Accent Therapeutics, a clinical-stage biopharmaceutical company, announced plans to present new data on two of its lead cancer therapeutics at the upcoming 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago from April 25-30.
The company will showcase preclinical findings for ATX-559, a first-in-class oral DHX9 inhibitor, and ATX-295, a potentially best-in-class KIF18A inhibitor, both representing novel approaches to targeting specific vulnerabilities in cancer cells.
ATX-559: Targeting Genomic Instability in Multiple Cancers
Preclinical data for ATX-559 will highlight the compound's activity across in vivo models of cancers characterized by genomic instability and replication stress. The poster presentation will focus on its efficacy in dMMR/MSI-H colorectal cancer and BRCA-altered triple negative breast cancer models.
ATX-559 selectively inhibits DHX9, a previously "undrugged" RNA and DNA/RNA helicase that plays critical roles in replication, transcription, translation, RNA processing, and maintenance of genomic stability. This makes it particularly effective against tumors with high levels of replication stress.
"We are excited to present foundational preclinical data supporting our clinical-stage ATX-559 program and our soon-to-be clinical-stage ATX-295 program," said Serena Silver, Chief Scientific Officer at Accent Therapeutics. "These data include key mechanistic, biological and pharmacological underpinnings that help to guide our current or future clinical development plans for these programs."
The compound is currently being evaluated in a first-in-human Phase 1/2 open-label dose-escalation and expansion study (NCT06625515). The trial focuses on patients with advanced or metastatic BRCA-1 and/or BRCA-2-deficient breast cancer or MSI-H and/or dMMR solid tumors.
ATX-295: Novel Approach to Ovarian Cancer Treatment
ATX-295, Accent's KIF18A inhibitor, has been selected for an oral presentation at AACR, highlighting its robust and selective activity across a panel of ovarian cancer cell lines. The presentation will provide rationale for using whole genome doubling as a viable enrichment biomarker for ATX-295 sensitivity in ovarian cancer models.
KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability but not in healthy cells. The inhibitor causes rapid cell death in cancers with an abnormal number of chromosomes (aneuploid) while sparing cells with normal chromosome numbers (euploid).
This selective mechanism of action makes ATX-295 a promising candidate for treating ovarian and triple negative breast cancers. The compound is expected to enter clinical trials in the first half of 2025.
Expanding Treatment Horizons
Both programs show potential beyond their initial target indications. According to Silver, the company has "uncovered significant patient opportunities in additional undisclosed indications" and is evaluating opportunities to explore these in current or future clinical studies.
For ATX-559, additional solid tumor indications characterized by replicative stress could be explored either alongside the initial indications or in subsequent studies. The company retains full worldwide rights to both the ATX-559/DHX9 program and the ATX-295/KIF18A program.
Presentation Details at AACR 2025
The oral presentation on ATX-295, titled "Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian Cancer Pre-Clinical Models," will be delivered by Maureen Lynes, Ph.D., on Monday, April 28, from 2:30 PM to 4:30 PM.
The poster presentation on ATX-559, "ATX-559, a First in Class DHX9 Inhibitor, and Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress," will be presented by Jennifer Castro on Monday, April 28, from 9:00 AM to 12:00 PM in Poster Section 22.
Accent's Precision Oncology Approach
Accent Therapeutics is pioneering a new class of small molecule precision cancer therapies targeting critical intracellular dependencies across multiple cancer types. The company builds upon expertise in RNA-modifying proteins (RMPs) and systematic mapping of both the RMP space and adjacent high-value areas for drug discovery.
This approach allows Accent to develop potentially transformative biomarker-driven cancer medicines for both novel and known, but suboptimally addressed, high-impact oncology targets. The company's focus remains on addressing significant unmet needs in large patient populations through innovative targeted therapies.
