~Paper Features Design and Preclinical Characterization of AP24534
~ Data Demonstrate Inhibition of all Known Variants of the CML Target Protein
CAMBRIDGE, Mass.--(Business Wire)--
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that the scientific
journal, Cancer Cell, has published a comprehensive paper describing the design
and preclinical characterization of AP24534, ARIAD`s investigational,
multi-targeted kinase inhibitor. The paper, "AP24534, a Pan-BCR-ABL Inhibitor
for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes
Mutation-Based Resistance," is co-authored by scientists from ARIAD, and
collaborating investigators from the Oregon Health & Science University Knight
Cancer Institute and the Howard Hughes Medical Institute.
The publication describes for the first time the chemical structure of AP24534
and its activity against all known BCR-ABL mutants, including the T315I mutant
that is resistant to currently marketed therapies for chronic myeloid leukemia
(CML). The paper provides a comprehensive description of the activity of AP24534
in a range of established cell-based and animal models of CML. AP24534 was
discovered by ARIAD scientists and is now in a Phase 1 dose-escalating clinical
trial in patients with refractory CML, acute myeloid leukemia (AML) and other
hematological malignancies.
"These data support the ongoing clinical study of AP24534 to develop a potential
much-needed treatment option for patients with resistant mutations such as
T315I, that could complement the currently available tyrosine kinase
inhibitors," said Timothy P. Clackson, Ph.D., senior vice president and chief
scientific officer at ARIAD and senior author of the paper. "Longer term, a
pan-BCR-ABL inhibitor such as AP24534 may offer important advantages by
minimizing the development of mutation-based drug resistance."
Treatment with BCR-ABL inhibitors is initially effective in most patients with
CML but can result in the emergence of BCR-ABL mutations that confer drug
resistance over time. In a preclinical experiment featured in the publication,
even when studied in modest concentrations, AP24534 completely suppressed the
emergence of resistant mutants. This finding is in contrast to results obtained
with other BCR-ABL inhibitors previously profiled in this in vitro assay. This
resistance profiling method has successfully predicted the specific mutations
that confer clinical resistance to marketed CML therapies imatinib (Gleevec®),
dasatinib (Sprycel®), and nilotinib (Tasigna®).
"We specifically designed AP24534 as a pan-BCR-ABL inhibitor and its novel
profile distinguishes it from all currently available therapies for CML," added
Dr. Clackson. "This preclinical work supports the ongoing clinical evaluation of
AP24534 in a broad set of CML patients with many different BCR-ABL mutations,
including the T315I mutation."
AP24534 is a product of ARIAD`s structure-based drug design platform. ARIAD
scientists first determined the structure of the T315I mutant of BCR-ABL to
discover how the mutation alters the drug binding site. A unique chemical linker
was then designed into the AP24534 structure to accommodate the mutation,
allowing potent inhibition of this and all other mutants tested.
The paper in Cancer Cell is the culmination of a productive, multi-year
collaboration between the ARIAD and Oregon groups to characterize the properties
and potential of AP24534. Brian Druker, M.D., director of the Oregon Health &
Science University Knight Cancer Institute, Howard Hughes Medical Institute
Investigator and JELD-WEN Chair of Leukemia Research at OHSU, is a senior author
on the paper.
The published paper on AP24534 can be accessed on the Cancer Cell website at
http://www.cell.com/cancer-cell/home
About ARIAD
ARIAD`s vision is to transform the lives of cancer patients with breakthrough
medicines. The Company`s mission is to discover, develop and commercialize
small-molecule drugs to treat cancer in patients with the greatest and most
urgent unmet medical need - aggressive cancers where current therapies are
inadequate. ARIAD`s lead product candidate, ridaforolimus, is an investigational
mTOR inhibitor in Phase 3 clinical development in patients with advanced
sarcomas and is being developed in collaboration with Merck & Co., Inc. ARIAD`s
second product candidate, AP24534, is an investigational multi-targeted kinase
inhibitor in Phase 1 clinical development in patients with hematological
cancers. ARIAD has an exclusive license to pioneering technology and patents
related to certain NF-κB cell-signaling activity, which may be useful in
treating certain diseases. For additional information about the Company, please
visit http://www.ariad.com.
Gleevec® and Tasigna® are registered trademarks of Novartis AG, and Sprycel® is
a registered trademark of Bristol-Myers Squibb, Inc.
This press release contains "forward-looking statements." Forward-looking
statements are based on management's expectations and are subject to certain
factors, risks and uncertainties that may cause actual results, outcome of
events, timing and performance to differ materially from those expressed or
implied by such statements. These risks and uncertainties include, but are not
limited to, preclinical data that may not be replicated in clinical studies, the
costs associated with our research, development, manufacturing and other
activities, the conduct and results of pre-clinical and clinical studies of our
product candidates, difficulties or delays in obtaining regulatory approvals to
market products resulting from our development efforts, our reliance on our
strategic partners and licensees and other key parties for the successful
development, manufacturing and commercialization of products, the adequacy of
our capital resources and the availability of additional funding, patent
protection and third-party intellectual property claims relating to our and any
partner's product candidates, the timing, scope, cost and outcome of legal and
patent office proceedings concerning our NF-κB patent portfolio, future capital
needs, and other factors detailed in the Company's public filings with the U.S.
Securities and Exchange Commission. The information contained in this press
release is believed to be current as of the date of original issue. The Company
does not intend to update any of the forward-looking statements after the date
of this document to conform these statements to actual results or to changes in
the Company's expectations, except as required by law.
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ARIAD Pharmaceuticals, Inc.
Maria E. Cantor, 617-621-2208
Copyright Business Wire 2009
