Foghorn Therapeutics Inc.

Selective EP300 Degrader Program

Poster Title: Anti-cancer Activity of Potent and Selective EP300 Degradation in Hematological Malignancies (Presentation on Wednesday April 30, 2025)

A potent and selective heterobifunctional degrader of EP300 has significant preclinical activity in hematological malignancies. Historically, selectively drugging EP300 has been challenging due to the high similarity between EP300 and CBP, while dual inhibition of CBP/EP300 has been limited by dose limiting toxicities. EP300 lineage dependencies are further characterized in multiple myeloma and diffuse large B cell lymphoma (DLBCL).

•Anti-proliferative activity in a broad range of hematological malignanciesin vitro, including DLBCL, multiple myeloma, and follicular lymphoma

•Achievedin vivo efficacy in the Karpas422 germinal center B-cell-like (GCB)-DLBCL xenograft model

•No thrombocytopenia observed in mice at efficacious doses

•Targeted selective EP300 degradation shows promise as a well-tolerated and effective treatment strategy to treat advanced hematological malignancies

Selective ARID1B Degrader Program

Investor Event: Selective ARID1B Degrader Program Overview

Successfully developing potent and selective degraders of ARID1B. ARID1B is a major synthetic lethal target implicated in up to 5% of all solid tumors. Attempts to selectively drug ARID1B have been challenging because of the high degree of similarity between ARID1A and ARID1B and the lack of enzymatic activity to target.

•Developed highly potent and selective binders to ARID1B

•Achieved selective degradation of ARID1B

•Program update expected in 2H 2025