Foghorn Therapeutics Inc

Selective CBP degrader program and Selective EP300 degrader program.

Foghorn is advancing two separate programs targeting either CBP or EP300, paralog histone acetyltransferases with a synthetic lethal relationship in tumor cells. Attempts to selectively drug CBP or EP300 have been challenging due to the high level of similarity between the two proteins. Additionally, dual inhibition of CBP/EP300 has been historically limited by hematopoietic toxicity.

Selective CBP degrader program. In April, Foghorn presented new pharmacodynamic and pharmacokinetic preclinical data at the 2024 AACR Annual Meeting and during a pipeline update call highlighting:

•Deep and sustained CBP degradation significantly inhibited tumor growth in mouse xenograft solid tumor models.

•Robust monotherapy preclinical anti-tumor activity that was not associated with significant body weight loss, thrombocytopenia or anemia.

•Identification of potent and selective CBP protein degraders with first-in-class potential to address tumors harboring EP300 mutations in many types of cancer, including bladder, gastric and endometrial cancers.

•IND-enabling studies on track to initiate by the fourth quarter of 2024.

Selective EP300 degrader program. In April, Foghorn presented new pharmacodynamic and pharmacokinetic preclinical data at the 2024 AACR Annual Meeting and during a pipeline update call highlighting:

•Well-toleratedin vivo with no observed decrease in platelet levels, with no effects on megakaryocyte viability at pharmacologically relevant concentrations inex vivo studies.

•Identification of potent and selective EP300 degraders with anti-tumor activity in prostate and hematological malignancies, including prostate cancer, multiple myeloma and diffuse large B cell lymphoma (DLBCL).

Selective ARID1B degrader program.

ARID1A is the most mutated subunit in the BAF Complex and amongst the most mutated proteins in oncology. These mutations lead to a dependency on ARID1B, in several types of cancer, including ovarian, endometrial, colorectal and bladder. Attempts to selectively drug ARID1B have been challenging because of the high degree of similarity between ARID1A and ARID1B and the fact that ARID1B has no enzymatic activity to target.

•In April, Foghorn presented data at the AACR Annual Meeting demonstrating potent and selective small molecule binders to ARID1B. The Company is in the process of converting these selective binders into heterobifunctional degraders.