Amelix at Goldman Sachs Conference: Clinical Progress and Strategic Outlook

On Tuesday, 10 June 2025, Amelix (NYSE:AMLX) presented at the Goldman Sachs 46th Annual Global Healthcare Conference, highlighting its diverse clinical pipeline and strategic plans. Co-CEOs Justin Klee and Josh Cohen detailed advancements in several programs, including Avexatide for post-bariatric hypoglycemia (PBH) and AMX-35 for Wolfram syndrome. While positive clinical data and financial stability were emphasized, challenges such as trial enrollments and market competition were also acknowledged.

Key Takeaways

• Amelix is progressing with a Phase III trial for Avexatide, targeting completion by year-end and data by 2026.
• The company reported a strong cash position of $204 million, ensuring operations through 2026.
• Positive Phase II results for AMX-35 in Wolfram syndrome were highlighted, with Phase II data for PSP expected next quarter.
• AMX114 for ALS is in early trials with Fast Track designation, showing promising potential.
• Collaboration with Gubra aims to develop a longer-acting GLP-1 receptor antagonist.

Financial Results

• Amelix ended the last quarter with $204 million in cash and no debt.
• The cash runway is projected to last through the end of 2026, excluding a potential Phase III PSP trial.
• Funding includes costs for the Phase III Avexatide trial and other ongoing programs.

Operational Updates

• Avexatide (PBH):

- Phase III trial enrollment is targeted for completion by the end of the year.

- 13 sites have been activated, with data expected in the first half of 2026.

• AMX-35 (Wolfram Syndrome):

- Positive data from the 48-week HELIOS trial showed increased C-peptide levels.

- Plans to meet with regulators for Phase III trial design discussions.

• AMX-35 (PSP):

- Phase II data readout is anticipated next quarter.

- The study has randomized 139 participants, with a focus on treatment duration.

• AMX114 (ALS):

- A Phase I study is underway, with safety and biomarker data expected by year-end.

- The drug has received Fast Track designation.

• Gubra Collaboration:

- Aims to develop a longer-acting GLP-1 receptor antagonist.

Future Outlook

• Avexatide (PBH):

- Potential commercial launch in 2027, subject to positive Phase III results.

- Exploring expansion into other hypoglycemia indications.

• AMX-35 (PSP):

- Evaluation of data to determine the feasibility of a Phase III study.

• Gubra Collaboration:

- Focus on achieving a weekly dosing interval for a new GLP-1 receptor antagonist.

Q&A Highlights

• PBH Market Size:

- Estimated 160,000 addressable patients in the US.

• Pricing Strategy:

- Monitoring rare endocrine launches for pricing analogs.

• Intellectual Property:

- Avexatide has patent protection until 2037 and orphan drug designation.

For further details, refer to the full transcript.

Full transcript - Goldman Sachs 46th Annual Global Healthcare Conference:

Unidentified speaker, Host, Goldman Sachs: Thanks for joining us here at the Goldman Sachs Annual Healthcare Conference.

Thrilled to be joined today by the co CEOs of Amelix. Maybe you guys could just start with an overview. The company has changed a lot in the past year, really, since the last time we were sitting on the stage. So maybe we can talk about the complexion of Amelix today and where you see some of the key value drivers.

Justin Klee, Co-CEO, Amelix: Yes. Thanks so much for having us. Thrilled to be here. So we have three different assets in four ongoing clinical trials. So our lead asset is Avexatide.

It’s a GLP-one receptor antagonist, so it lowers insulin and raises glucose. We are running a pivotal study in post bariatric hypoglycemia. This is the study. There are five prior studies of Avexatide and PBH that supported FDA Breakthrough Therapy Designation. We dosed the study participant in April and we are targeting completion of enrollment by the end of this year and have the pivotal data in the first half of next year.

So, very excited about our lead program. We then have AMX-thirty five, which is our small molecule targeting ER stress and mitochondrial dysfunction in two trials Wolfram’s syndrome, which is a rare neuroendocrine disease as well as PST, which is progressive supranuclear palsy. It’s a really devastating neurodegenerative disease. Wolfran syndrome, we announced positive data from our study a few weeks ago. That’s the HELIOS trial looking out over forty eight weeks now.

