Kronos Bio Announces First Patient Dosed in Phase 1/2 Clinical Trial of KB-0742, an Oral CDK9 Inhibitor Targeting MYC-amplified Cancers
- Category: Small Molecules
- Published on Thursday, 25 February 2021 14:54
- Hits: 762
KB-0742 generated using the company’s proprietary small molecule microarray (SMM) screening platform
Initial safety, pharmacokinetic and pharmacodynamic data expected in fourth quarter of 2021
SAN MATEO, CA and CAMBRIDGE, MA, USA I February 25, 2021 I Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, today announced that the first patient has been dosed in the Phase 1/2 clinical trial of KB-0742, a highly selective, orally bioavailable cyclin dependent kinase 9 (CDK9) inhibitor being developed to treat MYC-amplified solid tumors.
“KB-0742 represents a promising new approach to treating cancers that are transcriptionally addicted to MYC. We are excited to have initiated our clinical development program for KB-0742, which emerged from our internal discovery research efforts and moved quickly into clinical testing in under two years,” said Norbert Bischofberger, Ph.D., president and CEO. “We believe KB-0742 has the potential to be a meaningful advance in the treatment of MYC-amplified cancers, which represent approximately 30% of solid tumors.”
“MYC is one of the most sought-after targets in oncology but has eluded therapeutic treatment. Scientific research has established that MYC requires CDK9 to drive its own expression and to drive expression of its target genes. At Kronos Bio, we have observed that tumor cell lines that have extra copies of the MYC gene have heightened sensitivity to KB-0742,” said Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president, clinical development. “With KB-0742’s high selectivity for CDK9 and oral bioavailability, we have a unique opportunity in this Phase 1/2 clinical trial to investigate an optimal dose and schedule designed to provide appropriate target engagement and acceptable safety that could allow us to leverage CDK9 inhibition as an approach to treating MYC-amplified cancers.”
The open-label, multi-center Phase 1/2 clinical trial of KB-0742 is expected to enroll approximately 100 patients with advanced solid tumors or non-Hodgkin lymphoma. The trial will be conducted over two stages: dose escalation and expansion. The dose-escalation stage will assess the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile of KB-0742 and will seek to establish a pharmacologically active dose and schedule with an acceptable safety profile. This dose and schedule will be further studied in the subsequent expansion stage in patients with MYC-amplified solid tumors and other transcriptionally addicted cancers including soft tissue sarcomas.
Kronos Bio expects to report initial safety, PK and PD 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.
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.
About the Small Molecule Microarray (SMM) Screening Platform
Kronos Bio leverages its SMM screening platform to conduct high-throughput screens against traditionally undruggable target proteins, in particular transcription factors. The SMM platform directly addresses the historical challenges of targeting transcription factors by screening in conditions that preserve their associated context-dependent structures and multi-protein complexes. Using the company’s library of approximately 240,000 compounds in microarray format on slides, Kronos Bio screens for small molecule binders of the target transcription factor in context-relevant tumor nuclear lysates. Hits derived from SMM screening have the potential to act through a variety of mechanisms against various members of a transcription factor’s complex and, as such, hits are characterized for their ability to selectively modulate an oncogenic transcription factor’s activity as important criteria for further lead selection and optimization.
About Kronos Bio, Inc.
Kronos Bio is a clinical-stage biopharmaceutical company dedicated to discovering, developing and commercializing therapies that seek to transform the lives of those affected by cancer. The company focuses on targeting dysregulated transcription factors and the regulatory networks within cells that drive cancerous growth. Kronos Bio’s lead investigational therapy is entospletinib, a selective inhibitor targeting spleen tyrosine kinase (SYK) in development for the frontline treatment of NPM1-mutated acute myeloid leukemia (AML). The company is also developing KB-0742, an oral inhibitor of cyclin dependent kinase 9 (CDK9), for the treatment of MYC-amplified solid tumors.
SOURCE: Kronos Bio