Clene (NASDAQ:CLNN) said it is preparing to submit a new drug application, or NDA, in early fourth quarter for CNM-Au8 as a potential treatment for amyotrophic lateral sclerosis, following a series of meetings with the U.S. Food and Drug Administration.
President and CEO Rob Etherington said the company has held five meetings with the FDA, most recently in March, focused on whether its clinical and biomarker data could support an accelerated approval application in ALS. The FDA has indicated that survival data alone would not support accelerated approval and that Clene would need to demonstrate an effect on a biomarker that is reasonably likely to predict clinical benefit, Etherington said.
Company Cites Survival and Functional Analyses
Etherington said the FDA asked Clene to further assess whether the magnitude of the NfL reduction was clinically meaningful. The company subsequently analyzed natural-history data from more than 2,000 subjects across the ANSWER ALS and APST datasets, which he said showed a relationship between a 10% NfL reduction and survival.
Clene also examined outcomes among patients with stabilized or declining NfL levels and reported post hoc findings of statistically significant benefits on the ALS Functional Rating Scale-Revised, or ALSFRS-R, and slow vital capacity, a measure of breathing function. Etherington said the company observed a 38% lower risk of death in its survival analysis versus concurrent controls.
The concurrent-control dataset included patients randomized across three HEALEY trial regimens at the same sites and during the same period, according to Etherington. He said the two other programs did not continue in ALS development and their sponsors shared data from their placebo and active-treatment groups with Clene at the FDA’s request.
“The agency basically told us at that meeting in March, ‘Is 10% clinically meaningful? That is the key question,’” Etherington said, characterizing the FDA’s feedback. “We are not exactly sure. That is the reason we want this opportunity to accept an NDA, review it, dig into the data, but to really see how neurofilament light is tied to clinical benefit.”
NDA Package and Confirmatory Trial Plans
Etherington said clinical study reports supporting the application are largely complete, with the HEALEY clinical study report still being finalized. He said Clene expects to submit the full NDA package to its regulatory publisher after that work is completed.
CNM-Au8 is an oral suspension containing gold nanocrystals. Etherington described the candidate as a bioenergetic catalyst intended to affect mitochondrial metabolism, including reactive oxygen species, nicotinamide adenine dinucleotide and adenosine triphosphate. He said the company manufactures the product internally.
Clene has proposed a confirmatory Phase 3 ALS trial that the FDA has approved, according to Etherington. The planned study would enroll 800 subjects and use a time-to-event design over approximately two years, with survival as the primary endpoint. The endpoint would include death and the need for at least 22 hours of breathing support, he said.
Etherington said the FDA told the company that enrollment in the confirmatory trial would need to begin before the agency would consider an approval decision. He said Clene plans to begin the study in the first half of the year before a potential approval decision.
The company has not been told whether the FDA will convene an advisory committee meeting for the application, Etherington said. He added that Clene would be prepared for such a meeting if one is requested.
MS Program and Funding Outlook
Clene is also discussing a multiple sclerosis program with the FDA. Etherington said the agency agreed last August that Clene could potentially pursue cognitive improvement as an endpoint in a Phase 3 study involving MS patients whose disease is progressing despite disease-modifying therapy. He said the company expects to turn more attention to the MS opportunity in 2027.
CFO Morgan Brown said Clene has stated publicly that its current cash runway extends into the fourth quarter. The company will need additional capital to fund operations through NDA acceptance and a potential approval decision, he said.
- Brown said regulatory warrants held by investors including Vivo, Casdin Capital and Boxer Capital could provide an additional $7 million upon NDA acceptance.
- Clene also raised $7 million in May through the sale of 1 million shares at $7 per share to a single investor, Brown said.
Brown said the recent financing helps support the company into the middle of the fourth quarter, but additional fundraising will be required to reach key regulatory milestones.
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).
