Accent Therapeutics has halted work on a solid tumor drug due to adverse events in a phase 1/2 study.
The Cambridge, Massachusetts-based biotech had been investigating ATX-559, an oral inhibitor of the enzyme DHX9, in a study that included patients with advanced or metastatic patients with BRCA-1- and/or BRCA-2-deficient breast cancer or microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) solid tumors.
When Accent kicked off that study in December 2024, Chief Medical Officer Jason Sager, M.D., suggested that ATX-559 could find a role treating patients with BRCA1- and BRCA2-deficient breast cancer or MSI-H/dMMR colorectal cancer who had stopped responding to PARP inhibitors or PD-(L)1 inhibitors, respectively.
Accent had also previously said it was exploring the sensitivity of other tumor types to DHX9 inhibition, as well as considering whether to combine DHX9 inhibitors with other cancer treatments.
But, after terminating the ATX-559 study over its “adverse event profile,” the company told Fierce Biotech yesterday that it is “evaluating strategic options for the program.”
For now, Accent is channeling its resources to its other lead program, a KIF18A inhibitor dubbed ATX-295. The biotech took the oral drug into a phase 1/2 study in April 2025 for patients with advanced/metastatic platinum-resistant or refractory ovarian cancer.
“We are rapidly advancing the ATX-295 phase 1/2 clinical study to build on the promising data supporting ATX-295’s clinical development across multiple solid tumors, including in ovarian cancer, and will continue to expand this trial to other types of cancer with unmet need in the coming year,” a spokesperson for Accent told Fierce yesterday.
Luckily for the biotech’s employees, the company confirmed that this strategic shift hasn’t resulted in any layoffs.
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KIF18A is a kinesin that helps regulate microtubule dynamics in the cell cycle metaphase. Accent isn’t the only company exploring the potential of inhibiting KIF18A to treat tumors—Volastra has two candidates in phase 1 development, while Iambic Therapeutic is planning to take its own offering into the clinic.
Accent launched in 2018 with $40 million to develop cancer treatments based on epitranscriptomics, or the science around RNA structure, stability, function and translation in cell biology. Since then, the biotech has picked up a $63 million series B and a $75 million series C, as well as Big Pharma backers like Bristol Myers Squibb, Johnson & Johnson and AbbVie.
The company has also collaborated with some big names, including a $1.1 billion biobucks deal with AstraZeneca to develop develop RNA-modifying proteins for the treatment of cancer, as well as licensing a preclinical small molecule to Boehringer Ingelheim last October for an undisclosed sum.
