Accent Therapeutics Presents Data Supporting Therapeutic Potential of First-in-Class DHX9 Inhibitor, ATX-559, and Novel KIF18A Inhibitor, ATX-295, at the AACR Annual Meeting 2025

ATX-559, a first-in-class oral DHX9 inhibitor, shown to induce potent and selective tumor growth inhibition in preclinical models of cancers with high genomic instability and replication stress

Oral presentation showcases robust, selective activity of potentially best-in-class KIF18A inhibitor, ATX-295, in KIF18A-dependent ovarian cancer models exhibiting whole genome doubling

LEXINGTON, Mass., April 28, 2025 /PRNewswire/ -- Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering novel, targeted, small molecule cancer therapeutics, today announced new preclinical data on its first-in-class oral DHX9 inhibitor, ATX-559, and its potentially best-in-class KIF18A inhibitor, ATX-295, in poster and oral presentations, respectively, at the AACR Annual Meeting 2025 taking place April 25-30 in Chicago, Illinois. ATX-559 and ATX-295 are currently under investigation in Phase 1/2 clinical trials.

"Our presentations at the AACR annual meeting showcase the outputs of Accent's precision oncology approach to drug development, with strong foundational data that inform our current and future clinical development plans for our lead programs, ATX-559 and ATX-295," said Serena Silver, Ph.D., Chief Scientific Officer of Accent Therapeutics. "These preclinical data reinforce our assets' therapeutic potential across several cancer indications with high unmet need."

The company's poster presentation includes preclinical data supporting continued clinical evaluation of ATX-559, a first-in-class potent, selective, and orally bioavailable small-molecule inhibitor of DHX9. Results within characterize the compound's activity in cancer cell lines with genomic instability and elevated replication stress spanning several indications, including dMMR/MSI-H colorectal cancer and BRCA-altered triple negative breast cancer, and in subtypes of lung, gastric, ovarian, and prostate cancers. ATX-559 was shown to be well tolerated in vivo, leading to robust and dose dependent tumor growth inhibition and regression in BRCA deficient breast cancer and dMMR/MSI-H cell- and patient-derived xenograft models.

ATX-559 is currently under investigation in a first-in-human, Phase 1/2, open-label, dose-escalation and expansion study, with a focus on advanced or metastatic patients with BRCA-1 and/or BRCA-2-deficient breast cancer or MSI-H and/or dMMR solid tumors (NCT06625515). Additional undisclosed solid tumor indications undergoing replicative stress and representing significant patient populations may be explored either in parallel or in subsequent studies.

For Accent's second lead program, preclinical data included in the company's oral presentation demonstrates sensitivity to KIF18A inhibition across several solid tumor indications with high chromosomal instability, signaling significant opportunity for patient impact by leveraging KIF18A as a selective oncology target. Results further characterize ATX-295 as a potent and selective KIF18A inhibitor capable of inducing mitotic arrest, cell death, and anti-tumor activity in cancer models with high chromosomal instability. Studies in relevant cellular and xenograft models exhibiting whole genome doubling confirm selective anti-cancer activity, providing rationale for whole genome doubling as a predictive biomarker of ATX-295 sensitivity in ovarian and triple negative breast cancer.

Accent recently initiated clinical evaluation of ATX-295 in a first-in-human Phase 1/2 open-label, dose-escalation and expansion study designed to evaluate the molecule's safety, tolerability, and preliminary efficacy in patients with locally advanced or metastatic solid tumors, including high-grade serious ovarian cancer (NCT06799065).

Details for the presentations are as follows:

Presentation Title: Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian Cancer Pre-Clinical Models

• Abstract Number: 3784
• Session Type: Minisymposium
• Session Title: Novel Antitumor Agents
• Session Date and Time: Monday, April 28, 2:30 pm – 4:30 pm CT
• Location: Room S103 - McCormick Place South (Level 1)
• Presenter: Maureen Lynes, Ph.D.

Poster Title: ATX-559, a First in Class DHX9 Inhibitor, and Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress

• Abstract Number: 1758
• Session Title: Novel Antitumor Agents 1
• Session Date and Time: Monday, April 28, 9:00 am – 12:00 pm CT
• Location: Poster Section 22
• Poster Board Number: 10
• Presenter: Jennifer Castro

About ATX-559
ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, shown to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability, making it a compelling novel oncology target. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g., BRCA) and hyper-mutated states (e.g., MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients. Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial (NCT06625515), and the DHX9 program.

About ATX-295
Accent's second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells. KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) in vitro and in vivo, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent retains full worldwide rights to ATX-295, which is currently being evaluated in a Phase 1/2 clinical trial (NCT06799065), and the KIF18A program.

About Accent Therapeutics
Accent Therapeutics is pioneering a new class of small molecule precision cancer therapies targeting critical intracellular dependencies that span multiple types of cancer. Building upon industry-leading expertise in RNA-modifying proteins (RMPs) and the systematic mapping of both the RMP space and adjacent high-value areas for drug discovery, the company employs a flexible model that allows for a diversity of approaches to developing potentially transformative biomarker-driven cancer medicines. Accent's 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. 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.

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SOURCE Accent Therapeutics