Kronos Bio to Present KB-0742 Trial Update at 2024 ASCO Annual Meeting

Kronos Bio, Inc. has released promising new data on its investigational drug, KB-0742, which is currently being evaluated in a Phase 1/2 study. KB-0742 is an oral inhibitor targeting CDK9, a crucial cofactor in the activity of the oncogenic MYC transcription factor. The study has been presented at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting.

KB-0742 is being studied in patients with relapsed or refractory solid tumors or non-Hodgkin lymphoma. The trial, designated as KB-0742-1001, explores various dosing schedules, including a three-days-on, four-days-off regimen. The data encompasses findings from 103 patients, among whom 82 received a 60mg dose and 21 an 80mg dose.

The findings indicate that KB-0742 maintains a manageable safety profile, with no cases of grade 3/4 neutropenia. Mild to moderate side effects such as nausea and vomiting were the most common adverse events, occurring in 69.9% and 52.4% of patients, respectively. The majority of patients completed more than two treatment cycles, with the maximum being 14 cycles.

Particularly noteworthy is the pharmacokinetic behavior of KB-0742, which shows dose-linear characteristics up to 80mg. The 80mg dose demonstrated increased target engagement compared to the 60mg dose. Preliminary data also revealed a more profound reduction in CDK9-sensitive transcripts and MYC levels in tumor biopsies at the higher dose, suggesting enhanced therapeutic potential.

The study also included two case studies: a patient with platinum-resistant ovarian cancer and another with non-small cell lung cancer (NSCLC). Both patients showed encouraging anti-tumor activity, with the NSCLC patient achieving a stable disease state for 71 days and the ovarian cancer patient for over 195 days while still continuing therapy.

Kronos Bio is optimistic about the potential efficacy of the 80mg four-days-on, three-days-off dosing regimen. According to pharmacokinetic modeling, this schedule results in a significant increase in the time above a preclinically determined efficacy threshold compared to the 60mg dose.

The company plans to start enrollment for the expansion cohort at the 80mg dose in the third quarter of 2024, following the encouraging early results presented at ASCO and previous data shared at the 2023 AACR-NCI-EORTC meeting.

Kronos Bio is a clinical-stage biotechnology firm focused on developing small molecule therapeutics for cancers and other diseases driven by deregulated transcription. The company's proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors, leading to the optimization of small molecules targeted in a tumor-specific context. In addition to KB-0742, which targets CDK9, the company is also developing KB-9558 to address IRF4 dependence in multiple myeloma.

The company operates from San Mateo, California, with a research facility in Cambridge, Massachusetts.