Kronos Bio has ceased the development of istisociclib (KB-0742), its last remaining clinical asset, following a review of safety data from a Phase I/II trial (NCT04718675) involving patients with platinum-resistant high-grade serous ovarian cancer. The decision comes as the company explores strategic alternatives to maximize stockholder value.
The Phase I/II trial of the cyclin-dependent kinase 9 (CDK9) inhibitor enrolled seven patients, with five reporting neurological adverse events ranging from Grade 1 to Grade 3. These adverse events led to treatment discontinuation in three patients, while two others required dosage reductions. Given these safety concerns and the clinical development timelines of its other pipeline candidates, Kronos Bio has decided to discontinue istisociclib's development.
"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 maximising stockholder value," Kronos stated. The company is also planning cash-saving initiatives and is open to strategic options such as acquisition, reverse merger, or a standard merger. As of September 30, 2024, Kronos reported cash reserves of $124.9 million.
This decision follows a challenging year for Kronos, marked by multiple downsizing efforts. In November 2023, the company reduced its workforce by 19% to conserve cash and focus resources on its cancer therapies, including istisociclib and lanraplenib. A month later, Kronos discontinued the development of lanraplenib after patient discontinuation in a Phase Ib/II trial (NCT05028751) and difficulties in demonstrating clinical benefit when combined with Astellas Pharma’s Xospata (gilteritinib) in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML). In March 2024, another round of layoffs saw a further 21% reduction in staff, intended to maximize the potential of istisociclib.
Kronos is also seeking partnership opportunities for its preclinical assets KB-9558 and KB-7898, both of which are p300 lysine acetyltransferase (KAT) inhibitors. KB-9558 is being developed as a potential treatment for multiple myeloma and human papillomavirus (HPV)-driven cancers, with an investigational new drug (IND) application expected to be submitted to the US Food and Drug Administration (FDA) by the end of the year. KB-7898 is under evaluation for treating autoimmune disorders, with IND-enabling studies underway for Sjögren’s disease.
Other companies in the biotech sector have also recently implemented cash-saving measures. In April, Portage Biotech announced it was exploring strategic alternatives, including a potential wind-down of the company, citing the current funding climate and future funding needs. Similarly, TRACON Pharmaceuticals initiated cash-conserving measures after an efficacy analysis of a Phase II trial of its lead cancer therapy, envafolimab, indicated that it was unlikely to meet the efficacy threshold required for a biologics license application (BLA).
