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SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 or 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
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Date of report (Date of earliest event reported) March 15, 2000
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ALTEON INC.
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(Exact Name of Registrant as Specified in Charter)
Delaware 0-19529 13-3304550
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(State or Other Juris- (Commission (I.R.S. Employer
diction of Incorporation) File Number) Identification No.)
170 Williams Drive, Ramsey, New Jersey 07446
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(Address of Principal Executive Offices) (Zip Code)
Registrant's telephone number, including area code (201) 934-5000
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(Former Name or Former Address, If Changed Since Last Report)
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Item 5. Other Events.
On March 15, 2000 the Registrant issued the following press
release:
"Alteon's 'Crosslink Breaker' Alt-711 Shows Ability to Reverse
Age-Related Cardiac Stiffening in Pre-Clinical Study
"RAMSEY, N.J., March 15 -- Alteon Inc. (OTC Bulletin Board: ALTN),
announced today that a new pre-clinical study of ALT-711, Alteon's
lead Advanced Glycosylation End-Product ('A.G.E.') Crosslink
Breaker, has been published in the March 14th issue of the
Proceedings of the National Academy of Sciences (PNAS). The
article details ALT-711's ability to reverse cardiac stiffness in
aged dogs, restoring the cardiovascular system to a state found in
younger animals.
"In this study, administration of ALT-711 daily for one month
resulted in a 40% reduction in age-related ventricular stiffness,
or hardening. This decrease in stiffness was accompanied by an
overall improvement in cardiac function, as evidenced by increased
left ventricular end-diastolic volume, stroke volume and decreased
end-diastolic pressure.
"'This study directly supports the results from all of the
preclinical animals studies of ALT-711, including primate studies
conducted at leading research institutions,' said Kenneth I. Moch,
Alteon's President and Chief Executive Officer. 'ALT-711 has
already completed a series of Phase I human safety studies
encompassing 128 patients (94 receiving drug, 34 receiving
placebo). We look forward to initiating Phase II clinical testing
of ALT-711 in the near future to evaluate the drug's activity in
humans. This is not a test tube drug that is years away from
clinical development.'
"Alteon's clinical program on treating cardiovascular disease and
diseases of soft tissue compliance is focused on ALT-711, an agent
that breaks A.G.E. crosslinks that form as a result of the
interaction of glucose with structural matrix proteins such as
collagen. Alteon has an oral formulation of ALT-711, and has filed
an Investigational New Drug Application (IND) with the U.S. Food
and Drug Administration (FDA) in order to begin Phase II human
trials of this drug, initially to evaluate changes in
cardiovascular compliance.
"'An Advanced Glycation End-product Crosslink Breaker Can Reverse
Age- related Increases in Myocardial Stiffness' was authored by a
research team led by Timothy J. Regan, M.D., Professor of
Medicine, Division of Cardiology, University of Medicine and
Dentistry of New Jersey - New Jersey Medical School, Newark, N.J.,
and included researchers from The Kenneth S. Warren Laboratories,
Tarrytown, N.Y., and Alteon Inc., Ramsey, N.J.
"How ALT-711 Works
"Decreased elasticity of the cardiovascular system is one of the
hallmarks of the normal aging process. The key mechanism involved
is the reaction of glucose with proteins such as collagen and
elastin, resulting in the formation of advanced glycosylation end-
products. A.G.E.s crosslink to each other, forming complexes that
have been shown to be responsible for many age-related and
diabetic disorders. It was previously believed that the formation
of A.G.E. crosslinks was an irreversible process that resulted in
tissue damage by causing permanent biochemical and structural
alterations on proteins. ALT- 711 is the first in a new class of
compounds that have been shown to chemically reverse A.G.E.
crosslinking, thereby restoring more normal function to organs and
tissues that have lost flexibility.
"Alteon believes that ALT-711's mechanism of action is new and
novel, and is unrelated to that of any pharmaceutical agent either
currently prescribed or in development. Pre-clinical studies
demonstrate that one consistent molecular consequence of breaking
A.G.E. crosslinks is a reversal of the over- expression of genes
for proteins and growth factors known to be associated with the
pathological hypertrophy of tissues. Restoration of normal tissue
dynamics through breaking A.G.E. crosslinks appears to reinstate
normal control of gene function.
"In non-clinical studies in diabetic and hypertensive models, ALT-
711 reduced both the thickened left ventricle and aortic mass
caused by increased cardiac afterload in the hypertensive state.
The drug also restored elasticity to large and mid-sized vessels
and to the left ventricle.
"The A.G.E. Crosslink and the Development of Certain Disease
States
"Structural matrix proteins such as collagen and elastin play an
integral role in the maintenance of cardiovascular elasticity and
wall integrity. They are also prime targets for A.G.E.
crosslinking. For example, collagen isolated from tissues of
diabetics and aged individuals is more highly crosslinked than
that isolated from non-diabetics or younger individuals.
Restriction of movement arising from A.G.E. crosslinking of matrix
proteins appears to impair normal functioning of contractile
organs, such as blood vessels and cardiac muscle, which are
dependent on flexibility and distensibility for normal function.
