All right. Hello everyone. Welcome to the H.C. Wainwright 28th Annual Global Investment Conference. My name is Lander, VP of Equity Research at the firm. 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, CEO and President of Clene, a clinical-stage biopharmaceutical company developing unique nanotherapeutics for neurodegenerative diseases. Rob, over to you. Thank you, Lander, and thanks to H.C. Wainwright for inviting Clene to speak today at this meeting. Clene is indeed a unique company. We have a series of forward-looking statements here that speak to things that I'm about to speak to, and I'll refer to some of this forward looking during the course of this presentation. We are entirely, effectively now, focused on ALS, and as everybody in this room and on this viewing audience knows, ALS is a remarkably devastating disease. This notion of 100 being diagnosed every week is a tragedy because we also see 100 people dying every week, and data this week, in fact, shows that this number is an undercount. It is possible that this number could be well 60% north of 100 weekly passing away. Survival is an extraordinarily important thing in this area, and unfortunately, diagnosis remains very much compromised throughout America. I am familiar and definitely rest of world. I am familiar with friends of mine that have had diagnosis and symptom onset, rather, a year ahead of when they actually got to diagnosis. That year, in a disease like ALS, where mortality is two-four years before they pass, is way too much missing. By consequence, there remains no cure. Everybody agrees that there is complete burden. So what Clene's doing is a proprietary gold nanocrystal suspension that people drink to enhance cellular energy and to protect neuron function. The consequence, and that's a very relevant, extraordinarily important consequence, restore mitochondrial function. Now, how could this actually happen? Why could drinking a nanotherapeutic suspension drive function? Your brain and mine is only about 3%- 5% of our body weight, but it occupies and really needs 25% of the energy that you and I generate day in, day out, night and day. What our asset is doing as part of this massive energy-dependent process for our central nervous system, the way that you and I move and walk and talk and eat and chew and breathe, is driving not just the energy that our mitochondria requires through ATP or NAD+, but also reducing reactive oxygen species, and in the process, supporting neuron health. I like to think about it, and I've said this metaphor before, a little bit like a car. There needs to be gas in the engine. The engine needs to do its bit. The output of such gas in a combustible engine is a catalytic converter that is washing and protecting the exhaust. It is not that dissimilar at a cellular level to what is occurring. There must be energy in the engine, the neuron, to drive function. As part of this energetic process, the reactive oxygen species reduced. Our asset, crossing the blood-brain barrier, is able to affect these things. We have anchored our upcoming New Drug Application on neurofilament light. Let me talk about that for a second. Neurofilament light is a cytoskeletal protein remainder of a debris field, if you will, after the disease ALS and other neurodegenerative diseases attacks the neuron. By consequence, I can measure it in the blood. I can measure it in the CSF. ALS neurofilament matter immensely because if I was to ascertain my neurofilament levels today and see that they were rising and I had no present symptom onset, then I need to stand down, batten the hatches, and be prepared for compromise with my motor neuron function. That would be the case in many neurodegenerative diseases, but there is regulatory precedence in ALS because the agency has anchored neurofilament in the case of another example to give accelerated approval to another asset in SOD1-ALS. That is to say, individuals, very small subset, that are missing the SOD1 gene, a homogeneity ALS condition of missing SOD1 gene ALS individuals numbering in the hundreds in this country. The agency gave this asset and the company that sponsors it an accelerated approval process. Clene is, in fact, leveraging this thesis because we remain a heterogeneous phase II double-blind placebo-controlled studies, the only company thus far to have a double-blind placebo-controlled benefit on neurofilament that was statistically significant. It was modest, one could argue. However, I want to clarify modest, because the improvement of the reduction or the stability matters immensely in ALS. Extensive data, and here is one example, shows that neurofilament trajectory increase or stability is categorically applicable to mortality risk. Even modest changes drive survival. In consequence, after now a number of meetings in the last two years with the FDA, totaling five type C meetings, we have actually built an NDA in partnership with agency direction, really fundamentally around three programs. One is the HEALEY phase II double-blind placebo program, two is our phase II RESCUE program, and three is the $45 million that we got from the ACT for ALS Act, $100 million per year that Congress authorized for ALS research and expanded access. That $100 million over five years, $500 million, is 10% of which nearly, $45 million, was given to Clene for expanded use. In other words, compassionate use or the opportunity for us to put hundreds of individuals on drug for which we collected their neurofilament light data. In the spirit of that, from the double-blind HEALEY program, we saw pre-specified statistically significant 10% improvement in neurofilament, a reduction versus placebo. Similarly, the secondary endpoint pre-specified during the six-month randomized period was a 94% risk reduction in survival. These two data points from the HEALEY program really anchored the path that we are