Clene Reports Significant Long-Term Survival Improvement From CNM-Au8 Treatment in HEALEY ALS Platform Trial Compared to PRO-ACT Historical Controls

Clene Inc. recently announced long-term follow-up data for patients treated with CNM-Au8 30 mg for up to 133 weeks in the HEALEY ALS Platform Trial. These post hoc results show significantly improved survival with a 49% decreased risk of death for the covariate risk-adjusted analyses compared to the largest US clinical database of previous amyotrophic lateral sclerosis (ALS) trials (PRO-ACT) (hazard ratio: 0.510, 95% CI: 0.263 – 0.987, p=0.046).

The HEALEY ALS Platform Trial is a perpetual multi-center, randomized, double-blind, placebo-controlled clinical trial program designed to evaluate the efficacy and safety of multiple investigational products in people living with ALS. Enrollment in the CNM-Au8 Regimen was initiated in the summer of 2020. Participants received CNM-Au8 in addition to ALS standard-of-care and were randomized to the drug or placebo during the 24-week double-blind period. CNM-Au8 was then offered to all participants who were eligible, and 92% elected to continue into the Open Label Extension (OLE). CNM-Au8 30mg was selected as the dosage going forward after the double-blind period.

In ALS, clinical studies with shorter double-blind treatment duration such as 24 weeks have used historical placebo controls from prior trials to determine the relative survival benefit of investigational treatment over longer-term follow-up (open label data). The PRO-ACT dataset is derived from pooled ALS clinical trial data from 29 completed Phase 2 and Phase 3 ALS clinical trials. Millions of de-identified longitudinally collected records from more than 11,600 individuals with ALS were standardized across trials and merged to create the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. This database provides a useful and validated surrogate for survival status of past participants in ALS clinical trials with long-term follow-up.

In this analysis, 59 participants who were originally randomized to CNM-Au8 30mg were compared to matched placebo participants derived from the PRO-ACT dataset:

Survival Improvement

• Originally randomized CNM-Au8 30mg treated participants (n=59) demonstrated a statistically significant 49% decreased risk of death compared to PRO-ACT matched placebo patients through long-term follow-up (covariate adjusted HR=0.510; 95% CI 0.263-0.987, p=0.046).
• In a pooled analysis of the HEALEY ALS Platform Trial and the RESCUE-ALS Trial, participants originally randomized to CNM-Au8 30mg (n=82) demonstrated a statistically significant 59% decreased risk of death compared to PRO-ACT matched placebo patients through long-term follow-up (covariate adjusted HR=0.406, 95% CI: 0.220-0.749, p=0.004).

Safety

• More than 500 estimated years of collective exposure across ALS, multiple sclerosis (MS), and Parkinson’s disease participants in CNM-Au8 clinical trials and Expanded Access Protocol (compassionate use) programs without any observed safety signals.
• No serious adverse events have been assessed as related to CNM-Au8 treatment; adverse events observed with CNM-Au8 have been characterized as transient and predominantly mild-to-moderate in severity.

Benjamin Greenberg, MD, Head of Medical at Clene, said “To show such profound survival improvement using the HEALEY ALS Platform Trial data set alone and a pooled HEALEY and RESCUE data set is remarkable, and helps confirm the survival benefit seen in the prespecified secondary endpoint. Clene is extremely gratified to see this consistent long-term survival data from the HEALEY ALS Platform Trial OLE, with a continued clean safety profile, adding to the totality of the survival evidence.”

Merit Cudkowicz, MD, Chair, Neurology Department, Massachusetts General Hospital, Director, Sean M Healey & AMG Center for ALS, and the Principal Investigator of the HEALEY ALS Platform Trial, added “Improved survival status is an important measure of drug effect. We previously reported a benefit for decreased risk of death or permanent assisted ventilation and delayed time-to-clinical-worsening events associated with CNM-Au8 30 mg from the double-blind period, and we are pleased to see these data from our long-term follow-up as further support of a survival signal in our HEALEY ALS Platform Trial. I am also happy to see how helpful a shared open-source dataset such as PRO-ACT is to the field to analyze data from the OLE portions of clinical trials. We encourage all companies working in ALS to contribute their data to PRO-ACT once their trial is complete. I want to also thank all the people with ALS who are part of clinical trials and are helping the community find new treatments.”

Clene Inc. (Nasdaq: CLNN) (along with its subsidiaries), and its wholly owned subsidiary Clene Nanomedicine Inc., is a late clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson’s disease, and multiple sclerosis. CNM-Au8 is a federally registered trademark of Clene Nanomedicine, Inc. The company is based in Salt Lake City, UT, with R&D and manufacturing operations in MD. For more information, visit www.clene.com.