At the annual Global Investment Conference, my name is Lander, and I'm a Senior Research Associate at the firm. Please join us for one-on-one meetings, corporate presentations, and panels that will be available live and on demand during the week of September 8th to the 10th. We're pleased to have you with us today, and it is now my pleasure to introduce our next presenter. Please join me in welcoming Rob Etherington, President and CEO of Clene Inc., a clinical-stage biopharmaceutical company developing unique nanotherapeutics for neurodegenerative diseases. Rob, all yours.
Thank you, Lander. Thank you to you and Joe for the invitation to your conference. It's always our pleasure to join our colleagues at H.C. Wainwright at your September meeting. Grateful to have the opportunity to speak also to the investors that follow H.C. Wainwright, and I'm going to run through now a quick 20 minutes of a lot of things going on at Clene. Never been a more important and critical time, frankly. In front of you is a forward-looking statement slide. You're familiar with these.
I'll be making a number of forward-looking statements over the course of the next few minutes, and we're under no obligation to update these, but I wanted to make sure that you were aware that a lot is coming down the pike with Clene, and it's now crunch time, very much so, for our pioneering of catalytic nanotherapeutic we call CNM-Au8 for the treatment of ALS and MS. Indeed, what we're doing is targeting the improvement of mitochondrial diseases, and anybody who knows an MS patient with cognitive decline or functional challenges, and especially anybody who knows a family, a caregiver, or in particular, somebody who is diagnosed with ALS, what an extraordinarily difficult, devastating diagnosis. Clene is so grateful to be working to try to see if we could help here.
Now, we've completed two phase II POCs, proof of concept studies, a HEALEY study and RESCUE, we call them. HEALEY was six months with Merit Sudovich in more than 50 centers of excellence across the country. Dr. Merit and her colleagues at the Mass General and Harvard do such extraordinary work, and we are so grateful for the invitation to join as Regimen C in their program. The Fight Motor Neuron Association in Australia funded most of RESCUE, a nine-month program. Those two data sets, though, as I'll explain in a minute, both had a primary endpoint miss. We nonetheless have been able to see so much and learn so much in this devastating disease, and sadly, we're not alone.
There's been more than 12 drugs in the last couple of years that have failed ALS programs, and we are super grateful to have our drug be in front of the agency at the moment, and we'll see if that works soon. I'll explain in a second. We've also completed the VISIONARY-MS study and two other studies in Parkinson's and MS. Everything I'm talking to you about is organic to Clene. We grew CNM-Au8 here. We literally do that every day in our Maryland facility. Morgan and I are talking to you from our clinical development offices based in Salt Lake City, Utah. We founded Clene in Palo Alto and then moved the company to the Utah area, but Mark Mortensen, the Founder and Chief Science Officer, has always kept the manufacturing and R&D space in Maryland, and we're super grateful for everything Mark does.
This is Mark's invention on the left, 100 trillion nanocrystals. Patients who struggle with ALS are drinking every morning. It's an oral administration. I drink it, and if my eyes were blinded and I took a glass of water or our CNM-Au8, and I was blindfolded, that is, I would not know the difference. It's blood-brain penetrant, so it goes into the gut, comes into the bloodstream, and does its work, which is to say it improves nicotinamide adenine nucleotide. It reduces reactive oxygen species, this byproduct of energy metabolism in the neuron, and is acting as an electron donor and receiver to drive mitochondrial function and the way that my neuron either survives or functions. Why that's critical is because that is what you and I need just to give us longevity in life, but it's especially what a patient with multiple sclerosis or ALS needs.
We call the company Clene because we theorized from the beginning that an approach like this, a nanotherapeutic approach, whereby we use gold nanoparticles at nanoscale, so small that they can cut across the blood-brain barrier and go into the mitochondria of the cell to serve as an energy catalyst. We theorized, without any chemistry, that we'd have a strong safety profile, and indeed we do. There's now over 1,000 participant-years of exposure, CNM-Au8 treatment up to five and a half years, and we have, even despite all that data of patient base, not a single serious adverse event that's been related to CNM-Au8 across any of our clinical programs to date. We have side effects. We have nausea. We have headache, but that's not temporally associated. That is, as long as you're on the drug, it doesn't go up.
It's going down, and patients don't complain about this, and our asset is used on top of standard of care. Whatever the physician has prescribed, we want the patient to stay on it, and our drug goes on top of that. Now, I mentioned a minute ago that we missed the primary endpoint in the RESCUE-ALS nine-month and the HEALEY ALS Platform Trial six-month study, but that was ALS-FRS effectively, which is a functional endpoint across 12 different domains of function. Very unfortunately, we aren't alone. As I mentioned, there's 12 other drugs that have sadly had to shut down or otherwise figure out what to do that have missed their primary endpoint. There hasn't actually been success in ALS-FRS for 20 years. It's quite complicated. What we're doing is working for it at a different path because we achieved a survival benefit.
