Good morning, everyone, and thank you for joining the 2024 H.C. Wainwright 26th Annual Global Investment Conference. I'm Dr. Jade Montgomery, an associate biotech research analyst at the firm, and I'd like you to please join me in welcoming our next speaker, Joshua Cohen, Co-CEO of Amylyx Pharmaceuticals, a pharmaceutical company focused on diseases with unmet need. Josh?
Thank you so much, and I'm glad to be here today. I'm Josh. I'm the co-CEO of Amylyx Pharmaceuticals. I've been with the company a little over twelve years. So maybe just before diving in, you know, many of the things we say will be forward-looking statements, as, you know, aligned with the Securities and Exchange Commission definition of those. You can find more about our risk factors and otherwise on our website and in our SEC filings. So maybe at a high level, starting from our pipeline, we're quite excited about what we're developing. So our lead asset is avexitide. This is a compound with FDA Breakthrough Therapy designation. It's moving into phase III.
We expect to start a phase III in the first quarter of next year, with a data readout as soon as, you know, 2026 . That's based on some great, you know, prior data that had been generated in post-bariatric hypoglycemia with this compound. Additionally, we're advancing multiple other programs through clinic, AMX0035 and Wolfram syndrome, AMX0035 and PSP, and our ASO, AMX0114, we hope to be in clinic before the end of the year. So I'll spend most of today kind of going through the pipeline programs. Avexitide's our lead asset, so I'll probably spend the most of the time on avexitide. So moving to kind of our key milestones, there's a lot on the slide, but I'll go program by program.
Maybe starting with avexitide, we expect to start our phase III study in the first quarter of next year, data readout in 2026 , after completing enrollment by the end of 2025 . HELIOS, our program in Wolfram, is our, you know, our nearest data release. We expect to have Wolfram data mid-October of this year, so just right around the corner, and then we'll come back and discuss what our next steps will be, including our plans for phase III. You know, we also have a study ongoing in PSP. We expect interim data from that mid-next year, and then, as I said earlier, we're hoping to start our clinical trial in ALS with AMX0114 before the end of the year, with data readouts throughout the course of 2025 .
So as I said, I'll spend a lot of the time focused on avexitide and post-bariatric hypoglycemia. So avexitide is a compound that's moving into phase III. It is FDA Breakthrough Therapy designation. It's a GLP-1 receptor antagonist. People may be familiar with the agonist. This is an antagonist, so the other side of the coin. It's designed to target post-bariatric hypoglycemia. This is a debilitating orphan condition that can arise in some people after bariatric surgery. It's actually more common than you might think, mainly because bariatric surgeries have happened so much. We estimate it affects about 160,000 people in the U.S. There's a clear match of the mechanism of action of the drug to the mechanism of the disease, so this is a GLP-1 receptor antagonist, and it's thought that post-bariatric hypoglycemia is driven by GLP-1.
We've seen highly statistically significant and clinically meaningful results across multiple clinical trials, including on the outcomes that we're intending to use in phase III. We've already been building up endocrine experience with our Wolfram program, and this would not be our first launch either as a company, having already launched an ALS. And, you know, as I mentioned, we're moving into phase III, and we're gonna use an outcome agreed upon with the FDA that, again, we've already hit in phase II and phase IIb. So talking a bit about bariatric surgery, this is just kind of the numbers. Again, quite a common surgery.
Over two million people have had bariatric surgery in the United States over the last 10 years, and part of the reason for that is because this surgery results in, you know, large and sustained weight loss in general. Today there are still over 200,000 surgeries happening annually, and maybe going through a couple of the details, you know, bariatric surgery is, you know, one of the kind of go-to options, particularly if you need to lose quite a lot of weight. It's also been shown to potentially be cost-effective. You know, it's a you know more often covered by insurance type of approach, and especially again, for people who need to lose a lot of weight.
Every tool in the toolbox is used, whether that's diet and nutrition, whether that's GLP-1 agonist, or for people, especially who need to lose a lot of weight and want to lose it rapidly, bariatric surgery can be a great option. And so, you know, what is this condition? So post-bariatric hypoglycemia is a condition that affects some, you know, a subset of people who have undergone bariatric surgery. Specifically, people get a kinda overactive insulin response, so when they eat even a small meal, their body, with the changed anatomy of the gut, will interpret it as if it was a big meal and, you know, overshoot in terms of insulin. The result is their blood sugar drops very low, and probably everybody's experienced hypoglycemia before, but this can be even, you know, more severe.
