Kronos Bio Highlights Data at AACR Ovarian Cancer Research Symposium that Supports Clinical Evaluation of Istisociclib in Advanced Ovarian Cancer
23 Septembre 2024 - 2:55PM
Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing
small molecule therapeutics that address cancers and other diseases
driven by deregulated transcription, today highlighted new
preclinical data from a study of istisociclib (KB-0742). The poster
presentation took place over the weekend at the American
Association for Cancer Research (AACR) 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 (HGSOC).
"We’ve demonstrated preclinical evidence that istisociclib
induced DNA damage and subsequent cell death, which further
supports our clinical program focused on platinum-resistant
high-grade serous ovarian cancer," said Luis A. Carvajal, Ph.D.,
Director of Translational Development at Kronos Bio, the lead
author on the poster. "Importantly, platinum or PARPi insensitive
cell lines showed greater sensitivity to istisociclib in cell
viability assays. Moreover, ovarian cancer cells with PARPi
resistance were sensitized to PARP inhibition in the presence of
istisociclib.”
Dr. Carvajal added, “Based on new PK data from our ongoing
clinical trial, we conclude that plasma levels were consistent with
efficacious exposures observed in preclinical models of ovarian
cancer, and we are excited to be enrolling patients into an
expansion cohort of patients with platinum-resistant high-grade
serous ovarian cancer.”
From the presentation, “Preclinical and clinical data support
clinical expansion of istisociclib (KB-0742), 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 γH2AX, a sensitive
molecular marker of DNA damage
- Istisociclib disrupted homologous recombination (HR) 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 (PK/PD) 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 (PBMCs)
The poster from the presentation is available under the Science
& Pipeline section of the Kronos Bio website.
About Kronos BioKronos Bio, Inc. (Nasdaq: KRON)
is a clinical-stage company dedicated to developing small molecule
therapeutics that address deregulated transcription, a hallmark of
cancer and other diseases. Our proprietary discovery engine decodes
complex transcription factor regulatory networks to identify
druggable cofactors. We screen for and optimize small molecules
that target these cofactors in a tumor-specific context. These
efforts have yielded a preclinical pipeline along with two
internally developed drug candidates. Istisociclib (KB-0742)
targets CDK9 to address MYC deregulation in solid tumors and
KB-9558 targets p300 to address IRF4 dependence in multiple
myeloma.
Kronos Bio is based in San Mateo, Calif., and has a research
facility in Cambridge, Mass.For more information, visit
https://www.kronosbio.com or follow the Company on LinkedIn.
Contact Information:
Investors:
Margaux Bennett
Vice President, Corporate Development and Investor Relations, Kronos Bio
650-781-5026
mbennett@kronosbio.com
Media:
Kelli Perkins
kelli@redhousecomms.com
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