Welcome back, everyone. We have an update from Clene Inc. Trades on the NASDAQ under the symbol CLNN. It's a late-stage, clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases. Happy to welcome President and CEO Rob Etherington. Welcome, Rob. We're happy to hear your update.
Thank you, Anna. It's a pleasure to be here and to see everybody, virtually at least, on this hopefully pleasant July day for most of you, though I certainly recognize that the Eastern Seaboard has been slammed with a lot of rain of late. Where I am, though, in Utah, it's presently beautifully sunny outside, and I wish that you all have a good rest of July. Clene just met with the agency in June. We announced this just the Fourth of July week, and that enabled a very clear plan for our analysis of neurofilament, the biomarker neurofilament. Now, I think, Anna, for your listeners, let me just give an update of that. When the disease ALS attacks the neuron, it leaves a debris field in the bloodstream, and that debris field can be measured. It's a cytoskeletal protein remainder of what's called neurofilament light.
Similar to how glucose might be a measure of diabetes problems, cholesterol might be a biomarker measure of cardiovascular problems, high neurofilament levels are a biomarker or an indicator of ALS challenges in the neuron. What you and I and all the human family rely upon for this choreography of life that enables us to move and walk and talk and eat and chew and breathe, that is driven by neurons. What we've done is the FDA has proposed that we evaluate the neurofilament effect of CNM-Au8. That is, can it drop neurofilament in an ALS patient? If compromised neurofilament is rising because the neurofilament is leaching from destroyed neuron into the bloodstream, and our CNM-Au8 drug that we take by mouth orally can reduce neurofilament, that's very indicative of a clinical benefit.
We have levered the $45 million that the NIH gave us, bless them, that's funding 180 subjects, individuals, participants, people who struggle with ALS, said most, you know, more specifically. It has enabled them to be on drug now for at least six months and in many cases up to a year. Clene will be evaluating the neurofilament change of these individuals beginning next month through till September. I say that time period because we, per the FDA's request, had to get all of these individuals to at least six months of therapy, which has just happened this month. What we're doing is evaluating that, and we'll be submitting that data back to the agency.
If it is concordant, that is, says the same story, expresses the same argument that we saw in the double-blind, placebo-controlled HEALEY program, then we've asked the agency if we could submit this data consistent with HEALEY as a new drug application for the possibility of accelerated approval in ALS. Secondary to this, and not, you know, one could argue primarily to this, not secondarily, we've submitted a whole separate dossier to the FDA on survival alone because we achieved the secondary endpoint in the HEALEY point on the 30 mg dose for survival reduction. We've also announced earlier this year survival against a concurrent control, regimen A, that also showed a concordant or similar survival benefit. We've submitted this dossier to the FDA, and we have a meeting, as we announced, the Fourth of July week, also in the third quarter to discuss this.
Whether the FDA lets us put forward a new drug application based upon neurofilament or survival or both is a conversation that we'll be very much looking forward to having with the FDA over the course of the next 90 days.
Wonderful. Congratulations with that. Can you talk about when you might anticipate having new data, and a little bit more on filing that new drug application?
This data that I just spoke of is all coming to us in the very latter part of the third quarter. That data will be submitted to the FDA in the top of the fourth quarter with the ability, as we're planning and preparing, the filing of this new drug application by the end of the year. The way this works at the FDA is they would take all that data. It then becomes a review that they proceed with over the course of 60 - 70 odd days, which means that in the first quarter of 2026, we would find out if that new drug application is accepted. It is a very busy period over the next five months at Clene and then a very busy period waiting for the FDA's decisions in the first quarter of 2026.
Within nine months from now, we will have good clarity about the possibility of whether or not our drug is accepted for a complete review in ALS, that is, for the treatment of CNM-Au8 in ALS individuals.
Perfect. Talk a little bit about your plans for a phase 3 trial in terms of timing and design for the ALS indication.
The way accelerated approval works in the FDA's case is there needs to be a confirmatory phase III. If accelerated approval is accepted based upon surrogate biomarkers, and again, the surrogate biomarkers we're talking about here is neurofilament and/or a survival conversation or both, then we need to nonetheless start a phase III study. That phase III is planned to be primary endpointed on survival, that is, time to event. We've taken a page out of oncology or cancer clinical studies, a page out of cardiovascular studies, and we're literally looking to see if patients who take CNM-Au8 are living longer than the placebo individuals. That's called a time-to-event study. That study we're planning to commence with first patients on drug at the latter part of this year. We've already received permission in the first regulatory market to proceed with that study, and we'll be having an investigator meeting shortly.
That study will continue more broadly in a global fashion in 2026.
Our viewer, Matt, asks for how long does the neurofilament remain in the bloodstream, and after the reduction, has there been any regeneration?
To answer the first question, neurofilament elevation shows up before individuals who struggle with ALS start presenting clinical symptoms. In other words, if you were to measure my neurofilament right now, I would pray that my neurofilament would be undetectable. That is, that my neurons are doing their job. If I'm still functional, more or less, I can do everything I'd like to do. I just hit 59, so I have the inevitable, you know, nearly almost 60 aches and pains. Other than that, I'm doing fine. If my neurofilament was rising and I had that blood test, I would think, uh-oh, batten down the hatches. Clinical effects are about to hit me. To answer Matt's question, yes, neurofilament does still stay elevated unless Clene remains, by the way, the only drug in a phase II double-blind, placebo-controlled study that has shown a reduction in neurofilament.
The second part of Matt's question?
For how long does it remain in the bloodstream? After the reduction, has there been regeneration?
We don't know the regeneration in the case of amyotrophic lateral sclerosis (ALS) yet, but we've just presented data at the American Academy of Neurology in April that suggests that we're both remyelinating a damaged neuron and we are protecting the neuron that has been compromised. We've seen return of effect through paraclinical biomarkers using MRI and visual evoked potentials in the MS population. We have not yet concluded that same work in ALS. We've been focused, frankly, on all the things we're doing in ALS otherwise, but we do see it in MS. There could be a correlation in ALS as well, but we don't know for sure scientifically.
Can you talk a little bit more about the CNM-Au8, what it's being investigated primarily for? Is it one indication or multiple indications?
The way we think about this is a little bit of a pipeline-in-a-product, as we call it, because the MS data is actually being discussed with the agency also this quarter. We mentioned that as well in our June 30, 2023 update. In other words, we have three meetings with the FDA that are face-to-face on either ALS, two meetings, or MS, one. The MS discussion is what's called an end of phase II meeting. We've just sent them all of our dossier on our multiple sclerosis program. It was the same dose, same drug that we're talking about in the case of ALS. That's why we talk about this a little bit as a pipeline-in-a-product.
Mechanistically, the way this drug is working is it's driving the energetic return to the flailing or failing mitochondria, which is the energy powerhouse of the neuron or the cell, and that's driving what the neuron's doing. To be able to provide back the energetic metabolite support that the mitochondria needs to basically get its gas and its engine going, speaking colloquially, is very important. We also have concluded Parkinson's work already. We did Rett syndrome and early preclinical data a year ago. There is a whiteboard down the hall in my office here that has Huntington’s and frontotemporal dementia, et cetera, all as possibilities. I can go into other neurodegenerative diseases. At the moment, our key clinical focus has been MS and ALS with this early insight also into Parkinson's.
Fantastic update. Great work. Please continue to do this important work. For all of our viewers, it's Clene on the NASDAQ CLNN. Rob, thank you for your update today.
Thank you.
All right, everyone. We'll be right back.