Clene Presents Preclinical Data Supporting CNM-Au8® for the Treatment of Parkinson’s Disease

Rhea-AI Summary

Clene (NASDAQ:CLNN) announced promising preclinical data for CNM-Au8® in treating Parkinson's disease (PD), presented at the Michael J Fox Foundation H2 Therapeutics Stewardship Meeting. The study utilized an innovative model converting skin cells from 8 sporadic PD patients, 14 familial PD patients, and 13 healthy individuals into dopaminergic neurons.

Key findings showed that CNM-Au8 treatment improved mitochondrial health, reduced inflammation, restored cellular metabolism, and normalized gene expression in PD neurons. The drug demonstrated favorable safety with over 1,000 patient-years of exposure data in ALS and MS patients. The company plans to design and implement a Phase 2 clinical study for PD treatment while advancing late-stage studies in ALS and MS.

Positive

• Demonstrated improvement in mitochondrial health and volume in familial PD neurons
• Reduced inflammation markers (CD40 and CXCL10) in sporadic PD neurons
• Normalized expression of majority of PD-related genes to near-control levels
• Strong safety profile with 1,000 patient-years of exposure data
• Successfully restored cellular metabolism in both familial and sporadic PD neurons

Negative

• Effects were relatively milder in sporadic PD compared to familial PD
• Still in preclinical stage for Parkinson's disease treatment
• Phase 2 clinical study for PD treatment yet to be designed and implemented

Insights

Neuroscience Researcher

CNM-Au8 shows promising preclinical results for Parkinson's disease by improving mitochondrial function and reducing inflammation, supporting further clinical development.

Clene's preclinical data for CNM-Au8 represents a significant advancement in potential Parkinson's disease (PD) therapeutics. The study employed a sophisticated human neuronal model that preserves age-related characteristics—a crucial factor since PD is predominantly age-associated. By converting skin cells from both sporadic and familial PD patients into dopaminergic neurons, researchers created a highly disease-relevant testing platform.

The data reveals four key therapeutic effects that address fundamental PD pathologies: improved mitochondrial health (increased membrane potential and volume with reduced ROS), reduced neuroinflammation (decreased CD40 and CXCL10), restored metabolic function (improved NAD+/NADH ratio and normalized TCA cycle), and correction of dysregulated gene expression profiles.

What's particularly noteworthy is CNM-Au8's mechanism as a nanocatalyst that enhances energy metabolism—addressing the mitochondrial dysfunction central to PD pathogenesis. The compound's ability to correct 36% of metabolites in familial PD neurons and 17% in sporadic PD neurons suggests potential efficacy across different PD subtypes, though with stronger effects in genetic forms.

The safety profile is equally compelling, with no observed toxicity in these models, consistent with CNM-Au8's clean safety record across over 1,000 patient-years of exposure in ALS and MS trials. This established safety record could potentially accelerate the clinical development timeline.

The backing from the Michael J. Fox Foundation adds credibility to this research. While these results are preclinical, they build upon previous Phase 2 data showing CNM-Au8 favorably alters brain energy metabolites in PD patients. This suggests the compound's effects translate from lab to humans, increasing confidence in its therapeutic potential as Clene advances toward a Phase 2 PD study.

• Novel human preclinical neuronal model for Parkinson’s disease demonstrated CNM-Au8’s ability to improve mitochondrial health, restore cellular metabolism, reduce inflammation, and normalize dysregulated gene expression in both familial and sporadic Parkinson’s disease

• Results presented today at the H2 Therapeutics Stewardship Meeting in New York City, hosted by the Michael J Fox Foundation

• Taken together with results from a Phase 2 study that demonstrated orally dosed CNM-Au8 favorably alters critical brain energy metabolites NAD+, NADH, and ATP in PD patients, these new data support the continued development of CNM-Au8 as a treatment for PD
  

SALT LAKE CITY, Sept. 04, 2025 (GLOBE NEWSWIRE) -- Clene Inc. (Nasdaq: CLNN) (along with its subsidiaries, “Clene”) and its wholly owned subsidiary Clene Nanomedicine Inc., a clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurological diseases, today announced new preclinical data showing that CNM-Au8^® improved key measures of cellular health in a novel dopaminergic neuron model of Parkinson’s disease (PD). The study results will be presented today at the Michael J. Fox Foundation H2 Therapeutics Stewardship Meeting in New York City by Associate Professor Jerome Mertens, who conducted the study in collaboration with Dr. Fred Gage of the Salk Institute, and Karen S. Ho, Ph.D., Vice President of Translational Medicine of Clene. The work was supported by funding from the Michael J. Fox Foundation (MJFF).

The study used skin cells from 8 sporadic PD (sPD) patients, 14 familial PD (fPD) patients—13 with LRRK2 gene mutations and 1 with a PARK gene mutation—and 13 healthy individuals. The skin cells were directly converted into dopaminergic neurons, the brain cells essential for movement and the most vulnerable to degeneration in PD. This innovative method retains age-related characteristics from PD patient donors, enabling researchers to study disease processes as they occur in aged disease-relevant neurons.

Key findings from CNM-Au8 treatment include:

• Improved mitochondrial health in familial PD: CNM-Au8 increased mitochondrial health (membrane potential) and mitochondrial volume, while reducing harmful reactive oxygen species (ROS) in fPD neurons. Similar, relatively milder effects were observed in sPD neurons.
  
• Reduced inflammation in sporadic PD: CNM-Au8 lowered levels of senescence-related inflammatory proteins, including CD40 and CXCL10, in sPD neurons, helping to reduce neuroinflammation that exacerbates PD progression.
  
