Lexicon Pharmaceuticals, Inc. (NASDAQ:LXRX) is a biopharmaceutical company engaged in discovering and developing breakthrough treatments for human disease. The company was founded in 1995 in The Woodlands, Texas under the name Lexicon Genetics, Inc. The company has used its patented mouse gene knockout technology and extensive in vivo screening capabilities to study nearly 5,000 genes in its Genome5000™ program and has identified over 100 potential therapeutic targets. Lexicon has advanced multiple drug candidates into human clinical trials and has a broad and diverse pipeline of drug targets behind its clinical programs. Lexicon is pursuing drug targets in five therapeutic areas including cardiology, gastroenterology, immunology, metabolism, and ophthalmology.
The company's clinical drug candidates include LX1031 for the treatment of irritable bowel syndrome and other gastrointestinal disorders; LX1032 for the treatment of the symptoms associated with carcinoid syndrome; LX2931 for the treatment of autoimmune diseases, such as rheumatoid arthritis; and LX4211 for the treatment of Type 2 diabetes.
The company was founded in 1995 and is headquartered in The Woodlands, Texas (just north of Houston). The company also has a site located in Princeton, NJ that houses its chemistry operations.
Lexicon was founded by Drs. Arthur Sands and Allen Bradley in The Woodlands, TX in 1995. This university-based biotech start up, out of Dr. Bradley’s lab at Baylor University, obtained initial financing from Texas businessman, Gordon Cain. The company went public in April 2000 with one of the largest initial public offerings (IPO) in biotech history, $220 million.
The company initially focused on using gene knockout technology to define the function of genes. This effort complimented and benefited from the international effort to sequence the human and mouse genomes (see Human Genome Project). Using its proprietary gene trapping and gene targeting technologies, the company created the world’s largest repository of genetically modified mouse embryonic stem cells, known as OmniBank® and established a large-scale mammalian knockout program to discover the physiological and behavioral functions of the most druggable mammalian genes. The information collected from this program is stored in the company’s LexVision® database, the world’s largest repository of gene function information derived from knockout mice with almost 5,000 gene knockouts studied.
Over the years, Lexicon evolved from a genomics company into a drug discovery and development company focused on discovering and developing breakthrough treatments for human disease. The company currently has multiple drug candidates in various stages of clinical trials.
Lexicon's unique drug discovery process has yielded a rich and promising pipeline. Clinical trials are underway for the following drug candidates. In addition, the company also has a number of promising programs in preclinical research.
LX1031 is an orally-delivered small molecule designed to regulate gastrointestinal (GI) function by reducing the amount of serotonin available for receptor activation in the GI tract without affecting serotonin levels in the brain. Serotonin is a key regulator of GI function, and is associated with the most common symptoms of IBS: problems with bowel motility and GI discomfort.
The target for LX1031 is tryptophan hydroxylase (TPH), the rate-limiting enzyme for serotonin production found in enterochromaffin (EC) cells of the GI tract. From research conducted in the Genome5000 program, Lexicon scientists found that mice lacking the non-neuronal form of this enzyme, TPH1, have virtually no serotonin in the GI tract, but do maintain normal levels of serotonin in the brain.
In preclinical studies, LX1031 caused a dose-dependent reduction in the amount of serotonin in the GI tract of multiple species without affecting brain serotonin levels.
Lexicon initiated a Phase 2 clinical trial of LX1031 in patients with IBS in December 2008. The clinical trial is planned as a four-week, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and effects of LX1031 on symptoms associated with IBS.
Previously, Lexicon successfully completed Phase 1 clinical trials of LX1031. In all trials completed to date, all dose levels and dosing regimes were well tolerated with infrequent adverse events observed.
LX1032 is an orally-delivered small molecule under development as a potential treatment for the symptoms associated with carcinoid syndrome. LX1032 acts by inhibiting the enzyme tryptophan hydroxylase (TPH). Unlike LX1031, LX1032 was specifically designed to be better absorbed into the blood stream and, therefore, capable of reducing serotonin production both inside and outside the GI tract without affecting brain serotonin levels.
In June of 2008 Lexicon announced that it had received Fast Track status from the U.S. Food and Drug Administration (FDA) for development of LX1032, an orally-delivered small molecule drug candidate for managing gastrointestinal symptoms associated with carcinoid syndrome.
In July of 2009 Lexicon initiated Phase 2 studies with LX1032 and also announced that it had received Orphan Drug Designation from the European Medicines Agency (EMEA) for LX1032.
About Fast Track Status FDA’s Fast Track program facilitates the development of potential new drugs and expedites the review of new drugs intended to serve unmet medical needs in serious or life-threatening conditions. Fast Track status also provides formal mechanisms for sponsors to communicate with the FDA on product development issues, including clinical trial design. Fast Track benefits include eligibility for an early review process that may significantly shorten FDA approval times by allowing for the possibility of a “rolling submission” for marketing authorization. Carcinoid syndrome is the first therapeutic indication for which Lexicon has obtained Fast Track status.
