-- ARI-2243 is a highly potent DPP-4 inhibitor being developed for the
treatment of Type II diabetes
-- ARI-2243 produced a compelling 2.5% reduction in HbA1c in refractory
diabetic animal model
-- ARI-2243 is a first-in-class "soft drug" conferring functional
selectivity
-- Nonclinical toxicology evaluation shows ARI-2243 has high therapeutic
index
BOSTON, March 11 /PRNewswire/ -- Arisaph Pharmaceuticals, Inc., a
privately held drug discovery biopharmaceutical company, today announced
that the U.S. Food and Drug Administration (FDA) has accepted the company's
recently submitted Investigational New Drug (IND) application to evaluate
ARI-2243 in a phase I clinical trial in healthy volunteers. ARI-2243 is a
highly potent DPP-4 inhibitor, possessing superior preclinical efficacy and
a high therapeutic index established in nonclinical toxicology testing. In
addition to significant potency for inhibiting the DPP-4 enzyme, ARI-2243
possesses a first-in-class "soft drug" feature by which the compound
becomes inactive when unbound to the target enzyme, thereby contributing to
improvements in safety. Arisaph expects to initiate a first-in-man clinical
trial during the first half of 2008 and is developing the product for the
treatment of Type II diabetes, which afflicts about 20 million people in
the United States and in excess of 170 million people worldwide.(1,2)
"The FDA's acceptance of our IND marks an important milestone for the
company," said Christopher P. Kiritsy, President and Chief Executive
Officer of Arisaph Pharmaceuticals. "With ARI-2243, we are making progress
towards our goal of developing best-in-class medicines for validated
targets. We believe ARI-2243 has the potential to not only exhibit a
superior efficacy profile but also show a favorable safety profile by means
of the unique "soft drug" feature that our scientists have designed into
the compound, yielding a clinically differentiated product in this market."
"This important regulatory milestone enables Arisaph to begin the
process of demonstrating the compound's promise in the clinic," commented
Alexander "Zan" Fleming, M.D., clinical/regulatory consultant to Arisaph,
President and Chief Executive Officer of Kinexum and former head of
diabetes review at FDA. "As an endocrinologist, the unprecedented
preclinical efficacy of ARI-2243 is very intriguing and the potential
benefits for patients are very exciting. I look forward to working with
Arisaph to demonstrate the differentiated efficacy and safety of ARI-2243
in the clinic."
As part of the IND submission, Arisaph completed comprehensive
nonclinical safety pharmacology and toxicology studies, including 28 day
toxicology studies in rats and primates. The results show that ARI-2243 has
a favorable safety pharmacology profile and has a high therapeutic index.
Based on the preclinical efficacy of ARI-2243, the company believes that
low doses will produce superior blood glucose lowering compared with other
DPP-4 inhibitors.
Arisaph designed ARI-2243 as a once a day, orally active, smart DPP-4
inhibitor that is highly potent and functionally selective. In vitro,
kinetic studies show that ARI-2243 has an extremely high affinity (Ki of 27
picomolar) for the DPP-4 enzyme and drug dissociation from the enzyme is
very slow. Such kinetics confer potency and long activity. During OGTT in
normal mice, ARI- 2243 was 250 times more potent than sitagliptin and
maximally lowered blood glucose by 88%. Additionally, in ZDF rats, an
animal model that develops overt diabetes, ARI-2243 significantly reduced
hemoglobin A1c (HbA1c) by 2.5% versus no effect with vildagliptin.(3)
In addition to the compelling preclinical efficacy, ARI-2243 is
functionally selective through a smart, "soft drug" inactivation process.
