Benzinga | Apr 12, 2021 10:23AM EDT

Kronos Bio Saturday Morning Announced Preclinical Data For Oral CDK9 Inhibitor KB-0742 Demonstrating Sustained Inhibition Of Tumor Growth In Multiple Cancers At American Association For Cancer Research Conference

Kronos Bio, Inc. (NASDAQ:KRON), a company dedicated to transforming the lives of those affected by cancer, today presented preclinical data for KB-0742, a highly selective, orally bioavailable cyclin dependent kinase 9 (CDK9) inhibitor being developed to treat MYC-amplified solid tumors. The data showed that CDK9 inhibition on an intermittent dosing schedule with KB-0742 resulted in sustained inhibition of tumor growth in multiple types of solid tumors. The data also suggested that genomic amplification of MYC, a well-characterized transcription factor and a long-recognized driver of cancer, is a key factor of sensitivity to CDK9 inhibition. These findings were presented in a poster session today at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

"These preclinical data support our approach to leveraging CDK9 inhibition to treat cancers that express high levels of MYC. Furthermore, the anti-tumor activity seen with intermittent dosing of KB-0742 in multiple cancer cell lines suggests that constant inhibition may not be needed in order to achieve desired target coverage," said Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president, clinical development. "Having recently initiated our clinical development program for KB-0742, we are eager to determine if these preclinical results translate to the clinic. If this proves to be the case, we believe KB-0742 has the potential to be an important advance in the treatment of MYC-amplified solid tumors."

Kronos Bio researchers, in collaboration with colleagues from Baylor College of Medicine, the University of Washington and the Broad Institute, conducted several experiments to better define molecular sensitivity to transcriptional inhibition by profiling the sensitivity of various tumor types to KB-0742. They found that MYC genomic amplification emerged as a key driver of CDK9 inhibitor sensitivity, especially in non-small cell lung cancer. Additionally, MYC amplification and over-expression in tumor cells and patient-derived xenografts conferred sensitivity to CDK9 inhibition. In these CDK9-sensitive models, suppression of oncogenic transcription for more than eight hours was followed by cell death (apoptosis). Importantly, CDK9 inhibitor sensitivity was observed for both treatment-na?ve and heavily pretreated patient samples, and CDK9 inhibition on an intermittent dosing schedule achieved sustained target coverage, as evidenced by both direct readouts of CDK9 activity and corresponding transcriptional response, ultimately inhibiting tumor growth in multiple solid tumor types.

The poster is now available on the AACR Annual Meeting website and in the Publications section of the Kronos Bio website. Details of the presentation are as follows:

* Title: CDK9 inhibition is selective for transcriptionally addicted tumors harboring MYC genomic amplifications

* Abstract Number: 1141

* Session Category: Experimental and Molecular Therapeutics

* Session Title: Epigenetic Targets

In February, Kronos Bio initiated a Phase 1/2 clinical trial for KB-0742 in patients with advanced solid tumors or non-Hodgkin lymphoma. The company expects to report initial safety, pharmacokinetic and pharmacodynamic data from the dose-escalation stage of the study in the fourth quarter of this year. Initial data from the study's expansion cohorts are expected in 2022.

About KB-0742

KB-0742 is a highly selective, orally bioavailable inhibitor of cyclin dependent kinase 9 (CDK9) in development for the treatment of MYC-amplified solid tumors. CDK9 is a global regulator of transcription and plays an essential role in both the expression and function of MYC, a well-characterized transcription factor and a long-recognized driver of cancer that is amplified in approximately 30% of solid tumors, including those affecting the lungs, ovaries, esophagus, breast, stomach, pancreas and liver.1 KB-0742 was generated and optimized from a compound that was identified using the company's proprietary small molecule microarray (SMM) screening platform.