(9) Rimonabant is the first in a new
class of drugs called CB1 blockers.

(8) Pagotto U.
Alan Watson, Ph. The range of cellular proteins and
biological processes shown to be affected by acetylation/deacetylation
is rapidly growing.

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The two-year findings of the RIO-Europe trial are consistent with those of
the other two-year trial in the rimonabant phase III program, RIO-North
America, results of which were announced at the scientific sessions of the
American Heart Association in November 2004.001), respectively. Among patients
completing the study, 32.3% for 20 mg/day, 8 .D.

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D. Among patients completing the study,
HDL-cholesterol increased by 28.6% for placebo) and vomiting (5.24, S5-S7.

xeroderma trichothiodystrophy

D., Professor of Diabetology, Metabolism and Clinical
Nutrition, University Hospital of Antwerp, Belgium and principal investigator
of the study.7% of patients treated with rimonabant 20
mg/day lost more than 5% of their initial body weight vs 23.001).8% in patients treated with rimonabant 20 mg/day throughout the
two-year period vs an increase of 6. Side effects were mainly mild and transient and
appeared mainly in the first year.3% for 5 mg/day, 4.9% in the placebo, rimonabant 5 mg/day and rimonabant 20 mg/day groups,
respectively.
Circulation. Rimonabant in the
Reduction of Major Cardiovascular Risk Factors Data, presented at
ACC, 2004 .

(5) Sharma AM, Adipose tissue: a mediator of cardiovascular risk. Abdominal adiposity in U.

Elixir Extends Sirtuin Patent Portfolio; Signs Second Exclusive IP License Agreement with University of California

The
sirtuins are related to Sir2, a gene identified in yeast that is
conserved across species and implicated in the control of lifespan,
metabolism, resistance to stress and other cellular regulatory
pathways. Modulators of this enzyme class may provide important
therapeutic agents for metabolic diseases such as diabetes and
obesity, as well as HIV and cancer. Verdin, M .

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0% of patients
treated with rimonabant 20 mg/day lost more than 10% of their initial body
weight vs 6. (3) Obesity is typically measured by body mass index (BMI);
however, recent findings have shown that abdominal obesity is a much better
predictor of heart attack than weight or BMI. (7)

Rimonabant and the Endocannabinoid (EC) System
The EC System is a physiological system in the body that is believed to
play a key role in the central and peripheral regulation of energy balance,
fat accumulation as well as in glucose and lipid metabolism.
adults: prevalence and trends, 1960-2000. Verdin's
laboratory relating to SirT2 and SirT3, two other important members of
the sirtuin class.

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The first-year results of the RIO-Europe study had been
presented at the European Society of Cardiology meeting in August 2004.001).6% in the
rimonabant 20 mg/day group vs 12.

(2) Rimonabant in Obesity, North American Data. Prev Med.

(9) Horvath TL .
Eric M.

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9
inches) in patients treated with rimonabant 20 mg/day for the full two year
period vs.001).7% for 20 mg/day, 6.
International Journal of Obesity, Volume 26, Suppl. More
information about Elixir is available at www.

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The study was conducted on 1,507 patients at 40 centers in Europe and
20 centers in the US.
After a screening period of two weeks, patients were prescribed a
hypocaloric diet (designed to reduce daily caloric intake by 600 kcal from the
patients' energy requirements) and entered a four-week single-blind placebo
run-in period.8 cm (0. Overall discontinuation rates
due to adverse events in the two years of the study were 13.----Elixir
Pharmaceuticals, Inc. Dr.

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Afterward, patients were randomly assigned to one of the three
treatment groups: rimonabant 20 mg or 5 mg or placebo for 104 weeks of double-
blind treatment using a randomization ratio of 2:2:1. Among all patients who entered the study, 22.001).2% for placebo), dizziness
(9.2% for
20 mg/day, 7. The Lancet, Volume 364 Number 9438, September 11-
17, 2004. Treatment of obesity: need to focus on high risk
abdominally obese patients. 2003; 11:1223-1231.

Business Editors/Health Editors

CAMBRIDGE, Mass.

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7 cm (2.3% of those in the placebo group (P<.
Metabolic parameters, such as HDL-cholesterol and triglyercides, were
significantly improved in patients treated with rimonabant 20 mg/day
throughout the two-year period.2% in the rimonabant 20 mg/day group vs 16.

(7) Okosun IS, Chandra KM, Boev A, et al. The endocannabinoid system: a new player in reinforcement
and energy control functions. Last December, Elixir obtained an
exclusive license from UC to intellectual property from Dr.

