Good afternoon, everyone. I'm Sumant Kulkarni , Senior Biotechnology Analyst at Canaccord Genuity . It's my pleasure to have Clene Nanomedicine here with us today. They have a really interesting approach. It's mostly biophysical, I guess. It's not your classical chemical trying to modify things. We have CEO Rob Etherington here, and in the audience, we have CFO Morgan Brown. With that, I'll hand it over to Rob. Thanks for making the trip here. Please give us a bit of a background on what Clene is all about, where you are with your product, and what you expect to do next with it.
Thank you, Sumant. Appreciate the invitation. Sumant's correct, our asset is a nanotherapeutic suspension, an intersection of physics and material science into biology. Our particular focus is in ALS, and we have right now a discussion ongoing with the U.S. FDA to discuss whether or not an accelerated approval will be permitted for our asset in ALS using neurofilament as a biomarker, a meeting which we held with the agency last November and then this last June, all reflecting the $45 million NIH enabling EAP compassionate use program that is assessing neurofilament in 180 subjects ongoing as we speak to be concordant, intended to be concordant, I should be clear, with the NIH, or sorry, with the HEALEY program trial that had as a pre-specified endpoint in the double-blind placebo-controlled program a positive statistically significant neurofilament benefit.
The agency in November, when we met with them, proposed that we lever the ongoing NIH program to increase the persuasiveness of the HEALEY data. That's almost exactly the language they used in their communication to us, which we received in December. We met with them in June to ascertain and to verify the statistical analysis plan pre-specified for such analysis, which will be coming to Clene in the fourth quarter. We're looking very much forward to the possibility of applying for accelerated approval using the neurofilament biomarker path as our surrogate endpoint. Independent from that, in a second meeting with the FDA , which we've already announced publicly will be at the end of this quarter, we are meeting to discuss survival as the possibility of a secondary endpoint for accelerated approval.
That survival discussion at the FDA is part and parcel of a broader arc of survival. We achieve survival as the secondary endpoint in the HEALEY study. We've since submitted a fair amount of survival data to the public markets and to the FDA using propensity match covariate-adjusted controls. We also submitted publicly to the market and to the FDA in April, Regimen A survival data from the concurrently enrolled HEALEY program . That broader arc of survival discussion is happening at the end of this quarter to see if that could serve as an accelerated approval surrogate endpoint. Whether it's neurofilament on the one hand or survival on the other hand, or both, our hope would be both, it's a very active period regulatorily with the FDA .
I should just add independently of that, we just met with the FDA this month on multiple sclerosis. Though investors have, by and large, cared less about this, the MS path continues to be a very active path. We had a very nice meeting with the FDA to discuss our phase III design and cognition as the primary endpoint in this MS study based upon all the MS data we've already achieved. We have kind of two shots on goal presently for Clene: ALS on the near term, MS on the later term, and we're excited about the prospect.
Given that people don't think about it too much, I'm going to ask about MS. You mentioned cognition as an endpoint. What specific cognition endpoint will you be using in an MS trial?
The Visionary study had as the secondary endpoint symbol digit modality test, which is a substitution cipher that the FDA has used in MS studies for two decades as a secondary. The notion of SDMT as a cognition endpoint as a primary is still a work in progress, whether the FDA and otherwise. The MS community concurs and the FDA aligns that cognition is a very important endpoint, could be market leading. We're not talking about autoimmune suppression anymore. Our asset would indeed be used on top of DMT, on top of an autoimmune suppressant drug. The market need is still a function change, whether it's cognitively, fine motor, walk, or even vision. As the secondary in the VISIONARY study, we looked at all four as the MSFC, but the core anchor of that conversation was symbol digit modality.
Improvements we showed at the late breaking at American Academy of Neurology in April showed lovely concordance, statistically concordance between VEP on the one hand, MRI on the other with respect to cognition and vision. This is step one of an FDA discussion that we just concluded. The primary objective there was to align that cognition is a market need in MS and that a phase III could be built around cognition. Step two is an ongoing discussion that is continuing, understanding exactly how an endpoint could look. Is it a composite endpoint? Is it symbol digit by looking at some type of composite? That is a discussion that we haven't disclosed because we do not yet know. The FDA is going to give us that particularity in its end of phase II meeting notes, which we've not received.
in discussions with the FDA, at what point do you think the MS program could be ripe for potential strategic partnering?
