Very good. So I'm just going to do a quick introduction, then we'll go through some of your slides. For our audience out there, Alterity is a clinical stage company developing its novel drug candidate for a condition referred to as Multiple System Atrophy, or MSA. At the beginning of the year, Alterity achieved a major milestone with the completion of its phase II trial in MSA patients, and results from that showed that Alterity's drug led to significantly slower rates of decline across various symptoms in what is a fast-progressing condition. As always, attention for investors now focuses on what's next as the company looks to transition from the phase II and prepare for an upcoming phase III clinical trial. So with that, David, I'll pass it over to you to run through some slides, and we'll follow up with some Q&A afterwards.
Great. Thank you. All right, thanks, everyone. Before I get started, I would just like to say that we are targeting one of the final frontiers in medicine, which is really neurodegeneration. People know about the long-standing struggles with treating cancer, but neurodegeneration is really up there and something that I think by the end of this presentation, I hope you can appreciate that we've made some remarkable progress with our development candidate. These are forward-looking statements. By the end of the presentation, I hope to convince you that we have really generated data indicating that our drug candidate is potentially disease-modifying. As Thomas mentioned, we released data at the early part of this year showing beneficial effect on this drug, or sorry, this disease called multiple system atrophy. I will tell you more about that in a moment.
As you might expect, there is a large market potential because this is a very serious disease with no approved therapy. Importantly, and there are other drug companies that are pursuing this disease, we're one of a few that has an orally administered drug, which we think is really important for patient compliance and achieving efficacy. Finally, I've had the fortune of leading several development programs, including three of which have been approved by the FDA, three development programs. All right, this is our pipeline. I won't go through this in detail. Just know that in addition to multiple system atrophy, which are the first three studies on the top of the list, we're also very interested in Parkinson's disease. We have generated quite a bit of animal data supporting going in this direction, as well as other neurodegenerative diseases.
Let me tell you a little bit about Multiple System Atrophy, or MSA, as Thomas said. This is a Parkinsonian disorder with no approved treatment, but I hesitate to refer to it as a Parkinsonian disorder only because while it can look like Parkinson's disease early in its course, it progresses much more rapidly, closer to a disease you've probably heard of called ALS. You can see the evolution of this in the picture on the slide there. Patients can present with nonspecific symptoms such as low blood pressure when they stand up from a sitting position, or they can have problems walking. They have significant problems with coordination. As you can see by the time course under the diagram, the disease progresses very rapidly. Within five years, more than half of patients require wheelchair assistance.
Unfortunately, the survival is only 7-8 years after symptoms first appear. There truly is an urgent need to identify therapies that can slow the disease progression. The drug, which is called ATH-434, I sometimes refer to it just as 434, is pictured there on the right in that color diagram. As mentioned, it is orally administered. The other key thing is that we have generated an abundance of animal data. I will not go through that today, but just know that this several years ago really gave us the reason to believe that this drug candidate had potential to address this important neurodegenerative disorder. We have interacted with regulatory authorities extensively over the last several years. We have orphan drug designation in the U.S. as well as in Europe.
Earlier this year, we did receive a fast-track designation from the FDA, which gives us various benefits, including a priority review and really gives us seamless interaction to work with the FDA. All right, now let's just talk a little bit about the disease itself and the pathology, and this will help frame how our drug is targeting. Two key players that are involved in the pathology of MSA is this protein called alpha-synuclein, which you may not have heard of, but it's a protein that's in every neuron, and it's really important for allowing neurons to communicate with one another.
The other key player is iron, and iron is vital for various biologic functions, energy production, enzyme activity, but in the central nervous system, it's important for creating myelin, which is the nerve sheath that surrounds the, or the fat layer that surrounds the nerve sheath that allows rapid conduction. You also need iron for making neurotransmitters like dopamine. You really want these things to be working well. Unfortunately, in MSA, as well as Parkinson's disease, there's disruption of this normal balance between these two things. If you look at the first two text bubbles, that's really kind of how the drug works. We redistribute iron in the central nervous system, and in doing so, we reduce the pathology associated with that protein that I referenced.