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71 inches) in patients treated with
rimonabant 20 mg/day and the placebo group (P<. Among all patients who entered the study, 44.8%
in the placebo group (rimonabant 20 mg/day vs placebo (P<. Endocannabinoids and the regulation of body fat: the
smoke is clearing. is Associate Director at the Gladstone
Institute of Virology and Immunology and a Professor of Medicine at
the University of California, San Francisco (UCSF). The
Company 's research and discovery programs are based on a unique
understanding of the genetics and biochemical pathways of aging.

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The study also assessed improvement in waist circumference and in
metabolic risk factors (eg, dyslipidemia, glucose metabolism, and metabolic
syndrome) and evaluated the safety and tolerability profile of rimonabant over
the two-year period.1% for 5 mg/day, 5.9% and
18.
(6) The prevalence of abdominal obesity in the US has tripled in the last 40
years.

treacher shwachman

Principal Investigator
RIO-Europe
On behalf of the RIO Steering Committee

ANTWERP, Belgium , The results of a two-year phase
III study in 1,507 patients treated with rimonabant, the first in a new class
of therapeutic agents called selective CB1 Blockers, demonstrated that the
improvements in cardiovascular risk factors achieved with rimonabant 20 mg/day
at the end of the first year of treatment were maintained in the second year. BMJ. Poster presented at the Metabolic
Syndrome , Type 2 Diabetes and Atherosclerosis Conference, Marrakech,
19 - 23 May 2004.

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Improvement in Cardiovascular Risk Factors With Rimonabant Demonstrated in Two-Year Study

5 cm (2 .001).3% in the placebo group (rimonabant 20
mg/day vs placebo (P<. A statistical analysis of the data suggested that
approximately half of the improvements in HDL cholesterol and triglyceride
profiles observed in patients treated with rimonabant 20 mg/day were
independent of the weight loss achieved in this group.
Although people with diabetes were not included in the study, patients on
rimonabant 20 mg/day showed improved insulin sensitivity as measured by HOMA
(Homeostasis Model Assessment) compared with those on placebo (P<. Rimonabant in the
Reduction of Major Cardiovascular Risk Factors Data, presented at
AHA, 2004; Rimonabant in Obesity, Lipids Data.
) (4 Despres JP.

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"The RIO-Europe findings
demonstrated that in addition to maintaining body weight loss, two-year
treatment with rimonabant 20 mg/day compared with placebo reduced waist
circumference improved metabolic profile and reduced the number of patients
meeting the NCEP (National Cholesterol Education Program) criteria for
metabolic syndrome, thus diminishing cardiovascular risk factors in patients
studied," said Professor Van Gaal. Among
patients completing the study, 59.001)).

(1)

Safety + tolerability
The safety and tolerability of rimonabant 20 mg vs placebo were assessed
in this two-year study.

(6) Ford ES, Mokdad AH, Giles WH Trends in waist circumference among U.S. 2003;112:323-326." Elixir has a comprehensive patent
estate related to the sirtuins, including novel compositions and their
potential application to disease treatment and longevity .

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RIO-Europe findings
The findings presented today demonstrated the two -year benefits of
rimonabant 20 mg/day treatment vs placebo in the study population.6% of those in the placebo group (P<. Among patients completing the study, triglycerides were
reduced by 8. 2004 , 433-436. 2001;322;716-720. J Clin Invest.

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001).2% for placebo), diarrhea (8.1%, 10. (2)

Intra -abdominal adiposity
Obesity is a major public health burden and a key risk factor for the
development of cardiovascular disease, the leading cause of mortality
worldwide. (9) This system represents a promising target for intervention(s)
aimed at reducing cardiovascular risk.

References

(1) Grundy SM, et al., MBA, Chief Business Officer at Elixir,
commented, "This license agreement with the University of California
represents a valuable addition to our expanding intellectual property
portfolio surrounding the SirT family of deacetylases and broadens our
ability to fully explore the potential of the SirT1 target in our
discovery and development programs.

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Among all patients who entered the study,
triglycerides were reduced by 4.1% in patients treated with rimonabant 20
mg/day vs an increase of 10% in the placebo group (rimonabant 20 mg/day vs
placebo (P<. Definition of the Metabolic Syndrome: Report of
the National Heart, Lung and Blood Institute / American Heart
Association Conference on Scientific Issues Related to Definition.

(3 ) Yusuf et al, Effect of potentially modifiable risk factors associated
with myocardial infarction in 52 countries (the INTERHEART study):
case-control study. announced today that it has secured an exclusive
license to intellectual property from the Regents of the University of
California (UC) relating to work done by Eric Verdin, M.D. One focus area in
Dr.

About Elixir

Elixir Pharmaceuticals is a biopharmaceutical company focused on
exploiting its Optimal Aging scientific platform to discover, develop,
and market new drugs for the treatment and prevention of metabolic
disorders, as well as the prevention of age-related diseases.