I think it's right at the minute, actually, for strategic partnering potential. We indeed met with a number of companies at Bio here in this town only two months ago. We have been gratified by their interest. A number have come under CDA, and we're right now working with them to understand the totality of our MS program at large.
Now we'll kind of move on to the ALS side. I guess before that, how important is what happens on the ALS side with the FDA potentially as a determining factor for what might happen on the MS side in terms of partnering?
I don't think they're really that connected. In terms of partnering, most of the interest has been in MS. It's a much larger category. I think there is some reservation in ALS on the partnering side, primarily given all of the failures that have unfortunately occurred for the ALS community. The fact that there's not more partnering activity with ALS broadly and specific to Clene, I think it's a concern to the ALS community at large. I don't think there's really a correlation. I think they're kind of separate. From an investor perspective, most investors are naturally more focused on ALS.
Sure. You mentioned that you're now going to be focusing on survival. You've had some of the NFL discussions. Shouldn't survival be a gold standard? Why isn't it that way?
That is a good question that we're going to uncover in the aspect of this meeting. It's not that we're so much focused on neurofilament. The agency really has driven that focus. It was their recommendation in November when we met, as we publicly disclosed in December and in June, that neurofilament is a path that they're familiar with and comfortable with. We've already seen that evidentially with their use of neurofilament as the primary surrogate endpoint for the tofersen approval in Biogen's case. There is a broader arc that we've raised, you've just raised it, and the ALS community at large has raised, which is, should not clinical endpoints such as survival be the primary argument that ALS assets be evaluated upon? We would say yes. We did meet in the HEALEY case the secondary pre-specified endpoint of survival.
We have shown extensive data against propensity match covariate-adjusted controls and natural history data sets. We've presented publicly only a few months ago the concurrently enrolled Regimen A data set. Just to remind this audience, those were folks that were randomized at the same time to our regimen. The Regimen A, B, and C were recruited at the same time, same inclusion criteria, same exclusion criteria, same clinical trial sites, same master protocol. All of that was the same. Safe for randomization, these 482 subjects were randomized 162 into A, 161, 162, or 1 in C, and then off we went to the races. Regimen A, the unique piece about Regimen A is that it was negative in futility. DSMB, the Data Safety Monitoring Board, called that study. There was no effect. The drug was safe, but no effect.
For up to 36 months, those Regimen A participants, again randomized from the same data set, never had access to CNM-Au8. Yes, it's a post-hoc assessment, but with that important caveat, it's still an important concurrent control that showed survival of 28% with a p-value of less than 0.04. That Regimen A data set was only different in two ways. They were a little healthier, as evidenced by their functional status, TRICALS risk score specifically, and they were a little bit healthier, as evidenced by less neurofilament burden at baseline. If we take those covariates into account, then the p-value goes from 0.04 to 0.004 and goes from a 28% survival benefit of risk reduction to 44%. Pretty interesting discussion. Whether the agency aligns that survival could be a surrogate endpoint, we are about to discover in the coming weeks.
had several discussions now with the FDA, but has your understanding evolved of the FDA's understanding of what a relevant change on neurofilament light chain or NFL might be?
They themselves have said, as is their famous stating, this will be a matter of review. I think that they themselves don't know. What has evolved is the FDA. We read every headline almost every day of late. The FDA that we're facing today in summer of 2025 is very different than the FDA that we interfaced with last year. The good news is the Division of Neurology is still led by Teresa Buracchio, and our reviewer is still Dr. Emily Freilich. We're thrilled that both of those two, Dr. Buracchio and Dr. Freilich, are the same reviewers of our division, of our dossier, rather. Their bosses are quite different.
As we all know here, Martin Makary and George Tidmarsh and Vinay Prasad, now again at CBER, and for that matter, their boss, Secretary Kennedy, have all said a number of things that are indicative of orphan, uniformly fatal conditions. In particular, Dr. Makary has leaned into ALS specifically in multiple public comments, both at his Senate hearings and in other places, about the criticality in his mind of an improvement in the present ALS situation for patients that deal with this insidious, devastating disease. Is it the right time for Clene to come in front of the discussion? Possibly.
The critical thing that I think we're reflecting and that we're working to provide evidence for is the surrogate path of concordant neurofilament data, concordant survival data, and if those taken independently or together as a unit constitute the possibility of an accelerated approval, which, if so, we're planning to file that NDA around the end of the year, which would lead to the possibility of a decision for it to move from kind of an application stage to review stage with the possibility of a granted PDUFA date that would happen probably sometime in the latter part of the first quarter.
