CNM-Au8 & ALS Biomarkers - Clene announced statistically significant ALS biomarker results supporting an accelerated approval pathway for CNM-Au8® [1] - High NfL and GFAP levels are associated with mortality risk in ALS [21] - Substantiation of NfL biomarker effect may support acceptance of survival analyses [7, 28] - FDA guidance suggests that substantiation of NfL effects may allow 24-week data from the HEALEY platform trial and post-hoc analyses on long-term survival to provide evidence of clinical benefit [9, 10] - In the HEALEY ALS platform trial, CNM-Au8 demonstrated consistent effects on NfL and GFAP biomarkers [67] - In HEALEY trial, Plasma NfL W24 LS Mean GMR was 0.905 (95% CI: 0.822 – 0.996, p = 0.0403) and W24 AUC GMR was 0.901 (95% CI: 0.845 – 0.959, p = 0.0013) [69] - In HEALEY trial, Plasma GFAP W24 LS Mean GMR was 0.891 (95% CI: 0.798 – 0.995, p = 0.0401) and W24 AUC GMR was 0.913 (95% CI: 0.841 – 0.990, p = 0.0278) [72, 73] - In NIH-EAP trial, NfL and GFAP AUC decline is also consistent [75] Survival Analysis - NfL change significantly impacts ALS survival, with a joint-model hazard ratio of 1.40 (95% CI: 1.31 – 1.51) [108, 110] - Long-term survival evidence from the HEALEY ALS Platform Trial shows a 73% risk reduction at Month 12 in the Full Analysis Set and a 77% risk reduction in the Comparable Risk Set [113, 130, 133] - Improved long-term survival in ex-placebo to CNM-Au8 group, with a 51% risk reduction at 12-months post-CNM-Au8 treatment initiation [139, 140]