Clene (CLNN) Study Update summary

Key biomarker findings and study results

• Statistically significant reductions in neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were observed with CNM-Au8 in ALS patients across the HEALEY ALS Platform Trial and NIH Expanded Access Program, including advanced and bulbar onset populations.

• NfL and GFAP declines were highly concordant and strongly associated with improved survival, with the greatest biomarker reductions linked to up to 80% reduction in mortality risk.

• In the HEALEY trial, CNM-Au8 30 mg showed a 73% risk reduction in mortality at 12 months (HR=0.272, p=0.0144) and a 52% risk reduction at 16 months (HR=0.481, p=0.0356) compared to controls.

• Placebo participants who switched to CNM-Au8 demonstrated similar biomarker improvements and survival benefits, with an average of 30.7 additional days at one year and up to 51% risk reduction at 12 months.

• The expanded access cohort included more advanced ALS patients, supporting the generalizability of findings.

Survival and clinical benefit analyses

• Declines in NfL and GFAP AUC during the double-blind period were associated with significant survival benefits, with up to 80% risk reduction for those with the greatest biomarker decline.

• Joint modeling showed each 1-unit increase in log NfL was associated with a 40% higher risk of death in ALS.

• Additional analyses in external datasets (RESCUE-ALS, EAP01-02) confirmed improved long-term survival with CNM-Au8 versus matched controls.

• The approach to using matched controls in the expanded access analysis was robust, matching for key baseline characteristics.

• Updated survival analyses continue to show clinically meaningful and statistically significant benefits.

Safety and tolerability

• Over 1,000 patient years of exposure show no significant safety concerns or trends for CNM-Au8.

• No serious adverse events have been attributed to CNM-Au8 by investigators.