So at a minimum, this can be fatigue, shakes, dizziness, et cetera, but it can get as serious as falls, loss of consciousness, even seizures, you know, that people can experience after a meal. And it's not only after a meal. Some people that we've talked to with PBH will also report sudden hypoglycemic events sometimes after emotional stress, sometimes after exercise, and sometimes seemingly unprovoked, or in the middle of the night or otherwise. So this, you know, for people, feels dangerous, right? They're afraid to, you know, go without support, because at any time they could suddenly find themselves dizzy, losing consciousness, et cetera, which can also make it very hard to, you know, hold a job, drive, you know, operate their lives without kind of constant assistance.
Some quotes from people with PBH are on the right. So at the highest level, very serious disease that, you know, impacts people's quality of life quite substantially. So how many people have this? So in the last decade, there's been about two million people who have had bariatric surgery. The average age to have bariatric surgery is about 40 years old. So these are generally, you know, not, you know, the younger people who are having the surgery. If you do glucose challenge, you know, prospectively, in people who have had bariatric surgery, about 20%-40% of people will drop into the level considered, level two hypoglycemia. So about 20%-40% of people do have a, you know, hypoglycemic response, in the years following bariatric surgery.
However, some of these folks are able to manage with diet and otherwise, so we estimate that about 8% or 160,000 are those who will have persistent chronic symptoms, and I'll add that this is not a kind of on and off condition. In most cases, this is, you know, a chronic condition, and it can often be progressive as well. So in about 160,000 people, they're continuing to have these level two events, which impact their daily life, so maybe turning to the clinical data, I won't go through all five of the studies just 'cause it would take a long time, but focusing particularly on the phase II and phase IIb. Well, maybe first I'll say, across all the trials, what they've looked at is glucose and insulin.
You know, trying to see that GLP-1 antagonism reduces this kind of insulin overshoot and this resultant glycemic drop. That's what they saw on all five trials. You know, they've seen repeatedly statistically significant results at multiple doses in multiple trials on glucose and insulin. As we've gotten to the later stage trials, the focus has moved to so-called glycemic events. This is typically the regulatory outcome and is defined by certain milestones of how serious your hypoglycemia gets. Particularly in phase II and phase IIb , the focus has been on level two and level three hypoglycemic events. You can see those results here. You'll note the phase II uses a slightly lower dose than the phase IIb , and commensurate, we see a larger reduction in hypoglycemic events in the phase IIb .
But again, across these studies, highly significant results, reducing level two and level three events. And again, just for context, a level two event is when your blood sugar drops below 54. This typically means that somebody is, you know, quite, you know, often quite symptomatic. If you're below 54, you are not feeling good. You may be shaky, dizzy, at risk of losing consciousness, et cetera. Level three is defined by the requirement for third-party rescue. So by the time you get to level three, you're at a quite, you know, severe state. So in our phase III study, we're gonna use the 90-milligram dose once a day. We've already agreed with the FDA on using level two, a composite of level two and level three hypoglycemic events, as the primary endpoint for phase III.
And as you can see here, you know, these are outcomes we've hit, you know, repeatedly in the phase II and phase IIb study. So the big thing in phase III is it will be larger, it will be longer, but trying to show, and you know, a lot of confidence going in, that we can continue to show this reduction in hypoglycemic events in the setting of a larger and longer study. Safety has been generally good. You know, we've reported no treatment-related serious adverse events. The adverse events that were reported were generally, you know, a couple, you know, GI-related or headache, but nothing that caused, you know, there were no dropouts, you know, across these studies.
And I'll also add that you might wonder with a GLP antagonist, you know, would there be weight gain? You know, would there be hyperglycemia? We haven't observed that in our clinical studies or in any of our non-clinical animal tests, you know, as well. So again, for timeline, our phase III is gonna start in Q1 of next year, or as soon as Q1 of next year. We expect to complete recruitment before the end of 2025, have a readout in 2026 , and then to plan for commercial launch. The IP runway is, you know, long for this as well. We expect our patent position to last through 2037 before a patent term extension, possibly longer with the patent term extension.
