Kronos Bio Announces Selection of Recommended Phase 2 Dose for its Oral CDK9 Inhibitor, KB-0742, After Reaching Target Engagement Goal with Acceptable Safety Profile in Ongoing Phase 1/2 Clinical Trial
December 07 2022 - 4:05PM
Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to
transforming the lives of those affected by cancer, today announced
that data from the ongoing dose-escalation stage of its Phase 1/2
clinical trial of KB-0742, the company’s cyclin dependent kinase 9
(CDK9) inhibitor being developed to treat MYC-amplified and
transcriptionally addicted solid tumors, support a recommended
Phase 2 dose (RP2D) of 60 mg.
Results from the trial, including the Phase 1
stage and initial data from the Phase 2 expansion stage, will be
presented at a medical conference in the second half of 2023.
An analysis of the trial results demonstrated
that treatment with a 60 mg dose of KB-0742 led to a targeted
reduction of approximately 50% in levels of phosphorylated Ser2 on
RNA Polymerase II (pSer2), a direct substrate target of CDK9 in
PBMCs. This level of target engagement is consistent with
demonstrating anti-tumor activity based on preclinical models. The
analysis further showed that KB-0742 continues to demonstrate a
differentiated pharmacokinetic (PK) profile, with oral
bioavailability and dose-proportional exposure across all four dose
levels, and low to moderate variability between patients. A total
of 26 patients have been enrolled and treated in the dose
escalation phase of the study. Among those patients, PK data were
collected and analyzed for 25 patients and KB-0742 continued to
demonstrate a terminal half-life of 24 hours, with approximately
2.1 to 2.5-fold accumulation between Day 1 and Day 10. These
results are consistent with findings from an initial analysis
announced last year.
The long plasma half-life enables KB-0742 to
achieve sustained pharmacologically active concentrations while
avoiding potentially toxic peak (Cmax) concentrations. This PK
profile, combined with the biochemical selectivity of KB-0742 for
CDK9 over other CDK enzymes, is critical to supporting Kronos Bio’s
approach to defining a therapeutic window for CDK9 using a
three-day-on/four-day-off treatment regimen.
In addition to achieving 50% or greater
suppression of CDK9, the 60 mg dose appears to have an acceptable
safety profile and the maximum tolerated dose has not yet been
defined.
“These data represent important progress for our
KB-0742 program, demonstrating that we were able to reach our
target engagement goal, without broadly and unselectively
suppressing transcription,” said Norbert Bischofberger, Ph.D.,
president and chief executive officer of Kronos Bio. “CDK9 is a
target that has been pursued for many years with limited success
because of the difficulty of achieving a therapeutic window. We
believe we have identified that window for KB-0742 and look forward
to moving to the next stage of the study.”
While the dose escalation stage of the trial
will continue with the goal of reaching a maximum tolerated dose,
Kronos Bio will immediately move into the second stage of the
two-stage trial and begin assessing the anti-tumor activity of
KB-0742 at the RP2D. Kronos Bio will enroll two cohorts of patients
in this Phase 2 stage of the study. Cohort A will include patients
with MYC-amplified tumors: triple negative breast cancer, non-small
cell lung cancer and ovarian cancer. Cohort B will include patients
with transcriptionally addicted cancers, including chordomas,
sarcomas and small cell lung cancer.
“We are very pleased to have reached our RP2D
and to begin evaluating KB-0742 in patients who we believe are most
likely to benefit from treatment with the compound,” said Jorge
DiMartino, M.D., PhD., chief medical officer and executive vice
president of Clinical Development for Kronos Bio. “We look forward
to providing further updates on this program, as we now begin to
evaluate the efficacy of KB-0742 in these patient populations.”
The company expects to share detailed data from
the Phase 1 dose escalation stage of the trial, as well as initial
results from the Phase 2 expansion cohorts, at a medical conference
in the second half of 2023.
About Kronos Bio, Inc.Kronos
Bio is a biopharmaceutical company that is advancing two
investigational compounds in clinical trials for patients with
cancer. The company is developing the CDK9 inhibitor, KB-0742, as a
treatment for MYC-amplified solid tumors, and lanraplenib, a
next-generation SYK inhibitor, for patients with
relapsed/refractory FLT3-mutated acute myeloid leukemia. The
company’s scientific focus is on developing medicines that target
the dysregulated transcription that is the hallmark of cancer and
other serious diseases.
Kronos Bio is based in San Mateo, Calif., and
has a research facility in Cambridge, Mass. For more information,
visit www.kronosbio.com or follow the company on LinkedIn.
Forward-Looking Statements
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. This press release, in some cases,
uses terms such as “to be,” “will,” “expects,” “anticipates” or
other words that convey uncertainty of future events or outcomes to
identify these forward-looking statements. Forward-looking
statements include statements regarding our intentions, beliefs,
projections, outlook, analyses or current expectations concerning,
among other things: our plan to move into the Phase 2 stage of the
Phase 1/2 clinical trial of KB-0742 and the enrollment plans and
trial design for such stage; our expectation to present data from
such Phase 1/2 clinical trial at a future medical conference; the
potential safety profile of KB-0742; 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 we will be able to initiate
and complete ongoing enrollment for the Phase 2 stage of the Phase
1/2 clinical trial of KB-0742 on the timeline expected, or at all,
including due to risks associated with the COVID-19 pandemic; risks
inherent in the clinical development of novel therapeutics; risks
related to our lack of experience as a company in conducting
clinical trials; and risks associated with the sufficiency of our
cash resources and need for additional capital. These and other
risks and uncertainties are described in greater detail in the
company’s filings with the Securities and Exchange Commission
(“SEC”), including under the heading “Risk Factors” in our
Quarterly Report on Form 10-Q for the quarter ended September 30,
2022, filed with the SEC on November 8, 2022. 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, the company 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.Company Contact:Marni KottleKronos Bio
650-900-3450mkottle@kronosbio.com
Investors:Claudia StyslingerArgot
Partners212-600-1902kronosbio@argotpartners.com
Media:Sheryl SeapyReal
Chemistry949-903-4750 sseapy@realchemistry.com
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