. - The net cash used in investing activities for the six months ended June 30, 2024, was $83.6 million, significantly higher than $17.8 million in the same period of 2023, indicating a 370% increase [84]. - Net cash provided by financing activities was $213.8 million for the six months ended June 30, 2024, up from $162.5 million in 2023, representing a 31.6% increase [85]. - The company anticipates increased expenses related to ongoing clinical development and research activities, which may impact future cash flow requirements [86]. - The company has no off-balance sheet arrangements as of the reporting period [89]. - The company may require additional funding to support ongoing research and development programs, which could lead to dilution of existing ownership interests [87]. - The company is subject to various risks that could affect its ability to raise additional funds when needed, including adverse regulatory decisions and clinical trial delays [87]. Safety Profile - The majority of treatment-emergent adverse events in clinical trials were low-grade and reversible, indicating a favorable safety profile for bezuclastinib [56]. Tax and Accounting - The company has recorded a full valuation allowance against its net deferred tax assets, with U.S. federal and state net operating loss carryforwards of $195.7 million and $110.6 million, respectively [67]. - There have been no material changes in critical accounting estimates during the three months ended June 30, 2024 [88]. - There have been no material changes to market risks as described in the previous annual report [92].

Financial Performance - As of June 30, 2024, cash, cash equivalents, and marketable securities totaled $389.9 million, down from $435.7 million as of March 31, 2024, sufficient to fund operations into 2027[9] - General and administrative expenses for Q2 2024 were $10.1 million, up from $8.2 million in Q2 2023, indicating a 23% increase due to organizational growth[11] - The net loss for Q2 2024 was $59.0 million, compared to a net loss of $44.1 million for the same period in 2023, representing a 34% increase in losses[11] Research and Development - Research and development expenses for Q2 2024 were $54.3 million, compared to $38.9 million in Q2 2023, reflecting an increase of 39% primarily due to accelerated enrollment in clinical trials[10] - The company expects to complete enrollment in the global Phase 3 PEAK trial in Q3 2024 and report top-line results by the end of 2025[13] - The company anticipates completing enrollment in the registration-directed APEX Phase 2 trial by the end of 2024 and reporting top-line results by mid-2025[13] Clinical Trial Results - The median progression-free survival (mPFS) for patients treated with bezuclastinib and sunitinib was 10.2 months, with a mPFS of 19.4 months observed in a subset of patients with second-line gastrointestinal stromal tumors[4] - The objective response rate (ORR) for all patients treated with bezuclastinib and sunitinib was 27.5%, while the ORR for the subset of second-line patients was 33.3%[5] Corporate Developments - The company appointed Cole Pinnow as Chief Commercial Officer, bringing extensive experience from Pfizer, where he led a $5 billion cancer portfolio[6] - The company initiated IND-enabling studies for the ErbB2 program, demonstrating 80% brain penetrance in mice and well-tolerated at high concentrations[7]

SUMMIT is a randomized, global, multicenter, double-blind, placebo-controlled, multi-part phase II study for patients with nonadvanced systemic mastocytosis (Non-AdvSM). The study is designed to explore the safety and efficacy of COGT's most advanced candidate, bezuclastinib, in patients with moderate to severe NonAdvSM, which includes indolent systemic mastocytosis, smoldering systemic mastocytosis and bone marrow mastocytosis. Bezuclastinib is a selective tyrosine kinase inhibitor that is designed to pote ...

Patients treated with 100 mg bezuclastinib showed substantial reduction in their most severe symptoms and mast cell reactions "Nonadvanced systemic mastocytosis is a debilitating hematologic disorder and physicians and patients remain in search of more effective treatment options to fight this disease," said Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy at Duke University. "I am impressed with the rapid patient response and reductions seen ...

Patients treated with 100 mg bezuclastinib showed substantial reduction in their most severe symptoms and mast cell reactions "Nonadvanced systemic mastocytosis is a debilitating hematologic disorder and physicians and patients remain in search of more effective treatment options to fight this disease," said Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy at Duke University. "I am impressed with the rapid patient response and reductions seen ...

"We are thrilled to welcome Cole to our leadership team, as we begin preparations for commercializing bezuclastinib, a product we believe has clear potential to become a standard of care treatment for patients with systemic mastocytosis and advanced GIST," said Andrew Robbins, the Company's President and Chief Executive Officer. "Cole's broad commercial knowledge and leadership experience will be invaluable in helping Cogent expand from a research and development company to a fully-integrated commercial org ...