We see C peptide increasing over time, which is a direct measure of insulin production and therefore beta cell health. And then in PSP, we’ll have data from the Phase II readout next quarter. And then last, we have AMX114, which is our antisense oligonucleotide targeting calpane-two for ALS and potentially other neurodegenerative diseases. We just started our study in people with ALS. That’s a dose escalating placebo controlled study.

We dosed the study participant a couple of months ago, and we should have our safety and early biomarker data by the end of this year. So a lot going on, quite a few exciting milestones this year and hopefully more to come.

Unidentified speaker, Host, Goldman Sachs: Yes, very exciting. Let’s start with Exotide. You acquired this asset last summer for the treatment of post bariatric surgery hypoglycemia. What have you learned since taking on the development of this drug with respect to that market?

Josh Cohen, Co-CEO, Amelix: Yes, it’s a great question. I think this has been an asset that as we did the diligence to acquire it and even as we’ve continued to own it, we’ve just continued to kind of like it more and more as we’ve dug in. Next to that is FDA breakthrough therapy designation, lots of strong previous trials. We’ve also now been able to spend a lot of time talking to doctors who care for people living with PBH, talk to a number of people living with PBH. And what just comes across again and again is just how difficult and disruptive this disease is for people’s lives.

Endocrinologists describe it as these are some the most fragile patients. I’m kind of constantly trying to get ahead of their symptoms, but I’m still getting calls at midnight and everything like that. And then when you talk on the patient side, it just becomes incredibly limited. At any point, they could have one of these hypoglycemic drops, most commonly after a meal. But it can also happen due to stress, exercise, sometimes out of the blue without any obvious cause.

And when they happen, it can mean dizziness. It can mean loss of consciousness. It can mean confusion. And to have that possibly happening at any point of any day is just really tough for people. Usually, can’t drive.

They like to have people around them to rescue them if they’re in a tough spot. So really, really excited to be advancing of exotite for these individuals.

Unidentified speaker, Host, Goldman Sachs: PBH is kind of a new market for a lot of people, although I think it’s become a bit, since you guys bought the asset, people understand it a little bit better. But maybe help us understand the underlying assumptions. You’ve talked about 160,000 patients who are addressable. What does that embed with respect to the number of patients that exist and who are inadequately managed by the current standard of care?

Justin Klee, Co-CEO, Amelix: Yes, it’s a very important question. So, the thing we did is we looked through the literature. And I would say that they’re pretty good studies, both prospective and retrospective, looking at patient cohorts of thousands of people over time. The estimates are it’s always a range, but it’s about eight percent of people who get bariatric surgery will develop PBH in the future. Now, on average, it takes one to three years for symptoms to manifest, so it takes time.

But it’s been pretty consistent from study to study that that’s the estimate of how many people will get So if you back into how many surgeries there have been over the past, even just decade, there’s been well over two million bariatric surgeries, you get to about one hundred and sixty thousand people who would have PBH today. We then started looking in different claims data sets, and we found very similar numbers around that one hundred and sixty thousand estimate. There’s actually at the ENDO conference next month, the Stanford group who are actually the ones who invented Avexatide have done their own prevalence work using different methodology and come out with quite similar numbers, actually a little higher than the estimates of what we’ve found. Now, in terms of who’s diagnosed, who’s being regularly seen at clinics, that’s work that we’re still doing now. I can say that we’ve talked to quite a few clinics who have hundreds of people under their care, and there are a lot of clinics who might have tens of patients under their So, are definitely many people who are being followed up with regularly and participating as much as they can in active medical care.

And I think we see in the future that that might be a target population for us when we commercialize, of course, given positive data. But that’s all work that our commercial team and medical affairs teams are doing now to really zone in on what do we think that target population would be. But in terms of people who need a treatment who have not responded to diet, it’s the one hundred and sixty thousand people. So it sounds like a lot, but it’s really just because there have been so many bariatric surgeries over the past decade or so.

Unidentified speaker, Host, Goldman Sachs: And where are these patients being seen? Are they primarily in the endocrinologist office, community academic, by the surgeons? Who’s kind of catching this and helping manage their symptoms?