"Clinically, the loss of flexibility in the aorta leads to
isolated systolic hypertension, which in turn diminishes the range
of elasticity (compliance) of the aorta. Systolic hypertension
leads to an increased workload for the cardiac chambers (increased
afterload) and may lead to myocardial hypertrophy and possibly
cardiac failure. Continued ejection into a stiffened arterial
system has been implicated in the development of left ventricular
diastolic dysfunction and in the remodeling (hypertrophy) of the
myocardium. Congestive heart failure is a common outcome of this
stiffened ventriculo-arterial system.
"ALT-711 is the first compound that breaks the specific A.G.E.-
derived crosslinks between proteins, both in vitro and in vivo. In
the case of collagen, ALT-711 does not disrupt the natural
enzymatic glycosylation sites or peptide bonds that are
responsible for maintaining the normal integrity of the collagen
chain. Thus, normal structure and function is preserved while
abnormal crosslinking is reduced.
"Current Therapies Treat the Symptoms While ALT-711 Treats the
Cause of Disease
"Currently available antihypertensive agents improve arterial
elasticity indirectly, by reducing the pressure burden on the
vessel wall. This approach lowers peripheral resistance and
intravascular circulating volume, leading to a reduction in mean
blood pressure. A current debate is whether any marketed drug can
increase arterial elasticity beyond what would be expected from
restoring the dynamic range of the vessel wall, with a reduction
in blood pressure alone.
"Pharmacologic intervention with ALT-711 directly targets the
biochemical pathway leading to the stiffness of the cardiovascular
system.
"Alteon's Technology Platform - The A.G.E. Pathway
"A.G.E. Technology Impacts Broad Medical Applications
"The formation of A.G.E.s in the human body occurs through the
same biological process as that of the toughening and
discoloration of food during the cooking process. This Maillard or
'browning' reaction is temperature sensitive, and takes place in
the human body at a slow rate in some individuals and at an
accelerated rate in others, particularly diabetic patients.
"The progressive formation of A.G.E.s on proteins such as collagen
and elastin arises from the non-enzymatic reaction of glucose with
the amino groups of these long-lived structural proteins. With
time, A.G.E.s on one protein interact with adjacent proteins to
form stable covalent A.G.E. crosslinks. In tissues and organs that
depend on elastic properties to function, normal physiologic
functions are compromised by A.G.E. formation and crosslinking,
resulting in serious pathophysiologic consequences.
"The A.G.E. pathway may provide the scientific explanation for how
and why many of the complications of the aging process occur with
higher frequency and earlier in life in diabetic patients. These
individuals form greater amounts of A.G.E.s than non-diabetics.
From a pathological viewpoint, diabetes may be considered an
advanced form of aging.
"Because A.G.E.s have been implicated in a broad range of
pathologies, therapeutic intervention may provide relief for many
medical conditions where A.G.E. crosslinking has contributed to a
loss of normal function, elasticity and/or flexibility. These
diseases or disorders include nephropathy, end- stage renal
disease, retinopathy, neuropathy, vascular disorders such as
systolic hypertension, pulmonary hypertension, as well as
cardiomyopathies such as diastolic dysfunction and congestive
heart failure. Early clinical experience in Phase I human studies
of ALT-711 suggest that urinary elastic dysfunction (leading to
urinary incontinence) is a potential therapeutic target as well.
Alteon is also evaluating therapeutic opportunities in
dermatological conditions, stiff joint disorders and continuous
ambulatory peritoneal dialysis (CAPD).
"About Alteon
"Alteon is a leader in the discovery and development of
pharmaceuticals for the treatment of cardiovascular and renal
diseases and other disorders of diabetes and aging.
"Alteon's proprietary technology focuses on Advanced Glycosylation
End- products, or A.G.E.s, formed as a result of circulating blood
glucose reacting with proteins. These protein/glucose complexes
ultimately form crosslinks with adjacent proteins, leading to a
loss of flexibility and function in body tissues, organs and
cells. This A.G.E. pathway represents one of several pathological
processes believed to be responsible for aging, including
regulation of telomere length, DNA turnover, and build-up of
senescent products, among others. A.G.E.s have been shown to be
causative factors in many of the complications of diabetes and
age-related diseases, including kidney disease, cardiovascular
disease, nerve damage and retinopathy. Alteon's unique approach is
to inhibit or break A.G.E.s and their chemical crosslinks.
"Alteon's lead A.G.E. crosslink breaker, ALT-711, has completed a
series of Phase I human clinical trials and will enter Phase II
trials in the near future. The company is seeking a corporate
partner to help fund the continued development of its A.G.E.-
formation inhibitor, pimagedine, based on the results of a Phase
III trial in Type 1 diabetic patients with progressive kidney
disease. Alteon is also pursuing the development of a novel series
of glucose lowering agent (GLA) compounds.
"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 technology and product development,
regulatory approval processes, intellectual property rights and
litigation, competitive products, ability to obtain financing, and
other risks identified in Alteon's filings with the Securities and
Exchange Commission. Actual results, events or performances 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.
"More information on Alteon is available at the corporate web
site, http://www.alteonpharma.com"
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act
of 1934, the Registrant has duly caused this report to be signed
on its behalf by the undersigned hereunto duly authorized.
Alteon Inc.
By: /s/ Kenneth I. Moch
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Kenneth I. Moch
President and
Chief Executive Officer
Date: March 15, 2000
