All right. Okay, welcome to the Citi Global Healthcare Conference. I'm Geoff Meacham.
Global Head of Healthcare.
Global Head of Healthcare, thank you. And Senior Analyst, big cap and mid-cap biotech and pharma. Obviously, Jarwei Fang is up here with me from my team. We're thrilled to have Amylyx. So Justin Klee is with us, co-CEO. We won't trash the other co-CEO, you know. You got the look to Miami.
Yeah, yeah, yeah, exactly.
I saw Jim Frates, CFO, in the crowd here. But yeah, Justin, do you want to just give a bit of a kind of a two-minute drill, and then we get into some questions? How about that?
Sure, yeah, very happy to. Yeah, my fellow co-CEO, co-founder Josh is out at an ALS conference in San Diego, so we have some data planning to present there. So yeah, so we've had an exciting year, and we're especially excited about 2026. Our lead asset, avexitide, it's a pivotal study for post-bariatric hypoglycemia. That's following five prior trials that supported FDA Breakthrough Therapy designation. PBH has about 160,000 people in the country, no treatments approved for it, and very high unmet need. We anticipate completion of enrollment in the first quarter and top-line results in the third quarter, which then would mean commercialization in 2027. We're very excited about that program. We're also working on a potential long-acting, so it's a daily subcutaneous treatment. We think that's very appropriate for the market, but if we can make a long-acting, even better.
So we're working on that now, and that research has come along really nicely. So we expect to reach a decision point on a candidate to take into IND enabling studies in the next few months. And then we have two other candidates, AMX0035 in Wolfram syndrome and AMX0114 in ALS. So very exciting next 12 months for us.
Exciting, yeah. No, thanks, Justin. So let's talk about avexitide. So in PBH, I guess give us some context for this as an opportunity when you first brought it into Amylyx. You know, I know you were looking for in-licensing deals, and this is a home run. Put the context or put maybe the background of it, like help us with that first.
Sure, yeah, thanks so much. I'd say we've had an ongoing process for some years now looking for opportunities to in-license exciting assets, particularly I think in the sort of rare disease space, and while I think historically we've done quite a bit of work in neurodegenerative disease, we've done some work in rare endocrine as well. We've been working in Wolfram syndrome for about eight years now, and so we were always kind of on the lookout there as well, so we came across avexitide, which is a competitive inhibitor of the GLP-1 receptor, and it turns out that there are a whole series of conditions or diseases characterized by excess GLP-1 that drives hyperinsulinemic hypoglycemia, and hypoglycemia is super dangerous. The ADA says a single event of severe hypoglycemia is a medical emergency, and so we started doing diligence on the asset.
At that point, we had done deep diligence on well over 300 assets. And you know, drug development's tough, and you really want something that checks all the boxes. And avexitide really checked all the boxes. I mean, beautiful pharmacology, five prior trials, all of which were very strong in PBH Breakthrough Therapy designation. Actually, another three trials in congenital hyperinsulinism, separate Breakthrough Therapy designation, good CMC work, good toxicology, really ready for a Phase 3. And then as you learn about the unmet need in PBH, you almost can't believe it. I mean, it's really significantly debilitating. We estimate about 160,000 people in the country have it today, and we expect that number only to increase. And as you talk with endocrinologists, you hear again and again, these are some of the most severe people I have under my care, and I don't have anything for them.
So to your point, it was really like, whoa, you know, assets like this don't come along all that often. So we're very excited, frankly honored, to get to develop it further now into the Phase 3.
I guess the market awareness, typically in metabolic disease, there's a huge DTC component. This is obviously orphaned to the point where, but it's urgent unmet need. It doesn't seem like it's going to require a lot of activation energy from endocrinologists, right, just given the state of some of these patients. Is that a fair characterization?
Yeah, I think so. I think there's a bit of both components of the market as probably is typical for rare disease. There are a lot of patients who are actively under management today. There are a whole lot of clinics that have 100 plus people under care, under active management. But there's also, you know, I think historically there hasn't been that much you can do for PBH. It's mostly dietary intervention, do everything you can to prevent these events, but people still have them. So I think there's a big educational component as well. I think what's been nice to see though is that even before we've started any disease state education, marketing, and those sorts of things, organically there's been kind of a groundswell of increase in awareness of PBH. PBH is now on the endocrinology board exams.
There is a large group of physicians who have submitted a petition to CMS to get CGM coverage for PBH. There was just this past September, there was a presentation to the CDC saying there should be an ICD-10 code for PBH. So there's just a whole lot going on, and that's even before we start any of our pre-commercial efforts. So it's all the things that you'd hope to see. And again, as we go into the pivotal readout, we hope that we can help people with it as well.