Josh Cohen, Co-CEO, Amelix: Yeah, so the symptoms are primarily managed by adult endocrinologists. And as Justin said, speaking to adult endocrinologists, there are a number of them who see hundreds of these patients, many who see tens of these patients as well. In terms of their journey to get there, so they’ll have the surgery. And usually, a surgeon will follow them post op, maybe six, nine months, possibly a year. But the symptoms for PBH usually don’t appear for a year to three years.

So it’s rarely the surgeon who will be caring for this or seeing it. Then often, as they start to have symptoms maybe they’re getting dizziness or they’ve lost consciousness or confusion they’ll get triaged through the health care system to an endocrinologist who will take over their ongoing care.

Justin Klee, Co-CEO, Amelix: I think to Josh’s point, sometimes with rare disease it can be an amalgamation of symptoms. This is very clearly hypoglycemia, endocrinologists are very, very experienced at recognizing signs and symptoms of hypoglycemia. What we’ve found often is that when people get to an adult endocrinologist, one, they pretty quickly recognize the person’s had bariatric surgery, they have hypoglycemia. They try to rule out other causes, but it’s a pretty straightforward diagnosis. So to that

Unidentified speaker, Host, Goldman Sachs: end, is this an indication where you think there’s going to be education required to bolster diagnosis, or do you feel like this patient population is well identified it’s more a matter of bringing treatments?

Josh Cohen, Co-CEO, Amelix: Yeah. I think a little bit of both. I think there’s certainly a population who’s at the experts, well seen very frequently, etcetera, who I think there, I don’t think there will be an immense amount of education required. I think as you get out further and further from that, to kind of have a faster diagnosis, to have this high on the index of suspicion, I see somebody lose consciousness when they’ve had a bariatric surgery. This should be right at near the top of my There is education to do on that.

While we do think that many of these patients do get diagnosed, we have talked to patients who had bounced around the health care system for some time before somebody ultimately said, Okay, this is PBH. You

Unidentified speaker, Host, Goldman Sachs: mentioned originally that there’s a lot of clinical data supporting the drug’s activity in this indication and others. Maybe you just run us through the Phase IIs that are available.

Justin Klee, Co-CEO, Amelix: Yeah, very happy to. There have been five prior trials of bevaxatide in post bariatric hypoglycemia. The three were Phase I’s looking at dose, changing from IV to sub Q. What’s very striking is that you can see the effect of the drug with a single dose. So, very quickly the drug lowers insulin and raises glucose.

The Phase IIs were then looking kind of more in the real world setting, so to speak. So, they were 28 crossover studies. The phase II was a period, run-in period, placebo period, and then a twenty eight day crossover. The phase IIb was a run-in period and then a crossover. In those studies, they were looking at level two and level three hypoglycemic events.

These are medical events that have been defined by the American Diabetes Association and other groups for quite a few decades now. Level two is defined by a blood glucose that’s less than 54 mgs per deciliter. The reason that’s important is that’s the blood level where neuroglycopenia starts to occur. Neuroglycopenia, as you might imagine from the name, is where the brain is starved of glucose And so people start to have very significant symptoms severe confusion, maybe loss of consciousness, etc. A level three event is independent of blood glucose.

It means that the person needs independent rescue. They have had such significant symptoms that they need somebody to help them. A clear example, of course, would be loss of consciousness. But there are others maybe someone so severely confused, they don’t know where they are and they need someone to help them. In the phase II trial, they were looking at thirty milligrams twice daily or sixty milligrams once daily.

Again, significant reductions in level II and level III hypoglycemic events. In the phase 2b, they were looking at forty five mg twice daily or ninety mg once daily, again looking at level two and level three hypoglycemic In the ninety mg once daily dose, which is what we’ll be taking forward to the Phase III, there’s a 53% reduction in level II event with a p value of point zero zero four and a 66% reduction in level III event with a p value of point zero zero zero three. So very statistically significant, very strong reduction. And again, I think this is what supported FDA breakthrough therapy designation.

Unidentified speaker, Host, Goldman Sachs: Yes. So you’ve now disclosed the Phase III trial design. You mentioned you’ve initiated the study. I guess talk to us about the key parameters for the trial. How did the phase two inform it, etcetera?

Josh Cohen, Co-CEO, Amelix: Sure. So overall, the goal is to keep as many things the same from phase two to phase three as we possibly could. Probably the most important inclusion criteria in these studies is essentially the severity, the rate of events that you’re having. So in the previous studies, you had to have an event a week, a level two or level three event a week to be enrolled in the study in a run-in period. We’re doing the same in the phase three, so you have to be having an event a week.

