8-K: Clene's CNM-Au8 Boosts Brain Energy in MS Patients

Clene Inc. announced new clinical data at ECTRIMS 2025, demonstrating its drug candidate CNM-Au8 significantly improves brain energy metabolism in multiple sclerosis patients.

Summary

• Clene Inc. presented new clinical data for CNM-Au8 at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2025) held from September 24-26, 2025.
• The data showed CNM-Au8 improves brain energy metabolism, evidenced by an improved NAD+/NADH ratio, in patients with non-active progressive MS, relapsing MS, and Parkinson's disease.
• The mean NAD+/NADH ratio in the brain significantly increased by +0.449 units (95% CI: 0.093 to 0.805, p=0.0148), representing an 8.65% change (95% CI: 2.6% to 14.7%, p=0.0006) in the full REPAIR population (n=39) after 12 weeks of treatment.
• In REPAIR-MS participants alone (n=26), the NAD+/NADH ratio increased by +0.480 units (95% CI: -0.018 to 0.979, p=0.058), representing a 9.49% change (95% CI: 1.14% to 17.85%, p=0.0275) to Week 12.
• Secondary endpoints demonstrated statistically significant increases in the % fraction of brain NAD+ and decreases in NADH for both the full REPAIR population (p=0.0058) and REPAIR-MS (p=0.0232), respectively.
• Baseline deficits in the NAD+/NADH ratio were significantly associated with the Expanded Disability Status Scale (EDSS), a global measure of MS disease severity (Pearson Correlation: = 0.429, p=0.0127).
• Baseline measures of working memory and cognitive processing speed, as measured by the Symbol Digit Modalities Test, were significantly associated with average brain ATP levels (Pearson Correlation: =0.542, p=0.0009).
• Baseline measures of upper extremity function, measured by the 9-Hole Peg Test time, were also significantly associated with average brain ATP levels (Pearson Correlation: =-0.513, p=0.0032).
• CNM-Au8 treatment was safe and well-tolerated, with treatment emergent adverse events characterized as transient and predominantly mild-to-moderate in severity.
• The U.S. Food and Drug Administration (FDA) aligned with Clene acknowledging the limitations of the Expanded Disability Status Scale (EDSS) and expressed openness to considering other potential primary endpoints, including cognition, to evaluate broader treatment effects for MS.

Sentiment

Score: 8

Explanation: The clinical data presented is positive, showing significant improvement in brain energy metabolism and good tolerability for CNM-Au8. The FDA's openness to new endpoints is also a strong positive for future development. This indicates promising progress for Clene's drug candidate in a significant therapeutic area.

Positives

• CNM-Au8 significantly improved brain energy metabolism, as evidenced by an increased NAD+/NADH ratio, in patients with multiple sclerosis and Parkinson's disease.
• The treatment was safe and well-tolerated, with adverse events being transient and predominantly mild-to-moderate.
• The FDA expressed openness to considering alternative primary endpoints beyond the Expanded Disability Status Scale (EDSS), such as cognition, for future MS clinical trials, which could facilitate drug development.
• The clinical data reinforces the insight that bioenergetic failure is a key contributor to neurodegeneration and disease progression in MS, suggesting CNM-Au8 may help slow disability progression by addressing this deficit.

Risks

• General market conditions may impact the company's performance.
• Clinical trials may not demonstrate the efficacy and safety of drug candidates to the satisfaction of regulatory authorities.
• Clinical trials may not produce positive results, potentially leading to additional costs or delays in completing, or inability to complete, the development and commercialization of drug candidates.
• Clinical results for drug candidates may not support further development or marketing approval.
• Actions of regulatory agencies may affect the initiation, timing, and progress of clinical trials and marketing approval.
• The company's ability to achieve commercial success for its drug candidates, if approved, is not guaranteed.
• The company has a limited operating history and its ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates is a risk.
• Other risks and uncertainties are set forth in the company's most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q.

