Accent Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ATX-559, a first-in-class DHX9 inhibitor. This clearance paves the way for a Phase 1/2 clinical trial in patients with advanced solid tumors, particularly those with BRCA1/2-deficient breast cancer and microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors. The trial is anticipated to begin in the fourth quarter of 2024.
Clinical Trial Details
The Phase 1/2 trial (NCT06625515) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ATX-559. The study will enroll patients with BRCA1- or BRCA2-deficient breast cancer, as well as those with MSI-H and/or dMMR solid tumors, including colorectal, endometrial, and gastric cancers. More information can be found on ClinicalTrials.gov.
"The FDA’s IND clearance is a pivotal moment for Accent Therapeutics, propelling our lead program into the clinical arena," said Jason Sager, M.D., Chief Medical Officer of Accent Therapeutics. "ATX-559 has shown remarkable promise in preclinical studies, and we’re excited to now evaluate its potential to meaningfully improve outcomes for patients facing these challenging malignancies."
Clinical Advisory Board
To support the clinical development of ATX-559 and its broader pipeline, Accent has established a Clinical Advisory Board (CAB) comprised of leading clinician-scientists. The CAB includes:
- Lillian L. Siu, M.D., FRCPC, Director of the Phase I Program at Princess Margaret Cancer Centre
- Josep Tabernero, M.D., Ph.D., Head of the Medical Oncology Department at the Vall d’Hebron Barcelona Hospital Campus
- Sam Blackman, M.D., Ph.D., co-founder and Head of Research and Development of Day One Biopharmaceuticals
About ATX-559
ATX-559 is designed to inhibit DHX9, a DNA/RNA helicase involved in replication, transcription, RNA splicing, and genomic stability. DHX9 inhibition has shown promise in preclinical studies by exploiting key tumor vulnerabilities, leading to cancer-specific cell death. Accent Therapeutics retains full worldwide rights to ATX-559 and the DHX9 program.
KIF18A Program
Accent is also advancing a second program targeting KIF18A, a mitotic kinesin motor protein critical for cell division in chromosomally instable tumors. A Phase 1 trial for this program is anticipated to begin in early 2025. KIF18A inhibition has demonstrated rapid cell killing in vitro and in vivo in tumor cells with an abnormal number of chromosomes (aneuploid), while cells with normal numbers of chromosomes (euploid) are unaffected.
