The clock is ticking for Kronos Bio after the biotech discontinued its last remaining clinical-stage asset over neurological adverse events.
The San Mateo, California-based biotech said it had made the decision to halt work on istisociclib after reviewing safety data from an ongoing phase 1/2 trial in patients with platinum-resistant high-grade serous ovarian cancer. Specifically, five patients out of a cohort of seven who received an 80-mg dose of the CDK9 inhibitor exhibited “neurological events as characterized by involuntary movements, confusion and hallucinations ranging from Grade 1 to Grade 3,” Kronos said in its third-quarter earnings release.
Three of those five patients discontinued their treatment due to the adverse events, while the other two reduced their dose of the drug, the company added.
“While we believe istisociclib has provided benefit to a small number of patients in the phase 1/2 trial, the emerging profile in patients with platinum-resistant ovarian cancer suggests an unfavorable risk-benefit profile and does not warrant further clinical development,” CEO Norbert Bischofberger, Ph.D., said in a statement.
The biotech explained in the release that “after an overall review of its business and given the clinical development timelines of its additional pipeline candidates, the company will explore strategic alternatives with the goal of maximizing stockholder value.”
Kronos is considering whether to partner its two preclinical lysine acetyltransferase (KAT) inhibitor programs, which include a multiple myeloma and HPV-driven cancer-focused candidate dubbed KB-9558 that the company expects to be ready to submit for an IND by the end of the year. There’s also KB-7898, which is aimed at Sjögren’s disease and is currently in IND-enabling studies.
“Data from our early-stage p300 KAT inhibitor programs demonstrate that inhibition of key signaling pathways leads to restoration of tumor suppression activity in cancer cells or reduction of inflammation in autoimmune disease, underscoring the potential of this approach for patients that have limited or no targeted therapies,” Chief Scientific Officer Charles Lin, Ph.D., said in the release.
While it assesses its options, Kronos—which ended September with $124.9 million in cash and equivalents—said it will “implement significant expense reduction strategies.” Fierce Biotech has asked Kronos whether this will involve further layoffs at the company but did not receive a reply by time of publication.
Dropping istisociclib caps off a tough 12 months for Kronos that saw two rounds of layoffs and work halted on the SYK inhibitor lanraplenib.
While it didn’t warrant a mention in yesterday’s release, Kronos also has a partnership with Roche’s Genentech for several undisclosed discovery programs. The Roche unit jumped in to save the day for the struggling biotech in January 2023 with a $20 million upfront payment plus milestones that could top $177 million for the first program and $100 million for the first licensed product.