Clene Inc. (CLNN) February 2026 Conference Transcript

welcome back everyone next we have clean ink trades on the nasdaq under the symbol clnn it's a late 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 and cfo morgan brown welcome gentlemen to the conference we're happy to have you today thank you it's a pleasure to be back at emerging growth all right the floor is yours so a number of your listeners may be familiar with clean uh it's kind of crunch time here we expressed as much in our dear stockholder letter of yesterday i think though if some of you

are new listeners that is um uh it's worth taking a moment to do a quick introduction of clean and i'll get into the essence of our of our story first of all if you're in the northeast i hope you're digging out from a big snowstorm morgan and i sit uh just against the mountains of utah and if you've been following the utah ski situation this year we need your snow so uh sorry that you have to unbury in new york and boston and rhode island and elsewhere but feel free to send it to us we want as much snow as you can give us We also need as much help in ALS as you could possibly give us. Many of you have seen, with great sadness, the loss of Eric Dane. He was a good friend of mine. I know him very well. I've been with him many times. I love that man, and it is a tragedy the way ALS took him so quickly and so aggressively. So I wanted to start today's emerging growth with our sorrow, sympathy, and prayers to Eric's family, Rebecca, and his two lovely daughters. This is a classic case, though. ALS needs desperate help, and CLEAN is right now in front of the agency in the upcoming weeks, as we announced yesterday, to work to see if we can get the regulatory flexibility that this disease must have. So I'll get into that a little bit later, but wanted to take a moment to acknowledge, in fact, we lost two friends last week within 24 hours of each other, and this cannot happen. A diagnosis happens too late. People deal with systems too long before they get diagnosed. They can't get on therapies generally, and this must change. So let's now get into this a little bit more, what's going on here. So first of all, if you're new to CNMAU8, I'm holding here the acid in my hand. If I was blindfolded and took a drink from my water glass, I would not be able to tell the difference. This tastes like water because it is effectively mostly water. Now, that is a crazy thesis for many. What is it? It's a nanotherapeutic suspension. Nano means super small. We're talking so small to cross the blood-brain barrier. When I, if I were to drink this, which I'm not doing, but our patients are, nearly 800 of them have. And right now, through four different expanded access protocols, we have treated over 500 individuals with compassionate use on top of the clinical program. But in any event, if they were to drink this, they would not be able to tell a difference. But they're drinking trillions of nanocrystals. And what are those nanocrystals doing? They are driving right across the blood-brain barrier the ability of the neuron to take care of its own housekeeping. Now, I want to go forward a few slides to express my next point. So biomarkers have become super critical. Now, most of us don't think what a biomarker is, but all of us have heard of the word cholesterol. Cholesterol now is commonly measured in a laboratory at my primary care doctor with simple blood tests. And if my cholesterol is high, my doctor gets very concerned and he puts me on a statin. Similarly, now that I'm a guy of 59 years old, my doctor also would get concerned if my prostate-specific antigen is too high. Tells him and me my prostate's in trouble. So neurofilament is similar. If I have a blood test and my neurofilament is going high, then I need to bat in the hatches, become very concerned, and be very worried about what neurodegenerative disease is wrecking havoc in my body and especially that's the case in als because neurofilament is the debris field effectively of a damaged neuron and it correlates very directly with faster progression and short survival it's released when the neuron is pummeled when it's damaged and i can measure it in the bloodstream and in the CSF. And so neurofilament becomes really relevant because it is a key path for CLEAN. Now jumping back to where I just was, for those of you that don't know, CLEAN and every other ALS drug, mostly every other ALS drug in the last hundred years has missed the primary endpoint ALSFRS. Survival was the endpoint for years, decades, but nobody could achieve survival, so we moved in the field to ALSFRS, stands for ALS, amyotrophic lateral sclerosis, functional response scale. It's a measure of function across 12 domains. One domain would be, can I eat and chew my own food? Can I feed myself, swallow it on my own? That's a domain. And if I'm successful at that, the way you and I hopefully ate our breakfast, where we could feed ourselves, chew and swallow that food, that's a four. If I can't do that and it needs all my food and water need to go on into my mouth through a gastrostomy tube because I can't chew and swallow, that's a zero. Another example is if I can dress myself or handle my own bed clothes, get into my bed, pull my sheets, adjust my pillow, and go to sleep, that's a four. But if I can't do that and somebody else needs to help me do all of that, then that's, you know, progressive less numbers all the way down to a zero. So ALSFRS has really only been met by one or two drugs worldwide and clean, like multiple other drugs in the last few years, missed that primary endpoint. But we did achieve, as evidenced by this slide with the green check marks, survival. We did achieve preserved function. We did achieve the exploratory of clinical worsening, and we did achieve the biomarker benefit. And this becomes super relevant because survival matters in ALS, especially given how I opened, talking with tragedy about the loss of our friend Eric Dane, but also others that died this last weekend. So we saw as the pre-specified secondary endpoint in the Healy study, a 94% risk reduction. The FDA saw the data and they wanted more evidence than a singular secondary study. So we said, no problem. So that's been the discussion with FDA