Clene Inc Announces New Preclinical Data Showing That Its Lead Candidate, CNM-Au8, Improved Cellular Health In A Dopaminergic Neuron Model Of Parkinson's Disease

• 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
  
  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."