On March 25, 2025 Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering novel, targeted, small molecule cancer therapeutics, reported that it will present new data on its first-in-class oral DHX9 inhibitor, ATX-559, and its potentially best-in-class KIF18A inhibitor, ATX-295, at the 2025 AACR (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois (Press release, Accent Therapeutics, MAR 25, 2025, View Source [SID1234651425]).
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Data presented at the meeting will reinforce Accent’s approach focused on precision oncology for large patient populations in a poster highlighting the therapeutic potential of lead candidate ATX-559 and in an oral presentation for lead candidate ATX-295.
Preclinical data supporting continued clinical evaluation of ATX-559 will characterize the compound’s activity across in vivo models of cancers exhibiting genomic instability and replication stress, including in dMMR/MSI-H colorectal cancer and BRCA altered triple negative breast cancer. An oral presentation will discuss the preclinical activity of ATX-295 across a panel of ovarian cancer cell lines and provide rationale for whole genome doubling as a viable enrichment biomarker of ATX-295 sensitivity in ovarian cancer models.
"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. These data include key mechanistic, biological and pharmacological underpinnings that help to guide our current or future clinical development plans for these programs. For both programs, we are also excited to have uncovered significant patient opportunities in additional undisclosed indications, and we are evaluating opportunities to explore them in the clinic during our current or future studies " said Serena Silver, Chief Scientific Officer at Accent Therapeutics.
ATX-559 is currently under investigation in a first-in-human, Phase 1/2, open-label, dose-escalation and expansion study (NCT06625515), 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. Additional undisclosed solid tumor indications under replicative stress and representing significant patient populations have the potential to be explored either in parallel to the initial indications or in subsequent studies.
Accent’s potentially best-in-class KIF18A inhibitor, ATX-295, is anticipated to enter the clinic in the first half of 2025.
AACR presentations details 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
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
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 the KIF18A program, which is anticipated to enter the clinic in 1H 2025.