Islet Sciences, Inc. Presents Positive Clinical Results for Best-in-Class SGLT2 Inhibitor at American Diabetes Association (ADA) Annual Meeting

Novel Once-Daily Formulation of Remogliflozin Etabonate Achieves Ideal Safety and Efficacy Profiles

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Jun 16, 2014, 08:00 ET

RALEIGH, N.C., June 16, 2014 /PRNewswire/ -- Islet Sciences, Inc. (OTCQB: ISLT), a biopharmaceutical company developing new medicines and technologies for the treatment and diagnosis of metabolic disease, presented final results from its two Phase 2b clinical studies evaluating remogliflozin etabonate (a prodrug of remogliflozin, the active inhibitor) at the 74^th American Diabetes Association (ADA) Annual Scientific Sessions, showing that the differentiated sodium glucose co-transporter 2 (SGLT2) inhibitor demonstrated a potential best-in-class safety and efficacy profile, when dosed once-daily or twice-daily, respectively. Positive Phase 1 results were also presented for the company's novel once-daily biphasic formulation of remogliflozin etabonate, which achieved targeted pharmacokinetic and pharmacodynamic profiles, successfully combining the best-in-class properties of previous formulations.

Remogliflozin is a highly selective SGLT2 inhibitor in clinical development for the treatment of patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). Similar to other SGLT2 inhibitors, remogliflozin blocks the reabsorption of glucose by the kidneys. The chemical structure of remogliflozin confers a shorter half-life than other SGLT2 inhibitors, allowing for a unique target product profile with combined efficacy and safety benefits superior to long-acting SGLT2 inhibitors.

William Wilkison, Ph.D., Islet Sciences' Chief Operating Officer, stated, "The results of our two Phase 2b studies were highly encouraging and we are proud to present them to the diabetes community. Importantly, this data led us to the development of a biphasic formulation of remogliflozin etabonate designed to maximize efficacy while reducing side effects associated with nighttime inhibition of SGLT2. These positive Phase 1 results presented at ADA indicate that the pharmacodynamic profile of biphasic remogliflozin etabonate is on target with our expectations and we look forward to evaluating this formulation further in the clinic."

The clinical data presented at the ADA Annual Scientific Sessions are summarized below:

Best-in-Class Efficacy and Safety of Once- and Twice-Daily Remogliflozin Etabonate for the Treatment of Type 2 Diabetes Mellitus (Posters 1103-P and 1102-P)

The Phase 2b studies were multicenter, randomized, double-blind, placebo-controlled, pioglitazone-controlled, parallel-group, dose-ranging studies evaluating the efficacy, safety, and tolerability of multiple remogliflozin etabonate doses for 12-weeks in treatment-naive adults with type 2 diabetes. One study evaluated once-daily remogliflozin etabonate in 241 patients, while the other evaluated twice-daily remogliflozin etabonate in 323 patients.

As reported previously, twice-daily dosing of remogliflozin etabonate led to HbA1c lowering ranging from 1.0-1.4% compared to placebo (p<0.001), which is superior to that of other SGLT2 inhibitors. Twice daily dosing also resulted in a best-in-class reduction in body weight of 1.36 - 3.51 kg, compared to placebo (p<0.001). The side effect profile of the twice-daily dosing regimen included an increased incidence of urogenital infections and elevated LDLc comparable to other SGLT2 inhibitors. In contrast, once-daily dosing of remogliflozin etabonate, while less efficacious relative to twice-daily dosing, was on par with other SGLT2 inhibitors and exhibited a superior safety and tolerability profile that did not differ significantly from placebo. This is consistent with its shorter plasma exposure limiting the undesirable effects of nighttime inhibition of SGLT2.

As a result, Islet Sciences developed a novel once-daily biphasic formulation of remogliflozin etabonate that is designed to maintain the efficacy of twice-daily dosing and the improved safety and tolerability profile of once-daily dosing. This formulation was evaluated in a Phase 1 clinical study and the results were also presented at ADA.

Novel Formulation of Remogliflozin Etabonate Optimizes Efficacy and Reduces Side Effects Associated with SGLT2 Inhibition (Poster 1101-P)

The Phase 1 study enrolled 12 healthy volunteers in an open-label, randomized, single-dose, crossover study to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of the remogliflozin etabonate biphasic formulation.

The biphasic formulation, composed of a dose of instant release (IR) remogliflozin etabonate coupled with a dose of delayed release (DR) remogliflozin etabonate, demonstrated sustained remogliflozin serum concentration 0-16 hours post dose, including during the evening post-prandial glucose excursion. The results showed significantly lower serum concentrations during the sleep period, 16-24 hours post dose. The majority of urinary glucose excretion (UGE) (>75%) was observed from 0-16 hours post dosing, with the peak mean UGE seen at either 8 or 12 hours post dose, and consistent with the objective of limiting inhibition of SGLT2 and UGE during the sleep period.

The biphasic formulation was safe and well tolerated in this study, with no serious adverse events and few mild adverse events.

The observed PK and PD demonstrated that the biphasic formulation of remogliflozin etabonate provides the desired level of SGLT2 inhibition during the day while limiting inhibition during the sleep period, which may lead to a best-in-class combined safety and efficacy profile.

Based on these positive data, Islet is planning a Phase 2b clinical study in type 2 diabetics to examine select doses of the biphasic formulation of remogliflozin etabonate for advancement into phase 3 clinical studies.

About Islet Sciences
Islet Sciences, Inc., a biopharmaceutical company based in Raleigh, NC, is developing new medicines and technologies for the treatment and diagnosis of metabolic disease. On March 13, 2014, the Company announced the execution of a binding letter of intent to acquire BHV Pharma. The combined pipeline includes remogliflozin etabonate for the treatment of type II diabetes and NASH, a cell-based transplantation therapy for insulin-dependent diabetes; first-in-class immune-modulating small molecule IL-12 inhibitors targeting beta-cell preservation, and a PCR-based molecular diagnostic measuring beta-cell loss for the diagnosis of type 1 diabetes or onset of insulin dependent type 2 diabetes. For more information, please visit http://www.isletsciences.com.

Forward-Looking Statements
This press release contains forward-looking statements. Forward-looking statements for Islet Sciences, Inc. reflect current expectations, as of the date of this press release, and involve certain risks and uncertainties. Actual results could differ materially from those anticipated in these forward- looking statements as a result of various factors. Factors that could cause future results to materially differ from the recent results or those projected in forward-looking statements include the risks described in the Islet Science, Inc.'s reports filed with the Securities and Exchange Commission. The Company's further development is highly dependent on future medical and research developments and market acceptance, which is outside of the Company's control.

Contacts:
Tiberend Strategic Advisors, Inc.

Joshua Drumm, Ph.D. (Investors)
[email protected]; (212) 375-2664

Amy Wheeler (Media)
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Islet Sciences, Inc.
[email protected]; (919) 480-1518

SOURCE Islet Sciences, Inc.