Our run-in period’s three weeks, two weeks. We did that just to get a little bit more experience with all the technology, because the study does have CGM, finger sticks, diaries, things like that. So we wanted to make sure before they get into the main study they’re really good at all of this technology. And then I think probably other main elements previous studies were four weeks. The phase three will be sixteen weeks.

So it longer. But by and large, tried to keep as much the same as we could, essentially same endpoints, similar severity with the running criteria, and everything like that as well.

Unidentified speaker, Host, Goldman Sachs: And what is the study powered to show in terms of the difference versus placebo, and what is the underlying placebo expectation?

Josh Cohen, Co-CEO, Amelix: Sure. Maybe just as a reminder, as Justin said, too, previous study, fifty three percent effect on level 66% on level three. This study is looking at the composite of level two and level three, which actually gives you even a little more power because you’re getting both of the types of events contributing to the primary outcome. We have 90% power to see as little as a 35% effect. Again, that’s conservative compared to the 5366% effects that we saw in the Phase 2B.

And in that modeling, we put pretty conservative assumptions around standard deviation, around placebo. We modeled as high as a 50% placebo effect. So when I’m describing that 90% power at 35% effect, that includes a 50% placebo effect as well. All that being said, we don’t really expect a placebo effect in this indication. We didn’t see one in the phase two.

And also, patients really don’t want to be having these events. So just because a placebo patient starts injecting saline or otherwise, there’s not really a great opportunity for them to kind of miraculously substantially reduce their event rate. So we’re conservatively powered with a 50% placebo effect rate. We don’t really expect that it will actually come to be.

Unidentified speaker, Host, Goldman Sachs: Okay. And you also did extend the trial. You mentioned that already. But what gives you comfort in extending to sixteen weeks, both on the efficacy and the safety side?

Justin Klee, Co-CEO, Amelix: Yeah. So I think on the efficacy side, there’s nothing we’ve seen that would suggest a waning of effect in either the preclinical studies or the clinical studies thus far. So nothing like tachy phylaxis or neutralizing antibodies, ADAs, that sort of thing. The molecule itself also is a truncated exenatide, so there I think can be some read through from the experience with exenatide where they did not see any of that as well, and that was used in tens of thousands, if not hundreds of thousands of people. And then I’d probably say on the GLP-one agonist side as well, I think it’s been shown that you can engage the receptor over time and continue to have consistent effects.

So ultimately, the important thing is to run the and see the results. But going into it, there’s nothing that would suggest that you’d see a waning of effect.

Unidentified speaker, Host, Goldman Sachs: You’ve dosed the patient. You’re now enrolling. Can you give us any update in terms of site activations, patient enrollment, as you progress towards year end completion?

Josh Cohen, Co-CEO, Amelix: Yeah. So as you said, we’re targeting completing enrollment by the end of the year. Expect data in the first half of twenty twenty six. We’ve activated 13 sites and continuing to activate at a good clip. And the engagement eagerness from the sites, I think, has been very strong.

So we remain on track towards that target of year end enrollment.

Unidentified speaker, Host, Goldman Sachs: Okay. And then in terms of just the approvability of this trial, I guess what’s your level of confidence that this will be sufficient to support regulatory approval?

Justin Klee, Co-CEO, Amelix: Yeah. So I’d say, of course, the FDA always likes to reserve the right to review the data when they get But that being said, I think, one, breakthrough status helps a lot. It suggests that FDA thinks that there’s a real unmet need and that the data supports that this is a substantial improvement over standard of So I think that already helps. And then what breakthrough status also allows is much more frequent interactions with FDA. So with the previous owner and with us, we’ve had quite a lot of engagement with FDA, including on trial design.

It reviewed the Phase III protocol. And so we believe this is the pivotal study to support approval, of course, along with the very strong data from the phase IIs and phase Is as

Josh Cohen, Co-CEO, Amelix: well. Okay.

Unidentified speaker, Host, Goldman Sachs: Can you talk about pricing in this market? Obviously with the registrational study ongoing you have to start thinking about the commercial piece. What are the analogs you think are appropriate? And how does the size of the patient population factor into that?

