Foghorn Reports Key Progress In Novel Cancer Programs Targeting Gene Expression Pathways

Foghorn Therapeutics Inc., a clinical-stage biotech company pioneering novel treatments that correct abnormal gene expression, announced new updates for its Selective ARID1B, Selective CBP, and Selective EP300 degrader programs. These advancements will be highlighted during a Foghorn-hosted virtual investor event.

“We have made significant progress across our degrader portfolio, further highlighting our ability to address challenging and prevalent targets,” said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. “Earlier this week, we presented new preclinical data at the TPD and Induced Proximity Summit demonstrating significant progress for our first-in-class Selective ARID1B degrader, with potential as a new therapy for endometrial, gastric, gastroesophageal junction, bladder and non-small cell lung cancer. Our Selective CBP degrader, with potential in EP300-mutant cancers and ER+ breast cancer, is advancing towards IND in 2026 and on track for non-GLP toxicology studies this quarter. Additionally, our Selective EP300 degrader shows encouraging anti-tumor efficacy with favorable tolerability in hematological malignancies in preclinical studies. This is particularly exciting in multiple myeloma where we believe we are significantly differentiated versus dual CBP/ EP300 programs. These advancements along with our continued innovation and disciplined execution are positioning Foghorn at the forefront in the field of targeted protein degradation.”

ARID1A, one of the most frequently mutated subunits of the BAF complex, is among the most commonly altered proteins in cancer. Such mutations create a dependency on ARID1B in up to 5% of all solid tumors, including endometrial, gastric, gastroesophageal junction, bladder, and NSCLC. Developing selective ARID1B inhibitors has been difficult due to the high similarity between ARID1A and ARID1B and the absence of enzymatic activity in ARID1B. Foghorn’s Selective ARID1B degrader is progressing toward in vivo proof of concept in 2026, with key milestones achieved — including selective degradation of ARID1B, downstream gene modulation, and development of VHL- and cereblon-based bifunctional degraders with potential oral delivery.

Steven Bellon, Chief Scientific Officer of Foghorn, added, “ARID1B has long been difficult to selectively drug due to its high homology to ARID1A, lack of enzymatic activity, and its largely unstructured nature. Our demonstration of selective degradation of ARID1B represents a major scientific breakthrough that underscores the strength of our protein degrader capabilities to overcome challenges that have historically limited the field.”

In addition, Foghorn’s Selective CBP degrader program targets the synthetic lethality relationship present in EP300-mutated cancers such as endometrial, cervical, ovarian, bladder, and colorectal cancers. CBP has proven difficult to target selectively because of its similarity to EP300 and the toxicities that arise when both are inhibited simultaneously. Foghorn’s research aims to exploit CBP lineage dependencies seen in several cancers, including ER+ breast cancer, representing a potentially safer and more precise therapeutic approach.