Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to
transforming the lives of those affected by cancer, today announced
positive preliminary data from the Phase 1 dose escalation portion
of the ongoing Phase 1/2 clinical trial of KB-0742 at the
AACR-NCI-EORTC International Conference in Boston, Mass. KB-0742 is
the company’s internally discovered, highly selective, orally
bioavailable cyclin dependent kinase 9 (CDK9) inhibitor being
developed to treat transcriptionally addicted solid tumors. These
tumors include transcription factor fusion driven cancers such as
sarcomas, as well as MYC-dependent tumors, such as triple negative
breast, ovarian, and lung cancer.
The preliminary analysis included 28 patients
enrolled in a dose escalation study who received doses from 10 mg
up to 60 mg (data cut-off September 1st, 2023). KB-0742
demonstrated on-mechanism single agent anti-tumor activity in
heavily pre-treated patients with transcriptionally addicted tumor
types and exhibited a manageable safety profile, with no grade 3/4
neutropenia observed. KB-0742 also demonstrated dose proportional
exposure and target engagement and a 24-hour plasma half-life,
enabling intermittent dosing. The long plasma half-life enabled
KB-0742 to achieve sustained pharmacologically active
concentrations while avoiding potentially toxic peak (Cmax)
concentrations. The most common tumor types of these patients were
colorectal (5), chordoma (4), sarcoma (4), lung (3) and breast (3).
Because the maximum tolerated dose has not yet been identified,
enrollment in the dose escalation portion continues and dosing of
patients at the 80 mg dose level is underway. In parallel, the
ongoing dose expansion portion of the study, which commenced in
January 2023, is enrolling patients with MYC-dependent and other
transcriptionally addicted tumors across two cohorts at the 60 mg
dose level. Data from this dose expansion portion of the study are
expected in mid-2024.
“These positive preliminary efficacy and safety
data underscore the promise of KB-0742 to treat patients with
transcriptionally addicted tumors. The observed anti-tumor activity
and absence of grade 3/4 neutropenia are particularly encouraging
as we continue to enroll patients and explore a maximum tolerated
dose,” said Jorge DiMartino, M.D., Ph.D., Chief Medical Officer and
Executive Vice President, Clinical Development. “We look forward to
advancing the study and reporting additional results, including
data from the dose expansion portion of the study, mid next
year.”
“CDK9 has been an attractive yet elusive target
in oncology research. The results from today’s presentation,
however, demonstrate that KB-0742 has demonstrated on-mechanism
clinical activity and a manageable safety profile, which is a
significant achievement,” said Miguel Villalona-Calero, M.D.,
Medical Oncologist and Director of Early Therapeutics at City of
Hope National Medical Center. “Based upon the unique pharmacologic
properties of KB-0742 and data to date, I consider KB-0742 to be a
promising agent to treat a wide variety of cancers with high unmet
need.”
Single Agent Anti-Tumor Activity in
Heavily Pre-Treated Patients with Transcriptionally Addicted Tumor
Types
As of the September 1st, 2023 data cut-off date, 28 patients
were enrolled in the dose escalation portion of the trial with
doses ranging from 10 mg to 60 mg. Patients had received a median
of 3.5 prior lines of therapy and the median treatment duration was
57 (range 2 to 398) days and median follow up was 86 (range 57 to
114) days.
At the 60 mg dose level (n=14), evidence of
target engagement was observed by pSER2 reduction and proportional
changes to CDK9 responsive genes. Tumor reduction (1 PR, 1 SD) was
observed in two patients with myxoid liposarcoma, a
transcriptionally addicted tumor type characterized by a chimeric
fusion TF, consistent with on-mechanism activity. Of these two
patients with myxoid liposarcoma, one (7th line) had a partial
response (per RECIST v1.1) lasting 113 days and the second achieved
a 26% reduction in tumor diameters with stable disease. Nine (44%)
patients across numerous cancer types had stable disease as the
best response, and the overall disease control rate was 48%
(defined as a complete response, partial response, or stable
disease). Myxoid liposarcomas are driven by a transcription factor
fusion supporting the therapeutic hypothesis that CDK9 inhibition
with KB-0742 can selectively target these and other
transcriptionally addicted tumors.
Manageable Safety Profile with No Grade
3 or 4 Neutropenia
Treatment-emergent adverse events (TEAEs) that
occurred in >20% of patients included nausea (64%), vomiting
(68%) and fatigue (29%), all of which were grade 1/2. No grade 3/4
neutropenia was observed, and no treatment-related deaths were
observed. The most common reasons for treatment discontinuation
were progressive disease, TEAEs, and withdrawal of consent.
Webcast and Conference Call
Kronos Bio will host a virtual conference call
and webcast today, October 13, 2023, at 4:30 p.m. ET., followed by
a Q&A session. The event will feature key opinion leader and
trial investigator, Miguel Villalona-Calero, M.D, Medical
Oncologist and Director of Early Therapeutics, City of Hope
National Medical Center, along with Kronos Bio management, who will
provide an overview of the KB-0742 program and discuss the data
presented today.
A live webcast of the conference call can be accessed under
“Events & Presentations” on the investors section of the
Company’s website at ir.kronosbio.com/events-presentations. To
participate in the live call, please register using this link. It
is recommended that participants register at least 15 minutes in
advance of the call. Once registered, participants will be informed
of the dial-in numbers and PIN. An archived webcast will be
available following the event.
The poster presentation from the AACR-NCI-EORTC
International Conference is available on publications section of
Kronos Bio’s website at kronosbio.com/publications.
About KB-0742
KB-0742 is a highly selective, orally
bioavailable inhibitor of cyclin dependent kinase 9 (CDK9) in
development for the treatment of transcriptionally addicted solid
tumors. CDK9 is a global regulator of transcription and plays an
essential role in both the expression and function of oncogenic
transcription factors such as MYC, a well-characterized oncogene
that is amplified in approximately 30% of all solid tumors, and
amplified or highly overexpressed in lung, ovarian, and triple
negative breast cancers. KB-0742 was generated and optimized from a
compound that was identified using the company’s proprietary small
molecule microarray (SMM) screening platform.
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-dependent solid tumors and other
transcriptionally addicted solid tumors and lanraplenib, a
next-generation SYK inhibitor, for patients with FLT3-mutated acute
myeloid leukemia. The company’s scientific focus is on developing
medicines that target the deregulated 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. The press release, in some cases, uses terms such as
“on track to,” “plan,” “potential,” “will,” 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, Kronos Bio’s the expected timing for data from the dose
expansion portion of the study, the promise of KB-0742 to treat
patients with transcriptionally addicted tumors, KB-0742 being a
promising agent to treat a wide variety of cancers with high unmet
need, future results that may be implied from preliminary data, 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 progress its clinical trials on the timelines
anticipated, including due to 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; and
the risk that results of preclinical studies and early clinical
trials (including preliminary results) are not necessarily
predictive of future results. 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
June 30, 2023, filed with the SEC on August 8, 2023. 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.
Company Contact:Sarah Connors, Vice President
of Investor Relations and Corporate CommunicationsKronos
Bio857-290-7305sconnors@kronosbio.com
Agency Contact:Brendan Strong, Managing
DirectorArgot Partners 212-600-1902kronosbio@argotpartners.com
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