Cogent Biosciences Conference Call Summary Company Overview - Cogent Biosciences is a biotech company focused on developing novel small-molecule therapies for mutant-driven rare diseases with high unmet needs [2][3] Industry Context - The company is primarily involved in the treatment of gastrointestinal stromal tumors (GIST) and systemic mastocytosis, with a significant commercial opportunity in the second-line GIST market estimated at over $7.5 billion globally [3][35] Key Points from the Conference Call PEAK Trial Results - The PEAK trial results for bezuclastinib, a selective KIT inhibitor, were highlighted as a major advancement in treating second-line GIST patients [2][3] - Bezuclastinib combined with sunitinib showed a median progression-free survival (PFS) of 16.5 months, significantly outperforming sunitinib alone, which had a PFS of 9.2 months [12][25] - The trial demonstrated a nearly 50% objective response rate, which is a substantial improvement compared to existing therapies [13][25] Market Opportunity - Approximately 12,000 new GIST patients are diagnosed annually in the U.S. and Europe, with about 6,000 patients eligible for second-line treatment [27][28] - The standard of care for second-line GIST has not seen new drug approvals since sunitinib in 2006, creating a unique market opportunity for bezuclastinib [4][6] - The potential market for second-line GIST treatment is estimated at over $4 billion, with no direct competition [30] Safety and Tolerability - The combination therapy of bezuclastinib and sunitinib showed a marginal increase in dose reductions and discontinuations, indicating a favorable safety profile [16][18] - Adverse events primarily included neutropenia, with no significant additional risk from the combination therapy [17][19] - The safety profile of bezuclastinib is characterized by asymptomatic transaminase elevations and other manageable side effects [19][21] Future Plans - Cogent plans to submit a new drug application (NDA) for bezuclastinib in the first half of 2026, with potential priority review leading to approval by the end of 2026 [26][30] - The company is also preparing for data presentation from the APEX study, which focuses on advanced systemic mastocytosis, expected to provide competitive insights against existing therapies [31][34] Intellectual Property - Cogent holds a strong intellectual property position, with protections extending through 2038 and potentially until 2043 due to a proprietary formulation of bezuclastinib [35][36] Conclusion - Cogent Biosciences is positioned to capitalize on a significant market opportunity in the treatment of GIST and systemic mastocytosis, with promising clinical trial results and a robust pipeline leading to potential regulatory approvals in the near future [35]

Peak Trial Results - The combination of Bezuclastinib + Sunitinib demonstrates a 50% reduction in the risk of progression or death compared to Sunitinib alone in patients with GIST [25, 47] - Median Progression-Free Survival (PFS) for Bezuclastinib + Sunitinib is 16.5 months, compared to 9.2 months for Sunitinib alone (p<0.0001) [26, 47] - Objective Response Rate (ORR) per BICR for Bezuclastinib + Sunitinib is 45.6%, compared to 25.8% for Sunitinib alone (p<0.0001) [28, 47] - Complete Response (CR) rate in the Bezuclastinib + Sunitinib arm is 6.4%, compared to 1.9% in the Sunitinib arm [28] Safety and Tolerability - The incidence of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) is similar between the Bezuclastinib + Sunitinib and Sunitinib arms [29, 30] - Grade 3+ TRAEs occurred in 71.6% of patients in the Bezuclastinib + Sunitinib arm and 52.4% in the Sunitinib arm [29] - No TRAEs leading to death were reported in the Bezuclastinib + Sunitinib arm, while 0.5% of patients in the Sunitinib arm experienced TRAEs leading to death [29] Market and Regulatory Strategy - The company plans an NDA submission for Bezuclastinib in imatinib-resistant or intolerant GIST in the first half of 2026 based on the Peak trial results [47, 54] - An active Expanded Access Program is available, allowing immediate access to the Bezuclastinib combination for 2L patients with GIST [47, 48] - The estimated aggregate global annual sales opportunity for Bezuclastinib across indications is >$7.5 billion [57]