Josh Cohen, Co-CEO, Amelix: Yeah, great question. Of course, we haven’t priced the drug yet. We’ll wait on the phase three data and everything like that. But I’d say we have been keeping an on some of the other rare endocrine launches that have been happening, whether that’s for Celeno, whether that’s for Ascendis, Rhythm, others as well Chronicity, others as well. So I think it does depend a little bit, as we continue doing market research, who is that best target population that we’ll go after at launch.

But I think what we are seeing is that this does have orphan drug designation. It is a rare disease. What we are seeing is that there is a significant ability to create strong markets in rare endocrine conditions.

Justin Klee, Co-CEO, Amelix: I think our experience, too, with payers is that for rare disease, they really want to understand, is this a real unmet need? It clearly is. In fact, I think this is a population that are very high healthcare utilizers. Think that will be particularly interesting to payers. And then ultimately, do you have data to support the use of this treatment?

And again, if we show anything like what we’ve seen in the phase IIs, I think that’s a very strong data package to bring to payers. And then at that point, I think payers understand rare disease. They understand orphan drug pricing. So I think we’re in a nice especially when, unfortunately for people, there are no approved treatments for PPH today.

Unidentified speaker, Host, Goldman Sachs: Very good. Maybe remind us the intellectual property surrounding this agent.

Josh Cohen, Co-CEO, Amelix: Base case is 2,037. And we have both method of use and formulation composition type patents as well, and then orphan drug designation on top of that as well.

Unidentified speaker, Host, Goldman Sachs: Okay. You also have a collaboration with Gubra to develop a long acting GLP-one receptor antagonist. Maybe talk about the structure around that partnership and how that fits into the broader strategy.

Justin Klee, Co-CEO, Amelix: Yeah, so I think we’re very excited at the potential of the GLP-one receptor antagonist. We think it makes a lot of sense in PBH. We think there are other areas as well that it could be a really impactful candidate. So we feel like when you believe in a target like that, you want to invest for the future. Avexatide has a very nice profile as we go into the Phase III trial, But I think if efficacy, safety, etcetera were all equal, it would be great to have a longer acting version.

So we’re very excited to be partnering with Gubra. They’re one of the world leaders in peptide drug development, including in taking peptides and making them long acting. So we started that research partnership. Announced it at the end of last year. We’re moving along at a really nice clip.

Still a little early to say timelines for when that would be an IND enabling in clinic, but we’re making really nice progress. I think our hope would be that as we continue with Avexatide, as hopefully that’s commercial as soon as 2027, and we show what an impact this may have for people with PBH, then

Josh Cohen, Co-CEO, Amelix: we

Justin Klee, Co-CEO, Amelix: can come with something even better.

Unidentified speaker, Host, Goldman Sachs: Very cool. Maybe you can tell us a little bit more about the target product profile for that. How long of a dosing interval do you think would be useful? And you mentioned that there are other indications, so maybe quickly overview the other hypoglycemia indications you’re interested in.

Justin Klee, Co-CEO, Amelix: Yeah, maybe I’m happy to take it in reverse, if you don’t mind. Sure. I think there are some areas that we think are probably, I hate to say, almost obvious to start with. there are other surgeries that can cause the same persistent hypoglycemia. For example, gastrectomy, which is indicated for gastric cancer.

It’s a big deal here in Asian countries such as Japan, Korea and China. It’s one of the leading causes of death. There are many, many gastrectomies. It appears that any significant upper GI surgery, whether bariatric or gastrectomy or esophagectomy, can cause this same persistence of dramatic hypoglycemia. The phase IIb trial of exotide was used in people who had different surgeries that caused hypoglycemia, and the drug appeared very effective for those people as well.

We think that’s a clear area for us to look into in the future. Avextide also has breakthrough status in congenital hyperinfluenism. I think it’s just suggesting that targeting or having an antagonist of the GLP-one receptor is very powerful and I think may lend itself to be an important treatment in other areas. Now, and foremost, we have a pivotal study ongoing in PVH, so that’s where our focus is, but we’re very excited about those future programs too.

Josh Cohen, Co-CEO, Amelix: And yes, TPP with gubra. It’s early to be too definitive, I think. But the target is to make it longer acting. If there are other probably at least weekly.

