Accent Therapeutics has announced the dosing of the first patient in its Phase 1/2 clinical trial evaluating ATX-559, a first-in-class oral inhibitor of DHX9. The trial (NCT06625515) is designed to assess the safety and tolerability of ATX-559 across multiple dose levels, while also examining its pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with solid tumors, particularly those with BRCA1/2-deficient breast cancer and MSI-H or dMMR solid tumors.
ATX-559: A Novel Approach to Targeting Replication Stress
ATX-559 is a potent and selective inhibitor of DHX9, a helicase involved in DNA and RNA processing. DHX9 plays a critical role in tumors experiencing high levels of replication stress, including various cancers such as breast, ovarian, colorectal, endometrial, and gastric cancers. By inhibiting DHX9, ATX-559 aims to disrupt key tumor vulnerabilities in DNA repair-deficient backgrounds and hyper-mutated states.
Jason Sager, M.D., Chief Medical Officer of Accent Therapeutics, stated, "We are thrilled to begin evaluating ATX-559 in cancer patients. While PARP inhibitors are useful standard treatments for BRCA1- and BRCA2-deficient breast cancer, the majority of patients with metastatic disease will likely need a different treatment within a year or two. Likewise, about half of patients with MSI-H/dMMR colorectal cancer patients will need additional treatments following PD-(L)1 inhibitors."
Expanding the Pipeline: KIF18A Inhibitor
Accent Therapeutics is also advancing its second program, targeting KIF18A, with plans to initiate a Phase 1 trial in the first half of 2025. KIF18A is a mitotic kinesin motor protein crucial for cell division in tumors with chromosomal instability. Inhibition of KIF18A results in rapid cell death in aneuploid cancer cells while sparing euploid cells. This program aims to address a significant patient population across several cancer indications, including ovarian and triple-negative breast cancer (TNBC).
Leadership Transition
The company also announced that Serena Silver, Ph.D., has been promoted to Chief Scientific Officer, effective January 1, 2025. Dr. Silver, who joined Accent in September 2022 as Vice President of Biology, brings extensive experience in target discovery, drug discovery, and translational research. She succeeds Robert A. Copeland, Ph.D., Co-Founder, President, and CSO, who will retire on December 31, 2024.
Shakti Narayan, Ph.D., J.D., Chief Executive Officer of Accent Therapeutics, commented, "Since co-founding Accent in 2017 and serving as President and CSO, Dr. Copeland's visionary leadership has been instrumental in shaping our scientific direction. We want to thank Bob for his invaluable contributions to Accent and wish him the best for the future."
