Cogent Biosciences (COGT) Jefferies London Healthcare Conference 2024 summary

Key clinical programs and trial updates

• Three pivotal clinical readouts are expected in 2025 for bezuclastinib in mastocytosis and GIST, with a focus on selectivity and safety advantages over current KIT inhibitors.

• ASH presentations will provide longer-term follow-up data from APEX (ASM) and SUMMIT (ISM) trials, emphasizing durability and chronic use potential.

• SUMMIT Part 2, a 159-patient randomized study, is on track to complete enrollment in Q1 2025, ahead of schedule due to strong demand.

• APEX Part 2 aims to confirm improved safety and efficacy for ASM patients, particularly those with comorbid hematologic neoplasms.

• A new pan-KRAS inhibitor program is advancing, with candidate selection pending and a focus on sparing HRAS/NRAS to reduce toxicity.

Differentiation and clinical strategy

• Bezuclastinib is designed for high selectivity, avoiding CNS penetration and off-target effects, which may reduce cognitive and hematologic side effects.

• Optimized formulation improves bioavailability and reduces pill burden, with consistent efficacy and safety expected across formulations.

• A novel patient-reported outcome questionnaire (MS2D2) was developed and aligned with FDA, aiming to demonstrate clear symptomatic and quality-of-life benefits.

• Early data show 70% of patients achieved a 50% symptom improvement, compared to 25% for the current standard, indicating strong differentiation.

• Commercial strategy targets both patients inadequately controlled on current therapy and the large undiagnosed ISM population.

Market opportunity and future outlook

• Non-advanced SM represents a $2 billion U.S. market, with GIST offering a $1 billion opportunity due to lack of competition.

• The GIST program leverages bezuclastinib's selectivity for an add-on approach with sunitinib, aiming for a new standard of care.

• Phase I/II data in second-line GIST show a median PFS of 19.4 months for the combination, compared to 8.3 months for sunitinib alone.

• The pivotal GIST trial is fully enrolled, with results expected in about a year.

• The company anticipates regulatory submission and potential approval for ISM in the next few years, with a focus on demonstrating superior efficacy and safety.