over the last 14 months. We also showed FDA clinical worsening data from two studies, but it was the exploratory endpoint. Now, again, clinical worsening defined in ALS's case is whether or not I die, an obvious element of clinical worsening, but also whether or not I need breathing support mechanically, or as I said a minute ago, a gastrostomy tube because I can't swallow food or water. If those two things happen, I need to start having air hunger, which means I can't get my breath to power my body, or I can't get food or water unless I do it through a tube. those are huge entrees to clinical worsening even up to death. So that is the thing that's really trying to happen here is we're trying to avoid clinical worsening so we can avoid survival. Now the key thing is back to the biomarker. Clean also found in our pre-specified double blind phase two, Healy, a neurofilament statistically significant benefit, the only drug of the eight programs thus far completed in Healy to have showed a pre-specified neurofilament statistically significant difference. But the agency's like, well, hold it. That's one example, and it's 10%. So we said, okay, what do you want? And they gave us three options. They said, you can choose one of these three paths. You can go look at your EAP study. That is the NIH sponsored expanded access compassionate use program in which we have about three times the data because we have about three times the patients in that program, that $45 million that the NIH gave us. That's option A. Go see if you have concordant, similar, parallel data in neurofilament from EAP. Or look at the placebo people, that after the six months, this gray line, they went on drug and you followed them. Did they have a benefit in neurofilament? Or third, go look at another ALS-specific biomarker and see if you had a benefit there. So let's start at that third option, GFAP, gliofibrillary acidic protein. I showed you on the left of this screen what that is all about. That is a structural protein in astrocytes crucial for supporting the neuron, and when I measure that in my bloodstream, it shows that I've got a degenerative process going on that is contributing to motor neuron loss. So as a patient, I do not want to see neurofilament or GFAP levels at all, let alone rising. I want them to go down because that means that my neurons are benefiting by the drug and are helping my disease progress. So in the spirit of that, back to this slide, You see here that the pre-specified neurofilament on the left and the DFAP that we pre-specified with the agency, we would go look at the data. We had no idea previous to this. We see nearly identical p-value, both 0.4s, and nearly an identical reduction, 0.90 versus 0.89, 10 or 11% change. So that brings me to kind of the second pillar of this. Does even as modest of a 10% change in ALS matter? Yes. We show this data in a press release on December 3rd. Matters immensely. We're working on a publication. And that question, does even modest changes in neurofilament drive survival benefit became roughly half of the very extensive dossier we submitted to the FDA in December. Now, continuing here, the agency said, okay, well, does neurofilament and GFAP matter if they move together? And the answer is they moved very much together, first of all. We see p-values of 001 with respect to the 6-month, 9-month, or 12-month concordant reduction. So we see a very consistent reduction, meaning that if you're on our drug and your neurofilament drops, measured at 6 months and beyond, your GFAP is also dropping. You saw that in the previous example. You see it here. And then what we also showed is, does baseline neurofilament matter and baseline GFAP matter? And in this case, we looked at the top quartile and the top tertile for those that had the best declines on neurofilament and gfap and we see here a 90 or sorry excuse me an 80 reduction that was seen in survival for those that had the best response on neurofilament and gfap both significant at either of the tertile or the quartile. Now, we've already shown, if you've been around clean for a minute, we've shown six months ago or so that we showed twice the neurofilament reduction. And for those folks that just had any neurofilament drop, if we follow them out for a year, we see a 91% reduction in survival with a p-value of 001. So that's why there ends up becoming a lot of evidence here just supporting the thesis of neurofilament and gfap as a biomarker being tied to survival so again the agency gave us a couple you know legs of the stool to consider do you have other biomarker benefit does reduction in neurofilament matter and can you tie it to survival and as you've seen from these three elements uh there's there's there's a yes in all of that um but critically um there's something else and that is the survival data is quite relevant if we follow it against even larger concordant or rather concurrent randomized controls and if again if you've been around the block with clean a minute you've seen this data previously from Regimen A. This data we showed the FDA in September. They commented about it to us when we received the final meeting minutes in third week of November and this is what we showed them. We showed them that we took the Healy Protocol, the 480 odd subjects that were recruited originally and then randomized into A, B, or C. Those 480 subjects that were chosen had the same CLIN trial sites, 57 across the country, the same eligibility criteria, the same inclusion exclusion, the same master protocol, the same follow-up. They were then randomized into either Regiment A, B, or C. So they went on an active drug in Reg A, an active drug in Reg B, or they went on CNMAO8, our Reg C active drug. And we're looking here at the covariates. In other words, how well were these patients randomized, and it worked well. There was only two examples where there was apples and oranges as opposed to apple and apple. You see here these eight examples are apple to apple. There's two examples where it's a little apple and orange. That is how their function was at baseline and how their neurofilament was at baseline. So if we look at these two data sets, everybody, the apple and apple, and if we adjust to make the apple and orange apple