Alteon's ALT-2074 Demonstrates Ability to Reduce Infarct Size by 80 Percent in Mice with Haptoglobin 2-2 Genotype
13 November 2006 - 2:30PM
PR Newswire (US)
- Abstracts Presented at the American Heart Association Scientific
Sessions 2006 Suggest ALT-2074 May be Used For Significant
Myocardial Protection - PARSIPPANY, N.J., Nov. 13
/PRNewswire-FirstCall/ -- Alteon Inc. (AMEX:ALT) announced today
that data demonstrating the ability of its compound ALT-2074
(formerly BXT-51072 licensed from OXIS International, Inc., OTC
Bulletin Board: OXIS.OB), to reduce myocardial injury in mice is
the subject of an abstract being presented at the American Heart
Association Scientific Sessions 2006 in Chicago, IL, by a research
team from the Rappaport Institute, Israel. The study suggests that
a haptoglobin (Hp) genotype, specifically Hp 2-2, determines
myocardial infarction (MI) size in diabetes, and that the
administration of ALT-2074 to mice with this genotype undergoing
ischemic-reperfusion injury, resulted in a reduction in myocardial
injury by over 80%. The company believes that these significant
results support the development of ALT-2074, a glutathione
peroxidase mimetic, as a potential pharmacogenomically driven
therapy for diabetic patients with the Hp 2-2 genotype. ALT-2074 is
currently in Phase 2a human clinical trials. Additional abstracts
being presented at the meeting demonstrate that Hp genotyping may
play a role in predicting atherosclerotic risk, as well. The poster
presentation "Haptoglobin Genotype Determines Myocardial Infarct
Size in Diabetic Mice" by authors Shany Blum, M.D., and Andrew P.
Levy, M.D., Ph.D., of the Rappaport Institute of the Technion
University, Haifa, Israel, summarizes work using mice expressing
Hp1-1, the naturally occurring Hp in mice, and Hp 2-2 (introduced
transgenically). The mice were exposed to a model of myocardial
infarction called ischemia-reperfusion injury (IR). MI size was
significantly increased in Hp 2-2 mice as compared to Hp 1- 1 mice
(44.3 plus/minus 9.3% vs. 21.0 plus/minus 4.0%, p=0.03). These
larger infarctions were associated with significantly increased
redox active iron and lipid peroxidation and significantly
decreased levels of IL-10 (an anti- inflammatory cytokine). The
administration of ALT-2074 to Hp 2-2 mice reduced myocardial injury
after IR by over 80% (44.3 plus/minus 9.3 % vs. 7.0 plus/minus
3.1%, p=0.003) but no myocardial protection was provided by ALT-
2074 in Hp 1-1 mice. Dr. Levy noted, "these data suggest that the
Hp 2-2 genotype may confer significant cardiovascular risk in
diabetic patients and that strategies such as ALT-2074 designed to
decrease the iron-mediated lipid peroxidation associated with this
genotype may provide significant myocardial protection." "We
congratulate Dr. Levy and his colleagues for producing this
award-winning translational work that addresses the biology
underlying an epidemiological phenomenon he and his colleagues have
reported over the past several years, in which Hp2-2 may account
for more than 30% of the increased cardiovascular risk (restenosis
after angioplasty, and death or heart failure following myocardial
infarction) often attributed to diabetes," said Noah Berkowitz,
M.D., Ph.D., President and Chief Executive Officer of Alteon. "As
licensors of cardiovascular-related, haptoglobin technology from
the Rappaport Institute, we are pleased to see Dr. Levy's work
which has seamlessly connected epidemiology and mechanistic
biology." Additional studies being presented at the AHA by Dr. Levy
and colleagues at the Mount Sinai School of Medicine relate to
technology licensed by Alteon from the Rappaport Institute and
further elucidate the cardiovascular risks associated with the
haptoglobin 2-2 genotype. "Haptoglobin Genotype is a Determinant of
Oxidation and Inflammation in the Atherosclerotic Plaque"
demonstrates that atherosclerotic plaques from ApoE-/- Hp 2-2 mice
are associated with increased iron deposition, lipid peroxidation
and macrophage infiltration indicating that the Hp genotype may
play a critical role in the oxidative and inflammatory response to
intraplaque hemorrhage. Another preclinical study, summarized in a
poster entitled "Intra-Plaque Hemorrhage Is Associated With