• Restored cellular metabolism: CNM-Au8 dose-dependently increased the NAD+/NADH ratio, a measure of cellular energy metabolism. Further, CNM-Au8 corrected the intracellular levels of 36% of metabolites in fPD neurons and 17% in sPD neurons, particularly in the tricarboxylic acid (TCA) cycle for energy production and in nucleotide metabolism (e.g., xanthine, inosine) demonstrated by semi-targeted metabolomic analyses.
• Normalized dysregulated gene expression: CNM-Au8 treatment of PD neurons resulted in a reversal of the global disease-associated gene expression profiles in both sPD and fPD dopaminergic neurons, normalizing the expression of the majority of all top up- and down-regulated PD differentially expressed gene transcripts to near-control levels.
• Favorable safety profile: CNM-Au8 did not demonstrate evidence of toxicity toward the PD dopaminergic cells at all tested doses, a finding consistent with the clinical observation that CNM-Au8 treatment in humans has over 1,000 patient-years of exposure data in ALS and MS without significant safety concerns.

“Parkinson’s disease has complex and multifactorial causes, but mitochondrial dysfunction, chronic inflammation, and disrupted metabolism are consistent hallmarks,” said Dr. Mertens of the Salk Institute. “These results, generated in an advanced model that reflects both the genetics and the aging process of PD, add to the growing body of evidence that CNM-Au8’s catalytic metabolic effects on mitochondrial health, energy metabolism, neuroinflammation, and gene expression could have broad therapeutic potential for the treatment of Parkinson’s disease and other neurodegenerative disorders.”

“CNM-Au8 has a unique nanocatalytic mechanism of action that favors its application to many neurodegenerative diseases that have mitochondrial dysfunction and energetic failure at their core. As we advance CNM-Au8 through late-stage clinical studies to demonstrate its efficacy in treating ALS, and engage with the FDA to support a Phase 3 MS clinical program, we also look forward to designing and implementing a Phase 2 clinical study of CNM-Au8 for the treatment of PD,” said Benjamin Greenberg, MD, Head of Medical at Clene. “We are grateful to the MJFF for supporting this work, and to the Salk Institute for such a meaningful collaboration. These promising preclinical results strengthen the body of evidence supporting further clinical development of CNM-Au8 for the treatment of Parkinson’s disease.”

About Clene
Clene Inc., (Nasdaq: CLNN) (along with its subsidiaries, “Clene” 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 an investigational first-in-class therapy that improves central nervous system cells’ survival and function via a mechanism that targets mitochondrial function and the NAD pathway while reducing oxidative stress. CNM-Au8^® is a federally registered trademark of Clene Nanomedicine, Inc. The company is based in Salt Lake City, Utah, with R&D and manufacturing operations in Maryland. For more information, please visit www.clene.com or follow us on X (formerly Twitter) and LinkedIn.

About CNM-Au8^®
CNM-Au8 is an oral suspension of gold nanocrystals developed to restore neuronal health and function by increasing energy production and utilization. The catalytically active nanocrystals of CNM-Au8 drive critical cellular energy producing reactions that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. CNM-Au8^® is a federally registered trademark of Clene Nanomedicine, Inc.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the “safe harbor” provisions created by those laws. Clene’s forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding our future operations. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “contemplate,” “continue,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “will,” “would,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements represent our views as of the date of this press release and involve a number of judgments, risks and uncertainties. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update forward-looking statements to reflect events or circumstances after the date they were made, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Accordingly, forward-looking statements should not be relied upon as representing our views as of any subsequent date. As a result of a number of known and unknown risks and uncertainties, our actual results or performance may be materially different from those expressed or implied by these forward-looking statements. Some factors that could cause actual results to differ include general market conditions, whether clinical trials demonstrate the efficacy and safety of our drug candidates to the satisfaction of regulatory authorities, or do not otherwise produce positive results which may cause us to incur additional costs or experience delays in completing, or ultimately be unable to complete the development and commercialization of our drug candidates; the clinical results for our drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; our ability to achieve commercial success for our drug candidates, if approved; our limited operating history and our ability to obtain additional funding for operations and to complete the development and commercialization of our drug candidates; and other risks and uncertainties set forth in “Risk Factors” in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this press release, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to rely unduly upon these statements. All information in this press release is as of the date of this press release. The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this press release.

Media Contact Ignacio Guerrero-Ros, Ph.D., or David Schull Russo Partners, LLC Ignacio.guerrero-ros@russopartnersllc.com David.schull@russopartnersllc.com (858) 717-2310

Investor Contact Kevin Gardner LifeSci Advisors kgardner@lifesciadvisors.com (617) 283-2856

FAQ

What are the key findings of Clene's (CLNN) CNM-Au8 preclinical study for Parkinson's disease?

The study showed CNM-Au8 improved mitochondrial health, reduced inflammation, restored cellular metabolism, and normalized gene expression in PD neurons, with particularly strong results in familial PD cases.

How many patients were included in CLNN's Parkinson's disease preclinical study?

The study included skin cells from 8 sporadic PD patients, 14 familial PD patients (13 with LRRK2 mutations, 1 with PARK mutation), and 13 healthy individuals.

What is the safety profile of Clene's CNM-Au8 treatment?

CNM-Au8 has demonstrated a favorable safety profile with over 1,000 patient-years of exposure data in ALS and MS patients, showing no significant safety concerns.

What are the next steps for Clene's (CLNN) CNM-Au8 Parkinson's disease program?

Clene plans to design and implement a Phase 2 clinical study for PD treatment while continuing late-stage clinical studies in ALS and engaging with FDA for a Phase 3 MS program.

How does CNM-Au8 affect cellular metabolism in Parkinson's disease?

CNM-Au8 increased NAD+/NADH ratio and corrected intracellular levels of 36% of metabolites in familial PD neurons and 17% in sporadic PD neurons, particularly in energy production pathways.