and apple, which is the comparable risk set, we see here in either case a 73-77% risk reduction, both at a p-value of 0-1 at 12 months. So this showed something very critical, that there's a survival benefit as another evidence from the original six-month double blind program. And so that becomes very relevant because as we looked at this and looked at it for longer term, because we had a lot longer term to look at, data out to 36 months, three years, we see that that survival benefit remains durable. It endures. In fact, in the apple and orange adjusted to apple and apple data set, we see a 44% risk reduction with a p-value of 004. So the agency looked at this data that you're seeing here, and they said the following. I will read to you what they said. Clean. If you're able to provide, and I've already announced this by the way in a previous press release if you're able to provide substantiation of the effects on neurofilament light substantiation of the effects of neurofilament light we would be willing to consider the six-month data from healy which i'm going back to that slide is this data here and this is the 94 survival p04 and the post hoc analyses on survival, which is all of this other survival I've shown you, including this data here out to three years, as capable of providing evidence that the change in neurofilament light, going back again, sorry for the slide move, but I just want to make sure you're tracking what I'm saying here, the change in neurofilament light, which is here, as reasonably likely to predict clinical benefit and serve potentially as confirmatory evidence and then they also asked us um to see if we could give them further data on this including regimen b so all of this data has been sent to the agency as a large dossier and as we announced yesterday um in my dear shareholder note. We're right now waiting for the agency to hold a meeting with CLEAN, and as we announced the timing of SAIM, that this dossier was extensive. The timing didn't work exactly as we thought. There's a lot going on at the agency, as you certainly know. You've read this in multiple headlines, including an op-ed in the journal this morning, and more data from the commissioner of the fda martin mccary yesterday so so you know the fda is following to some degree its own time tables um we're grateful for all the work they're doing um uh we're we're we're planning for this meeting we're taking opinion leaders with us to it and this meeting will be occurring and we can't wait for said meeting because what we're planning to talk about there is survival and biomarker and And the relevance of small changes matter immensely for survival. Modest changes matter immensely. And CLEAN has arguments on all of these. And significant in all these cases, survival, clinical worsening, neurofilament, pre-specified significant changes matter. Now, the agency is going to have to exercise a little reg flex, a little regulatory flexibility, because accelerated approval is the path we are seeking, and that requires a confirmatory phase three. A confirmatory phase three is what we have planned, and the hope here is, as we've shown and talked about, is that we can provide patients access to CDMAO-8 as early as around this time next year. And the reason we speak to that is because if I'm about to have my meeting and I'm expecting to announce the final meeting minutes of that in the second quarter, and I'm soon to file thereafter my new drug application, And if the FDA gives me a PDUFA and if the FDA reviews this drug in their classical six to eight month timeline for an orphan asset that has designations such as cleans does for ALS, that leads to the possibility of a commercialization at the top of 27 somewhere again this time next year in the first quarter. And that means, too, that we can start helping and commercializing in sporadic heterogeneous disease, an asset, and help physicians diagnose this disease earlier. So people like our friend Eric Dane can get diagnosed earlier when symptoms occur, and there is a lot of developing therapies that regulatory flexibility should be required for a disease as heinous, as devastating, as extraordinarily compromising to the patient as amyotrophic lateral sclerosis is. The time is now to actually provide regulatory flexibility, and we are so grateful that over these last 14 months, the agency has met with us four times. We are super grateful for all the dialogue we've received, and we sit here at this key moment to see if we've given the agency sufficient data to discuss multiple biomarker analyses and to be quite prepared to run a confirmatory Phase III study. Now, let me have Morgan take a moment and talk about the finances, but I want to just spend a minute on MS. We have not forgot about MS. Categorically not. We believe that this asset is a pipeline and a product. We showed the FDA all of this data you're seeing now where we saw vision improvement, cognition improvement. We saw it sustained also same drug, same dose for three years out. We saw the placebo individuals who converted active drug had a similar benefit in vision improvement and in cognition. We talked to the agency in August. We reported already that data in September. We'd like to go to a phase three study. We need to do that either with ALS commercialization funding or partnership funding. such a study will cost us, but we think there is a deep market need to take this asset in MS individuals who otherwise have controlled their MS lesions, but still have a vision or cognitive impairment. And so we're working with the agency now to basically adjust three decades of precedent where the agency has used a primary endpoint of EDSS, that stands for Expanded Disability Status scale, and to rather look, in Clean's case, at cognition improvement. We think that's the market need, and the agency has already had a number of back and forth with us on the MS side, so we're simultaneously working on that. But again, most of you are, and frankly Clean, are entirely focused on ALS because ALS is the devastating mortality that we'd like to see if we can resolve with survival and biomarkers as the path. So we just announced in January that we have a fair amount of cash runway. Morgan, do you want to talk about this?