Future Outlook

Clene anticipates further analysis of the REPAIR data to understand progressive MS and how targeting brain bioenergetics can treat MS and other neurodegenerative disorders. The company also notes the FDA's openness to considering broader treatment effects and alternative primary endpoints, such as cognition, beyond the Expanded Disability Status Scale (EDSS) for future MS clinical trials.

Management Comments

• "These results not only demonstrate a direct correlation of brain bioenergetics with disability, but they also demonstrate the ability of CNM-Au8 to rescue this deficit." Benjamin Greenberg, MD, Head of Medical at Clene.
• "Further analysis is ongoing to tell us more about progressive MS and may show how targeting brain bioenergetics can treat MS as well as other neurodegenerative disorders." Benjamin Greenberg, MD, Head of Medical at Clene.
• "These promising clinical results strengthen the body of evidence supporting further clinical development of CNM-Au8 for the treatment of MS." Rob Etherington, CEO of Clene.
• "Additionally, the openness from the FDA to discuss disability outcome measures beyond the EDSS, such as cognition and other broader treatment effects, marks a new milestone for MS clinical trials." Rob Etherington, CEO of Clene.

Industry Context

The announcement highlights a significant development in the treatment of neurodegenerative diseases, particularly Multiple Sclerosis and Parkinson's disease, by focusing on mitochondrial health and neuronal function. The emphasis on improving brain energy metabolism via the NAD pathway and reducing oxidative stress positions CNM-Au8 as a potential first-in-class therapy. The FDA's willingness to consider alternative endpoints beyond the traditional EDSS for MS trials reflects an evolving understanding of disease progression and treatment efficacy in the neurological field, potentially paving the way for more comprehensive assessment methods.

Comparison to Industry Standards

• The FDA's alignment with Clene acknowledging the limitations of the Expanded Disability Status Scale (EDSS) as a primary endpoint for MS trials suggests a potential shift in industry standards towards more comprehensive and nuanced measures of disability and treatment effect.
• The focus on improving brain energy metabolism (NAD+/NADH ratio) and its correlation with cognitive and motor function (Symbol Digit Modalities Test, 9-Hole Peg Test) represents a novel therapeutic approach compared to many existing MS therapies that primarily target inflammation or immune modulation.
• While no specific comparable companies or projects are named, the discussion around EDSS limitations implies a broader industry challenge in accurately capturing the full spectrum of MS disease progression and treatment benefits, which Clene's approach may help address.

Stakeholder Impact

• Shareholders: Positive clinical data and the FDA's flexibility on endpoints could increase investor confidence and potentially lead to share price appreciation.
• Patients (MS & Parkinson's): The promising results offer hope for a new treatment option that addresses a fundamental aspect of neurodegeneration (brain energy metabolism).
• Medical Community: The data provides new insights into the bioenergetic failure in MS and the potential of CNM-Au8, influencing future research and treatment paradigms.

Next Steps

• Further analysis of the REPAIR data is ongoing to provide more insights into progressive MS.
• Continued clinical development of CNM-Au8 for the treatment of MS and other neurodegenerative disorders is expected.

Key Dates

Recommendation

The filing presents compelling positive clinical data for CNM-Au8, demonstrating significant improvements in brain energy metabolism in MS and Parkinson's patients, coupled with a favorable safety profile. The FDA's expressed willingness to consider broader treatment effects and alternative primary endpoints beyond EDSS for MS trials is a crucial de-risking factor and opens new avenues for regulatory approval. These developments strengthen the commercial potential of CNM-Au8 and position Clene favorably in the neurodegenerative disease market, making it an attractive investment opportunity.

Keywords

Clene Inc., CLNN, CNM-Au8, Multiple Sclerosis, MS, Parkinson's Disease, Neurodegenerative Diseases, Brain Energy Metabolism, NAD+/NADH Ratio, ECTRIMS 2025, Clinical Data, Biopharmaceutical, Mitochondrial Health, Neuronal Function, FDA, REPAIR-MS, REPAIR-PD