Justin Klee, Co-CEO, Amelix: If

Josh Cohen, Co-CEO, Amelix: there are other things we can continue to if we can make it even longer, great. But I think the goal is just to make something even more convenient, if that makes sense.

Unidentified speaker, Host, Goldman Sachs: Perfect. Maybe we’ll switch gears to Wolfram’s syndrome for a few minutes. At a high level, maybe just give us the quick lay of the land. What is Wolfram’s syndrome, and what is the therapeutic agent in this trying to accomplish?

Josh Cohen, Co-CEO, Amelix: Sure. So Wolfrim is a monogenic disease that is a monogenic form of diabetes. So we’ve recently come to light that classically diabetes was type one, type two. But in fact, there are a number of forms of diabetes that are genetic, of which Wolfram is one of those. So it starts by looking like type one diabetes.

Children usually present with diabetes between six and nine years old. But as they get older, it becomes clear that it’s not just diabetes. Usually in early adolescence, they’ll start going blind, becoming usually fully blind in adulthood. They start showing other symptoms like deafness, walking difficulties, breathing difficulties, swallowing difficulties. And it kind of transitions from a diabetic disease to a neurodegenerative disease as the patients get older.

It’s caused by mutations in a gene called WFS1, which makes it nice from a preclinical modeling perspective as well. All of our preclinical models were WFS1 models, where we showed quite strong differences with the drug as opposed to vehicle or otherwise. And it’s also I’ll say it’s also a progressive disease. People get worse both on the diabetes and all the neurodegenerative markers as they get older, typically passing away in early 30s, mainly due to complications of the breathing and swallowing challenges that the patients have.

Justin Klee, Co-CEO, Amelix: Okay. And I think what’s nice is so we’ve been working in Wolfram syndrome for about eight years now. And I think it’s becoming more and more recognized, which is nice for people and their families. There are now genetic panels for diabetes and Wolfram syndrome mutations are on those. I think people are recognizing now if you see early onset diabetes and start the progressive vision loss, maybe this is Wolfram syndrome.

There’s even a patient listening session at FDA last month focused on Wolfram syndrome. I think it’s nice to see it start to be recognized because these people and families really need better options. Okay. You recently published clinical data on a forty eight week study. Maybe what were some of

Unidentified speaker, Host, Goldman Sachs: the key takeaways for that trial?

Justin Klee, Co-CEO, Amelix: I think what we’ve seen, we’re quite excited about. So the primary things we were looking at were measures of glycemic control. So people with Wolfran syndrome, their pancreatic beta cells become dysfunctional and degenerate, which means their bodies can’t produce insulin the way that they’re supposed to. We saw not just a slowing of that loss of insulin production, but we actually saw an overall increase in the amount of insulin produced by the pancreatic beta cells, as well as faster time to produce that because you want the insulin to happen in response to a meal. So we saw both earlier and more insulin production.

It’s the time in any trial of diabetes we’re aware of that has seen that, So we’re very excited at what that means. We think what it means is that the patient’s beta cells are functioning better. We saw concomitant changes in the other glycemic measures as well. Hemoglobin A1c went down, time and target glucose range went up. Then we looked at other measures of function impacted by Wolfram’s syndrome.

Visual acuity, we saw stabilization or even improvement in a couple of people. We saw overall changes in things like clinician and patient reported impression of change. So in short, every outcome we looked at went in the right direction, which in a progressive disease is very exciting.

Unidentified speaker, Host, Goldman Sachs: You’re now planning to meet with regulators on a phase three trial design. What are some of the key things you want to establish with the regulators as you think about the length of the study, the right endpoints, whether it’s controlled? Talk to us about that.

Josh Cohen, Co-CEO, Amelix: Yeah, great question. So similar as we discussed with the vexatide as well, we try to keep as much similar as we can phase two to phase three. And in our phase two, our primary outcome was a C peptide. We then had other glycemic measures. We also had visual acuity and various measures of global change as well.

I think to the extent those outcomes can be central to our next trial, I think that would be to our benefit, given that we’ve already seen effects there. In terms of duration, we did see continued change as we went out to forty eight weeks. So there’s some trade off in terms of how long do you want the study to be, etcetera. But it does seem like the separation grows over time. And so that certainly factors into the thinking as we go forward towards a potential Phase III trial.

