Cogent Biosciences (COGT) Piper Sandler 36th Annual Healthcare Conference summary

Key clinical program updates

• Lead asset Bezuclastinib is in three pivotal clinical programs: APEX (advanced systemic mastocytosis), SUMMIT (non-advanced systemic mastocytosis), and PEAK (second-line metastatic GIST).

• APEX and SUMMIT studies will have phase 1/dose escalation updates at the ASH conference, with pivotal results expected in mid to late 2025.

• PEAK study in GIST completed enrollment of 413 patients, with results anticipated by end of 2025.

• SUMMIT Part 2 enrollment is ahead of schedule, now expected to complete in Q1 2025 due to strong investigator and patient demand.

• SUMMIT Part 1 established 100 mg as the recommended phase 2 dose for non-advanced SM.

Differentiation and product profile

• Bezuclastinib is designed as a highly selective KIT inhibitor, sparing other class III RTKs and minimizing CNS penetration to reduce off-target toxicities.

• The drug aims to provide a favorable therapeutic index, allowing full target engagement with fewer side effects compared to other KIT inhibitors.

• Clinical data suggest a superior symptom improvement profile compared to Avapritinib, with a focus on deep, durable responses.

• Safety profile characterized by asymptomatic, reversible transaminase elevations, with no evidence of clinically relevant liver toxicity.

• Inclusion of patients intolerant to Avapritinib in trials may support future commercial switching.

Market opportunity and commercial considerations

• Second-line GIST represents a $1 billion+ market opportunity in the U.S., with Bezuclastinib positioned as a potential best-in-class therapy.

• Rapid enrollment in SUMMIT Part 2, despite availability of Avapritinib, indicates strong demand for improved therapies.

• Commercial differentiation may rely more on real-world symptom improvement than on proprietary scoring systems.

• Physicians value improvements in patients' most severe symptoms, which will be highlighted in upcoming data presentations.

• Advanced SM treatment goals focus on survival and tolerability, with Bezuclastinib aiming to match efficacy while reducing serious side effects seen with Avapritinib.