To investigate the efficacy of CNM-Au8 for treatment of ALS.

CNM-Au8 is a suspension of catalytically active gold nanocrystals shown in models to enhance neuronal metabolic energy. Two trials, RESCUE-ALS and the HEALEY ALS Platform trial (Regimen C) did not show benefit on primary or secondary endpoints. Survival analyses from both studies and an expanded access program (EAP) were investigated.

Survival analyses were conducted from the two placebo-controlled trials: (i) long-term follow-up of RESCUE-ALS (Phase 2 randomized, double-blind, placebo-controlled trial (RCT)), and (ii) 24-week HEALEY ALS platform trial (Phase 2/3 perpetual multi-center, RCT). Also presented are data from a single-center EAP compared to ENCALS predicted survival.

In RESCUE-ALS, while primary analyses did not reach significance over 36-weeks, analyses of all-cause mortality comparing participants originally randomized to CNM-Au8 30mg to those initially randomized to placebo and followed up to 31.5 months demonstrated a significant survival benefit with CNM-Au8 treatment, resulting in >70% decreased risk of death (5 vs. 14 events, log-rank hazard ratio = 0.291; 95% CI: 0.118 to 0.718, p=0.0115).

In the HEALEY-ALS platform trial Regimen C, primary analyses did not show a benefit. Exploratory analysis showed a >90% reduction in risk of death alone or death/permanently assisted ventilation (PAV) at week 24 for the 30mg dose, but not 60mg, when adjusted for baseline imbalances in risk (Regimen C: PAV and death, 4 vs. 1, p=0.028, death only, 3 vs. 1, p=0.057; unadjusted for multiple comparisons).

Survival data from the EAP of CNM-Au8 30mg will be presented.

Despite the absence of effect on primary and secondary analyses in the RESCUE-ALS and HEALEY ALS Platform trials, the survival results are notable. Exploratory long-term follow-up from RESCUE-ALS and 24-week treatment in the Healey ALS platform trial provide evidence for enhanced survival with CNM-Au8 30mg. EAP data will be presented.