We achieved a clinical worsening benefit in the exploratory, and we achieved a biomarker neural filament benefit during the pre-specified double-blind period. Let's talk about these. On the secondary endpoint of survival, we saw p = 0.4 with a 94% risk reduction in time to death or PAV for CNM-Au8 versus placebo. In the clinical worsening side, we saw a 71% reduction in RESCUE-ALS, and we saw a 74% reduction in HEALEY ALS Platform Trial with a p-value of 0.1 and 0.3.
Clinical worsening is defined as whether I die, need a tracheostomy cut into my neck because I can't breathe anymore myself, so I have to have a machine do it for me, whether or not I need to have full-time BiPAP or CPAP because my lungs have lost their energetic power to breathe on my own and oxygenate my blood and my body, or whether or not I can no longer swallow food or water, and so I need a gastrostomy tube. Obviously, four extraordinarily bad outcomes, and we did achieve a statistically significant risk reduction in these four with a p = 0.1 and p = 0.3, as I said. Now, neural filament.
Neural filament, I hope you've never heard of on some level because if you have, that means you're aware of how compromised a patient with high neural filament is, which means that the neuron has been attacked, and it leaves a cytoskeletal protein remainder in the blood. If I can measure that destroyed neuron through a blood test in somebody's blood, that's bad, really bad, because it teaches me that high neural filament levels are associated with neuron damage and that high neural filament level is indicative of disease progression. Let's talk about what our drug did. In the phase II HEALEY ALS Platform Trial program, we saw p = 0.4 reduction in neural filament light, and the longer you're on the drug, the better benefit is occurring. Equally relevant, this is the placebo individuals with their neural filament rising.
They convert to active drug here because we gave everybody the opportunity to go on active drug. Now we're competing against ourselves here. These are placebo folks now on active drug and original active folks that are still on active drug, and the neural filament is continuing to fall for now both groups once they're on active drug. That six months lost in a disease like amyotrophic lateral sclerosis, ALS is never helpful, quite the contrary, quite compromising. There's actually a bigger improvement against placebo the longer you're on the asset. Why that's relevant? Because neural filament burden at baseline before you come into a program is hugely relevant to survival. The longer, or rather the higher neural filament levels are at baseline, the worse off folks do. For those individuals with high neural filament at baseline, they came on CNM-Au8.
We then tracked them, and those individuals have a highly significant benefit of survival benefit. We're seeing here that if you have a high neural filament either in the top tertile on the left or the top median on the right, and you're on our drug, the neural filament's dropping, and your survival benefit is improving. Now, also, we wanted to look at just by count what's happening with neural filament, and we see it's about 2x of the neural filament improvement in terms of the people that are demonstrated in neural filament decline during the double-blind six-month period. Of those individuals, there's even a stronger connection to risk reduction, p =0.01, of 91% risk reduction for those individuals that have a reducing neural filament at baseline. That's all well and good, but it also speaks to something different. What about independent of neural filament? What about independent of neural filament?
I'm going to get to that in a minute, but before I do, let me explain where we are. We took this neural filament data I've just sent you, these exact slides, to the FDA, and we spoke to them last November. They came back with answers to Clene in December, which we communicated publicly in a press release that we, you know, this data is important, but it's not sufficient. They wanted more neural filament data, and they recommended that we lever the $45 million National Institutes of Health-funded Compassionate Use Program, it's called an Expanded Access Program, that we commenced last June. We started enrolling subjects a year ago, last June of 2024. We started enrolling subjects a year ago in June of 2023 on CNM-Au8 in a Compassionate Use Program.
In that program, the government is paying for neural filament to be ascertained regularly, up to every six weeks from baseline. That data is all going to come to everybody; it will be at six months this summer, and a fair number of them will be at nine months here in the coming weeks, actually. That data is all going to be collected and evaluated over the coming next few months so that we can ascertain if the neural filament data I've shown you in these last few slides is concordant in a completely different data set for individuals that had no earlier access to CNM-Au8. If it is, we're planning to file a New Drug Application based upon neural filament as a biomarker for the possibility of accelerated approval. Independent of that, you ask, what about survival? In that respect, there's evidence supporting long-term survival benefit.
We did this against real-world Expanded Access Program controls, people that never had access to Au8 but are matched by what's called covariate adjustment and propensity matching. We see, using very conservative statistical methods, that we have over the long term, over three years, a significant difference of our active drug participants versus matched controls. These are both significant, both around the same percentage i mprovements. Independent of whether you're in our clinical study, if you're just looking at real-world access of long-term survival from individuals in the Compassionate Use Protocol who were so sick they never had access to Au8 in a clinical program, and we gave them free drug that Clene paid for, even those individuals who, again, are followed over the long term, in this case up to four years, are seeing a concordant similar risk reduction.
You see this all in the 30% range, and you see p-values here of 0.2, 0.1, 0.6 in terms of risk reductions. What we're doing is now taking a new data set to the FDA, and we've already announced in June, late June, that we are having this conversation with the FDA on survival as a whole separate dossier. I've talked about the neural filament period piece. That's presently in investigation. The data will come to fruition whether or not it's concordant with the HEALEY ALS Platform Trial data, and we'll take that to FDA. In the coming weeks, we're also going to discuss a survival conversation with the agency. Could that serve as a surrogate endpoint for clinical, the possibility of commercial approval for CNM-Au8 in an accelerated approval?
