Cogent Biosciences(COGT) - 2025 Q3 - Quarterly Report

Drug Development and Trials - Bezuclastinib is a highly selective tyrosine kinase inhibitor targeting the KIT D816V mutation, crucial for treating Systemic Mastocytosis (SM) and gastrointestinal stromal tumors (GIST) [87]. - The SUMMIT trial for Non-Advanced Systemic Mastocytosis (Non-AdvSM) completed enrollment with 54 patients in Part 1 and 179 patients in Part 2, demonstrating significant clinical improvements [91][92]. - In the SUMMIT Part 2 trial, bezuclastinib achieved a mean reduction of 24.3 points in total symptom score (TSS) at 24 weeks, compared to 15.4 points in the placebo group, with a placebo-adjusted improvement of 8.91 points [93]. - The APEX trial for Advanced Systemic Mastocytosis (AdvSM) completed enrollment with 58 patients in Part 2, with top-line results expected in December 2025 [95]. - As of October 11, 2024, the APEX trial reported an objective response rate (ORR) of 52%, with 61% for TKI-treatment-naïve patients and a median progression-free survival (PFS) rate of 82% at 24 months [97][98]. - The PEAK trial for GIST enrolled 413 patients, with a median progression-free survival of 10.2 months and an overall response rate of 27.5% [102][103]. - Bezuclastinib has received orphan drug designation from the FDA and EMA for both SM and GIST treatments [100][102]. - The company plans to submit its first New Drug Application (NDA) for bezuclastinib by the end of 2025 for Non-AdvSM patients [92]. Financial Performance - As of September 30, 2025, the company reported net losses of $226.4 million for the nine months ended, compared to $187.9 million for the same period in 2024 [112]. - The accumulated deficit as of September 30, 2025, reached $1,085.9 million, indicating ongoing financial challenges [112]. - Cash, cash equivalents, and marketable securities totaled $390.9 million as of September 30, 2025, expected to fund operations into 2027 [116]. - Total operating expenses for the three months ended September 30, 2025, were $83.4 million, an increase of $7.9 million (10.5%) compared to $75.4 million in the same period of 2024 [132]. - Research and development expenses for the three months ended September 30, 2025, were $69.0 million, up $5.4 million (8.5%) from $63.6 million in 2024, driven by ongoing clinical trials and increased personnel costs [133]. - General and administrative expenses for the three months ended September 30, 2025, were $14.4 million, an increase of $2.6 million (22.0%) compared to $11.8 million in 2024, primarily due to higher personnel and support costs [134]. - Net loss for the three months ended September 30, 2025, was $80.9 million, an increase of $10.3 million (14.6%) compared to a net loss of $70.6 million in 2024 [132]. - Total operating expenses for the nine months ended September 30, 2025, were $233.9 million, an increase of $31.7 million (15.7%) from $202.2 million in 2024 [138]. - Research and development expenses for the nine months ended September 30, 2025, were $194.2 million, up $23.6 million (13.8%) from $170.6 million in 2024, driven by ongoing clinical trials and increased personnel costs [139]. - General and administrative expenses for the nine months ended September 30, 2025, were $39.6 million, an increase of $8.1 million (25.6%) compared to $31.6 million in 2024 [140]. - Interest income for the nine months ended September 30, 2025, was $9.2 million, a decrease of $5.0 million (35.2%) from $14.2 million in 2024 [141]. Funding and Capital Structure - The company entered into a loan and security agreement providing for a non-dilutive term loan facility of up to $400.0 million, with the first tranche of $50.0 million fully funded as of June 30, 2025 [148]. - The company completed a public offering of 25,555,556 shares at $9.00 per share, raising approximately $215.8 million in net proceeds after expenses [149]. - As of September 30, 2025, the company had 164,155,222 shares outstanding, including 139,827,662 shares of common stock [150]. - For the nine months ended September 30, 2025, the company used $185.3 million in operating activities, primarily due to a net loss of $226.4 million [153]. - Net cash used in investing activities for the same period was $76.8 million, mainly for property and equipment purchases [155]. - Financing activities provided $289.6 million in cash, including $215.8 million from the public offering and $47.0 million from a credit facility [157]. - The company anticipates increased expenses related to clinical development and research activities, with funding needs expected to grow [159]. - The company expects to finance operations through equity offerings and debt financing, which may dilute existing ownership interests [161]. - The company has no off-balance sheet arrangements as of the reporting date [163]. Clinical Development Pipeline - The company plans to submit IND applications for CGT4255 and CGT1145 in 2026, indicating ongoing development efforts [108][111]. - CGT4859 demonstrated low nanomolar potency on WT FGFR2 and FGFR2/3 mutations, with complete regressions at 5 mg/kg PO in a mutant-driven mouse model [106]. - CGT4255 showed low nM potency against ErbB2 wild-type and oncogenic mutations, with complete regressions at 100 mg/kg PO BID in the NIH3T3 ErbB2-L755S model [108]. - CGT6297 exhibited >95% inhibition of pAKT in a H1047R PD model, outperforming alpelisib in tumor growth inhibition [109]. - CGT6737 achieved 90% PD inhibition in mouse xenograft models, demonstrating robust PK/PD and tumor growth inhibition [110]. - CGT1145 displayed JAK2 V617F cellular IC50s of 76nM, with >150-fold selectivity over JAK2 WT [111]. Adverse Events and Safety - The majority of treatment-emergent adverse events (TEAEs) in the SUMMIT trial were low grade, with serious adverse events occurring in 4.2% of patients treated with bezuclastinib [94].