And I’d also say overall, this would be the pivotal study ever run-in Wolfram. So we do want to make sure as we interact with FDA that we’ve kind of cleared up the necessary questions and that hopefully if we have a successful study that we’re clearly moving towards a registration approval, things like that.

Unidentified speaker, Host, Goldman Sachs: Okay, great. And then maybe we can spend a minute on the progressive supranuclear palsy. Phase III interim data is expected in the third quarter. Remind us what exactly we’re going to see with that result?

Justin Klee, Co-CEO, Amelix: So we’re running this Phase IIb trial to basically serve as the gono go point to determine if we enroll in a Phase III. We’ve randomized 139 people, three to two active to placebo. We’re following them over time. The analysis point we’re using is that everyone will have at least twenty four weeks of treatment. For people who have longer treatment, we’ll use all available data.

PSP, as I mentioned, is a really tough neurodegenerative disease. Sadly, there’s nothing approved for It’s a progressive movement disorder disease that’s ultimately fatal within generally six to eight years. Probably the thing of note we’re going to be looking at in the interim analysis or in the phase two analysis is the PSP rating scale. Pretty well validated scale. It’s been used in quite a few large studies in PSP.

So, I think that’s generally looked at as kind of the gold standard in the field. We’ll be looking at other clinical outcomes as well. People may be familiar with from Parkinson’s or Alzheimer’s or other such clinical scales. We’ll also be looking at a number of biomarkers, including MRI. There’s particular patterns of brain degeneration that one sees in PSP, as well as the typical CSF biomarkers one looks at in neurodegenerative disease.

We’ll very much be looking at the totality of the data to determine if we go into that phase three portion of the study. That being said, we’re going to have a high bar if plan to embark on a phase III study in PSP, we want to have high confidence that this is

Unidentified speaker, Host, Goldman Sachs: a good shot on goal. Okay. Maybe we’ll spend one second on the next generation candidate in ALS, AMX one hundred fourteen. Maybe just give us a quick why isn’t ASO something you guys felt you should bring into the clinic? And what is kind of the goal for this phase one?

Josh Cohen, Co-CEO, Amelix: Yeah, great question. So it started with the target, actually. So we got very interested in KALPAN two as a target. In the time we were in ALS, we continued to kind of accumulate knowledge, information, dug very deep into literature. And KALPAN2 emerges one of our absolute favorite targets, in part because there’s decades of evidence linking it to axonal degeneration.

It’s central in neurofilament processing, so this insight of increased neurofilament may be saying something about calpane as well. And as we thought about how to target it, there are many calpains in the calpain family. Calpain two seems to be the one that’s really central to neurodegeneration and things like ALS. And so to get that kind of exquisite targeting of just calpain two in ASO made a lot of sense. I’ll say we worked with others who had done ASOs before, help us as we developed this ASO.

And now in clinic, just got Fast Track designation as well. One other thing I’ll mention just at the NCALS conference just recently as well, there was new genetic data presented that actually showed CALPN-two emerging as a genetically potentially genetically validated target in ALS as well, which was kind of nice to see as kind of further confirmation also. But then maybe last, preclinically, we’ve seen neurofilament reductions. We’ve seen benefits on external degeneration, which was kind of what we hoped to see based on all the literature and the science that kind of led us to CALPAN too. Great.

Unidentified speaker, Host, Goldman Sachs: Maybe in our last minute here you can just give us an update on the cash runway and what activities are embedded in that guidance.

Justin Klee, Co-CEO, Amelix: I’d say we ended last quarter with $2.00 $4,000,000 We have no debt. That gives us cash runway through the end of twenty twenty six. Essentially everything that we’ve been talking about is included in that cash runway guidance, probably most notably in the first half of next year, pivotal vexatide PVH study readout. The one thing not in that runway would be the Phase III PSP trial. But I think our feeling is if we have very positive data in PSP, there are a number of options we can consider to progress into a Phase III trial.

But we’re very excited because we have, I think, genuine exciting milestones in the coming twelve to fourteen months. And we’re excited to keep progressing across all of our programs.

Unidentified speaker, Host, Goldman Sachs: Perfect. Well, thanks so much for joining me, guys.

Justin Klee, Co-CEO, Amelix: Excellent. Thanks so Thank you so much.

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