What's important really is the next two text bubbles, which is the overall goal, and we've shown this in animal studies, is to preserve neurons and to preserve those support cells that allow that myelination of the neurons to progress. The overall aim is to really stabilize or improve patient function over the course of treatment. All right, let's talk about our development program. This is a rather busy slide. I won't have time to go through all of these studies, but just know that we did take a very systematic and diligent approach towards understanding our patient population before we began our phase II program. What I would say is that this is the study I want to tell you about, which is called the 201 study. It's a randomized double-blind placebo-controlled trial, really the gold standard of drug development trials.
As you can see in the diagram, we randomized about 75 patients to three different dose groups: 75 mg twice a day, 50 mg twice a day, or placebo. They were treated for 12 months. We assessed various endpoints, including a key clinical endpoint called the Unified MSA Rating Scale. Quite a mouthful, but I'll tell you more about that scale in a moment. We looked at other efficacy endpoints, and we also looked at various neuroimaging endpoints, which I really don't have time to go into, but if need be, we can. That information is at our website, or perhaps Thomas wants to talk about that in the Q&A. This is the MSA Rating Scale.
As you can see, this assesses 12 domains that are largely affected in MSA, things that can have a profound impact on quality of life, things like speech, swallowing, fine motor control, walking, falling, and then that orthostatic hypotension. That is the drop in blood pressure that happens when these patients move from a sitting to a standing position. In all of us, we correct our blood pressure. In these MSA patients, it stays down, and it leads to lightheadedness, and sometimes they pass out. This scale is quite important, and this importantly is the scale that the regulators, including the FDA, are very interested in seeing efficacy on. Now, this is a rather busy slide, so let me walk you through it. On the x-axis is the MSA Rating Scale score. Higher scores are worse. You see on the gray line, that is the placebo patients.
Over the course of 12 months, these patients declined by about eight points overall. If you look at the two blue lines, the blue and the teal line, you see that they decline by, on average, either 30%-48% less than the placebo group, or as you can see, 2.4-3.8 points less. A very significant reduction in that disease severity over the course of 12 months. As you can tell from the table, the effect that the 75 mg dose group is lower, and that's caused questions from various groups. We've been looking at this carefully since we unblinded the data, and we now know that there were significant baseline imbalances between the two dose groups where we saw this severe orthostatic hypotension was much more prevalent in the 75 mg dose group.
When we incorporated that as a covariate into our analysis, the efficacy signal at 75 strengthened considerably. What's important is both these dose groups have clinically meaningful effects on this scale. A treatment effect of 1.5 points is deemed to be clinically meaningful, and we exceed that at both dose groups. Now, as mentioned, orthostatic hypotension is another very important symptom that causes morbidity in these patients. We see the placebo patients declined on average by six points on this patient-reported outcome, whereas the two active dose groups stabilized or potentially even improved a lot. This is quite an important finding. These are wearable movement sensors, kind of, if you will, a biomarker for activity in the outpatient setting. Patients would wear a pendant around their neck for two weeks at baseline and then every three months thereafter.
What we see, if you look at the top right, that's total walking time, that over the course of 12 months, the placebo patients lost about 28 minutes of walking per day, whereas the two active dose groups had about half that loss. If you think back on that diagram I showed you where patients really become dependent on a walker or a wheelchair, preserving activity is a cardinal symptom that we really want to improve. This is a very important finding as well. From a safety standpoint, we really did not see any safety signals. Overall, we saw the same rate of adverse events between the active dose groups as well as placebo. That was true for overall adverse events, the most common adverse events you see listed there, as well as serious adverse events and severe adverse events.
Regarding those serious adverse events, none of those were attributed to study drug. We recently completed an updated commercial assessment that was based on the phase II data that I just showed you. This is a rigorous analysis that was independent from Alterity. This group basically did a qualitative study with experts in the field, both one-on-one interviews as well as interviews with focus groups. Based on that information, where they really determined what the clinical needs were and what the available therapy was for treating MSA, they then used that to create a discussion guide that was then used to survey 100 physicians to really develop a sophisticated model to determine what sort of uptake and interest there was in the product.