presently on. A neurofilament benefit seen in the double-blind placebo program, a survival benefit as the secondary seen in the double-blind program. Just to be clear, we missed the primary ALSFRS, which unfortunately for the sake of ALS people worldwide, everybody keeps missing. There was another phase II program this morning that read out negative in ALSFRS. If you were to plug the question into your ChatGPT, AI is the topic now all the time it seems, how many patients or rather drugs have failed in ALS? You would get tens of thousands, I mean, tens of dozens rather. I think the number is 80- 100 assets that have failed on ALSFRS in the last number of decades, including Clene. What we did achieve is the secondary survival, the exploratory of clinical worsening, and neurofilament light. The agency, wanting to understand the clinical relevance of a neurofilament change, asked us to replicate that in the NIH-sponsored study I referenced earlier. Despite a completely different patient subset, the HEALEY phase II were about 6- 12 months diagnosed, earlier rather ALS diagnosis. The EAP were patients that could not get into any clinical program. They were appreciably worse on their ALS. They were, in some cases, four or five years diagnosed, and that is saying something in a disease that is uniformly fatal in two-five years. They were long in the tooth with their ALS, sadly. Again, such that they could not get into any clinical program because they did not meet inclusion and exclusion criteria. They nonetheless saw this different patient group on CNM-Au8 about the same 10% reduction in neurofilament light change over the pre-specified SAP that we submitted to the agency, and that is a nine-month period versus six. We see two concordant arguments on neurofilament. The agency really came back to Clene and asked three questions. One, does Au8-treated participants have a neurofilament response that correlates with a clinical response? Two, is that neurofilament response versus randomized controls demonstrative of clinical benefit? Three, can you independently replicate in an independent study, in this case RESCUE, the same benefit? There is a whole fourth piece that is, can you prove this in a causal-based randomization analysis as well? In the spirit of that, we have used HEALEY to address point one and two, questions one and two, and we have used the RESCUE study to answer question three. Now, about question two, this becomes a very interesting situation that is unique to Clene. When HEALEY was organized, HEALEY randomized 480 subjects into regimen A, B, and C at the same time. Same master protocol. Same inclusion and exclusion criteria. Well, similar, to be precise. There were some drug-specific things on each regimen. For instance, our patients could not have a gold allergy. That is an example of similar. Same eligibility criteria, same clinical sites treated, same follow-up, same duration. We have a very long set, now nearly four years' worth of data. Gratefully, regimen A and B, as the agency has asked us to see if they would be willing to share, have done so, and all of that is put into our regulatory filings. What it means is we have 480 subjects that were 160 per arm, there is 320 placebos effectively as concurrent controls because both regimen A and B was completely negative. Unfortunately, in HEALEY, there was no primary, secondary exploratory benefit. Both programs have stopped all clinical development for those two assets, yet we have them for an assessment period in our case. This is very relevant because the FDA does not like natural history controls. They have said this in multiple programs, other places. They wanted to see a concurrent control, and that is what we have sent them. In the spirit of that, we have seen in the HEALEY case that the survival in neurofilament responsive individuals was a 52% reduction, with RESCUE showing a 76% reduction in survival. This is on top of multiple other survival arguments that Clene has made in different presentations, and anybody that follows us for the last couple of years has seen survival as a preeminent theme. It continues with the neurofilament response of individuals. This shows this in the dark blue. Those individuals who had neurofilament stability or a decrease whilst on CNM-Au8 are appreciably different than the concurrent control. As you see, this is going out to four years of data, or versus the individuals that were not neurofilament responsive at all. What it shows us is a P value of 0.03 for individuals that are on our drug, have a neurofilament response. They are the ones that are having a concurrent clinical benefit of a reduced hazard, a longer survival period, versus those that are not responsive to drug at all or were never on our drug in terms of a placebo control. If we look at the RESCUE data set as a second proof source, we see that that is even a stronger benefit, though in smaller numbers. The agency is really going to anchor, we believe, we suspect, HEALEY, as opposed to RESCUE, but RESCUE shows a similar story with a stronger P value of 0.01. In this case, we do not have a concurrent control. That was only in HEALEY. In RESCUE's case, the only option is to use a natural history control, but still shows a similar benefit. New to Clene, which investors, other companies, and the FDA have been asking us for some time is, do you have a functional benefit? What we see, we already announced in the HEALEY program as the exploratory endpoint, that we see a reduction in clinical worsening defined as first incidence of need for gastrostomy tube, so I can eat, need for CPAP so I can breathe, need for a trach so I can continue to breathe by mechanical, or death. We had a benefit statistically significant on time to clinical worsening, again, defined as one of those horrible outcomes. But also too now, when we look at neurofilament responsive