Yeah, happy to do that. Hopefully each of you guys heard the excitement in Rob's voice. I mean, I think both he and I, as we get closer and closer to hopefully filing this NDA, that excitement level increases. And we're hopeful that we'll have a positive interaction with the FDA this quarter and then be able to file that as rob mentioned by middle of this year most of you guys are probably wondering does clean have enough cash to get through all these really important milestones and the answer to that to rob's point is yes you know roughly a month and a half ago we entered into a very interesting sort of structured transaction in which we raised you know minimal amounts now but enough to get us through and into the fourth quarter so it gets us through this fda interaction type c meeting it gets us through an NDA filing without any problem at all. Like I said, we raised $6 million at $6.50 and then we actually structured this financing such that we have two additional tranches of financing that would come into the company on regulatory success. The first one being an NDA filing and acceptance of that filing, not approval, just acceptance. That would bring in another $7 million, which would stretch our runway into early 2027. And then upon approval, the second tranche of financing would hit, which would raise another $13 million, which would carry our runway well into 2027. So I think, you know, as you look back and step back and say, number one, we've got a lot of exciting things happening here in the very near term.

And we have the finances that allow us to get through those milestones and fund the company adequately to get to these success points so with that anna maybe we open the the remaining time we have to some questions yes uh thank you gentlemen and thank you for acknowledging the loss of eric day and i'm sure many of us grew up watching his work i know i certainly did so our thoughts and prayers are with his family um let's remind our audience please rob uh some upcoming milestones for als and specifically the what do you expect the type c meeting to occur with the fda and those meeting minutes um so we just announced yesterday that we're expecting um the type c meeting to occur