And so that's the second half of next year, Q3. Maybe at a high level, give us kind of what you would view like success looks like. It doesn't seem like you would be stat-sig, but not clinically meaningful. It's like they're the one and the same in an underserved population like this.
Yeah, I think that's a good way to characterize it. You know, what we consistently hear from physicians is a single hypoglycemic event. Severe hypoglycemic event is a medical emergency. And so if you think about it from their perspective, they're getting calls from their patients all the time. You know, I've had this event, I've had this event, and then I fell, I hurt myself, I ended up in the hospital. And as a physician, they feel like they can't really do much about it. So they really want to keep their patients safe. So they really tell us any reduction in these hypoglycemic events would be meaningful. That's the same thing we hear from people with PBH also, is that this is really debilitating. I mean, they're afraid often to leave their homes because they don't know when they're going to have an event.
They're afraid to be alone because they don't know when they're going to have an event. So any sort of return to normalcy in their lives would be just really appreciated. So I think you're exactly right, high unmet need. And so the clinical meaningfulness, the bar is very low.
So, maybe, Justin, maybe just remind investors kind of the bar that you guys already set with Phase two data, and then also just the powering that you have with the Phase 3 Lucidity and what that means and your probability of success and your views on encouraging physicians to identify this disease more now that they may have a potential treatment on market?
Yeah, yeah, those are great points. So Phase 2 trials, so I'll particularly go to the Phase 2b where they tested the 90 milligram dose. That's what we've taken forward to the Phase 3. There's a 64% reduction in the Level 2, Level 3 hypoglycemic events, highly statistically significant. And that is what supported the FDA Breakthrough Therapy designation. Now, as we've gone into the Phase 3, we're powered to see a much smaller effect size than that, so we have greater than 90% power to see a 35% treatment effect. And that's even using conservative assumptions. If you kind of think about the trial design, and again, the goal of the trial design was really to be as consistent with the Phase 2s as possible because strong Phase 2 trials try to get as close to replication in the design and conduct as you can.
And if you just sort of add up the events, not assuming a treatment effect, one event per week, because that's what we're looking for in the screening period, and we expect to continue into the study, times 16 weeks, times 75 participants is 1,200 events. So it's just the design is very robust. It lends itself to very strong statistical powering. And then I think all of this is, we think, a really nice foundation as then we go into the market. And I think for people, for endocrinologists who already have many patients under their care, this is the type of data that I think they'd be excited to see. For people who need more education on PBH, I think there's very strong literature on the unmet need, but then to your point, hopefully strong data as well that now we can actually do something about it.
And given the frequency of administration, I know you said, Justin, you're working on the longer acting, but in a general sense, what's your persistence rates? What are you modeling when people in the Phase 2 have dropped off? Is it because of just the dosing issues, or has it been breakthrough, or what's been the characteristics of that?
Yeah, yeah. So actually in the Phase 2s, there was basically perfect compliance, full completion in the studies. And I think it speaks to the unmet need. And there were exit interviews in the Phase 2s as well. And to a person, they said, like, "Oh my gosh, I felt so much better." So I think people can really feel the difference, which makes sense, right? When you're severely hypoglycemic, you feel terrible. And so I think if you can help return to that more normal glycemic range, I think people just feel a lot better. So I'd say then as we go into the market, sadly for people with PBH, the condition does not appear to go away. It seems like once the body has sort of upregulated this GLP-1 response, it stays. And so we therefore expect that this would be chronic treatment.
But I think what's also nice is that we really do think that what's driving the PBH, what's driving these hypoglycemic events is this sort of GLP-1 bolus. So if you block that from happening, then you prevent those downstream events from happening.
Yep. So maybe give us a sense of your prioritization for other life cycle options beyond lucidity, right? You have the long acting in play as well, but then right now lucidity is also only concentrated on Roux-en-Y patients, right? So how do you think about moving on to sleeve gastrectomy and maybe other indications that may be amenable to GLP-1 antagonism?
Yeah, we think there's a whole heck of a lot to do here, which is really exciting and powerful biology. We've certainly seen that on the GLP-1 receptor agonist side. We kind of view it as that's 50% of the equation. The other 50% of the equation is hypoglycemia, is not enough blood glucose and too much GLP-1. So I'd say first starting with avexitide, so we think indeed other surgeries, it's been known actually since the discovery of GLP-1 that it seems like virtually any upper GI surgery can cause the same persistent hypoglycemia. We've studied in the bariatric surgery population predominantly. To your point, in the Phase 3 trial, we're studying people who had Roux-en-Y gastric bypass PBH, which we believe is the majority of the population in the United States who have PBH. But there's also sleeve gastrectomy.
