Update on Lead Diabetes Regenerative Therapy E1-I.N.T. Clinical Trials (DIABETIC FREEPERS)

TORONTO, Dec. 5 /CNW/ - Transition Therapeutics Inc. ("Transition")(TSX: TTH), announces an update on the ongoing exploratory Phase IIa clinical studies of its lead diabetes regenerative therapy, E1-I.N.T.™ for type I and type II diabetes patients as well as blinded safety and efficacy data for the type I diabetes clinical study. The main objective of these studies is to identify well-tolerated and safe doses of E1-I.N.T.™ in diabetes patients, and signs of efficacy by measuring parameters including insulin usage and HbA1c levels. Preliminary data from the first four type I diabetes patients completing the 4 week treatment period (E1-I.N.T.™ or placebo) showed a reduction in daytime insulin usage and a favourable safety profile when the therapy was titrated to maximal doses. E1-I.N.T.™ is a short course combination therapy aimed at stimulating the regeneration of the body's insulin-producing cells, called islet cells.

"Although preliminary and blinded, these interim data show diabetes patients tolerating escalating doses of E1-I.N.T.™ treatment and 3 of 4 type I diabetes patients reducing their daytime insulin usage by 35% - 75%." said Sherwyn Schwartz, MD, a noted diabetes researcher and the Director of the Diabetes & Glandular Disease Research Associates in San Antonio, Texas who enrolled these first patients in the study. Dr. Schwartz commented that "Any therapy that can reduce or eliminate insulin usage by diabetics would have a significant impact on the management of the disease."

"These early data, while preliminary, are very encouraging and represent an important step in the development of the first diabetes regenerative therapy at Transition," said Dr. Tony Cruz, Chairman and Chief Executive Officer at Transition, "Now with some early signs of efficacy, we can begin our planning for future clinical trials to optimize the E1-I.N.T.™ therapy."

The exploratory Phase IIa clinical studies for E1-I.N.T.™ are randomized, double-blind, controlled trials to evaluate the safety, tolerability and efficacy of daily E1-I.N.T.™ treatments for 28 days with a 6-month follow-up. The Type I diabetes clinical study will examine 20 Type I diabetes patients (15 E1-I.N.T.™, 5 placebo) and the Type II diabetes clinical study will examine 30 Type II diabetes patients (20 E1-I.N.T.™, 10 placebo).

To date, there have been 10 patients enrolled in the type I diabetes study. Four patients have completed the treatment phase and at least three months of follow-up post treatment, 5 patients are entering into the screening phase and one patient has withdrawn from the study. Recently, five new clinical sites have been initiated in addition to the lead site in San Antonio, Texas to facilitate the completion of enrolment which is expected in Q1 2006. The reporting of final study data is planned for mid-year 2006.

The four patients that received a dose escalation successfully completed the 28 days of daily treatments. The sole patient that withdrew from the study received only the maximal dosage with no dose escalation. The principal adverse events observed in the study were nausea and headaches. There have been no serious drug-related adverse events noted during the study to date including no injection site irritations, no modification of blood pressure, and no hypoglycaemic events. These preliminary safety findings are consistent with the positive profile observed in the previous single dose Phase I studies.

Patients in the study are randomized 3:1, treatment vs. placebo. Daytime insulin usage was reduced 35-75% in 3 of 4 Type I diabetes patients that completed treatment. These reductions of daytime insulin usage are evident after the 28-day treatment period and peak between 1-2 months post-treatment. During this period, these patients have maintained stable blood glucose control as measured by glycosolated hemoglobin levels (HbA1c). These early efficacy findings in Type I diabetes patients are consistent with effects demonstrated in diabetes animal models where maximal levels of regeneration were observed 3-6 weeks post-treatment.

