Praxis Precision Medicines, Inc. announced further data from two additional analyses of the Essential1 study for ulixacaltamide. Ulixacaltamide is a differentiated and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing in the Cerebello-Thalamo-Cortical (CTC) circuit correlated with tremor activity and being developed for Essential Tremor. Open-Label Extension: Following completion of the initial 8-week double-blind treatment phase in Essential1, eligible patients had the option to continue their access to ulixacaltamide in an open-label extension (OLE) phase.

Participants who continued to the OLE phase remained blinded for a 6-week lead-in period. There was no change to the overall safety results through 14 weeks of treatment. 65 patients who completed the double-blinded portion of Essential1 were eligible to participate in the OLE and completed the week 14 assessment.

Patients who were eligible and continued on ulixacaltamide (n= 39) experienced an additional mean improvement in mADL11 of 1.7 points from 3.09 at Week 8 (95% CI: 0.98, 5.2) to 4.81 (95% CI: 2.38, 7.23) after 14 weeks of treatment. Patients who switched from placebo during the double-blind phase of Essential1 to ulixacaltamide treatment during the OLE 6-week lead-in (n= 26) experienced mean improvement in mADL11 of 3.15 points, from 1.21 at Week 8 (95% CI: -1.04, 3.46) to 4.36 (95% CI: 1.68, 7.05). Randomized Withdrawal Sub-Study: Following the announcement of the Essential1 study topline results, Praxis amended the open-label protocol to further assess the criteria to be used in the upcoming randomized withdrawal Phase 3 study.

In this sub-study, patients were re-randomized in a blinded fashion to either receive placebo or continue to receive ulixacaltamide. Twenty-one patients who completed assessments at week 14 of the OLE were eligible to participate in the blinded sub-study. Patients were evaluated weekly over a total of 6 weeks, with 11 patients assigned to ulixacaltamide and 10 to placebo for the initial 3-week period, crossing over to either placebo or ulixacaltamide for an additional 3-week period.

Blinded rescue was triggered for patients on placebo if loss in the mADL11 exceeded 2 points at any timepoint. Patients who switched from ulixacaltamide to placebo experienced an average loss of effect in their mADL11 per week of 47% (mean loss of effect of - 1.15 points/week), compared to 6% improvement in global mean change per week (mean improvement of 0.16 points/week) for the periods receiving ulixacaltamide. In addition, 10 patients assigned to placebo met the rescue criteria to restart ulixacaltamide.

85% of the patients who received ulixacaltamide (17 of 20) and 52% who received placebo maintained their mADL11 within 3 points compared to baseline, confirming the definition of patient stability to be used in the Phase 3 program. No new safety signals emerged and there was no change to the overall safety results observed in the 8-week double-blind treatment phase. The results from the sub-study supported a number of proposed design elements for the upcoming Phase 3 randomized withdrawal study, including the responder criteria and feasibility of rescuing patients with ulixacaltamide.

Additional study design elements will be discussed in more detail at an upcoming R&D portfolio event in early October 2023.