Lexicon Files Application for Potential Diabetes Treatment

THE WOODLANDS, Texas-- Lexicon Pharmaceuticals, Inc. (Nasdaq:LXRX) has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for LX4211, an oral small molecule drug candidate for type 2 diabetes.

The initial Phase 1 clinical trial of LX4211 is planned as a double-blind, randomized, placebo-controlled, ascending single- and multiple-dose study in healthy volunteers. This study is designed to evaluate the safety, tolerability, and pharmacokinetics of LX4211. Upon initiation of testing following FDA review, LX4211 would constitute Lexicon's fifth drug candidate to enter human clinical trials as part of its 10TO10 program.

"We observed the remarkable potential and biological specificity of the target of LX4211 in our Genome5000 program, a finding corroborated by human genetic studies," said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer at Lexicon. "The mechanism of action of LX4211 specifically blocks reabsorption of glucose by the kidney, which may help to improve glucose control in patients with type 2 diabetes. We believe that LX4211 will be favorably distinguished within an emerging new class of agents being developed for the treatment of diabetes."

LX4211 was developed at Lexicon as a potent inhibitor of the sodium glucose transporter 2 (SGLT2), a transporter that is responsible for most of the glucose reabsorption performed by the kidneys. Compounds that inhibit SGLT2 can potentially treat diabetes by increasing urinary glucose excretion, thereby lowering blood glucose levels as well as caloric load. This mechanism contrasts with that of certain drugs for type 2 diabetes which cause glucose calories to be stored rather than released, further stressing the insulin producing pancreatic beta cells. In preclinical studies using a diabetic mouse model, LX4211 increased urinary glucose excretion and decreased levels of both blood glucose and hemoglobin A1c (HbA1c), the latter of which is an indicator of long-term blood glucose levels. Loss of calories through increased glucose excretion could also have beneficial metabolic effects. Support for this possibility was recently provided by results from an SGLT2 inhibitor already in clinical trials which, in addition to reducing levels of HbA1c, has shown weight loss in studies of diabetic patients. Currently, there are no marketed products targeting the SGLT2 mechanism of action to treat diabetes.

Source: Lexicon Pharmaceuticals, Inc.