We have studied in some sleeve gastrectomy patients as avexitide appeared to be just as effective there. So I think we'll make the case to FDA that we think it should be appropriate for people with post-bariatric hypoglycemia. But if they say, "Well, this is the Phase 3 population that you studied and we need to generate additional data," I think we can do that. And I think to your point, then there's even other surgeries, for example, gastrectomy, which is often used for gastric cancer, one of the leading causes of death in Japan and China and Korea and other countries, same with esophagectomy. Sure enough, when you have this significant upper GI surgery, you get this same persistent hypoglycemia. And we think that's also driven by the body upregulating the GLP-1 response. So we think there's a whole lot to do there.
And then there's even other areas like congenital hyperinsulinism or other reasons that people develop hyperinsulinemic hypoglycemia. I think if you can get the efficacy and safety profile equivalent, then actually a long acting would be even more convenient. All of our market research suggests that with such an unmet need, a daily subcutaneous injection is perfectly appropriate. But certainly a long acting would be more convenient. So we started a research partnership with a company called Gubra at the start of the year. They're one of the world experts both in peptide drug development as well as GLP-1 receptor biology. That's been a really nice partnership. We've been very impressed with their platform. And we expect in the next few months to come to a decision point on a candidate to take into IND enabling studies.
We've seen in vivo potency in PK and those sorts of things that we'd want to see to support a long acting GLP-1 receptor inhibitor. So yeah, long story short, we think there's a lot more to do here. It's a really powerful area of biology that could have major impact on human health.
How far from a PK/PD perspective, Justin, can you push a long acting? I know you can't antagonize GLP-1 receptor for that long, right? So I mean, is it weekly? Is it longer?
Yeah, I think we'll find out as we have the sort of tool compounds to test. Now I'll say what's interesting, preclinically, actually you can knock out the GLP-1 receptor and the mice seem to be just fine. And certainly on the agonism side, it seems like you can dose these pretty chronically and people continue to benefit. So we'll find out on the antagonist side. I think the way I view it is that the GLP-1 receptor is kind of a potentiator of the response, right? We're not directly targeting insulin, that sort of insulin glucose system. We're targeting the potentiator of the system. And I think that's why it seems to be pretty robust to continued intervention. But we'll see. We'll find that out as we now have the compounds to study that.
Is there a faster way? Do you have to go to the traditional IND route, or is there maybe a bridge with a newer compound that you can kind of deploy?
Yeah, it's a great question. I'd say we haven't defined that yet, but high on our minds because you're right. We have a lot we can leverage from avexitide, and so we don't think we should have to just reinvent the wheel. Now it is a new drug, so I would still expect we'd need the requisite IND enabling studies, but then as we chart the clinical path, I certainly think there are a lot of learnings from the avexitide experience that we should be able to leverage to hopefully have a more expedited clinical path.
Especially in today's FDA, right, that they're willing to be flexible.
Yeah, certainly in areas of high unmet need like this.
Yeah, and I'd imagine that play out also potentially with the labeling that you had talked about with beyond just the currently studied type of bariatric surgery too.
Yeah, absolutely. And I think that's what's so nice about we have such, I think, clear pharmacology here. We're talking about conditions of hypoglycemia, and we're measuring the outcomes by measuring blood glucose, right? It's a very straightforward development path. And I think that helps a lot as we're making the case about label expansion and other populations where this can be beneficial.
The other piece, Justin, I wanted to ask you about if you look at the metabolic companies, so Lilly or Novo, that they have their market model has evolved to be more consumer-centric portals, et cetera, but that's set up for high volume kind of cash pay. This is the opposite. It's more rare disease, labor intensive. But you still have to have some supply chain, patient connectivity, care pathways. So talk about your efforts today to maybe in advance of the pivotal data, how you're thinking about maybe doing the continuity of care.
Yeah, I really appreciate you asking. So I think we have the benefit of having launched a rare disease product successfully in the past, and our leadership team is still the same, so that's exactly the sorts of things that we're mapping out now. So I think the first thing is really understanding the patient journey. I think that's the most important thing to start with. I think what we can say pretty confidently is that we do think that the adult endocrinologist, especially their particular experts, will be the first primary call points. There are a number of expert surgeons as well who also, though, follow their patients over longer periods of time, and I think there will be some focus there as well. Then in terms of the continuity of care, we do think that this would be chronic treatment.
