Business
Overview
Lexicon Pharmaceuticals is a biopharmaceutical company focused on the discovery and development of breakthrough treatments for human disease. We have used gene knockout technologies and an integrated platform of advanced medical technologies to systematically study the physiological and behavioral functions of almost 5,000 genes in mice and assessed the utility of the proteins encoded by the corresponding human genes as potential drug targets. We have identified and validated in living animals, or in vivo, more than 100 targets with promising profiles for drug discovery. For targets that we believe have high pharmaceutical value, we engage in programs for the discovery and development of potential new drugs.
We have five drug programs in various stages of clinical development:
We have also advanced small molecule compounds from a number of additional drug programs into various stages of preclinical development and research and believe that our systematic, target biology-driven approach to drug discovery will enable us to continue to expand our clinical pipeline.
We are working both independently and through strategic collaborations and alliances to capitalize on our technology, drug target discoveries and drug discovery and development programs. Consistent with this approach, we seek to retain exclusive rights to the benefits of certain of our small molecule drug programs by developing drug candidates from those programs internally and to collaborate with third parties with respect to the discovery, development and commercialization of small molecule and biotherapeutic drug candidates for other targets, particularly when the collaboration provides us with access to expertise and resources that we do not possess internally or are complementary to our own. We have established drug discovery and development collaborations with leading pharmaceutical and biotechnology companies which generated near-term cash while offering us the potential to retain economic participation in products developed from the collaboration. In addition, we have established collaborations and license agreements with other leading pharmaceutical and biotechnology companies, research institutes and academic institutions under which we received fees and, in some cases, are eligible to receive milestone and royalty payments, in return for granting access to some of our technologies and discoveries.
Lexicon Pharmaceuticals was incorporated in Delaware in July 1995, and commenced operations in September 1995. Our corporate headquarters are located at 8800 Technology Forest Place, The Woodlands, Texas 77381, and our telephone number is (281) 863-3000.
Our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934 are made available free of charge on our corporate website located at www.lexpharma.com as soon as reasonably practicable after the filing of those reports with the Securities and Exchange Commission. Information found on our website should not be considered part of this annual report on Form 10-K.
Our Drug Development Pipeline
We have five drug programs in various stages of clinical development and have advanced small molecule compounds from a number of additional drug programs into various stages of preclinical development and research:
Drug Program
Potential Indication
Stage of Development
Preclinical
Development
IND
Phase 1
Phase 2
Phase 3
NDA
LX4211
Type 2 Diabetes
LX1032
Carcinoid Syndrome
LX1033
Irritable Bowel Syndrome
LX2931
Rheumatoid Arthritis
LX7101
Glaucoma
LX4211 is an orally-delivered small molecule compound that we are developing for the treatment of type 2 diabetes mellitus. We initiated a Phase 2b clinical trial in June 2011 to evaluate the safety and tolerability of LX4211 and its effects on glycemic parameters associated with type 2 diabetes, and completed enrollment in the trial in February 2012. The Phase 2b trial has enrolled 299 patients with type 2 diabetes who are not adequately controlled on metformin monotherapy in a double-blind, randomized, placebo-controlled study of 75mg once daily, 200mg once daily, 200mg twice daily and 400mg once daily doses of LX4211, each administered in combination with standard metformin therapy over a 12‑week treatment period. The primary efficacy endpoint under evaluation in the trial is the change in hemoglobin A1c, or HbA1c, from baseline to week 12. Secondary efficacy endpoints include percentage of patients achieving HbA1c levels of less than 7%, as well as changes in fasting plasma glucose levels, 3-hour glucose tolerance testing, weight, blood pressure and triglyceride levels.
