Study CMD-2016-001 was a first-in-man, multicenter, open-label dose-escalation study in sALS with disease duration ≤3 years. In phase 1, successive cohorts of patients (n=6) were evaluated following a single dose, followed by a 4-week repeated dose study. At investigator discretion, treatment was continued for up to six 4-week cycles. In phase 2a, an expansion cohort (n=15) received up to six 4-week cycles at the RP2D of 72 mg/day determined in Phase 1.  Efficacy assessments (ASLFRS-R, ECAS, FVC) were conducted at baseline and after 1 and 6 cycles in Phase 1 and after 1, 2, 4 and 6 cycles in phase 2a.  Phase 2a used ECAS A-B-C to avoid practice effects.

All patients treated at RP2D had sALS; 0/4 in Phase 1 and 5/15 in Phase 2a had bulbar onset.  ALSFRS-R decrease was 0.5 points/month for all 19 subjects. Non-bulbar cases in Phase 1 and 2a had comparable mean change in ALSFRS-R over 24 weeks (-0.4 versus -0.3 points/month).  ECAS A-B-C score increased by +7.8 points (p = 0.02) which is comparable to the ECAS increase in the Phase 1 cohort (+10.25).

Marked CuATSM treatment effects on disease severity and cognitive function relative to historical controls were observed in sALS in both phase 1 and phase 2a cohorts. These results stimulated the ongoing multicenter, randomized, double-blinded, placebo-controlled study to definitively establish the efficacy of CuATSM.