About Orphan Drug Designation The EMEA is a regulatory agency in the European Union (EU) primarily responsible for the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use. The goal of EMEA’s orphan drug program is to promote the development of drugs intended for the prevention or treatment of life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the EU. Incentives for developing new drugs under orphan drug designation in the EU include 10 years of marketing exclusivity, regulatory assistance, reduced regulatory fees associated with applying for marketing approval, and assistance with clinical trial design.
The target for LX1032 is TPH, the rate-limiting enzyme involved in serotonin biosynthesis and present in metastatic carcinoid tumor cells. From research conducted in the Genome5000TM program, Lexicon scientists found that mice lacking the non-neuronal form of the TPH enzyme (TPH1) have virtually no peripheral serotonin, but do maintain normal levels of brain serotonin.
In preclinical studies, LX1032 was able to reduce peripheral serotonin levels in several different species without affecting serotonin levels in the brain.
Lexicon initiated a Phase 2 study in patients with carcinoid syndrome in July 2009. The clinical trial is planned as a four-week, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and effects of LX1032 on symptoms associated with carcinoid syndrome. Previously, Lexicon successfully completed Phase 1 clinical trials of LX1032. In all trials completed to date, LX1032 was well tolerated at all dose levels.
LX2931 is an orally-delivered small molecule under development for the potential treatment of autoimmune diseases such as rheumatoid arthritis.
Inappropriate activation of lymphocytes is associated with autoimmune diseases, a spectrum of disorders in which the immune system malfunctions and causes the body to attack its own organs, tissues, and cells. LX2931 is intended to regulate lymphocyte activity in the body during an inflammatory response.
The target for LX2931 is sphingosine-1-phosphate lyase (S1P lyase), an enzyme in the sphingosine-1-phosphate (S1P) pathway associated with the body's inflammatory response. From research conducted in the Genome5000 program, Lexicon scientists discovered that mice lacking this enzyme have increased retention of immune cells in the thymus and spleen with a corresponding reduction in the deployment of T-cells and B-cells into the circulating blood, resulting in a reduced immune response.
In preclinical studies, LX2931 produced a consistent reduction in circulating lymphocyte counts in multiple species. In addition, LX2931 reduced joint inflammation and prevented arthritic destruction of joints in mouse and rat models of arthritis.
Lexicon initiated a Phase 2 study with LX2931 in patients with rheumatoid arthritis in August 2009. The clinical trial is planned as a 12 week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX2931 and its effects on symptoms associated with rheumatoid arthritis.
Previously, Lexicon successfully completed Phase 1 clinical trials of LX2931. Initial results in healthy volunteers demonstrated a potent, dose-dependent reduction in circulating lymphocytes, suggesting that the target of LX2931 may represent a new mechanism for regulating the immune response. Lexicon also completed a drug-drug interaction study of LX2931 in patients with rheumatoid arthritis in March 2009. Top-line results from the trial indicated that LX2931 was well tolerated in combination with methotrexate, and no clinically significant drug-drug interactions were observed. Methotrexate is the current standard of care for patients with rheumatoid arthritis.
LX4211 is an orally-delivered small molecule under development as a potential treatment for diabetes, which works by inhibiting the sodium-glucose cotransporter type 2 (SGLT2). SGLT2-inhibiting compounds can potentially treat diabetes by increasing urinary glucose excretion, thereby lowering blood glucose levels.
The primary target of LX4211 is SGLT2, a transporter responsible for most of the glucose reabsorption performed by the kidney. Lexicon scientists found that mice lacking SGLT2 have improved glucose tolerance and increased urinary glucose excretion.
In preclinical studies, animals treated with LX4211 demonstrated increased urinary glucose excretion and decreased blood HbA1c levels (a marker of long-term blood sugar levels). Importantly, urinary glucose excretion returned to baseline after treatment was discontinued.
Lexicon initiated a Phase 1 clinical trial of LX4211 in January 2009. The clinical trial is planned as a double-blind, randomized, placebo-controlled, ascending single- and multiple-dose study in healthy volunteers.
Formal preclinical studies
Lexicon is developing LX7101 as a potential treatment for glaucoma that works by inhibiting a protein that regulates intraocular pressure (IOP) in the eye.
The target of LX7101 is a kinase that is responsible for regulating intraocular pressure. IOP levels can become elevated due to increased resistance in the fluid outflow facility in the eye. LX7101 is intended to lower IOP by enhancing the fluid outflow facility of the eye. The goal of the LX7101 program is to develop a once-daily eye drop that lowers IOP by increasing the fluid outflow facility in the eye, a novel mechanism not currently addressed by approved products for glaucoma.
In preclinical studies, a single topical dose of LX7101 significantly reduced IOP in a model of ocular hypertension. Formal preclinical studies are in progress.
Lexicon operates from two locations found in Texas and New Jersey. Lexicon’s corporate headquarters are set up in The Woodlands, Texas just north of Houston. This location serves as Lexicon’s primary research facility to discover and validate the company's drug targets and test drug candidates in preclinical research.
Lexicon’s small molecule and medicinal chemistry efforts are housed in a state-of-the-art 76,000 square foot facility in Princeton, New Jersey. This site serves as Lexicon's primary medicinal chemistry site to create new chemical entities for therapeutic development.