And so we're working through our sort of pharmacy model, our patient services models in order to support people in chronic treatment as well. You're exactly right, though. This is rare disease and rare endocrine. And I think what's also good is that there's been a number of recent rare endocrine launches that have both supported premium orphan drug pricing with good market access, as well as helped with all of these various models and stuff. So I think we have a nice set of analogs to look at and to take learnings from as we plan our go-to-market strategies.
So maybe we can touch a little bit about the commercialization sequence that maybe you guys are thinking about, whether it be across bariatric centers, endocrinology specialty channels, and whatnot. So maybe talk a little bit about that. And also just you've previously highlighted that there's about 160,000 patients in the U.S. with medically important PBH. There is growing awareness, but diagnosis, we could argue it's still underdiagnosed by a long shot. And so what can be done to continue raising awareness about PBH beyond just educating doctors? And what type of centers, what type of networks do you think would be best to penetrate as many patients as possible?
Yeah, yeah, totally. And again, those are all the things we're working on now with our medical affairs and commercial team. So I'd say starting, the nice thing is that we're starting from a place where there's a very straightforward diagnosis. I think oftentimes in rare disease, you get the case where it's like, "Well, if we could just get the right test," and then you find the proverbial needle in the haystack. That's not this case, right? The diagnosis is if someone gets, particularly to an adult endocrinologist, clear signs of hypoglycemia, you measure blood glucose, you see if they react or if they improve with glucose, and then they've had a bariatric surgery, right? So I think it's a pretty straightforward diagnosis, which helps a lot.
And so even before there's an ICD-10 code or something like that, having that medical support, I think, is really, really helpful because then as we go to educate other physicians on what to look for or try to make sure that people are getting to the right centers, it's a lot easier. You kind of know what to flag. I'd say as well, looking in the claims databases, we've done quite a bit of work in the major claims databases now. First, I'd say, again, it's been a reasonably easy kind of algorithm to find people with PBH. Again, while there's not yet an ICD-10 code, and I'll go into that in a second, there are codes for hypoglycemia. We know that everyone's had a bariatric surgery, and we also know that people are having signs and symptoms of hypoglycemia.
So all of our claims work has just supported the kind of roughly 160,000 population that exists today. And it's helped us understand the patient journey as well. Now, actually, just as of yesterday, there was now what's called a SNOMED code, which helps with electronic health records. In September, there was a presentation to the CDC on the need for an ICD-10 code for PBH, and they'll make a determination on that in April. Now, this would go via the pharmacy benefit route to payers. So payers and health systems don't need an ICD-10 code for this for reimbursement of the product. But it is helpful.
But I think it all really goes back to having a clear understanding of what PBH is and that medical support that then helps as we branch out into the broader medical community and develop our own materials for disease state awareness and those sorts of things.
Justin, just on the patient journey, is there a theme or a common path that someone develops PBH post-surgery? I wasn't sure if you could maybe go one click earlier and identify maybe people at risk that would kind of help you with maybe assessing better, I think, the opportunity.
Yeah, yeah, great point. And I would say as we think about kind of commercialization, I think first, while it's orphan disease, it's large orphan disease. And so I think the first thing is there are 160,000 people today. And so I think really making sure we get to the centers and address that first is probably the most important. But I also think as our team has started to talk with the American Society for Metabolic and Bariatric Surgery, for example, they have expressed strong interest to work with us on educational materials to raise awareness of this, especially, of course, if there's something you can do about it. And so I think that's more kind of, as you were saying, to the front end of the funnel, so to speak.
I think what often one finds in rare disease is that, sadly, if there isn't something you can intervene or do, then the kind of urgency to diagnose isn't there. I think while there's already a substantial population, I do anticipate that if there really is a meaningful treatment intervention, then that really kind of boosts up the desire to find people to diagnose even earlier in the stage of the condition. Today, the general sort of patient journey is, on average, it takes about one to three years for someone to both develop PBH symptoms and then also get a diagnosis. But it can be even longer than that. I'll say what's interesting biologically, this doesn't seem to happen right after the surgery. It seems like it takes time that the body really upregulates this GLP-1 response.
And so that's why it seems to take years after the surgery. But then also, of course, there's less of an urgency to diagnose today. And hopefully, we can start to change that in the future.
