Novel KIF18A inhibitor, ATX-295, shows enriched activity in ovarian and TNBC preclinical models with whole genome doubling
First-in-class DHX9 inhibitor, ATX-559, demonstrates potent activity in preclinical models of MSI-H and BRCA-deficient cancers
Both ATX-295 and ATX-559 programs are currently being evaluated in Phase 1/2 clinical trials
LEXINGTON, Mass., Oct. 22, 2025 /PRNewswire/ — Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering a new class of small molecule precision cancer therapies, today announced new preclinical data on its two lead programs: the novel KIF18A inhibitor, ATX-295, and the first-in-class DHX9 inhibitor, ATX-559. The company will share the data, which highlight the potential to target key tumor vulnerabilities for selective cancer cell death, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (the “Triple Meeting”), being held October 22-26, 2025, in Boston, Massachusetts.
“The data presented for our KIF18A and DHX9 programs continue to validate the success of our biomarker-driven strategy against challenging, genetically diverse cancers,” said Serena Silver, Ph.D., Chief Scientific Officer of Accent Therapeutics. “By precisely targeting the vulnerabilities created by genomic instability, we are excited about the potential of ATX-295 and ATX-559 to address significant unmet needs for patients.”
In the presentation entitled “Addressing Novel Oncology Targets for Tumors with Genomic Instability,” (Concurrent Session 9, October 25th at 4:45 PM ET) Dr. Silver will discuss the promise of ATX-295 and ATX-559 as precision cancer therapeutics that exploit the genomic instability of cancer cells to effect cancer-selective growth inhibition in vitro and in vivo. She will highlight the potential for KIF18A inhibition by ATX-295 in cancers with high levels of chromosomal instability (CIN) such as ovarian and triple negative breast cancer, and for DHX9 inhibition by ATX-559 in multiple tumor types with high levels of replication stress including dMMR/MSI-H and BRCA alterations.
Additional Poster Presentations
ATX-295 (KIF18A Inhibitor)
- Title: Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian and TNBC Preclinical Models
- Summary: Inhibition of KIF18A by ATX-295 is a compelling strategy for chromosomally unstable cancers, supported by new data identifying whole genome doubling (WGD) as a strong predictive biomarker for tumors such as ovarian cancer and TNBC. This biomarker-driven approach was validated in preclinical models where ATX-295 induced dose-dependent tumor regression in WGD-positive models.
- Session Details: October 24th, Session B, 12:30-4:00 PM ET
ATX-559 (DHX9 Inhibitor)
- Title: ATX-559, a First-in-Class, Clinical-Stage DHX9 Inhibitor, as a Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress
- Summary: Preclinical data show the first-in-class oral DHX9 inhibitor, ATX-559, increases replicative stress and DNA damage, leading to selective cell death in cancers with genomic instability. This activity led to robust, dose-dependent tumor regression in preclinical models with BRCA alterations and microsatellite instability-high (MSI-H).
- Session Details: October 24th, Session B, 12:30-4:00 PM ET
About ATX-295
ATX-295 is a potential best-in-class inhibitor for KIF18A, a mitotic kinesin motor protein essential for cell division in select tumors with chromosomal instability. A subset of tumors with an abnormal number of chromosomes (aneuploid), such as those found in ovarian and triple-negative breast cancer (TNBC), are reliant on KIF18A. Treatment with a KIF18A inhibitor leads to rapid cell death in these chromosomally unstable cancer cells while leaving healthy cells with normal numbers of chromosomes unaffected. Accent retains full worldwide rights to the KIF18A program, including ATX-295, which is being evaluated in a Phase 1/2 clinical trial (NCT06799065).
About ATX-559
ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a DNA/RNA helicase that plays a critical role in tumors with high levels of replication stress. Such tumors include those with BRCA loss of function (breast, ovarian), mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) cancers (colorectal, endometrial, gastric), and others representing large patient populations with significant unmet medical need. DHX9 is a compelling oncology target as its inhibition exploits key tumor vulnerabilities related to replication, transcription, and the maintenance of genomic stability, resulting in cancer-specific cell death. Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial (NCT06625515), and the DHX9 program.
About Accent Therapeutics
Accent Therapeutics is a clinical-stage biopharmaceutical company pioneering a new class of small molecule precision cancer therapies. The company’s pipeline is fueled by its distinct ability to prosecute novel tumor vulnerabilities in cancers with high genomic and chromosomal instability. Accent’s innovative, biomarker-driven therapies are designed for both novel and known, but suboptimally addressed, high-impact oncology targets with the potential to benefit large patient populations with significant unmet need. The company’s two lead programs— ATX-295, targeting KIF18A, and ATX-559, targeting DHX9—are currently being evaluated in Phase 1/2 clinical studies. For more information on Accent’s mission to translate extraordinary science into life-changing therapeutics for patients living with cancer, visit www.accenttx.com or follow us on LinkedIn.
Media Contact
Amanda Sellers, Deerfield Group
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