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Results from RIO-Europe trial demonstrated that first-year improvements in
cardiovascular risk factors are seen through two-year study period

Luc Van Gaal, M. Among
patients completing the study, waist circumference, was reduced by 7.9% of those in the placebo
group (P<.6% in the placebo group (rimonabant 20 mg/day
vs placebo (P<.5% for 5 mg/day, 1. (8) CB1
receptors are found in the brain as well as in peripheral tissues of the body
such as adipocytes (or "fat cells"), which are involved in lipid and glucose
metabolism. (9) Results from clinical trials show that rimonabant reduces
cardiovascular risk factors by reducing intra-abdominal adiposity and
improving metabolic parameters beyond the level expected through weight
reduction alone. and his
research group with SirT1, a member of the sirtuin class of enzymes,
and the HIV TAT (Transcriptional Transactivation) protein.
The three institutes include the Gladstone Institute of Cardiovascular
Disease, the Gladstone Institute of Virology and Immunology and the
Gladstone Institute of Neurological Disease, and are located at a new
research facility adjacent to the Mission Bay campus of the University
of California, San Francisco (UCSF ).

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The objectives of the trial were to assess the effects
of rimonabant on weight loss for a period of one year and to determine
rimonabant's potential to maintain weight loss during a second year of
treatment.24 inches) and 1. Metabolic syndrome
includes a series of health risks or conditions that increase a person's
chances to develop heart disease, stroke and diabetes. The most common side effects included
nausea (13. (3) Abdominal obesity can be
simply measured by waist circumference (4), and is an indicator of
intra-abdominal adiposity, the hidden fat present deep within the abdomen (5). 2004;39:197-206.D.elixirpharm.

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RIO-Europe is a phase III, multinational multicenter, randomized ,
double-blind, and placebo-controlled trial comparing two fixed-dose regimens
of rimonabant (5 mg and 20 mg once daily) to placebo for a period of two
years.
Among all patients who entered the study, waist circumference was reduced by
5.001).001)).001)). Of
particular note is that the number of patients completing the study who met
the diagnostic criteria for metabolic syndrome was reduced by approximately
50% in patients treated with rimonabant 20 mg/day vs a decrease of
approximately 20.0% in the placebo group (P<0.6% for placebo). (5) Approximately 46% of adult Americans have a waist circumference
that exceeds the at-risk level (40 inches for men and 35 inches for women). By selectively blocking both centrally
and peripherally the CB1 receptors, rimonabant regulates the overactive EC
System.

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3 inches) for patients in the placebo group (P<.4%of those in the
placebo group (P<.1% of patients treated with rimonabant 20 mg/day lost
more than 10% of their initial body weight, vs 10.001).0% for 5 mg/day, 5. Verdin's group has demonstrated that SirT1
deacetylates the HIV TAT protein , a component of the viral
transcription machinery that is required for transcription of the HIV
provirus , and could therefore play a critical role in the progression
of HIV infection. David Gladstone Institutes
are focused on three of the most important clinical problems of modern
times: cardiovascular disease , AIDS, and neurodegenerative disorders.

This area contains many subcategories of uncommon types of disorders .

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4 cm (1. In the RIO-Europe trial and in two preceding studies (RIO-Lipids
1-year and RIO-North America 2-year), rimonabant demonstrated a safe
cardiovascular profile with no significant EKG, blood pressure or heart rate
changes on average.S.com

About the Gladstone Institutes

The primary research efforts of the J.

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3. Among all
patients who entered the study, HDL-cholesterol increased by 22.
It is this intra-abdominal adiposity (inside the abdomen) which is one of the
most significant contributors to the development of cardiovascular risk
factors such as dyslipidemia, insulin resistance, or metabolic syndrome and
which may lead to diabetes, heart attack, stroke or other cardiovascular
disease .
adults. Obes Res. Verdin's laboratory is the role of protein acetylation and
deacetylation in biological processes, specifically the activity of
histone deacetylase enzymes (HDACs) that remove acetyl groups from
histones and non-histone proteins.

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The study also demonstrated the safety and tolerability profile of rimonabant
versus placebo.
The two-year results of the RIO-Europe trial were presented today at the
Scientific Sessions of the American College of Cardiology in Orlando , Florida
by Luc Van Gaal, M.

RIO-Europe objectives and design
The RIO-Europe trial is one of four phase III studies comprising the RIO
program, which assesses the efficacy and safety of rimonabant in weight
reduction and metabolic risk factor improvement in over 6,600 overweight and
obese patients studied world-wide.4% of
patients treated with rimonabant 20 mg/day lost more than 5% of their initial
body weight vs 15.2% for 20
mg/day, 2. While independent, Gladstone is
formally affiliated with UCSF, and Gladstone investigators hold
university appointments and participate in many university activities,
including the teaching and training of graduate students.

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