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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) April 6, 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 April 6, 2000 the Registrant issued the following press
release:
"ALTEON INITIATES PHASE II CLINICAL TRIAL OF LEAD A.G.E.
'CROSSLINK BREAKER' ALT-711 FOR POTENTIAL REVERSAL OF
CARDIOVASCULAR DISEASE IN AGING AND DIABETES
"RAMSEY, N.J., April 6 Alteon Inc. (OTC Bulletin Board: ALTN)
announced today that it has initiated a Phase IIa clinical trial
of its novel therapeutic agent, ALT-711. ALT-711 is the first
compound to enter clinical development that has demonstrated the
potential to reverse age-related cardiovascular disease and
restore the cardiovascular system to a more youthful state by
cleaving pathological protein-glucose structures called Advanced
Glycosylation End-product (A.G.E.) Crosslinks.
"The double-blind, placebo-controlled study will involve 72 men
and women over age 50 whose cardiovascular systems show measurable
stiffening due to aging and/or diabetes. Patients will receive
doses of ALT-711 in tablet form once a day over an 8-week period.
The patients will be monitored for increased cardiovascular
compliance, as measured by multiple parameters including
ultrasound cardiography and pulse wave velocity. Completion of the
study is expected by year end.
"In pre-clinical testing, ALT-711 has demonstrated a consistent
ability to reverse diabetes and age-related cardiovascular disease
and to restore the cardiovascular system to a more youthful state.
In as short a dosing period as 2 to 6 weeks at 1 mg/kg, ALT-711
reversed the stiffening of the aorta and left ventricle in
rodents, canines and primates. In primates, the resulting
improvement in cardiac output and arterial compliance was
persistent for up to 5 weeks following the last dose.
"Based on the results of the Phase IIa study, Alteon and its
clinical consultants will evaluate the data to determine specific
cardiovascular indications for further clinical development. These
indications may include congestive heart failure, peripheral
vascular disease or isolated systolic hypertension of the elderly.
"Nine clinical sites are participating in the study, including
Johns Hopkins University Medical Center; The Gerontology Research
Center at the National Institute on Aging; Rush Hypertension
Center at Rush Presbyterian/St. Luke's Medical Center; Orange
County Research Center; St. Paul Heart Clinic; VA Medical Center,
Minneapolis; University of Maryland at Baltimore; University of
Minnesota; and Memorial Research Medical Clinic, Long Beach,
California.
"'Arterial stiffening with advancing age plays a major role in
diseases such as atherosclerosis, hypertension, stroke and heart
failure in older people,' said Edward G. Lakatta, M.D., Chief of
the Laboratory of Cardiovascular Science at the National Institute
on Aging and a researcher who conducted preclinical studies on
ALT-711 in primates. 'Safe therapy to prevent or reduce arterial
stiffening in humans would likely have substantial implications in
the morbidity and mortality of these diseases. If clinical studies
in humans bear out the results we have seen in animals, substances
like ALT-711 could be the breakthrough we've been working toward
to reverse some types of age-related heart and vessel disease.
Human clinical studies will tell the tale, and we must wait for
those results.'
"Alteon had previously announced that it had completed a series of
Phase I human safety and dose escalation studies with ALT-711 in
128 healthy volunteers, 94 on drug. Analyses of the safety data
did not show any medically relevant side effects. Preliminary data
relating to bladder compliance and urinary incontinence was
observed during the Phase Ib clinical trial of 12 patients.
"'We are excited to initiate Phase II clinical trials of ALT-711
in cardiovascular compliance with this prestigious group of
clinicians,' said Kenneth I. Moch, President and Chief Executive
Officer of Alteon. 'We believe that Alteon's patented crosslink
breaker technology platform will prove to be beneficial in the
treatment of many different disorders of aging and diabetes, based
on the pathological consequences of A.G.E.s (the A.G.E. pathway).
We are actively pursuing our strategy for clinical development of
ALT-711 in a number of other indications that are related to the
loss of tissue elasticity.'
"ALT-711: A Drug for Reversing Diseases of Diabetes and Aging
"The Pathological Role of A.G.E. Crosslinks
"Decreased elasticity of the cardiovascular system and the
stiffening of other tissues and organs is one of the hallmarks of
the normal aging process, with an accelerated time course in
diabetic patients. A 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).
Once A.G.E.s form on proteins, they eventually crosslink to other
proteins, 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.
"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 elasticity (compliance) in the aorta
leads to isolated systolic hypertension. Systolic hypertension in
turn causes increased workload for the cardiac chambers (increased
afterload) and is believed to be responsible for myocardial
hypertrophy and 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.
"'The combined loss of distensibility in both the systemic
arteries and the heart can critically limit the reserve capacity
of the cardiovascular system resulting in exertional fatigue and
dyspnea,' notes David A. Kass, M.D., Professor of Medicine and
Biomedical Engineering at the Johns Hopkins Medical Institutions.
'This limitation may play a particularly central role in the
expanding elderly population who have cardiac failure symptoms yet
relatively preserved ventricular systolic function. Current
therapy has fallen short, and if an agent such as ALT-711 proves
effective, it could have great impact on this syndrome.'
"How ALT-711 Works
"ALT-711 is the first in a new class of compounds that have been
shown in vitro and in vivo to 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 clinical
development. Importantly, 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.
"In addition to restoring elasticity of stiffened tissues by
breaking pathological crosslinks, ALT-711 consistently
demonstrates the ability to reverse the over-expression of genes
for proteins and growth factors known to be associated with the
pathological hypertrophy (enlargement) of tissues. Hypertrophy of
the aorta and the left ventricle is correlated with the
development of heart failure. These results indicate that
restoration of normal tissue dynamics through breaking A.G.E.
crosslinks may restore normal control of gene function.
"In pre-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.
"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 evaluating therapeutic opportunities in peritoneal
dialysis, bladder compliance, dermatological conditions and
restenosis.
"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, based on
slowing or reversing a fundamental pathological process caused by
protein-glucose complexes called Advanced Glycosylation End-
Products (A.G.E.s).
"A.G.E.s 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 cardiovascular disease, kidney
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 entered
Phase IIa clinical testing to evaluate its effect on
cardiovascular compliance. 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: April 11, 2000