I think what you can see, the bottom line is that we estimated peak sales, or they estimated peak sales of $2.4 billion U.S. for the treatment of MSA globally. That was driven by the factors that you see on the slide. They clearly recognize there is a substantial unmet need. They recognize that we are targeting a very important aspect of the pathology with alpha-synuclein. There was a strong intent to prescribe, with more than 70% of the physicians being very likely or extremely likely to prescribe. In summary, we've generated robust data from our phase II study. I haven't had a chance to review, but we did also generate data from our open-label study that we released earlier this year that showed very consistent results in a more advanced patient population. We are actively preparing for phase III at this moment.
We have a series of meetings that are being planned to discuss all the data required to get us to phase III. What you see on the right-hand side of the slide are just the various presentations, many oral presentations of our data at the neurology meetings over the last nine months. That is it, and thank you for your attention. Back to you, Thomas.
Very good, David. Thank you for that thorough run-through. All right, we've got some time for some questions. You just mentioned there you now finished the phase II, and you showed some data there. Looks really compelling, especially on those clinical endpoints. Now we turn to the phase III. What needs to be done from now onwards so that you can get that phase III trial up and running?
Right. So we've been working on various aspects of the development planning to make that happen. Everyone focuses on the trial, the phase III trial, which we have a very good sense of what that's going to look like. To get there, we have to complete all the non-clinical studies. We have to qualify metabolites. We have to assess the clinical pharmacology and the dose response from the phase II data. We're doing all that right now. We began that work in earnest after we got the phase II results, and we're generating those data to actively prepare for those meetings with the FDA. That's one work stream. We expect that first meeting is going to happen early next year, hopefully in the first quarter. That's one. The next is the chemistry and the manufacturing.
Obviously, we have to have drug that is not only at a high quality and a high scale, but something that the FDA is convinced will be commercially available if the drug is approved. We've been working very hard on making that manufacturing process as streamlined and as robust as possible. We're also using those data that we're generating to prepare for a similar meeting with the FDA that's just focused on the chemistry and the manufacturing. We think that will also happen early next year. Based on those two studies, or those two meetings, sorry, being under our belt, we then will have the definitive end of phase II meeting. What we wanted to do is have that meeting just focused on the data, the phase II data, any discussion the FDA wants to have, as well as the phase III study design.
By taking a staged approach, we think it's really the best way to come out of that end of phase II meeting with definitive feedback so we know exactly what the path forward will look like.
All right. It sounds like you've got a couple of meetings before the end of phase II meeting, and that's going to be pharmacology and some CMC stuff. You'll get all that together. Then you'll have your phase III protocol, have that final meeting with the FDA, perhaps sometime towards the end of next year. From that point, assuming all looks good, kick the phase III trial off.
That's right. That's right. We're targeting the middle of next year for the end of phase II meeting. Obviously, there are issues at the FDA with staffing, with the government shutdown. We don't know exactly how the meeting sequence will progress, but we obviously are working as hard as we can to move that timeline forward as much as possible.
Okay. Just going back to the phase II trial and then looping in, you've done some research or contracted some research to interview a whole bunch of clinicians and KOLs, by the sounds of it. What were some of their biggest highlights when they looked at the phase II data that stood out to them? It seems like there was a pretty strong willingness to want to prescribe this product if that data replicates in a phase III trial. What really were their key takeaways from when they looked at the phase II?
Yeah, I think the orthostatic hypotension symptoms came up. I think that was.
Can I just interrupt? Can you just elaborate for the audience?
Yeah.
The link between orthostatic hypotension and MSA? Because I don't think it'll be super clear to people.
Yeah, no, it's not. It's one of the cardinal symptoms of MSA. As mentioned, orthostatic hypotension is the drop in blood pressure that occurs when someone goes from the sitting to the standing position. It actually is caused by degeneration of a certain portion of the spinal cord that's also affected. That's called the intermediolateral cell column for the neuroanatomists in the audience. That actually governs a lot of the autonomic symptoms, everything from sweating to blood pressure. That portion of the central nervous system degenerates in MSA. Patients can respond to symptomatic treatments, but anything that you can do to slow down the progression of those symptoms is tremendously important. As you can imagine, the lightheadedness and sometimes passing out when people go from a sitting to a standing position is extremely debilitating. That was one symptom that clinicians noted.