I just wonder if over-utilization of GLP-1s in the broader obesity diabetic communities in the next three years, I mean, there's going to be 50-70 million people to get those drugs, to have access to them at least, if that somehow is going to front-end load the front part of the funnel.
Yeah, I mean, it certainly could. And I'd say I think one of the warnings and precautions on the GLP-1 receptor agonists is indeed that they can cause hypoglycemia. So as I was saying, it really is the other side of the equation, and we think it's a really important one.
Maybe just going back to the ICD-10 code and based on what Justin was saying about the continuity of the patient treatment journey, maybe just help us better understand whether or not the ICD-10 code, if that were to come in April, would that be viewed as an inflection point for identifying the patients that are out there? Also, what implication does that mean for avexitide and whether or not if there is no connection whatsoever? Thanks.
Yeah, yeah, important question. So I would characterize in this case an ICD-10 code as kind of a nice to have, but not a need to have. And the reason I say that is because I think it really starts with the diagnosis. PBH is already on the endocrinology board exams. So all endocrinologists are trained to recognize PBH. So I think from that perspective, if someone is presenting with signs and symptoms of PBH and has the medical history to suggest so, I think a given endocrinologist can diagnose the patient. And indeed, in both our market research as well as directly talking with clinics, I think a given adult endocrinology clinic is quite familiar, often has quite some patients under their care with PBH. That all being said, where an ICD-10 code can be very helpful, I think is first in sort of claims databases.
I think it helps you even more strongly kind of triangulate where people are, even better understand the patient journey. I think in large health systems, it can help as well. Sometimes, unfortunately, in large health systems, people can get kind of lost in the systems, in the funnel. And so I think the ICD-10 code can help there as well. And I also think over time, it just helps building awareness as well. So I do think it's a very nice thing to have. But as I said, I don't think we need to have it. But we'll look forward to next year to see if they indeed adopt the code.
Yeah, absolutely. And to your point about helping the health system as much as you can, one of the aspects of rare disease is that sometimes we see a bolus at launch, and then the uptake kind of just peters out. So I mean, how do you think about that helping with consistent identification of patients even well into avexitide's future?
Yeah, I think there's going to be again, we're just doing our sort of market insights work now. But I do think there's going to be both aspects to the market. And we're already seeing this in the claims data. And again, to your point, I think with an ICD-10 code, we may see it even further. There are already many patients, many thousands of patients who are very actively under management. And so I think my hope is that with a pretty targeted team, a pretty targeted field force, we can address those centers and people with PBH. But then I think you get into the broader market, and that's indeed where I think all of these tools are very helpful to make sure that they're at the right physicians, that the right physicians are educated on the product, et cetera.
So again, I think what's nice about having a team that's done this in rare disease before is that these are all the things we're laying the groundwork for now. And our first focus, of course, is to make sure lucidity is executed really well. And we look forward to those results. But we're planning very actively for commercialization because we think that there's really strong potential here. But it's rare disease. You really need to lay the groundwork the right way.
Makes sense. Should we move on to ALS?
Yeah, definitely.
Josh was at the meeting.
He is, yeah.
So, the 114 data. So, maybe talk a little bit about the Phase 1 data we're going to see. And I know you guys have a long history on this indication. So, talk about maybe the conviction here and kind of the potential investment dollars behind 114.
Totally, yeah. So I'll say, I'll start from the last point. So the vast majority of our capital is going towards avexitide, pre-commercialization efforts, et cetera, as you might expect. Supply chain, as you were saying, to prepare for potential commercialization. We're also very excited about 114, but just earlier in development. I think one investor put it to me not too long ago. They said, "Oh, yeah, calpain-2, that's been hiding in plain sight for decades." And I think that's certainly what we found. calpain-2 is one of the key effectors in axon degeneration. And one of the first hallmarks of ALS and what continues to happen is that the long processes of the nerves to the neuromuscular junction retract and then degenerate. And one of the key actors in that is calpain-2. The question then is, "Okay, well, this has been hiding in plain sight.
Why has nobody targeted it?" And the challenge, I think, has been twofold. One is there are like 15 calpains, and we think you very particularly want to target calpain-2. And the second is that you want to get enough CNS exposure. And so that's where we thought, "Well, an intrathecal ASO would be perfect," right? Because you can be very clear targeting just calpain-2 and not the other calpains. And you know that you're getting enough CNS exposure because you're directly injecting into the CNS. So we've been working on this for a few years. We now have our first cohort. That's 12 people with ALS in the first dose group, 9 on active, 3 on placebo. And at the international ALS-MND meeting this week, we'll be presenting on the safety and tolerability data.
