Avalon Pharmaceuticals Announces Positive Interim Results for AVN944 Phase I Trial
December 13 2006 - 4:55PM
PR Newswire (US)
Multiple Patients with Stabilized Disease and Affirmative Biomarker
Data GERMANTOWN, Md., Dec. 13 /PRNewswire-FirstCall/ -- Avalon
Pharmaceuticals, Inc. (Nasdaq and NYSE Arca: AVRX), today released
updated interim results from its Phase I study of AVN944, the
company's lead product candidate for the treatment of hematologic
malignancies. Interim data from the study indicates that AVN944 is
well tolerated, has dose-dependent pharmacokinetics, induces
biomarkers of programmed cell death in cancer cells from patients,
and has resulted in stabilized disease after a one-month treatment
cycle in half of the patients that have been treated thus far. "We
are encouraged by the positive interim results from the AVN944
trial," said Michael Hamilton, M.D., Avalon Pharmaceuticals' Chief
Medical Officer. "The fact that we have not seen any drug-related
serious adverse events, combined with several indications of
biological drug effects and disease stabilization in multiple
patients indicates that there will likely be a good therapeutic
window from which to establish an effective treatment protocol.
Based on pre-clinical data and the positive trends that we have
seen thus far in the Phase I, we believe that the immediately
upcoming dose levels in the Phase I trial should provide sufficient
information to support a goal of initiating multiple Phase II
studies during the first half of 2007." Background: AVN944 is an
oral small molecule drug that inhibits inosine monosphospate
dehydrogenase (IMPDH), a critical enzyme for synthesis of guanosine
triphosphate (GTP), a molecule required for DNA synthesis and
cellular signaling. IMPDH is over expressed in many cancer cells,
especially from hematological malignancies. Pre-clinical studies
showed that AVN944 is a highly specific inhibitor of IMPDH,
suppresses pools of GTP, and in cultured cells has a selective
growth inhibition effect on cancer cells vs. normal cells. An
earlier single-dose, dose-escalation, healthy volunteer clinical
trial conducted in the United Kingdom showed that AVN944 was well
tolerated at all tested doses with no notable side effects; had
good pharmacokinetic properties; and had a significant inhibitory
effect on IMPDH enzyme activity. Study Design: The current U.S.
Phase I study is a repeat-dose dose escalation trial in patients
with advanced hematologic malignancies. Patients are dosed for 21
days on a 28-day cycle. A minimum of three patients are treated at
each dose level. The study is divided into two arms, one for
treatment of leukemia patients and the other for treatment of
patients with lymphoma and myeloma. For the leukemia arm of the
study, patients are currently being treated at the fourth dose
level, 100 mg twice daily. For the lymphoma and myeloma arm,
patients are currently being treated at the fifth dose level, 125
mg twice daily. Positive Safety and Tolerability Data: The goal of
the Phase I study is to establish the safety, tolerability and
pharmacokinetics of the drug. Thus far, 63 one-month cycles of
AVN944 have been initiated in 28 patients. There have been no
drug-related Serious Adverse Events (SAEs), indicating that AVN944
is being well tolerated thus far at all dose levels.
Pharmacokinetics measurements indicate dose proportional plasma
levels of AVN944 during treatment and sustained plasma
concentrations at the dose levels tested thus far. Early Activity
Indicators: This Phase I study has also been designed to evaluate
several pharmacodynamic and efficacy-related endpoints. Upon
entering the trial, all patients have refractory, progressive
disease and have failed all prior therapies. Thus far, 12 of 24
patients have had stabilized disease after one cycle of treatment
with AVN944. These include patients with both leukemia and multiple
myeloma. Patients who have achieved stable disease following
completion of a one-month treatment cycle with AVN944, as
determined by the clinical investigator, may be advanced to a
subsequent cycle. Four multiple myeloma patients in the study have
maintained stabilized disease for several months of treatment with
AVN944; two of these patients completed five months of treatment
and two others completed eight successive cycles. These two
patients continue to have stable disease and are in their ninth
month of treatment. Affirmative Biomarker Data: Using Avalon's
proprietary biomarker technology, AvalonRx(R), analysis of selected
markers from patient samples showed a correlation of changes in
gene expression to dose level and duration of exposure.
Importantly, several of these markers displayed a durable,
sustained stress response indicative of cancer cell death,
particularly in cancer cells from AML patients. Specifically, it
was found that the gene HspA1A, a marker of stress response found
to correlate with depleted GTP pools in cancer cell lines, is
induced within hours of the first treatment of the drug in
patients, even at the trial's lowest doses. Other genes directly
related to IMPDH inhibition showed similar response
characteristics. Teleconference and Webcast: The company will host
a conference call on Thursday, Dec. 14, 2006 at 8 a.m. Eastern
Standard Time to discuss the interim results of the AVN944 Phase I
clinical trial. Interested investors, analysts, members of the
media and the general public can listen to the call live over the
Internet from the investor section of the company's Web site or by
dialing the numbers listed below. A detailed PowerPoint
presentation will accompany the webcast. Conference Call Details:
------------------------ Dial-In: (866) 202-4367 (U.S.) (617)
213-8845 (International) Pass code: 78269925 Webcast: Please go to
http://www.avalonrx.com/, Investor Relations, within 15 minutes
prior to the call and select the webcast link. The conference call
replay will be available through June 1, 2007 on Avalon's website
(http://www.avalonrx.com/). 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), preclinical programs to
discover inhibitors for the Beta-catenin, Aurora and Survivin
pathways, and drug discovery collaborations with MedImmune,
Novartis, ChemDiv and Medarex. Avalon Pharmaceuticals was
established in 1999 and is headquartered in Germantown, Md. About
AvalonRx(R) AvalonRx(R) is a comprehensive, innovative and
proprietary suite of technologies based upon large-scale gene
expression analysis. This platform facilitates drug discovery by
expanding the range of therapeutic targets for drug intervention,
including targets and target pathways frequently considered
intractable using conventional HTS approaches, allows more informed
decisions about which compounds to advance towards clinical trials,
and facilitates drug development through identification of
biomarkers of efficacy that can stratify patients or provide early
indicators of response. Safe Harbor Statement This announcement
contains, in addition to historical information, certain
forward-looking statements that involve risks and uncertainties, in
particular, related to 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 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 Gary Lessing Wendy Lau (Media)
Executive Vice President & CFO Tel: (212) 845-4272 Tel: (301)
556-9900 Fax: (301) 556-9910 The Trout Group LLC Email: Chad Rubin
(Investors) Tel: (212) 477-9007 ext. 47 DATASOURCE: Avalon
Pharmaceuticals, Inc. CONTACT: Gary Lessing, Executive Vice
President & CFO of Avalon Pharmaceuticals, Inc.,
+1-301-556-9900, Fax: +1-301-556-9910, ; or Media: Wendy Lau of
Noonan Russo, +1-212-845-4272; or Investors: Chad Rubin of The
Trout Group LLC, +1-212-477-9007 ext. 47 Web site:
http://www.avalonrx.com/
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