Lexicon Genetics Incorporated has submitted an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) for LX1031, an internally-developed small molecule compound for gastrointestinal disorders such as irritable bowel syndrome. Following FDA review, Lexicon intends to initiate a phase 1 clinical trial of LX1031 in healthy volunteers to assess the compound's safety, tolerability and pharmacokinetics.

In preclinical studies, LX1031 has demonstrated the ability to reduce peripheral serotonin, a neurotransmitter that is known to play a major role in gastrointestinal function. LX1031 works locally in the gastrointestinal tract with little systemic exposure and has exhibited an excellent safety profile in preclinical studies.

"We believe that LX1031, which operates through a new mechanism of action, may offer an attractive therapeutic alternative for millions of patients with irritable bowel syndrome and other gastrointestinal disorders who currently have limited treatment options," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer. "LX1031 is the second program from Lexicon's internal target and drug discovery pipeline that has advanced to an initial regulatory filing in 2006. We expect additional Lexicon programs to reach this stage next year."

The target of LX1031 is an intracellular enzyme that is found mainly in the gastrointestinal tract. Lexicon discovered that mice lacking this enzyme have virtually no peripheral serotonin, yet their gastrointestinal function is preserved. Serotonin plays an important role in modulating gastrointestinal function and signals feelings of gastrointestinal discomfort to the brain. LX1031 reduces the serotonin available for receptor activation in the gastrointestinal tract, without affecting serotonin levels in the brain or its central nervous system functions. In human clinical trials, serotonin will serve as an effective biomarker by which to evaluate the activity of LX1031.

Lexicon discovered the target of LX1031 in its Genome5000TM program. In this program, Lexicon is analyzing 5,000 genes using its proprietary gene knockout technologies and its extensive physiological and behavioural analyses to discover new drug targets from the human genome. To date, Lexicon has completed the analysis of approximately 3,900 of these genes and has harvested more than 100 promising targets related to major medical needs.

Lexicon Genetics is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon is systematically discovering the physiological and behavioural functions of genes to identify potential points of therapeutic intervention, or drug targets. Lexicon makes these discoveries using its proprietary gene knockout technology to model the physiological effects that could be expected from prospective drugs addressing these targets.