If that's the case and Clene enters this possibility of CNM-Au8 being on a considered approvability path with an NDA under review and an advisory committee around this quarter next year, you can appreciate it could mean quite a bit for the ALS patients more broadly and for Clene investors specifically.
Have you considered or have you already filed for the Commissioner's National Priority Voucher process?
We have considered it. We have not yet filed for that. We felt that the timing of such filing would be best appropriate after we saw concordant neurofilament data and we completed the survival data. This is a very important, we think, initiative that Commissioner Makary has organized because it does indeed enable an accelerated review possibility, which Clene would be grateful to and thrilled to participate in, and wanted to do so in the right stepwise fashion after we knew that the agency was aligned with our enthusiasm for the data.
Have you had or do you plan to have any direct interactions with either Makary or RFK Jr. on this product, given the unmet need in ALS?
I've not met either of them. I'm thrilled that they're both talking actively about ALS and about nanotherapeutic suspension options like our asset. I am aware that different advocates in the ALS patient community have either already or are planning to meet with both of them. I think that's important because we had only four, three years ago now, the Act for ALS approved in a rare form of congressional bipartisanship, that $500 million that has been basically focused on ALS research, which Congress approved, and of which Clene received nearly 10% of it in the EAP sponsored NIH program for $45 million. It is that money, that 10% of the money that we're levering right now to do the neurofilament assessment we're uncovering with the FDA .
That's coming up for reappropriation, and all of us in the ALS community would like to see that money continue beyond two years from now. That's a long way of saying I have not met with either of them. I would look forward to doing so if they're willing to grant such a meeting. I do know that the ALS community is also very much aligned that ALS needs important new therapies to help this disease.
What's the key risk you see from an FDA perspective on everything you've submitted so far? Is it simply a function of too many changes at the FDA or anything else?
I think even the last three months have provided evidence that the FDA is less predictable than they were. Whether that affects Clene on the positive side or the negative, I am not certain. What I am thrilled by, however, is that in November, when the path was carved for the neurofilament assessment that we're presently on, when I showed up at the FDA for our last face-to-face on this exact same topic in June, despite a lot of new leadership changes, not only was that alignment still consistent with what we saw in November, but there was an even more cordial, more friendly, I would say even a stronger alignment to this path. It didn't backtrack. If anything, we felt more of a lean in. Is that evidential? I don't know. As to whether all that's been said about the criticality of new ALS therapies, I'm not sure.
That all said, we've still seen where advisory committees have recommended against something and it's been approved or recommended for approval and it's been withdrawn. I think the core answer in Clene's specific case will become obvious in the coming months.
The concept of the term regulatory flexibility, how has that specifically affected your discussions and what's the, I guess, the temperature at the FDA on using that flexibility within ALS?
We're gratified by the fact that we have three meetings face-to-face with the FDA , even despite the challenges they're seeing in four months. I think that's a bit unusual, two of which we've already held and one of which is coming up, that the agency, despite the pressures that it's under, that this division, the Division of Neurology, under two different aspects of the division, DN I and DN II, have met with us three times in four months. I think that does speak to regulatory flexibility, frankly. I also think that though we missed the primary endpoint, famously on the HEALEY study , that we're having even a dialogue with the agency on a carved path for neurofilament light chain as a surrogate endpoint that they recommended speaks to regulatory flexibility.
Third, and critically, I think also, if the meeting happens positively, and I don't yet know, I've not yet been there, but the fact that we have another granted face-to-face discussion on survival, that we already navigated one aspect of the survival discussion last July, unfavorably, as we announced then, July of last year, now that there's another discussion that's been granted Clene based upon the new survival data and dossier that we've sent them, I think that also is indicative of regulatory flexibility. Are we grateful for the agency's focus? Yes. Are we bullish about the opportunity? We are. Do we have confidence about the data we've presented? We do.
With all that you've said so far, what's your thought process on the potential to utilize a Canadian approval process, given things are done slightly different in Canada? You could get that equivalent of, I guess, an accelerated approval there or with the EMA.