We reported top-line data in January 2010 from a Phase 2a clinical trial evaluating the safety and tolerability of LX4211 and its effects on glycemic parameters associated with type 2 diabetes. The Phase 2a trial enrolled 36 patients with non-insulin dependent type 2 diabetes in a double-blind, randomized, placebo-controlled study of 150mg and 300mg doses of LX4211, each administered once daily over a four-week treatment period. The efficacy endpoints under evaluation in the trial included urinary glucose excretion, fasting plasma glucose, response to oral glucose tolerance testing, and hemoglobin A1c, also known as HbA1c or A1c, a measure of blood glucose levels over time. Top-line data from the study showed that treatment with 150mg and 300mg of LX4211 provided improvements in glycemic control and demonstrated statistically significant benefits in the primary and multiple secondary efficacy endpoints. A marked and statistically significant decrease in fasting plasma glucose was observed at each measurement point throughout the treatment period in both dose groups relative to placebo. After four weeks of dosing, patients in both dose groups exhibited statistically significant reductions in HbA1c as compared to patients receiving placebo. Patients in both dose groups also exhibited statistically significant improvements in glucose tolerance in response to oral glucose tolerance testing. Consistent with the mechanism of action of LX4211, there was also a significant, dose-dependent increase in 24-hour urinary glucose excretion in both dose groups at each measurement point throughout the study period relative to placebo. Patients in both dose groups also showed positive trends in broader metabolic and cardiovascular parameters, including weight reduction, decreased blood pressure and lower triglyceride levels. LX4211 demonstrated a favorable safety profile in the trial, with no dose-limiting toxicities observed. Adverse events were generally mild and equally distributed across all groups, including the placebo group.
We previously completed a combined Phase 1 single ascending-dose and multiple ascending-dose study of LX4211. In the Phase 1 clinical trial, LX4211 was well tolerated at all dose levels and produced a dose-dependent increase in urinary glucose excretion.
LX4211 was internally generated by our medicinal chemists and inhibits both sodium-glucose cotransporter type 2, or SGLT2, a transporter responsible for most of the glucose reabsorption performed by the kidney, and sodium-glucose
cotransporter type 1, or SGLT1, a transporter responsible for glucose and galactose absorption in the gastrointestinal tract, and to a lesser extent than SGLT2, glucose reabsorption in the kidney. Our scientists identified mice lacking either SGLT1 or SGLT2 as having potent anti-diabetic phenotypes across multiple measures of glucose control and metabolism. In preclinical studies, animals treated with LX4211 demonstrated improvements in multiple measures of glycemic control and increased urinary glucose excretion, with urinary glucose excretion returning to baseline after treatment was discontinued.
LX1032 (Telotristat etiprate)
LX1032, or telotristat etiprate, is an orally-delivered small molecule compound that we are developing for the treatment of symptoms associated with carcinoid syndrome and are currently preparing for the initiation of pivotal Phase 3 clinical trials.
We reported top-line data in August 2011 from a Phase 2 clinical trial evaluating the safety and tolerability of telotristat etiprate and its effects on symptoms associated with carcinoid syndrome. The Phase 2 trial enrolled 23 patients with symptomatic carcinoid syndrome who were refractory to octreotride therapy in a double-blind, randomized, placebo-controlled study of 150mg, 250mg, 350mg and 500mg doses of telotristat etiprate, each administered three times daily over a 28-day treatment period in combination with octreotide therapy. The efficacy endpoints under evaluation in the trial included the number of daily bowel movements, stool form, urgency, a global assessment of symptoms associated with carcinoid syndrome, flushing episodes and an assessment of pain and discomfort. Top-line data from the trial showed evidence of efficacy across multiple endpoints, including improvements in bowel movement frequency, decreased levels of urinary 5-HIAA, the primary metabolite of serotonin and a biomarker for serotonin production, and improvements in the assessment of pain and discomfort. Telotristat etiprate demonstrated a favorable safety profile in the trial, with no dose-limiting toxicities observed. Adverse events were generally mild to moderate and similarly distributed across all groups, including the placebo group.
We also initiated a complementary open-label Phase 2 clinical trial of telotristat etiprate in June 2010, and completed enrollment of 15 patients in February 2012. We previously reported preliminary data from the open-label trial which indicate that the administration of the drug is associated with biochemical and clinical benefits, including improvements in the frequency of bowel movements and flushing episodes, urinary 5-HIAA levels and adequate relief of gastrointestinal symptoms.
We previously completed a Phase 1a single ascending-dose study and a Phase 1b multiple ascending-dose study of telotristat etiprate. In Phase 1 clinical trials, telotristat etiprate was generally well tolerated at all dose levels, and results demonstrated a potent dose-dependent reduction in both blood serotonin levels and urinary 5-HIAA which was consistent with the reductions observed in preclinical animal models.