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FDA Accepts Investigational New Drug Application for ARI-2243 and a First in Man Clinical Trial Set to Begin During the First Half of 2008

-- 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


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.


(1) American Diabetes Association Web site. Available at: 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.
Copyright©2008 PR Newswire.
All rights reserved

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