Clinical Programs & Catalysts - Cogent Biosciences has multiple clinical and preclinical programs with upcoming catalysts, including top-line results for Bezuclastinib in AdvSM expected in July 2025, NonAdvSM in 2H 2025, and GIST by EOY 2025 [7, 8, 11] - The company is conducting a registration-directed study of Bezuclastinib in NonAdvSM with 179 patients, using a 24-week MS2D2 primary endpoint [11] - A registration-directed study of Bezuclastinib monotherapy is underway in AdvSM with 58 patients, using ORR as the primary endpoint [11] - PEAK Part 2 is a global Phase 3 trial of Bezuclastinib in 2nd-line GIST, with top-line results expected by the end of 2025 [8] Financial Position - As of Q1 2025, Cogent Biosciences has $245.7 million, expected to fund operations into late 2026 [9] Market Opportunity - The aggregate US annual sales opportunity for Bezuclastinib across AdvSM, NonAdvSM, and GIST is greater than $3 billion with limited competition [12] - The US annual market opportunity for NonAdvSM is estimated at $2 billion, with differentiated symptom improvement potentially leading to market leadership [11] - The US annual market opportunity for 2nd-line GIST is estimated at over $1 billion, with limited competition [11] - The US annual market opportunity for AdvSM is estimated at $300 million, with differentiated safety/tolerability results potentially leading to market leadership [11] Competitive Landscape - Cogent believes Bezuclastinib offers a best-in-class KIT inhibitor opportunity with minimal late-stage competitive activity [10, 13, 30] Safety and Efficacy - In ISM patients, only 25% of Ayvakit patients achieved clinically meaningful improvement [18] - In PIONEER Part 2, low-dose Ayvakit (25 mg once daily) was associated with an improved safety profile, with 13% experiencing eye edema and dizziness [19]

Core Insights - Cogent Biosciences, Inc. presented preclinical data from four pipeline programs at the AACR 2025 Annual Meeting, highlighting its focus on developing precision therapies for genetically defined diseases [1][2] Pipeline Programs - The first program involves a potent KRAS (ON) inhibitor that shows selectivity for mutant KRAS over HRAS and NRAS, achieving 90% tumor growth inhibition in a mouse model with a 30 mg/kg oral dose [2][3] - The second program features CGT6297, a novel PI3Kα H1047R mutant-selective inhibitor, which demonstrates efficacy against PI3K helical mutations and broad cellular profiling across resistant cell lines [3][4] - The third program is CGT4859, a reversible and selective FGFR2/3 inhibitor that shows superior target coverage of resistance mutations and demonstrated complete tumor regressions in a model at doses greater than 2.5 mg/kg [5][6][7] - The fourth program is CGT4255, an EGFR-sparing, pan-mutant HER2 inhibitor with potential best-in-class brain penetration, showing high oral bioavailability and stability in human blood [8] Leadership Changes - Cogent announced the appointment of Ray Frost as Senior Vice President of Market Access and Adam Boyd, Ph.D., as Senior Vice President of Corporate Strategy, both bringing extensive industry experience [10][11][12] Inducement Grants - The company approved inducement equity awards for new employees, including Mr. Frost and Dr. Boyd, totaling nonqualified options to purchase 446,000 shares of common stock [13] Company Overview - Cogent Biosciences is focused on developing precision therapies for genetically defined diseases, with its most advanced clinical program targeting the KIT D816V mutation associated with systemic mastocytosis and gastrointestinal stromal tumors [14]