AVN944 Biomarker Study Identifies Gene Signatures Important for Patient Stratification
April 17 2007 - 6:30AM
PR Newswire (US)
GERMANTOWN, Md., April 17 /PRNewswire-FirstCall/ -- Avalon
Pharmaceuticals, Inc. (NASDAQ:AVRX), today announced the results of
an AVN944 biomarker study that utilized Avalon's proprietary
AvalonRx(R) technology to identify gene signatures that may be
useful for patient stratification. The poster presentation entitled
"Modulation of Gene Expression and Guanosine Pools by Inhibition of
Inosine Monophosphate Dehydrogenase (IMPDH); correlating In Vitro
Cell Resistance with Biomarker Response in Patient Samples from the
Phase I Trial," was given at the American Association for Cancer
Research Annual Meeting held April 14-18, 2007, in Los Angeles. The
study described the generation of biomarkers that may have utility
in identifying patients most likely to benefit from AVN944 therapy.
"Our biomarker-driven approach to drug development allows us the
opportunity to enrich our clinical trials with patient populations
more sensitive to AVN944 therapy," stated Jeffrey Strovel, Ph.D.,
senior scientist at Avalon and lead investigator in the study. "We
can now validate these gene signatures for utility in patient
stratification in our upcoming Phase II trials, as well as for
their use as prognostic signatures. If this approach works, it
could significantly accelerate the development of AVN944 and
enhance its utility as a marketed product." AVN944 is an orally
bioavailable inhibitor of inosine monophosphate dehydrogenase 1 and
2 (IMPDH). IMPDH2 is highly up-regulated and required for the
production of guanine nucleotides in many malignancies, including
hematologic cancers. AVN944 has been in a repeat-dose, dose
escalation trial in patients with advanced hematologic cancers
including AML, CLL, Multiple Myeloma and lymphomas. To identify
modes of sensitivity and resistance to AVN944 therapy, Avalon
developed a resistant Multiple Myeloma cell line, RPMI- 8226R.
RPMI-8226R was subjected to microarray gene expression profiling,
and guanosine triphosphate (GTP) level was determined with the
objective of comparing these biomarkers to the same markers in
patient samples from the Phase I clinical trial. Upon comparison of
gene expression signatures from patients enrolled in the AVN944
clinical trial to RPMI-8226R, a gene signature was identified that
distinguished patients receiving multiple rounds of therapy from
those that derived no benefit from AVN944. These gene expression
signatures will be evaluated further in a Phase II trial to examine
their utility in the enrichment of patients likely to benefit from
AVN944 therapy. Currently, Avalon researchers are developing
additional AVN944 resistant cell lines derived from solid tumor
cells to develop a better understanding of the molecular modes of
sensitivity and resistance in preparation for upcoming clinical
trials in solid tumors. About AVN944 AVN944 is an oral small
molecule drug candidate that inhibits inosine monosphospate
dehydrogenase (IMPDH), an enzyme that is critical for cells to be
able to synthesize guanosine triphosphate (GTP), a molecule
required for DNA synthesis and cellular signaling. IMPDH is over
expressed in some cancer cells, especially in the case of
hematological malignancies. In laboratory experiments, AVN944 has
been shown to inhibit IMPDH activity in cells, and suppress pools
of GTP. Anticancer activities of IMPDH inhibitors correlate with
sustained depletion of GTP pools both in cellular models and in
human subjects. AVN944 appears to have a selective effect on cancer
cells in that deprivation of GTP in normal cells results in a
temporary slowing of cell growth, while GTP deprivation in cancer
cells induces cell death, or apoptosis. Results from preclinical
studies of AVN944 indicate that AVN944 inhibited the proliferation
of lymphoid and myeloid cells, the principal cells involved in the
most common types of human leukemias. In a single-dose, dose-
escalation Phase I clinical trial of AVN944 conducted in the United
Kingdom in healthy volunteers, AVN944: (1) was well tolerated at
all tested doses with no notable side effects; (2) demonstrated
good pharmacokinetic properties; and (3) had a significant
inhibitory effect on IMPDH enzyme activity. Avalon filed an IND
with the FDA in August 2005 and initiated U.S. Phase I clinical
trials in January 2006 for the treatment of hematological cancers.
About Avalon Pharmaceuticals Avalon Pharmaceuticals is a
biopharmaceutical company using its proprietary technology,
AvalonRx(R), to discover and develop cancer therapeutics. Avalon
has a lead product in Phase I clinical development (AVN944 - IMPDH
inhibitor), as well as preclinical programs to discover inhibitors
for the beta-catenin and aurora pathways now in late stage lead
candidate optimization. Avalon also has discovery programs on
modulators of survivin function and a drug discovery program
targeting the MYC oncoprotein, one of the most important and
previously intractable cancer targets. The company has value
generating partnerships with Merck, MedImmune, Medarex, and
Novartis. Avalon Pharmaceuticals was established in 1999 and is
headquartered in Germantown, Md. Safe Harbor Statement This
announcement contains, in addition to historical information,
certain forward-looking statements that involve risks and
uncertainties, in particular, related to progress in our drug
discovery programs and our collaborations, and clinical progress in
the development of AVN944. Such statements reflect the current
views of Avalon management and are based on certain assumptions.
Actual results could differ materially from those currently
anticipated as a result of a number of factors, risks and
uncertainties including the risk that the discovery programs and
collaborations may not be successful and that AVN944 will not
progress successfully in its clinical trials, and other risks
described in our SEC filings. There can be no assurance that our
development efforts will succeed, that AVN944 will receive required
regulatory clearance or, even if such regulatory clearance is
received, that any subsequent products will ultimately achieve
commercial success. The information in this Release should be read
in conjunction with the Risk Factors set forth in our 2005 Annual
Report on Form 10-K and updates contained in subsequent filings we
make with the SEC. Contacts: Avalon Pharmaceuticals, Inc. Noonan
Russo David Muth Greg Geisman Executive Vice President Tel: (619)
814-3510 & Chief Business Officer Tel: (301) 556-9900 Fax:
(301) 556-9910 The Trout Group LLC Email: Chad Rubin (Investors)
Tel: (646) 378-2947 DATASOURCE: Avalon Pharmaceuticals, Inc.
CONTACT: David Muth, Executive Vice President & Chief Business
Officer, of Avalon Pharmaceuticals, Inc., +1-301-556-9900, or fax,
+1-301-556-9910; or Greg Geisman of Noonan Russo, +1-619-814-3510;
or Chad Rubin, Investors, of The Trout Group LLC, +1-646-378-2947
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