US-based biopharmaceutical company Accent Therapeutics has initiated dosing in an open-label Phase I/II clinical trial evaluating ATX-295, its novel oral kinesin family member 18A (KIF18A) inhibitor, for patients with advanced solid tumors.
The trial represents a significant milestone for the Massachusetts-based company, marking its second investigational drug to enter clinical development following ATX-559 late last year.
Trial Design and Patient Population
The dose-escalation and expansion study is designed to evaluate ATX-295's safety profile across multiple dosage levels while assessing pharmacokinetics, pharmacodynamics, tolerability, and preliminary efficacy signals. The trial is currently enrolling patients with locally advanced or metastatic solid tumors, with a particular focus on high-grade serious ovarian cancer.
ATX-295 targets the mitotic kinesin motor protein KIF18A, which plays a crucial role in cell division specifically in tumors exhibiting chromosomal instability. This mechanism of action represents a novel approach to treating certain aggressive cancers with limited therapeutic options.
Promising Preclinical Data
Preclinical models have demonstrated encouraging results for ATX-295, showing selective dose-dependent tumor growth inhibition in ovarian and triple-negative breast cancers. These early findings provided the scientific rationale for advancing the compound into human clinical trials.
The therapeutic potential of ATX-295 has been further validated by the U.S. Food and Drug Administration (FDA), which granted Fast Track designation for the treatment of adults with advanced or metastatic platinum-resistant or refractory ovarian cancer – a population with particularly poor prognosis and limited treatment options.
Expanding Clinical Pipeline
ATX-295 joins Accent's lead asset ATX-559 in clinical development. ATX-559, a selective inhibitor of DExH-box helicase 9 (DHX9), is being evaluated for treating adults with unresectable or metastatic deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) colorectal cancer who have previously received checkpoint inhibitor therapy.
"With the launch of our Phase I/II clinical trial of ATX-295, we now have two investigational drugs in the clinic, bringing us closer to achieving our mission of transforming cancer care," said Jason Sager, Chief Medical Officer at Accent Therapeutics. "Additionally, receiving FDA Fast Track designation for both of our lead assets underscores the power of our approach and the potential for these investigational drugs to urgently address high unmet medical needs."
Company Focus on Intracellular Cancer Dependencies
Accent Therapeutics specializes in developing small-molecule therapies targeting critical intracellular dependencies in various cancer types. The company's strategic approach focuses on both novel oncology targets and established targets that currently lack effective treatment options.
This dual-pronged strategy reflects the company's commitment to addressing significant gaps in cancer treatment through innovative scientific approaches. By targeting fundamental cellular processes essential for cancer cell survival and proliferation, Accent aims to develop therapies with potentially broad applications across multiple tumor types.
Significance for Ovarian Cancer Treatment
The development of ATX-295 holds particular promise for patients with platinum-resistant or refractory ovarian cancer, a condition associated with poor outcomes and limited therapeutic options. Current standard treatments for this patient population typically yield low response rates and short progression-free survival.
The Fast Track designation from the FDA acknowledges both the serious nature of this condition and the potential for ATX-295 to address this significant unmet medical need. This designation may facilitate expedited development and review processes, potentially accelerating the therapy's path to patients if clinical trials demonstrate favorable results.
Looking Forward
As the Phase I/II trial progresses, key milestones will include completion of the dose-escalation phase, determination of the recommended Phase II dose, and preliminary efficacy signals in the expansion cohorts. The company has not yet disclosed a timeline for when initial data from the trial might be available.
The advancement of both ATX-295 and ATX-559 into clinical trials represents significant progress for Accent Therapeutics as it works to translate its scientific insights into potential new treatment options for cancer patients with limited alternatives.
