BOULDER, Colo.–(BUSINESS WIRE)–OnKure, Inc. and the University of Colorado Cancer Center today
announced enrollment of the first patient in a first-in-human phase 1
clinical trial testing investigational anti-cancer agent OKI-179, a
novel and Class-selective HDAC inhibitor, in patients with advanced
solid tumors. The study represents a milestone in the ongoing
partnership between OnKure and the University of Colorado system, with
the drug discovery and development company built around basic research
from CU Boulder and the clinical trial taking place in partnership with
CU Cancer Center on the Anschutz Medical Campus.
“This CU homegrown, clinical-stage drug is the result of a multi-year
collaboration, so our team is very excited. We’re happy to report that
we successfully dosed the first patient and the patient is doing well,”
says Jennifer Diamond, MD, Medical Director of the CU Cancer Center
Cancer Clinical Trials Office, Co-director of the Women’s Cancer
Developmental Therapeutics Program, and principal investigator of the
OKI-179 phase 1 clinical trial.
OKI-179 is a potent and selective inhibitor of a family of enzymes known
as histone deacetylases (HDACs), specifically inhibiting Class 1 HDACs,
which are implicated in the development and growth of a range of solid
and hematologic cancers. While previous HDAC inhibitors have shown
promise in preclinical studies, clinical benefit has generally been
limited by toxicity.
“We’re very optimistic that OKI-179 will fill a hole in what is
currently available,” says Anthony D. Piscopio, PhD, President and Chief
Executive Officer of OnKure. “It also stands out from FDA-approved HDAC
inhibitors based on its unique potency and selectivity profile.”
The compound is an analog of the naturally occurring chemical largazole,
named for Key Largo, Florida, where largazole is bio-manufactured by a
type of coral-colonizing bacteria indigenous to the region. After its
structure and anti-proliferative effects were described in 2008, work by
Xuedong Liu, PhD, Professor of Chemistry and Biochemistry at CU Boulder,
showed that largazole and the chemical analog that would become OKI-179
achieve their anti-proliferative effects through the mechanism of HDAC
inhibition. Dr. Liu also serves as Chief Science Officer of OnKure.
“Basically, HDAC enzymes remove a kind of speed limiter from cells,
allowing them to proliferate more readily and HDAC inhibitors like
OKI-179 block this effect,” Dr. Diamond says.
The phase 1 clinical trial (NCT03931681)
is offered exclusively at CU Cancer Center to patients with solid tumors
for whom no standard therapy exists, and is meant to explore drug
safety, tolerability, and dosing. Additional research, including a 2017
study by CU Cancer Center investigators published in the Journal of
Clinical Oncology, shows that in addition to possible single-agent
use, OKI-179 may sensitize tumor tissue to targeting via immunotherapies
including anti-PD1 checkpoint inhibitors.
“This drug is a compelling part of our portfolio of innovative clinical
trials in the CU Cancer Center Women’s Cancer Developmental Therapeutics
Program,” Dr. Diamond says.
OnKure, Inc. is a biopharmaceutical company focused on the discovery and
development of targeted small molecule drugs to improve the outcomes of
patients afflicted with cancer. OnKure’s drug candidates aim to treat
patients by targeting malignant cells directly, by working in
combination with other small molecule therapies and by priming the tumor
microenvironment such that checkpoint inhibition is optimized. For more
information about OnKure and OKI-179, please visit www.onkuretherapeutics.com.
About University of Colorado Cancer Center
The University of Colorado Cancer Center, located at the Anschutz
Medical Campus, is Colorado’s only National
Cancer Institute-designated comprehensive cancer center, a
distinction recognizing its outstanding contributions to research,
clinical trials, prevention and cancer control. The CU Cancer Center is
a member of the prestigious National
Comprehensive Cancer Network®, an alliance of the nation’s leading
cancer centers working to establish and deliver the gold standard in
cancer clinical guidelines. CU Cancer Center also is a member of the Oncology
Research Information Exchange Network (ORIEN), a unique research
partnership among North America’s top cancer centers leveraging multiple
data sources and matching patients to targeted treatments. CU Cancer
Center is a consortium
of approximately 400 researchers and physicians at three state
universities and three clinical institutions, all working toward one
goal: Translating science into life.