Either enhancer of zeste homolog 2 (EZH2) or its homolog EZH1, the enzymatic core subunit of polycomb repressive complex 2 (PRC2), acts an essential role in the maintenance of transcriptional repression by the methylation of histone H3 lysine 27 (H3K27). The dysfunctions of EZH2 or the alterations of regulatory proteins have been reported to be associated with the development and progression of a variety of malignant tumors. Dual inhibition of EZH1 and EZH2 could be more effective than EZH2 inhibition alone in blocking PRC2 functions as anti-cancer therapy.
Therefore, we have developed HM97662 which is an oral, highly potent next generation EZH2 inhibitor with enhanced EZH1 inhibitory activity.

1. Antitumor activities of HM97662
   • Effective target modulation profiles (inhibition of H3K27me3, induction of B-cell differentiation, etc.)
   • Potent growth inhibition of a variety of cancer cells associated with EZH2 or regulatory proteins such as ARID1A.
   • Proven effective inhibition of Tazemetostat-resistant cell growth with elevated EZH1.
   • Excellent inhibition of tumor growth in xenograft models of cancer cells with altered EZH2 or regulatory proteins.
   • Potential of restoring weakened anticancer immunity of immune checkpoint inhibitors in cancers with LKB1 loss.

IND enabling GLP-toxicity studies were completed in late 2021 and a first-in-human (FIH) phase 1 clinical study for multiple cancers will be initiated in 2Q 2022.

A novel and potent EZH1/2 dual inhibitor, HM97662, demonstrates antitumor activity in malignant tumors

Poster, American Association for Cancer Research (AACR) 112th Annual meeting, 2021

Overcoming immune checkpoint blockade resistance via EZH1/2 dual inhibition by HM97662 in KRAS/LKB1 mutated NSCLC

Poster, American Association for Cancer Research (AACR) 113th Annual meeting, 2022