individuals, those individuals have an ALSFRS benefit, and they have an SVC, slow vital capacity benefit, both of which are highly significant. What we see now is again, tying the neurofilament reduction for somebody on our drug. If you're neurofilament responsive, if your neurofilament is declining or stable as opposed to placebo that continues to rise, those are the individuals that are having a functional change, ALSFRS, a breathing capacity delta, SVC, as well as all the survival data I've just otherwise spoke to. There's significant preservation of both in neurofilament responding groups. The agency's also been talking to Clene at length about something they like, which is called clinical assessment function and survival. As you see from this slide, we've shown you here the active patients and the neurofilament responsive individuals in dark blue, which is the function survival connected to ALSFRS in the top, versus the function survival connected to SVC, breathing capacity, in the bottom. In both cases, you see examples of, for those non-neurofilament responsive individuals, as you can see, the delta curves are quite different with a P value of 0.03 and 0.003 respectively between those that are surviving and having a functional change. In both cases, significant if you look specifically at neurofilament as the driver. CAFS purposely prioritizes survival outcomes before it ranks functional outcomes. But in both cases, we're doing, as you see, strongly significant in neurofilament responsive individuals. This becomes a relevant addition to the outcome of our discussions with the agency because ALS regulatory guidance in the context of New Drug Applications is heavily really geared on CAFS. In addition to this, I mentioned at the top of this presentation that the agency also wanted to have us talk about causation and to look at predictive. In that spirit, the agency asked us to do a randomization-based causal analysis of these individuals. We found indeed through this statistical model, which is complex, that nonetheless we also saw in predicted neurofilament responders, we see a clinical benefit that concentrates in those individuals who are neurofilament responsive. In all these cases, you can see a P value for overall survival of 0.02, 0.004 with restricted mean survival as you play out all the way to day 878. Then you see CAFS and ALSFRS again at 0.01, 0.001, and 0.006. So in all these cases, this randomization-based causal analysis shows this other, if you will, sense of proof to an argument on neurofilament responsiveness. All of that has to be taken into the context of safety. We've been doing this a moment. Our first patients were placed on our drug in the case of ALS in late 2019. I know these individuals. I just was on a Zoom with two of them a few days ago. We have collectively now 1,250 collective years of patient exposure. Still to date, we have not a single, sorry for repetitive, but this is very important from a benefit risk discussion with the agency, serious adverse event that has been related to our drug from any clinical provider Countrywide, we have no CNM-Au8 serious events. Some people have headaches, some people have nausea. They don't complain about this. Talk to any clinician or the patients, and they'll talk about our drug being easy to take across a lot of programs. So where are we? We are now finalizing the last little pieces of a New Drug Application, which we are planning to send in to the agency. They have given us a lot of chapter and verse discussion. I have already hinted to these. It took us a moment longer than we anticipated. Over the course of this summer, we have been very busy, May, June, July, finalizing these clinical study reports based around a series of things they ask us to do, like randomization-based causal analysis plus plus, as part of our New Drug Application. We have announced publicly we are submitting that at the top of the fourth quarter. The top of the fourth quarter, you all know, is very soon. We have already started to see pumpkins show up in the stores and on people's houses. It is coming. We will be submitting that New Drug Application to the agency, and then they have asked us to be sure that we have a phase III confirmatory study ready to go. We, in fact, are preparing that now. We have already had a discussion with the agency about its concept struct. Its construct is a time to event overall survival study in nearly 700 people over 108 weeks. What is more definitive than to validate and confirm the survival story that we have already argued our data shows through a phase III confirmatory study that we are planning to have first patients on drug in the first half of the year. Because the agency has been clear, if you file a New Drug Application with us, and if we decide to give you a PDUFA review period, accept your application, then we need to know that your phase III is underway before we consider a commercialization decision. We are going to be prepared for doing exactly that. This morning we announced a $4 million capital raise that was entirely insider led by our Chairman with participation from our founding investor and myself and a few other long-term investors that have been with me this entire journey. It has been a long road, but that capital infusion gives me opportunity to get to the backside of this PDUFA decision from the agency, whether or not they accept our New Drug Application, and then some other warrants come into play at that point. We will see how this plays because, as you have certainly seen, this is an interesting story, and we look very much forward to seeing if we can have the opportunity by summer of next year to commercialize our drug if the FDA agrees to review our NDA, a decision which will be coming to Clene by the end of the year, top of the year. Thank you very much for your attention. It is a pleasure to talk to you.