We also have a granted orphan drug designation and the drug's position for new chemical entity exclusivity as well. So I realize I burned some a good amount of my time, so I'll move a little quickly through the other pipeline programs. So maybe starting with Wolfram syndrome. So Wolfram syndrome is the disease we've been working on for about seven years, actually, at this point, probably more like eight years. You know, we've done quite a lot of preclinical work, including in knockout models of the disease and otherwise, and have generally seen you know, pretty nice results. The disease impacts about three thousand people in the United States. It's a monogenic disease, so it's caused by loss of function of the WFS1 gene. It's usually initially diagnosed as diabetes.
People usually six to nine years old start showing diabetic symptoms, and so usually they'll get a diabetes diagnosis. It becomes suggestive that it might be something else when other symptoms start appearing, such as visual acuity loss, deafness, diabetes insipidus, and then eventually other neurodegenerative symptoms such as, you know, ataxia, breathing difficulties, swallowing difficulties, et cetera. So this is quite serious. People typically pass away in their early 30s, and we estimate there's about 3,000 cases. This is broadly considered, too, one of the monogenic diabetes. So from a mechanism standpoint, WFS1 is one of the ways that the cell helps to resolve ER stress. So, you know, ER stress is a way the cell deals with unfolded proteins, and, you know, WFS1 is a way that the cell turns that off.
In people who have defective WFS1, ER stress can kinda run rampant and get to a stage that can result in cell death and dysfunction. Our compounds are designed to reduce ER stress and a very related pathway of mitochondrial dysfunction, so with AMX0035, we have sodium phenylbutyrate, a chemical chaperone, helps proteins to fold, as well as taurursodiol, which has shown both ER stress impacts, as well as mitochondrial impact. So we view this as being right on mechanism. You know, this is a disease of overactive ER stress, and that's what we're targeting here, so I'll move quickly kinda to the clinical data. We did have some very nice preclinical data, where we showed in mouse models of the disease, as well as cellular models, pretty striking improvements.
But, you know, maybe moving to the clinical data, our primary endpoint in our clinical study, called HELIOS, was the C-peptide response. So C-peptide is a marker of beta cell function. It basically tells you how well the beta cells, which are pancreatic cells that produce insulin, how well the beta cells are surviving and functioning. Usually in diabetes, C-peptide gradually declines as the beta cells decline and die. And that's similarly true in Wolfram syndrome. What we saw, surprisingly, was actually an increase in C-peptide. Again, you know, these are initial results, eight patients at 24 weeks. As I mentioned at the start, we're gonna present on 12 patients at 24 weeks, coming in October, as well as some longer-term data.
But here, what we actually saw was C-peptide increase, and that was quite surprising, mechanistically suggestive that we are improving the beta cell function and health. Alongside that, we also saw improvement in other diabetic outcomes, which you might expect. If the beta cells are doing better, you can control your glucose better. So we saw better time in range on average. We saw, you know, a reduction in the Hemoglobin A1c, another marker of glycemic control. So, you know, overall, showing a very kinda concordant data set, in terms of the effects that we're having on the beta cell and the diabetic phenotypes of this disease. We also see a trend in the, you know, direction of improvement, for best-corrected visual acuity.
As I mentioned, these, you know, people with Wolfram syndrome also lose visual function, and it's from the same mechanism. It's from this overactive ER stress. You know, it's... You know, the vision is a little more variable, a little more noisy, but I think what we're most excited about is we're not seeing a decline. We're seeing, you know, a trend in the direction of improvement. AEs were kind of as expected with AMX0035, which we've dosed in thousands of people. Generally, some GI discomfort, but generally not particularly notable. And then, you know, talking about timeline here, we expect to have data October of this year, and then to come back shortly thereafter with our plans towards our registrational path. So I'll be excited to update on that soon.
Maybe moving to our two other pipeline programs, so we have progressive supranuclear palsy. This is with the same compound, AMX0035. Progressive supranuclear palsy is actually, you know, maybe a more common neurodegenerative disease than is often recognized. About 23,000 people have it in the United States. It's typically initially diagnosed as Parkinson's, but as people, you know, progress, some of the symptoms make it clear it's not Parkinson's, plus, dopamine therapy doesn't work, which is another one of the signals that it's not Parkinson's. People have, you know, walking, movement, gait disorders. They also eventually have more profound, kind of motor coordination and motor disorders. Eventually, PSP individuals with PSP present as fairly locked in, you know, kind of frozen in their own body.
