Kronos Bio highlights istisociclib data at Ovarian Cancer Research Symposium

Kronos Bio highlighted new preclinical data from a study of istisociclib. The poster presentation took place over the weekend at the American Association for Cancer Research 15th Biennial Ovarian Cancer Research Symposium. Kronos Bio is currently evaluating istisociclib, a CDK9 inhibitor, in an expansion cohort of a Phase 1/2 clinical trial to explore single agent activity in platinum-resistant high-grade serous ovarian cancer. From the presentation, “Preclinical and clinical data support clinical expansion of istisociclib, an oral CDK9 inhibitor, into platinum-resistant ovarian cancer,” a summary of results is outlined below. In vitro data demonstrate that istisociclib induced apoptosis/cell death; Istisociclib resulted in the accumulation of gammaH2AX, a sensitive molecular marker of DNA damage; Istisociclib disrupted homologous recombination DNA damage repair by downregulating BRCA1 and RAD51 creating a “BRCAness” phenotype in platinum and PARP resistant HR-proficient ovarian cancer cells; From the dose escalation portion of the Company’s ongoing Phase 1/2 trial of istisociclib in relapsed or refractory transcriptionally addicted advanced solid tumors, new pharmacokinetic/pharmacodynamic results were presented. From the dose and schedule optimization portion of the trial evaluating 60mg and 80mg of istisociclib administered once daily on a 4 days on/3 days off schedule:; Clinical exposures resulted in a long half-life of approximately 24 hours, and increased and prolonged weekly exposures consistent with efficacious levels observed in preclinical models; Concurrent with increased and prolonged istisociclib exposure, deeper and more sustained downregulation of CDK9-dependent genes was observed in peripheral blood mononuclear cells.