LX9211 Clinical Trials

We are developing LX9211, an orally-delivered small molecule drug candidate, as a treatment for neuropathic pain. We identified the target of LX9211, adapter-associated kinase 1, or AAK1, in our target discovery efforts as a promising approach for the treatment of neuropathic pain, and identified LX9211 and another development candidate in a neuroscience drug discovery alliance with Bristol-Myers Squibb from which we hold exclusive development and commercialization rights. In preclinical studies, LX9211 demonstrated central nervous system penetration and reduction in pain behavior in multiple models of neuropathic pain, and has been demonstrated not to affect opiate pathways. We have reported top-line results from two Phase 1 clinical trials of LX9211, and are now conducting a Phase 2 clinical trial of LX9211 in diabetic peripheral neuropathic pain and a second Phase 2 clinical trial of LX9211 in post-herpetic neuralgia.

Phase 1 Clinical Trials

We have completed two Phase 1 clinical trials evaluating the safety, tolerability and pharmacokinetics of LX9211. The first trial enrolled ten cohorts of healthy volunteers in a randomized, double-blind, placebo-controlled, ascending single dose study of daily doses of LX9211. The second trial enrolled five cohorts of healthy volunteers in a randomized, double-blind, placebo-controlled, ascending multiple dose study of daily doses of LX9211, followed by a maintenance dose for 14 days. In both trials, LX9211 demonstrated a safety, tolerability and pharmacokinetics profile identifying the maximum tolerated dose and supportive of once-daily dosing, while exhibiting dose proportional pharmacokinetics. The most common adverse events were headache and dizziness, and there were no drug-related serious adverse events.

RELIEF-DPN-1 Phase 2 Clinical Trial

We successfully achieved proof-of-concept in a Phase 2 clinical trial of LX9211 in diabetic peripheral neuropathic pain, or DPN. The trial enrolled 319 patients experiencing DPN in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating three treatment groups who received an initial loading dose of 100mg or 200mg of LX9211 or placebo, followed by once daily doses of 10mg or 20mg of LX9211 or placebo, respectively. LX9211 achieved the primary endpoint of the study, demonstrating a statistically significant reduction in average daily pain score (ADPS) at week 6 compared to placebo in the low dose arm with results that plateaued in the high dose arm. The results on the primary endpoint showed a reduction from baseline in ADPS of 1.39 points (p=0.007 versus placebo) in the low dose arm and 1.27 points (p=0.030 versus placebo) in the high dose arm, compared to 0.72 in the placebo arm. Under the statistical analysis plan for the study, a p-value of less than 0.028 was considered statistically significant. Separation from placebo was seen by week 1 in both dose arms, and the effect was consistent across age, sex, concurrent use of medications for painful diabetic neuropathy, and baseline pain score.

Patient reported outcomes (global impression of change) were improved in patients treated with LX9211 compared to placebo. Adverse events were more frequent in the LX9211 treatment arms and at the higher dose, with the most common being dizziness, headache and nausea. Nearly all adverse events were reported as mild or moderate. There were no drug-related serious adverse events reported in the study.

RELIEF-PHN1 Phase 2 Clinical Trial

We are conducting a second Phase 2 clinical trial, RELIEF-PHN-1, evaluating the safety and tolerability of LX9211 and its effects on post-herpetic neuralgia, or PHN. The trial is expected to enroll approximately 74 patients experiencing PHN in a randomized, double-blind, placebo-controlled study evaluating two treatment groups receiving an initial loading dose of 200mg of LX9211 or placebo, followed by once daily doses of 20mg of LX9211 or placebo, respectively. The effects of LX9211 will be assessed over an 11-week evaluation period. The primary efficacy endpoint under evaluation is the reduction in an average daily pain score at 6 weeks, with secondary endpoints including the proportion of patients with 30% or greater and 50% or greater reduction in pain intensity at 6 weeks and the proportion of patients discontinuing treatment due to lack of efficacy. Certain patient-reported outcome measures will also be assessed.