by the end of the month and again there's kind of three the end of the quarter thank you thank you the end of the month of march thank you i'm already thinking march morgan thank you for that the end of the first quarter so by the end of march we'll expect that meeting to occur and um that's why we've also announced similarly that we're going to see the minutes in the top of uh somewhere the second quarter there's there's basically a couple doors that could be opened there door one is the agency say we've given you the whole dossier we're ready to go let's submit this nda door two is the opposite of that which we really pray doesn't happen but that is go to your phase three and come back and talk to us in a couple years door c is well you've given us so much data it's hard for us to really comment just this moment but we'll be willing to accept your nda to kick the tires, dissect the engine, look at the data in our hands, and then let you know if you have a PDUFA date. And that's probably the most likely catalyst. So to your point, by the end of the quarter, we'll have the meeting. In the top of the second quarter somewhere, we'll have received those minutes from the FDA. We'll report them. We're expecting to file the NDA by the end of the second quarter, if all these timelines work. And then, as we've stated, there could be a PDUFA date somewhere in the third quarter because the fda's rules are once they receive nda they have 60 to 72 days to review that and then there's a review process that takes about six months so that's why all together we're saying we're kind of a year out before we could be commercialized perfect and what readouts should investors expect in the next six to 12 months and how do you define success for each uh well the core readout which every investor cares about and frankly clean is what the FDA thinks about this asset and this data. Will they let us file? Will they give us a PDUFA date? Will they reprove the drug? Those are the three critical ones. If I just narrowed them to one, two, and three, does the agency agree that there's enough biomarker data here, that there is enough argument of these three stools? Is there biomarker data? Is it concordant throughout more than one data set? And does that biomarker data matter because it connects to survival? That's the way we're kind of thinking about it Because that's the way they've thought about it. That's the way they've expressed it to us in their minutes, as we've stated previously. And if they agree now that that volume of data for a disease such as ALS deserves accelerated approval, regulatory flexibility, you know, Martin McCary has said, even in the last three days, about the criticality of orphan rare diseases, and that the FDA needs to be a beacon for the world in helping rare diseases get new drugs. And if that applies in his mind to ALS, and if the review division agrees that our data also applies to ALS, then off we go to the races. And we're about to find that out. So we're working hard, we're praying. And frankly, the excitement is, you know, Clean feels confident about this data. So we hope we have, you know, two of these positive doors and are not told, come back and talk to us in three more years.

Perfect. Well, we do have more questions for you, but we are out of time. Do you have any closing remarks for our viewers today, Rob or Morgan?

Sorry for not giving questions. We're happy to take individual calls with investors. I think what we've seen here is we've got data that we obviously feel pretty compelled about. If you sense excitement, because we feel we have compelling data, we have a phenomenal safety profile. We have survival in nearly every group we assess. We have statistically significant at neurofilament change and biomarker change. And we are super grateful that the FDA is engaged with CLEAN. And so stand by because we'll be reporting about these engagements with agency.

Wonderful. We'll keep up this important work. We appreciate you coming back on the conference today.

Thank you.

All right, everyone, we'll be right back.