Speaking first to the notice of compliance with conditions, which is your Health Canada example, I was watching very closely my friend Alon Ben-Noon 's experience with NeuroSense, and I was more of an enthusiast for that path until I just learned, as we all learned publicly in the last month, that NeuroSense was not effective. NeuroSense didn't have a dossier in front of the FDA, so they approached this entirely through Health Canada. I do have a dossier in front of the FDA, and we purposely focused on FDA for a number of reasons, and I'm still grateful for and confident with that path.
I think the key thing for Health Canada for Clene would be similar to the way Amylyx approached this in the past up in Canada, which is to, once we have a dossier and a NDA filed here, take that same to the agency up there in Canada and then explore it fully. I think from your perspective in EMA's case, the previous experience of a lot of individuals, including Amylyx, on the fact that there needs to be concluded phase III data, and for that matter, Mitsubishi's Radicava, same argument. I think that all indicates that there's not an opportunity in Europe until we conclude our phase III. There are, however, other places that one could take an FDA positive package to, including MENA, basically different key countries like Dubai and Qatar. We could take it to Japan. We could take it to Australia.
We could take it to select countries in Europe. Those we would pursue, but we want to do that with the tailwind of a U.S.A. NDA in progress, an NDA under review, and an NDA onwards to a commercialization path.
Your product is nanocrystalline gold. We've seen a safety profile like almost no other product we've seen so far. Given that background, do you expect to see an advisory committee meeting on this product?
Let's talk about the safety for a second. If anybody in the audience is unfamiliar, we have now over 1,000 collective years of patient experience across multiple clinical programs, including four FDA-approved expanded access compassionate use programs. That over 1,000 years of total collective patient years is up to 5.5 years of chronic continuous use. Despite that, we have not a single example, not a single example of a serious adverse event that's attributable to drug across our program. We call the company Clene because we theorized from the beginning that we would see a clean safety profile. For what it's worth, Clene, as we spell it, C-L-E-N-E, is the Anglo-Saxon spelling of the word clean before the French added an A in the Norman Conquest. There's your etymology lesson for today.
In essence, what I'm really getting at is that the asset has a very clean drug, a clean safety profile. The reason why this is relevant, back to your point, is because the senior leadership of this FDA have said for safe drugs, there could be a risk-reward ratio considered. We'll see if that's reflected in our case.
It might seem like a trivial question, but it's not. Your product is nanocrystalline gold. We've had lots of geopolitical risks, currencies, and all that being affected. Do you expect to see the cost of goods of gold increase a lot?
We're about, we were about at peak, as we've seen it in the last few months. We have not, I mean, we're talking nanoscale use of gold. These assets are 13 nm in size. We do use gold. It is a very material input into our nanotherapeutic suspension. The variable price of gold, which indeed is variable, is not that much of an impact for us. It's relevant, but not game-changing. The price of electricity, the price of water, these are equal measurements. The price of labor, these are equal measurements for us. The gold geopolitical differences don't matter that much. Having said that, I was thrilled to see that Mr. President Trump, that is, took gold off his tariff list yesterday. That helps us immensely.
In terms of ALS, the next step, I guess, is waiting for what the FDA is going to say on the survival.
The way we're thinking of catalysts is, actually, very, very, very good question. The way we're thinking of catalysts is what is the neurofilament data from the EAP NIH program going to show? We'll have that data in the fourth quarter. Is it concordant to what the HEALEY data showed? If so, we file on a surrogate endpoint in that respect. Also in the fourth quarter, we're going to have the final meeting minutes from our survival conversation about the broader survival dossier. We'll have, therefore, the answer, can we file using that as an NDA submission? One or both, as I've mentioned. The next catalyst that follows this would be the successful filing of our NDA. That's off to the agency for its review.
The third or fourth catalyst following that would be that there is an alignment from the agency that they've moved it from the application process to a proper clinical review, and a PDUFA date is granted. Finally, the catalyst would be an advisory committee and the possibility of commercialization approval somewhere in the second half. We view the next four months, really, September through, I guess it's about six months, in fact, September through March as key. What happens there with respect to that filing and its acceptance thereof.
Last few seconds here. Could you remind us about your cash runway and how you're thinking about that given such an action-packed period coming up?
As of our last quarter, which is through March, we have $10 million on hand, which, as we've said publicly, takes us into the third quarter. We're imminently about to announce our second quarter, and standby, but that will also be evidential of some extra runway that we've been able to capture.
Thanks again for attending, and thank you for tuning into the webcast.
Thank you. Thank you for your attention.