Specifically, ARI-2243 binds rapidly and tightly to DPP-4 and once bound,
the complex dissociates very slowly, thereby preventing the degradation of
GLP-1 at the site of action. Unbound ARI-2243 then undergoes a unique
non-enzymatic conversion as it passes through the gut and into systemic
circulation, which limits the exposure of the active species to unwanted
targets, such as DPP 8 and 9. Such "soft drug" properties of ARI-2243
confer functional selectivity and are believed to contribute to a favorable
therapeutic index in animals.(3)
About Arisaph
Arisaph, located in Boston, Massachusetts, is an emerging drug
discovery biopharmaceutical company with active programs to develop
differentiated therapies for diabetes, cancer and cardiovascular disease.
Arisaph utilizes proprietary drug discovery platforms to develop
ultra-smart drugs that are efficacious and act on select targets. Arisaph
has successfully applied its specificity profiling and retro-inversal
chiral chemistry technology platforms to synthesize promising candidate
drugs for seven targets, including ARI-2243, a lead candidate for DPP-4
inhibition to treat Type II diabetes and ARI-1778 or reverse D-4F, an
orally active mimetic peptide, being developed in collaboration with Abbott
Laboratories to treat atherosclerosis. Through a licensing agreement with
Tufts University the Company has exclusive worldwide rights to several
important issued patents in the diabetes area and several pending patents
that have utility for the treatment of cancer and cardiovascular disease.
About DPP-4:
Dipeptidylpeptidase (DPP) - 4 is a naturally occurring, proteolytic
enzyme that rapidly degrades the incretin hormones, gastric inhibitory
polypeptide (GIP) and glucagon-like protein (GLP-1). GLP-1 has a favorable
anti-diabetic role because it stimulates glucose dependent insulin
secretion from the pancreas, slows gastric emptying and decreases glucagon
secretion. Inhibitors to DPP-4 improve glycemic control in patients with
Type II diabetes by increasing the half-life of native GLP-1. DPP-4 is a
validated target for the treatment of Type II diabetes and inhibitors of
DPP-4 have been shown to lower post-prandial glucose and HbA1c levels.
Diabetes is a major healthcare problem throughout the world with the
prevalence of the disease projected to double to 360 million cases
worldwide by the year 2030 according to the World Health Organization.(2)
Certain statements in this press release, including statements
regarding the Company's research and development effort, the Company's
expectation to initiate human clinical studies, the Company's ability to
finance its development programs into human clinical testing, and the
Company's ability to successfully capitalize on the early stage research
are subject to risks and uncertainties. These risks and uncertainties
include risks and uncertainties related to: our ability to discover and
develop new compounds and products using a novel approach to drug
discovery; the early stage of all of our discovery and development efforts;
our ability to complete preclinical and clinical development of our
products; our ability to obtain and maintain regulatory approvals for our
products; competition from other technologies and technologies similar to
ours; obtaining, maintaining and protecting intellectual property utilized
by our products; changes in legislation and regulations affecting our
products and potential product candidates; our need to obtain additional
funding to support our business activities; our dependence on collaborators
and other third parties for development, manufacture, marketing, sales and
distribution of products; the ability of our licensees to achieve
developmental, regulatory and other milestones and to commercialize their
products; the effect of conditions in the pharmaceutical industry and the
economy in general, as well as certain other risks and uncertainties.
References:
(1) American Diabetes Association Web site. Available at:
http://www.diabetes.org/about-diabetes.jsp. Accessed March 10, 2008
(2) Wild S, et al.: Global Prevalence of Diabetes, Estimates for the
year 2000 and projections for 2030. Diabetes Care 27: 1047-1053, May 2004
(3) Sanford DG, et al: ARI2243, a highly potent and selective
dipeptidyl IV (DPP4) inhibitor with exceptional anti-hyperglycemic activity
for the treatment of Type 2 diabetes. 2007 Chicago American Diabetes
Association. Abstract Number: 604-P
SOURCE Arisaph Pharmaceuticals, Inc.
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Related links:
http://www.arisaph.com/
CONTACT:
Joe Suarez, Director of Business Operations
of Arisaph Pharmaceuticals, Inc., +1-617-292-3322
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