Clene (NASDAQ:CLNN) executives used a conference presentation to outline near-term regulatory plans for CNM-Au8 in amyotrophic lateral sclerosis (ALS), discuss biomarker and survival analyses from prior studies, and provide an update on the company’s cash runway and financing structure.
Company focus and CNM-Au8 overview
President and CEO Rob Etherington described Clene as a late clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function in neurodegenerative diseases. Etherington said the company is in a critical period as it engages with the U.S. Food and Drug Administration (FDA) on a potential path toward accelerated approval for CNM-Au8 in ALS.
Biomarkers highlighted: neurofilament and GFAP
A central theme of the presentation was the role of biomarkers in ALS. Etherington emphasized neurofilament as a marker associated with neuronal damage and said rising neurofilament correlates with faster disease progression and shorter survival in ALS. He compared the use of biomarkers in neurodegeneration to established lab measures such as cholesterol and prostate-specific antigen.
Etherington said the company’s program has focused on demonstrating biomarker effects alongside clinical outcomes, and he described the ALS Functional Rating Scale (ALSFRS) as a primary endpoint that most ALS drugs have historically failed to meet. He stated that Clene’s ALS program missed ALSFRS as a primary endpoint, but he pointed to what he described as positive findings in other areas, including survival, preserved function, clinical worsening, and biomarkers.
According to Etherington, Clene observed a statistically significant neurofilament benefit as a pre-specified endpoint in the double-blind Phase II portion of the HEALEY platform trial. He said CNM-Au8 was the only one of eight completed HEALEY programs to show a pre-specified, statistically significant difference in neurofilament.
Etherington said the FDA requested additional substantiation beyond a single dataset and provided Clene with three possible avenues:
- Assess concordant neurofilament results in an NIH-sponsored expanded access program (EAP), which he said contains about three times as many patients and is supported by a $45 million NIH grant.
- Analyze placebo participants who switched to active drug after six months and evaluate subsequent neurofilament changes.
- Evaluate another ALS-related biomarker.
Etherington focused on the third option, discussing glial fibrillary acidic protein (GFAP), which he described as a structural protein in astrocytes. He said Clene observed results similar to neurofilament, including nearly identical p-values (“both 04s,” as stated in the presentation) and a roughly 10% to 11% reduction (0.90 vs. 0.89). Etherington also described analyses showing that neurofilament and GFAP moved together over time and said the company observed statistically significant associations between declines in these biomarkers and survival outcomes in certain responder subgroups.
Survival and clinical worsening analyses
Etherington highlighted survival as an important endpoint in ALS and discussed clinical worsening, which he defined to include death, the need for mechanical breathing support, or the need for a gastrostomy tube due to loss of swallowing function.
He said Clene observed a 94% risk reduction for survival as a pre-specified secondary endpoint in the HEALEY study, and he noted that the FDA requested further evidence over the past 14 months. He also discussed post-hoc survival analyses comparing CNM-Au8 (Regimen C) to other regimens within the HEALEY master protocol framework, stating that patients were enrolled under the same sites, eligibility criteria, and follow-up procedures and then randomized to different regimens.
Etherington said Clene showed a 73% to 77% risk reduction at 12 months (p=0.01) in certain analyses and described longer-term follow-up out to 36 months, citing a 44% risk reduction (p=0.004) after adjusting baseline differences. He also quoted FDA feedback, stating the agency indicated it would consider the six-month HEALEY data and post-hoc survival analyses as potentially supportive evidence if Clene could substantiate the neurofilament effect as “reasonably likely to predict clinical benefit.”
Regulatory timeline and funding update
Etherington said the company is awaiting a Type C meeting with the FDA, which he later clarified is expected by the end of the first quarter (by the end of March). He said Clene expects meeting minutes in the early part of the second quarter and is targeting an NDA submission by the end of the second quarter, depending on timelines. He also outlined possible outcomes, including an FDA request to proceed directly to an NDA submission, a request to run a Phase III trial before filing, or the FDA accepting an NDA to conduct a more detailed review before setting a PDUFA date.
Chief Financial Officer Morgan Brown addressed liquidity and financing. Brown said the company raised $6 million at $6.50 in a structured transaction, which he said should provide runway into the fourth quarter and support the Type C meeting and an NDA filing. He added that the financing includes two additional tranches tied to regulatory milestones:
- An additional $7 million upon NDA filing and acceptance (not approval), which Brown said could extend runway into early 2027.
- An additional $13 million upon approval, which Brown said would extend runway well into 2027.
Multiple sclerosis program also discussed
Etherington also discussed CNM-Au8 in multiple sclerosis (MS), saying the company has not “forgot about MS.” He said Clene has shown vision and cognition improvement in MS data presented to the FDA, including sustained effects out to three years and similar benefits among placebo participants who crossed over to active drug. Etherington said the company would like to proceed to a Phase III study in MS, but that funding would likely need to come from ALS commercialization or a partnership. He also said Clene is working with the FDA to consider cognition improvement as an endpoint, rather than the historically used Expanded Disability Status Scale (EDSS).
In closing remarks, Etherington said Clene believes it has compelling data, a strong safety profile, survival benefits across multiple assessed groups, and statistically significant biomarker changes, and he said the company expects to provide updates as FDA discussions progress.
About Clene (NASDAQ:CLNN)
Clene (NASDAQ: CLNN), also known as Clene Nanomedicine, is a clinical-stage biopharmaceutical company developing proprietary nanoparticle therapies aimed at treating neurodegenerative and demyelinating disorders. The company’s flagship product, CNM-Au8, is a suspension of catalytic gold nanocrystals designed to enhance cellular energy metabolism, promote remyelination, and reduce oxidative stress. Clene’s platform leverages the unique physicochemical properties of its nanoparticles to support neuronal health, with a focus on diseases that currently lack effective disease-modifying treatments.
Clene’s lead candidate, CNM-Au8, is undergoing multiple clinical trials targeting conditions such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and multiple sclerosis (MS).