Decreased Content of Macrophage Scavenger Receptor CD-163 in
Diabetic Atherosclerosis" demonstrates a link between the
haptoglobin 2-2 genotype and the atherosclerotic plaque instability
associated with diabetes mellitus. The CD163 haptoglobin receptor,
found on many cell types of the immune system, is known to scavenge
free hemoglobin from circulation and tissues, thus eliminating a
major source of oxidative stress and damage resulting from free
iron found in the vasculature after hemorrhage. The study suggests
that in diabetics with the Hp 2-2 genotype, a decrease in the CD163
on scavenger macrophages may be responsible for enhanced damage and
instability within atherosclerotic plaque. About Alteon Alteon is a
product-based biopharmaceutical company engaged in the development
of small molecule drugs to treat and prevent the inflammatory
aspects of cardiovascular disease and diabetes. The Company has
identified several promising product candidates that it believes
represent novel approaches to some of the largest pharmaceutical
markets. Alagebrium, a product of Alteon's drug discovery and
development program, is being developed for the treatment of
diastolic heart failure. This disease represents a rapidly growing
market of unmet medical need, particularly common among diabetic
patients. Alagebrium has demonstrated relevant clinical activity in
two Phase 2 clinical trials in heart failure, as well as in animal
models of heart failure and nephropathy, among others. Alagebrium
has been tested in approximately 1,000 patients in multiple Phase 1
and Phase 2 clinical trials, which represents a sizeable human
safety database. The Company's portfolio also includes orally
bioavailable, organoselenium mimics of glutathione peroxidase that
metabolize lipid peroxides and have the potential to limit
myocardial damage subsequent to a myocardial infarction. Alteon's
lead compound for that program, ALT-2074, is in Phase 2 clinical
trials. The Company also has rights to a diagnostic assay that
identifies a large subset of diabetic patients at highest risk for
cardiovascular complications, because of a defect in oxidized lipid
metabolism that results in increased cardiovascular inflammation.
For more detailed information about Alteon's research and
development, please visit Alteon's website at
http://www.alteon.com/. Any statements contained in this press
release that relate to future plans, events or performance are
forward-looking statements that involve risks and uncertainties
including, but not limited to, those relating to the impact of the
preclinical results described in this press release on the future
clinical development of Alteon's product candidates (including the
possibility that early preclinical or clinical trial results may
not be predictive of results that will be obtained in large-scale
testing or that any clinical trials will not demonstrate sufficient
safety and efficacy to obtain requisite approvals or will not
result in marketable products), Alteon's ability to obtain
sufficient funding to continue as a going concern and continue the
development of alagebrium and ALT-2074, technology and product
development regulatory approval processes, intellectual property
rights and litigation, competitive products, and other risks
identified in Alteon's filings with the Securities and Exchange
Commission. Further information on risks faced by Alteon are
detailed under the caption "Risk Factors" in Alteon's Annual Report
on Form 10-K for the year ended December 31, 2005 and in its
subsequent Quarterly Reports on Form 10-Q. These filings are
available on a website maintained by the Securities and Exchange
Commission at http://www.sec.gov/. The information contained in
this press release is accurate as of the date indicated. Actual
results, events or performance may differ materially. Alteon
undertakes no obligation to publicly release the result of any
revision to these forward- looking statements that may be made to
reflect events or circumstances after the date hereof or to reflect
the occurrence of unanticipated events. DATASOURCE: Alteon Inc.
CONTACT: Investor Relations, +1-201-818-5537 Web site:
http://www.alteon.com/
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