Usually, people only live six to eight years with this disease, and PSP is a tauopathy. The genetic link of tau to PSP is incredibly strong. You know, I believe the P value has over a 100 zeros on the genetic link of tau to PSP. And additionally, both from a biomarker, fluid biomarker, as well as when you look at postmortem pathology, you can see profound tau pathology in PSP. So why did we think about PSP? We had run earlier in development, earlier in the company, we had run a small, randomized, placebo-controlled study on Alzheimer's disease, focused on biomarkers, and one of the things we observed there was a highly statistically significant reduction in total tau and phosphorylated tau in the CSF.
And, you know, upon observing these results, one of our questions was: Maybe we should, you know, study this drug in, you know, in a tauopathy, and PSP kinda rises to the top in terms of tauopathies. I'll also add that our drug gets intracellular. You know, a lot of the approaches to tau, antibodies and the like, are really only focused on extracellular, and in some cases, even peripheral. You know, antibodies don't typically cross the blood-brain barrier that well. You know, extracellular and peripheral tau, this, to our knowledge, would be the first, candidate in PSP that's really focused on the intracellular, tau. Just adding, too, in that Alzheimer's study, we also did proteomics. We used an Olink panel, looked at 288 different proteins, and the number one most changed one, again, was tau.
So where are we now? We expect to have interim data from a hundred patients in the middle of next year. We're gonna use that as a go, no-go decision. If those results are highly promising, we'll move rapidly into phase III development, and if those results are less promising, we'll reprioritize our resources. So I think we have a nice point to get some good data you know, in the middle of next year. And then last, you know, I'll kind of touch on our program in ALS, AMX0114. So I won't go through this too much. ALS, of course, is an incredibly serious disease, median survival two years. About 30,000 people have it in the U.S.
Often diagnosed or most typically diagnosed at 55, but there's a wide range, including some very young people, you know, have been diagnosed with this disease, and it's defined by a progressive and generalized paralysis. People basically lose voluntary motion in pretty much every limb and part of the body. So AMX0114 is an ASO inhibitor of calpain-2 , so it knocks down calpain-2 . The result of this is, you know, calpain-2 is a protein deeply involved in axonal degeneration and axonal biology. We got very interested in calpain-2 . You know, in our roughly 10 years that we were in ALS, we were prioritizing what targets might be of the most interest, and calpain -2 rose to the top, in terms of just an immense amount of literature that's been done on this target in neurodegenerative disease.
We've found that, when you knock down AMX0114, and this has been in the literature as well- or sorry, when you knock down calpain -2, and this has been done in the literature as well, you also see a, you know, commensurate reduction in neurofilament. The ASO is quite potent. We've seen, you know, survival benefits in relevant ALS models. So we're trying- we're attempting to get into clinic, you know, before the end of the year. We intend for that study to be in patients living with ALS, and one nice thing here is we also have, biomarker readouts. Biomarkers have moved along quite a lot in ALS. As you saw in the preclinical data, we've seen reductions in neurofilament. That would be something we'd really hope to see clinically.
And I know I'm over time, so I'm gonna go really fast, or maybe I'm not. Well, it seems like I can't advance the slide, but maybe I'll just kind of talk through the end. So, maybe just kind of summarizing, you know. Now it will work? Okay. So, you know, we also have, you know, strong patent portfolio through all of these. You know, if there are questions, we can certainly answer on the IP portfolio as well. We expect our cash into 2026, and the way we're strategically thinking about our cash is managing through our key milestones, probably most importantly, the phase III readout in avexitide. You know, we want our cash to last beyond that. And so maybe just kind of final overall summary. Our lead candidate is avexitide, going after post-bariatric hypoglycemia.
This has FDA breakthrough designation. It's already hit the endpoint that we're interested in for phase III and phase II and phase IIb. But, you know, moving into phase III, we'll have a larger and longer study to kind of reconfirm that. We expect to have data by 2026. If positive, hopeful commercialization by 2027. We're also advancing in other clinical indications, including Wolfram, where we'll have data in October, and then define our kind of path forward, as well as progressive supranuclear palsy, where we'll have data mid-next year, which will allow for a go/no-go decision. Then finally, our ASO, advancing to clinic before the end of the year, or expected to advance to clinic before the end of the year. Then with data readouts, including on biomarkers over the course of 2025.
Thank you all very much.
Thank you so much, Josh. We really appreciate you coming out and presenting at the conference. Hope you have a great rest of your day.