Amylin Pharmaceuticals, Inc.
(Nasdaq: AMLN) announced the initiation of a Phase 2B clinical study
evaluating various dosing combinations of pramlintide, an analog of the
natural hormone amylin, and recombinant human leptin (r-metHuLeptin;
metreleptin) for the treatment of obesity. The objective of this
dose-ranging study is to support dose selection for Phase 3, and to inform
the ongoing development of a convenient delivery system for this
combination regimen. The six-month, randomized, double-blind,
placebo-controlled multi-center study will enroll approximately 600
overweight and obese subjects and is expected to complete in mid-2009.


"There is a tremendous medical need and market demand for a weight loss
product that meets both safety and efficacy expectations of patients and
physicians, and we believe that our integrated neurohormonal approach to
obesity holds great promise for achieving this profile," stated Christian
Weyer, M.D., Vice President of Clinical Research, Amylin Pharmaceuticals.
"Building upon the positive results of our translational research program
published today in PNAS, and the extensive clinical experience with both
pramlintide and metreleptin as monotherapies, the newly initiated Phase 2B
study will bring us one step closer to our goal of offering obese
individuals a safe and effective therapy that results in meaningful weight
loss."



The Phase 2B study will include a broad range of overweight and obese
subjects (body mass index 27 to 45 kg/m2) and will compare various
pramlintide/metreleptin combination regimens with each compound alone and
with placebo.



PNAS Publication



Also today, comprehensive preclinical findings of amylin/leptin
synergy, along with positive results of a translational Phase 2A clinical
study were published online in PNAS, Proceedings of the National Academy of
Sciences of the United States of America, in a scientific paper entitled,
"Leptin Responsiveness Restored by Amylin Agonism in Diet-Induced Obesity:
Evidence from Non-Clinical and Clinical Studies."



"Leptin is a fundamentally important hormone in energy metabolism with
a unique role in inducing fat-specific weight loss and in preventing weight
loss counterregulation," remarked Steven Smith, M.D., Professor and
Assistant Associate Director of Clinical Research, Endocrinology Laboratory
at the Pennington Biomedical Research Center. "The intriguing and important
findings published today constitute a strong scientific basis for the
development of peptide hormone combinations, and provide renewed hope of
harnessing the therapeutic potential of leptin as part of an integrated
neurohormonal approach to obesity pharmacotherapy."



The scientific studies included in the PNAS publication provide
preclinical and clinical evidence that leptin responsiveness is at least
partially restored by amylin agonism. In several independent experiments in
diet-induced obese rats, co-administration of amylin, together with leptin,
resulted in synergistic reductions in food intake (up to 45%) and body
weight (up to 15%), effects considerably greater than with leptin or amylin
treatment alone. Importantly, weight loss with amylin/leptin treatment was
fat-specific, and not accompanied by a reduction in lean mass.
Neurohistological studies provided important insights into the
neurobiological basis of amylin/leptin synergy. Finally, the translational
clinical research confirmed that findings in the non-clinical experiments
are relevant to human obesity and suggest that metreleptin may be an
effective partner to pramlintide in the treatment of obesity.



The full paper, published in the May 5, 2008 early edition of PNAS, is
available online at http://www.pnas.org. PNAS is one of the world's most
prestigious multidisciplinary scientific journals.




About Obesity



Obesity is a chronic disorder that affects millions of people and is
linked to increased health risk of several medical conditions including
type 2 diabetes, high blood pressure, heart disease, stroke,
osteoarthritis, sleep disorders and several types of cancers. According to
The Obesity Society, obesity is the second leading cause of preventable
death in the United States. The total direct and indirect cost attributed
to overweight and obesity health issues exceeds $100 billion in the United
States each year. Obesity is also rapidly becoming a major health problem
in all industrialized nations and many developing countries.



Amylin's Approach to Obesity Research and Development



Physicians and patients seeking prescription medications for weight
loss have limited therapeutic options. New scientific advances have
established the key role of neurohormones in regulating appetite and energy
balance, as well as the importance of studying the interaction among these
hormones (within the brain) to uncover their full therapeutic potential.
Amylin scientists discovered that combination treatment with neurohormones
such as amylin and leptin can produce additive and synergistic weight loss
in animal models. These findings formed the basis for Amylin's innovative
integrated neurohormonal approach to the development of obesity treatments.



About Pramlintide and Metreleptin



Pramlintide is a synthetic analog of amylin, a neurohormone secreted by
the pancreas that is known to play a role in the regulation of appetite,
food intake and postprandial glucose concentrations. Pramlintide is the
active ingredient in SYMLIN(R) (pramlintide acetate) injection, which is
indicated for use by patients with type 1 and type 2 diabetes who use
mealtime insulin. Since launch, over 80,000 patients have been exposed to
SYMLIN. To date, more than 6,000 individuals have received pramlintide in
clinical trials, including more than 800 in obesity studies. In previous
clinical studies, obese subjects treated with pramlintide 360 micrograms
twice daily for 1 year experienced an average weight loss of approximately
8 percent from baseline compared with a 1 percent weight loss in patients
receiving placebo. The most common side effect observed with pramlintide
treatment in previous obesity studies was mild, transient nausea.



Metreleptin (methionyl recombinant leptin; r-metHuLeptin) is an analog
of human leptin, a neurohormone secreted by fat cells that plays a
fundamental role in the regulation of energy metabolism and body weight.
Amylin acquired exclusive rights to the leptin molecular franchise and
clinical program in 2006. To date, more than 1,000 individuals have
received metreleptin in clinical trials, several hundred of which were
obese and treated for 16 weeks or more. In multiple previous human clinical
trials with metreleptin treatment alone, minimal weight loss was observed.
This observation is consistent with findings in diet-induced obese rats,
and suggests the presence of leptin resistance. In contrast, and consistent
with findings in ob/ob (leptin deficient) mice, long-term treatment with
metreleptin has been shown to elicit profound, fat-specific weight loss in
severely obese individuals who are rendered leptin deficient by rare
genetic mutations of the leptin gene. The most common side effect observed
with metreleptin treatment in previous obesity studies was injection site
adverse events.



About Amylin Pharmaceuticals



Amylin Pharmaceuticals is a biopharmaceutical company committed to
improving lives through the discovery, development and commercialization of
innovative medicines. Amylin has developed and gained approval for two
first-in-class medicines for diabetes, SYMLIN(R) (pramlintide acetate)
injection and BYETTA(R) (exenatide) injection. Amylin's research and
development activities leverage the company's expertise in metabolism to
develop potential therapies to treat diabetes and obesity. Amylin is
headquartered in San Diego, California with over 1,900 employees
nationwide. Further information on Amylin Pharmaceuticals is available at
http://www.amylin.com.



This press release contains forward-looking statements about Amylin,
which involve risks and uncertainties. The Company's actual results could
differ materially from those discussed due to a number of risks and
uncertainties, including that our clinical trials may not start when
planned and/or confirm previous results; our preclinical studies may not be
predictive; our product candidates may not receive regulatory approval; and
inherent scientific, regulatory and other risks in the drug development and
commercialization process. These and additional risks and uncertainties are
described more fully in the Company's most recently filed SEC documents,
including its Form 10-Q. Amylin undertakes no duty to update these
forward-looking statements.


Amylin Pharmaceuticals, Inc.

http://www.amylin.com