Five US clinical sites have been initiated and study enrolment is expected to be completed by Q1 2006. To date, 19 patients have been enrolled in the type II diabetes study. For the six patients that have completed the treatment phase and the eight patients that are in the baseline or treatment phase, the principal adverse events observed are similar to those in the Type I diabetes study and are consistent with the safety findings from the single dose Phase I studies. Two patients decided not to continue in the study after experiencing nausea. Three patients are currently being screened in preparation for the treatment phase. At a time when sufficient patients have completed the treatment phase and a 2-3 month follow-up post-treatment, Transition will report interim safety and efficacy data from this study with final results expected mid-year 2006.

In August 2004, Transition signed an exclusive license agreement with Novo Nordisk A/S to develop and commercialize a series of diabetes regenerative therapies including E1-I.N.T.™ and GLP1-I.N.T.™.

The I.N.T.™ technology platform, covered by a broad patent portfolio, is based on the discovery that a short course of injections of naturally occurring peptides can regenerate insulin-producing cells in the body. Two lead I.N.T. products are currently under development: 1) E1-I.N.T.™, a combination of Transition's epidermal growth factor analogue ("E1") and gastrin analogue ("G1"), has completed two Phase I clinical trials, commenced enrolment for exploratory Phase IIa clinical trials in type I and type II diabetes patients; and 2) GLP1- I.N.T.™, a combination of one of the leading diabetes drug candidates, Glucagon-Like-Peptide-1 ("GLP-1"), with G1, is currently in pre-clinical development.

No, it's not a cure, but I do think this may be a better therapy than synthetic insulin. A 40% reduction in insulin requirements would mean most Type 1 diabetics could completely get off their basil and only bolus for meals. I think this is the best new therapy for T1 diabetics since the invention of insulin. I'd like fellow FReepers' thoughts!

Is this treatment for insulin-dependent diabetics only? My husband is Type II and takes GlucoVance 250 2X daily. His last a1C was 5.8. He is hoping to be able to control his sugar with diet and exercise only within 6 months. He was diagnosed 9 months ago when his a1C was 13.9.

You left a disclaimer from the original article out:

/NOT FOR DISTRIBUTION TO UNITED STATES NEWSWIRE SERVICES OR FOR DISSEMINATION IN THE UNITED STATES/

I honestly thought it was ok. I originally found the article, printed in full, at another website that's quite strict about these things.

If I'm wrong, then the mod can cut out the article and just leave the link.

What generic and brand names are in play?

Typically at this stage, the only existing "name" is something like the "E1-I.N.T.™" used in this case. Brand/generic names arise farther down the line in the development of the drug. Announcements such as this are often targeted at investors in order to raise money for the company to continue its work.

It'd be wonderful to someday be able to take the active human role out of glycemic control and replace it with an "automatic pilot". The physiology of glucose regulation in the body of an individual who does not have diabetes is intricate and essentially impossible to replicate "manually".

6 posted on 12/06/2005 12:34:48 PM PST by Pirate21 (The liberal media are as sheep clearing the path along which they will be led to the slaughter.)

I've been watching this drug for awhile and it was approved (and is available) for T2 diabetics. Only available by prescription.

For your husband, lookup Benfotiamine. My kid takes it and it did bring down his A1C. It also appears to stop diabetes-related illnesses.

Scratch that last post! I was confusing this drug with Exenatide! NOT the same thing!

Scratch that last post! I was confusing this drug with Exenatide!

Whew! I thought that was maybe what you meant. Exenatide and Symlin both look very promising. Have a couple friends with type 1 DM using Symlin, and both love the results -- decreased insulin requirements leading to decreased appetite and ensuing decreased weight. With Exenatide, the main side effect is nausea; however, this may actually be a person's being unfamiliar with how it feels to not be hungry.

9 posted on 12/06/2005 12:45:38 PM PST by Pirate21 (The liberal media are as sheep clearing the path along which they will be led to the slaughter.)

Symlin is good, but I'd *love* it if the diabetic's won body could do the job itself (with a little help). Nothing beats Mother Nature!

(I'm having the mod kill my messed up post.)

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