IMPACT THERAP-B (07630) announced that it has designated IMP2794 as a preclinical candidate compound (PCC), a KAT6A-specific degrader PROTAC discovered through its proprietary targeted protein degradation platform.

IMP2794 is the first PCC generated from IMPACT THERAP-B's Targeted Protein Degradation Platform. It is a potent and selective KAT6A degrader, exhibiting over 1000-fold selectivity over KAT6B. The compound demonstrates significant cytotoxic activity against tumor cells in vitro, with low blood toxicity. In sensitive and non-sensitive breast cancer CDX models, IMP2794 shows excellent in vivo anti-tumor efficacy. Notably, it displays very high oral bioavailability in multiple rodent and non-rodent species, suggesting potential for ideal drug exposure in humans.

KAT6A, a member of the MYST family of histone acetyltransferases (HATs), catalyzes histone acetylation to promote open chromatin and activate gene transcription. It is highly expressed in various cancers, especially estrogen receptor-positive (ER+) breast cancer. However, its homolog KAT6B shares structural and sequence homology, making selective inhibition of KAT6A difficult with traditional small-molecule inhibitors, and inhibition of KAT6B is linked to potential blood toxicity.

This designation marks the first PCC from IMPACT THERAP-B's proprietary Targeted Protein Degradation Platform, which includes proteolysis-targeting chimeras (PROTACs), validating the platform's technical maturity and output capabilities. The company has established a degradation platform with E3 ligase and linker libraries, enabling rapid assembly of PROTAC molecules with excellent oral bioavailability. These tools allow selective and regulated degradation of previously "undruggable" targets, widening the therapeutic window and reducing toxicity. The platform complements the company's ADC platform, supporting multi-dimensional exploration of cancer targets.