Chk1 Inhibitor Enhances Anti-Tumor Activity of Chemotherapeutic Agents
BOULDER, Colo.--(BUSINESS WIRE)--Apr. 21, 2009--
Array BioPharma Inc. (NASDAQ: ARRY) today announced the presentation of
two abstracts which detail positive preclinical data for a novel class
of oral, potent and selective checkpoint kinase 1 (Chk1) inhibitors. The
data demonstrate that Chk1 inhibition and checkpoint abrogation disrupt
natural tumor cell repair mechanisms and suggest that a potent,
selective Chk1 inhibitor may bolster the anti-tumor effects of commonly
used chemotherapies such as Campostar® (irinotecan), by heightening
sensitivity to these DNA damaging agents. Based on the potency,
selectivity and efficacy data seen with its Chk1 inhibitors, Array
intends to select a compound for development in the first half of 2009.
The full posters are available as PDFs on Array's website at www.arraybiopharma.com.
“Our selective, oral Chk1 inhibitors enhance the activity of
chemotherapeutics at tolerable doses,” said Kevin Koch, Ph.D., President
and Chief Scientific Officer. “The multi-day dosing required for optimal
efficacy can be conveniently achieved with oral administration. We
believe this oral approach represents a significant advantage over IV
competitors.”
Abstract No. 4599 entitled “Schedule-dependence and extended
target-coverage of selective Chk1 inhibitors enhances the anti-tumor
activity of chemotherapy in vivo,” details the in vivo
schedule-dependence and tolerability of Chk1 inhibitors in combination
with irinotecan, a topoisomerase I inhibitor. Results indicated that,
using an optimized dosing schedule, Chk1 inhibitors demonstrate dose
dependence, as well as extended dosing superiority, in preclinical
models of colon cancer. In pharmacokinetic and pharmacodynamic studies,
our Chk1 inhibitor prevents Chk1 activation by 100 percent for up to 12
hours following a single 25 mg/kg oral dose.
Abstract No. 1803 entitled “Characterization of a Novel, Oral
Chk1 Inhibitor,” investigates the activity of a novel class of oral,
potent and selective Chk1 inhibitors and characterizes a lead analog,
Chk1-A. Data showed that Chk1-A improves the activity of multiple
cytotoxics up to 17-fold. In vivo, Chk1-A demonstrated good
exposure, moderate clearance and good bioavailability. In addition,
Chk1-A demonstrated rapid Chk1 inhibition lasting for up to 12 hours in
tumor-bearing mice. In colon cancer models, Chk1-A demonstrated
dose-dependent potentiation of irinotecan’s anti-tumor effects with a
significant increase in growth delay compared to irinotecan alone. All
dosing regimens were well tolerated.
About Chk1 Inhibitors for Cancer
Checkpoint kinase 1 (Chk1) is a protein kinase that regulates resistance
in cancer cells after chemotherapy-induced DNA damage by arresting cell
cycle progression until completion of DNA repair. Inhibiting Chk1 after
treatment with chemotherapy can enhance tumor cell killing by preventing
these cells from recovering from DNA damage. Checkpoint
inhibition therefore represents a promising approach to improving the
clinical activity of existing cancer therapeutics.
Array’s program comprises the first oral, selective Chk1 inhibitors. In
preclinical models, Array Chk1 inhibitors combined with cytotoxic
treatment showed significantly enhanced anti-tumor activity compared to
the cytotoxic alone at well tolerated doses. The optimal activity of
Chk1 inhibitors requires prolonged multi-day dosing that can be most
conveniently achieved with oral dosing.
About Array BioPharma
Array BioPharma Inc. is a biopharmaceutical company focused on the
discovery, development and commercialization of targeted small molecule
drugs to treat patients afflicted with cancer, inflammatory and
metabolic diseases. Our proprietary drug development pipeline includes
clinical candidates that are designed to regulate therapeutically
important target proteins and are aimed at significant unmet medical
needs. In addition, leading pharmaceutical and biotechnology companies
collaborate with Array to discover and develop drug candidates across a
broad range of therapeutic areas. For more information on Array, please
go to www.arraybiopharma.com.
Forward-Looking Statement
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements about our future plans for advancing certain of our
proprietary drug programs, the potential to earn future milestone
payments, license fees or royalty revenue and the plans of our
collaborators to further develop drugs we have out-licensed or on which
we are collaborating. These statements involve significant risks and
uncertainties, including those discussed in our annual report filed on
form 10-K for the year ended June 30, 2008, and in other reports filed
by Array with the Securities and Exchange Commission. Because these
statements reflect our current expectations concerning future events,
our actual results could differ materially from those anticipated in
these forward-looking statements as a result of many factors. These
factors include, but are not limited to, our ability to continue to fund
and successfully progress internal research efforts and to create
effective, commercially viable drugs, our ability to achieve and
maintain profitability, the extent to which the pharmaceutical and
biotechnology industries are willing to in-license drug candidates for
their product pipelines and to collaborate with and fund third parties
on their drug discovery activities, our ability to out-license our
proprietary candidates on favorable terms, risks associated with our
dependence on our collaborators for the clinical development and
commercialization of our out-licensed drug candidates, the ability of
our collaborators and of Array to meet objectives tied to milestones and
royalties and our ability to attract and retain experienced scientists
and management. We are providing this information as of April 21, 2009.
We undertake no duty to update any forward-looking statements to reflect
the occurrence of events or circumstances after the date of such
statements or of anticipated or unanticipated events that alter any
assumptions underlying such statements.
Source: Array BioPharma Inc.
Array BioPharma
Tricia Haugeto, 303-386-1193
thaugeto@arraybiopharma.com
or
MacDougall
Biomedical Communications
Cory Tromblee, 781-235-3060
ctromblee@macbiocom.com