Because the Regimen A participants that are serving as a concurrent control of post-hoc analysis comparing survival in individuals who received 30mg versus Regimen A data who are the same inclusion, same exclusion, same clinical protocol, recruited at the same time, and yet randomized to A versus C. These were concurrent protocols happening at the same time. In HEALEY, we see a 28% risk reduction there and a less than p = 0.05 significance. Again, you see this theme of 30% risk reduction around no matter how I've sliced this over the 36-month period. If you take into account our planned phase III, looking at a certain neural filament baseline as well as a certain compromise of risk value, and you look at those individuals, then the risk reduction that we saw compared from HEALEY data to regimen is even higher with higher significance of p = 0.4
We're looking very much forward to this upcoming discussion with the agency, and the plan therefore, as I'll get to in a minute, is to come back to them and talk about a regulatory filing of a New Drug Application and whether or not they will accept such will be something we'll learn in the top of the year. Now, changing gears for a few minutes more. The VISIONARY-MS trial was started before our ALS work. It was stopped flat because of the COVID pandemic. Anybody that's taking a disease-modifying therapy that's tamping down their immune system so they don't have MS attacks, the last place they wanted to go for most of 2020 and 2021 and 2022 was into a clinic where there were lines of patients with COVID outside that could infect them. By consequence, MS clinical research took a major back step, including in our case.
We struggled mightily to recruit this study before the COVID pandemic hit. We had it about half enrolled, and we were able to keep those individuals, but that was effectively it. We thought we would see nothing. We talked to the FDA, "What do you want us to do?" We submitted a pre-specified statistical threshold at p = 0.01, and we realized that we were going to get an enrollment bias if we continued. We opened this data expecting to see nothing on a primary endpoint of vision or a secondary endpoint of cognition and fine motor and walk, and cognition, fine motor, walk, and vision. Six different composite endpoints and a primary of vision. Yet here is the data. We barely missed the classic low five, and we did get a nice PO2 on the composite endpoint of cognition as well as fine motor and vision and walk.
The point is that this is a very interesting data set over 48 weeks, but it even became more interesting over the two further years of blinded follow-up. This is now three total years of assessment, and we see the vision improve from strength to strength to strength. This improvement of seven, eight, nine letters is the equivalent of somebody being able to read two lines nearly on an eye chart. What's equally relevant is the placebo individuals, once they converted to active drug, you see it here switch from gray to green, they started to improve at the same level. Cognition tracked.
The cognition individuals, here's cognition improvement, and then over the double blind, here's placebo, and then over the double blind, once they converted to active drug, this improvement of seven, eight points on a single-digit modality is well north of the ability for somebody to go back to work again, somebody who earlier couldn't but now can. What this basically means, because all this data was correlated, those who had a vision improvement, cognition improvement was nicely tied, is that this led to our FDA discussion that we're having this quarter on an end of phase II meeting to design a phase III on cognition, which is the market need in MS. DMTs do a great job of tamping down future lesions. Indeed, our Head of Medical, Ben Greenberg, made the point that in his clinic, he really never sees new lesions anymore. Cognition and function improvement is critical.
There are also these ongoing FDA discussions about whether or not Clene can file a New Drug Application, which we're hoping to file either on neural filament or on survival or both by the end of the year. Here's our last slide. A pretty interesting story, a gold nanocatalyst that could drive improvement in ALS and MS with the possibility for an investor of commercialization by sometime in late 2026, and more importantly, for the ALS patient. Now let's talk about our financial position with Morgan.
Yeah, thanks, Rob. As you can see, lots of exciting stuff has happened and is going to happen here in the very near future. It is important that we have the cash runway to achieve all these very near-term milestones. In fact, we can. We just announced our cash position as at the end of June last week with $7.3 million in cash. Subsequent to the end of June, we've also raised about $1.9 million from our ATM, and we actually increased our debt facility size by another $1.5 million. On a pro forma basis, we have close to $11 million in cash, which is sufficient to take our cash runway into the first quarter. This allows us to get beyond all these upcoming FDA interactions, get beyond the NFL data readout, and more importantly, the ability to file an NDA.
Very grateful for the ability to have that amount of cash and to move this asset forward. Rob, do you want to have closing remarks?
I just want to thank you again, investors, for all that you do to support Clene and our neurodegenerative mission. More importantly, I want to thank the ALS and MS patients who have participated in our clinical studies that have taken us to this point. Lander, thank you again to you and Joe for the invitation. It's a pleasure always to talk to H.C. Wainwright investors and their interest in Clene.
Of course, yeah. We look forward to upcoming regulatory and clinical updates for CNM-Au8. With this, I want to thank Rob, Morgan, and Clene for what was a very informative presentation. To all those in the audience who have joined us today, thanks again from the H.C. Wainwright team.
Thank you.