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SCIENCE & technologies
The Disease

Insulin is a hormone released from islet cells located in the pancreas that is needed to convert sugar, starches and other food into energy needed for daily life. Type 2 diabetes usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin increases, the pancreas gradually loses its ability to produce it. Current treatments for type 2 diabetes include lifestyle changes, oral medications, incretin therapy and insulin therapy. Type 2 diabetes accounts for about 90-95% of all diagnosed cases of diabetes.

Obesity is considered to be the primary cause of type 2 diabetes in people who are genetically predisposed to the disease. Thus, weight management is an important clinical objective for treating type 2 diabetes patients as well as obese people.

The Drug Candidate and Mechanism of Action

The fastest growing segment of the diabetes market is the class of GLP-1 single-agonist therapies. TT401, a once-weekly administered peptide for the treatment of type 2 diabetes and associated obesity, is a dual agonist of the GLP-1 (Glucagon-Like Peptide-1) and glucagon receptors. These receptors play an integral role in regulating appetite, food intake, satiety and energy utilization in the body. Stimulating both these receptors, TT401 has the potential to regulate blood glucose levels with important additional outcomes, such as weight loss.

Completed Clinical Studies

Phase 2 Clinical Trial in Type 2 Diabetes

TT401 development collaborator Eli Lilly and Company performed the Phase 2 study enrolling 420 type 2 diabetes subjects into a 24 week study consisting of a 12-week randomized blinded stage followed by a 12-week open-label stage. The study included four once-weekly dose arms of TT401 (10mg, 15mg, 30mg, 50mg), a placebo arm, and an active comparator arm (exenatide extended release – 2mg). The study was completed in February, 2016.

Link to press release

Key Findings from the Phase 2 Study
  • TT401 showed statistically significant improvements in HbA1c of up to -1.43% (comparable to exenatide) at weeks 12 and 24
  • TT401 demonstrated dose-dependent weight loss (up to -3.3 kg)
  • Weight loss observed in the highest dose arm (50mg TT401) was statistically significant relative to both the placebo and exenatide arms at weeks 12 and 24
  • Acceptable safety and tolerability profile
Proof-of-Concept Study

TT401 has been tested in a recent proof-of-concept study with 50 obese diabetic patients (five dose levels) as well as 10 non-diabetic obese patients (one dose level). During the study, patients received TT401 or placebo once weekly for five weeks.

Link to press release

Key Findings from the Proof-of-Concept Study
  • Three highest dose groups showed significant reduction in fasting plasma glucose relative to placebo
  • Significant body weight reduction from baseline in three highest dose groups
  • A similar reduction in body weight in the non-diabetic obese subjects
  • An acceptable safety and tolerability profile at all doses
  • Decreased appetite was the most common adverse event noted
  • Some subjects in the highest three dose groups experienced mild nausea and vomiting, which are consistent with studies of other GLP-1 agonist drug candidates

© 2015 Transition Therapeutics Inc.