Telotristat Ethyl

XERMELO (telotristat ethyl) was discovered by our scientists and inhibits tryptophan hydroxylase, or TPH, the rate-limiting enzyme for serotonin production found primarily in enterochromaffin cells of the gastrointestinal tract.
As part of our life cycle management of the program, we are conducting a Phase 2a clinical trial evaluating the safety and tolerability of telotristat ethyl and its effects on biliary tract cancer. The trial is expected to enroll approximately 54 patients with unresectable, locally advanced, recurrent or metastatic biliary tract cancer in an open-label, two-stage study of a 250mg three times daily dose of telotristat ethyl over an initial 7-day treatment period, followed by a 500mg three times daily dose of telotristat ethyl over subsequent 21-day treatment cycles until cessation of treatment for disease progression, toxicity or patient withdrawal. Standard of care, first-line chemotherapy doses of cisplatin and gemcitabine will be administered on days one and eight of each 21-day treatment cycle. The trial is designed to be conducted in two stages, each of which is expected to enroll approximately 27 patients. The primary efficacy endpoint under evaluation is the progression-free survival rate at six months, with secondary endpoints including progression-free survival at 12 months, overall survival rates, disease control rates and weight change.

LX2761

LX2761 is an orally-delivered small molecule compound that we are developing for the treatment of diabetes. LX2761 was discovered by our scientists and is designed to inhibit SGLT1 locally in the gastrointestinal tract without any significant inhibition of SGLT2 in the kidney.

We reported top-line data in December 2018 from two Phase 1 clinical trials evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of LX2761. The Phase 1a trial enrolled five cohorts of healthy volunteers and two cohorts of type 2 diabetes patients in a randomized, double-blind, placebo-controlled, ascending single dose study of daily doses of LX2761. Patients with type 2 diabetes were washed off metformin for three days prior to dosing. LX2761 demonstrated minimal absorption and no systemic effect, with no increase in urine glucose excretion from baseline. LX2761 also reduced postprandial glucose in diabetic patients while increasing plasma levels of glucagon-like peptide-1, or GLP-1, a hormone produced in the small intestine that stimulates insulin secretion and inhibits glucagon secretion. The most common adverse and dose-limiting event was diarrhea.

The Phase 1b trial enrolled 51 patients with type 2 diabetes in a randomized, double-blind, placebo-controlled ascending multiple dose study of daily doses of LX2761, administered as a single dose or twice per day over an 8-day treatment period. Patients were treated with metformin at the time of screening and for the duration of the study. LX2761 showed reduced postprandial glucose, demonstrating delayed and reduced intestinal glucose absorption while increasing plasma levels of GLP-1 with minimal effect on urinary glucose excretion. The most common adverse event was diarrhea. We are presently evaluating the further clinical development of LX2761.

We have granted Sanofi certain rights of first negotiation with respect to the future development and commercialization of LX2761.

LX9211

LX9211 is an orally-delivered small molecule compound that we are developing for the treatment of neuropathic pain. LX9211 was discovered by scientists working within our drug discovery alliance with Bristol-Myers Squibb and inhibits adaptor associated kinase 1, or AAK1. Our scientists discovered that mice lacking AAK1 exhibit increased resistance to induced neuropathic pain in preclinical models.
We reported top-line data in December 2018 from a Phase 1a clinical trial evaluating the safety, tolerability and pharmacokinetics of LX9211. The trial enrolled ten cohorts of healthy volunteers in a randomized, double-blind, placebo-controlled, ascending single dose study of daily doses of LX9211. LX9211 demonstrated a safety, tolerability and pharmacokinetics profile identifying the maximum tolerated dose and supportive of once daily, or less frequent, dosing.  Pharmacokinetics results were dose proportional over substantially all of the dose range. The most common adverse event was headache and there were no drug-related serious adverse events.We are conducting a Phase 1b clinical trial further evaluating the safety, tolerability and pharmacokinetics of LX9211.  The trial is expected to enroll up to 40 healthy volunteers in a randomized, double-blind, placebo-controlled, ascending multiple dose study of daily doses of LX9211 over a 14-day treatment period.

 

We have obtained exclusive research, development and commercialization rights to LX9211 and additional compounds acting through AAK1 from Bristol-Myers Squibb