Kronos Bio Announces First Patient Dosed in Phase 1/2 Clinical Trial of KB-0742, an Oral CDK9 Inhibitor Targeting MYC-amplified Cancers
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, Calif. and CAMBRIDGE, Mass., Feb. 25, 2021 (GLOBE NEWSWIRE) -- 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.
Statements in this press release that are not statements of historical fact are forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release, in some cases, uses terms such as "believe," "potential," represents," "opportunity, "could," "allow," "expects," "expected," "will," "seek," "further" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding Kronos Bio’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the design of the KB-0742 Phase 1/2 clinical trial, including to establish clinical proof of concept to enable potential further development, and other statements that are not historical fact. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: whether Kronos Bio will be able to complete the Phase 1/2 clinical trial of KB-0742, including due to risks associated with the COVID-19 pandemic and risks inherent in the clinical development of novel therapeutics; risks related to Kronos Bio’s lack of experience as a company in conducting clinical trials; the risk that results of preclinical studies and early clinical trials are not necessarily predictive of future results; the risk that due to the relatively small number of patients that Kronos Bio plans to dose in the planned Phase 1/2 KB-0742 clinical trial, the results from such trial, once completed, may be less reliable than results achieved in larger clinical trials, which may hinder Kronos Bio’s efforts to further develop and obtain regulatory approval for KB-0742; and risks associated with the sufficiency of Kronos Bio’s cash resources and need for additional capital. These and other risks are described in greater detail in Kronos Bio’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in its Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed with the SEC on November 18, 2020. Any forward-looking statements that are made in this press release speak only as of the date of this press release and are based on management’s assumptions and estimates as of such date. Except as required by law, Kronos Bio assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
- Schaub, F.X., Dhankani, V., Berger, A.C., et al. (2018). Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas. Cell Systems, 6(3), 282–300.
Executive Director, Investor Relations and Corporate Communications