I think they clearly recognized the scale, this unified MSA rating scale, is very important because it looks at the 12 domains that are affected in MSA. To see an effect on that scale, I think, was striking. They did actually see the data that I presented. They could appreciate the magnitude of that treatment effect as compared to placebo. It's not been shown before. I mean, there have been several trials that people have looked at over the years, dating back to maybe 10 or 15 years ago with different therapeutics, where there's been no effect. No one has ever seen an effect, the magnitude that we showed with this. That's why we're so excited because we have seen target engagement on these various biomarkers as well as objective evidence of efficacy.
I think based on the aggregate data, the clinicians are very excited. They've not seen anything work in this disease.
Yeah, very good. Yeah, certainly that clinical endpoint as well, the or UMSARS, or however you want to pronounce it.
Yeah, MSA Rating Scale is the easy way to say it.
That was obviously a big positive from the phase II trial. It's probably going to be the primary endpoint of a phase III trial, is that right?
That's what we expect, exactly. That's a discussion with the FDA. We expect because that scale assesses how patients really function. What the FDA really cares about for clinical endpoints and trials is how they feel or how they function.
Okay. All right, we've got a few minutes still to go. I really want to touch on the commercial market. MSA is a rare condition, but not ultra rare. I think you shared about 50,000 patients in the U.S.
Up to 50,000, yes.
Okay. And so you've had this analysis done, and they've estimated a potential peak sales opportunity of $2.4 billion. What were some of the kind of key assumptions? Is that 75% of the market of patients are going to be taking your drug, or is it 10%? What are some of the factors at play to get an idea of?
Yeah. I think the biggest kind of key, the biggest assumption, is the number of patients. That's probably the hardest thing to assess in this disease because, as mentioned early on, it can look so much like Parkinson's. We don't really know. It's hard to put a finger on. That's why some prevalence estimates put it around 15,000-20,000. The NIH and other bodies say it's up to 50,000. I think it just reflects that uncertainty. We assumed around 20,000, a little less than 20,000. We did not assume 50,000, which would really significantly increase that. There was an assumption on pricing, and that assumption was based on the strength of the data. I think that assumes an annual price of around $300,000 U.S. for an orphan drug.
The percentage of the market share, we actually assumed that we were not going to be the first drug to the market. There is another drug that's in phase III, an antibody that does not have the level of efficacy that we had. We did assume I might have to go back and check. I haven't looked at the data recently, that we do get the majority of the market share once we reach peak. Obviously, we do have to play a little bit of catch-up on this assumption. Those are the key assumptions that we went into.
Okay. All right. And just touching on your balance sheet, you mentioned, I think, on one of the slides, you've got over $50 million in cash. So pretty healthy war chest there. What's that going to be able to allow you to accomplish over the next couple of years?
Yeah. So we're quite comfortable with where we sit from a cash standpoint. We think that is going to really allow us to do everything we need to do clinically, non-clinically, from manufacturing to get to phase III. Obviously, the phase III program, which we haven't talked about, is going to be a study that's perhaps double or a little bit bigger than what we did in phase II, about maybe up to 200 patients.
Up to 100, yeah.
We think, at some point, we will need to raise additional capital to conduct that phase III study. Everything up to and even preparing and engaging with the relevant organizations to kick that study off, we're very comfortable with.
Okay, great. I just want to touch on IP, intellectual property. What can you tell us about what patents you've got or other IP that will protect this product if and when it does come onto the market?
Yeah. I think the first thing that we have is before we released the data from the phase II study, we actually filed a new patent to protect the dosing, the dosing range, as well as the clinical endpoints. That's something that's commonly done. We've also filed a patent that looks at the physical form of the drug that is quite robust.
A formulation patent?
No, not a formulation patent, but more a patent that looks at the, if you will, the physical structure of the drug, so-called polymorphs. That is a patent, if granted, will give us significant protection beyond the orphan exclusivity that we're bringing to the table. That is bulletproof, if you will.
Regardless of your patents.
Exactly. Those are things we're actively looking at, but we hope to disclose information on those patents as we get further information.
Okay. All right. I'm just looking here. We are out of time, unfortunately, David. We'll have to wrap things up. It's been a really great run-through. Thanks for coming in and sharing an update where you're at. Clearly, you've got some important engagements with the FDA next year. It sounds like around middle of calendar year 2026, we'll get some important updates as to how the preparations for that phase three trial are tracking.
All right, great. Thank you so much.