That data will also go to the dose escalation committee to determine if we can now go to cohort two to the next dose group as well. Now, that being said, we do think it's quite a potent ASO. So we do think there's potential to see activity even at this dose level. Now that we're through the clinic visits, we can collect all the CSF, send it out to the lab, and analyze the biomarker results as well. I'd say the last thing is on the biomarker side, we're starting our sort of method development work on evidence of calpain activity. Very early days, but I think it's exciting. There are particular markers of calpain activity like spectrin breakdown product 145 or like particular neurofilament fragments that we may see evidence of upregulation in ALS CSF.
And so one of our collaborators will be presenting some of that very early data as well. But again, we'll plan to, as we get the CSF biomarker data from this first cohort, we'll plan on presenting that in the first half of next year.
Obviously, you guys have a history here in ALS, and you probably have novel and the typical biomarkers. If you put calpain-2 in kind of that context, have you looked at it before? And are there other predictive biomarkers that you found in prior research that you would be kind of excited about, not excited about in terms of the direction of how the 114 data is going to play out?
Yeah, yeah, great point. So yes, there are novel calpain biomarkers, and we think we may see evidence that those are upregulated in ALS CSF. Again, early days, but we're encouraged by what we're seeing. And then what's very interesting as well is I think there's been this finding that maybe hasn't been talked about enough in ALS, which is probably the most well-known biomarker right now is neurofilament light chain, NFL. We see this in a number of neurodegenerative diseases. But what's actually measured in the CSF is not full-length NFL. It's NfL fragments. And there's a particular fragment that is most prevalent that we think may be an indication of calpain protease activity. So we're starting to do more work looking at these NfL fragments because we think that perhaps what we're seeing in this NfL signal might actually be evidence of excess calpain activity.
And it would make sense mechanistically, being one of the key drivers of axon degeneration, that may be what we're seeing in ALS. So again, early days, we're doing all of this discovery work now. But we're very excited about the path because we think there's a rich history from the literature going back several decades now. But I think it's nicely jiving with what we found more recently in ALS, which is these NfL signatures, which seem to be indicative of progression rate in ALS.
So on the topic of ALS, I mean, the treatment landscape is just evolving, it seems like, with breakneck speed. I mean, there's monotherapy, combinations. And so with 114 and its calpain-2 inhibition, how do you envision that, whether supplanting or adding on to existing treatment paradigms? We'd love to get your thoughts on that.
Yeah, well, I think research in ALS is. I totally agree. It's going at breakneck speed, which is great. And we have treatments now, which we certainly didn't always have, which is very exciting. I would say, though, what's sad, ALS is still a rapidly progressive fatal disease. And so I think we're strong believers that the future, what ultimately where we're going to get to real cures, I think, is combination therapy. We've certainly seen that in oncology. It's rare to have just a single perfect drug. It's almost always things in combination with one another. I think the way that we view a drug like 114, we're targeting axon degeneration, which is one of the neurodegenerative, right? There's a disease of neurodegeneration. And the first part of that neurodegeneration is the axon degeneration. I'd sort of liken it to like chemo in cancer, right?
In cancer, one of the fundamental theories is we have these cells that are highly proliferative and growing and metastasizing. And so you very often have chemo in combination with something else because you want to, no matter what, you want to stop that growth, and you want to kill these rapidly dividing cells. Neurodegeneration is kind of the opposite side. We have these rapidly degenerating cells. And so I think our feeling is, no matter what, you want to stop that process. And perhaps there are other genetically targeted treatments or other things like that that you do in combination.
But we really do think a mainstay has to be, how do you stop this degeneration from occurring?
Just in the few minutes we have, so a thought on AMX0035 for Wolfram?
Yeah, yeah, yeah, certainly.
Status update?
Yeah, yeah. So we've been working on this for about eight years now. Wolfram is caused by mutations in WFS1. That's a transmembrane protein that causes stress and downstream mitochondrial dysfunction. It's a neuroendocrine disease that is very challenging and unfortunately causes early mortality as well. Very strong data presented this year from our first trial, 12-patient open-label study. All the outcomes went in the right direction, which is very exciting. We're now working on the Phase 3 design. Pending FDA alignment, we're working to initiate the Phase 3 trial in the second half of next year.
Potential for a faster path, sort of a streamlined trial just given the unmet need, obviously.
Certainly, and given how rare it is as well.
Yeah, awesome. Okay, Justin, thank you very much.
Yeah, thanks so much for having me.