Amelix Pharmaceuticals at 24th Annual Needham: Strategic Pipeline Progress

On Wednesday, 09 April 2025, Amelix Pharmaceuticals (NYSE: AMLX) presented at the 24th Annual Needham Virtual Healthcare Conference, providing a strategic overview of its clinical pipeline and financial health. The company highlighted positive developments in its Avexatide, AMX thirty five, and AMX114 programs while addressing financial strategies to sustain operations without further capital market engagement.

Key Takeaways

• Amelix aims to complete Avexatide's phase three trial recruitment by year-end, with top-line results expected in the first half of next year.
• The company holds a strong cash position, ensuring funding through the Avexatide readout, with no immediate need to re-enter capital markets.
• AMX thirty five's HELIOS trial in Wolfram syndrome is set to release week 48 data soon, with plans for a phase three program underway.
• AMX thirty five's Orion trial in PSP will provide crucial data in Q3 2025 for a phase three decision.
• AMX114 has dosed its first patient in an ALS study, with early cohort data expected by year-end.

Financial Results

• Cash on hand at the end of last year was $176.5 million, increasing to approximately $240 million pro forma after an offering at the start of the year.
• Amelix anticipates its cash runway will last through the end of 2026, aiming to reach the Avexatide readout without needing additional capital.

Operational Updates

Avexatide (PBH):

• Phase three pivotal study is actively recruiting, targeting completion by the end of the year.
• Top-line results are expected in the first half of next year, with a potential commercial launch in 2027.
• Intellectual property rights extend to 2037 before patent term extension.

AMX thirty five (Wolfram syndrome):

• HELIOS trial week 48 data is expected in the coming months.
• Phase three program design is in progress, with updates anticipated this year.

AMX thirty five (PSP - Orion trial):

• Data is expected in Q3 2025, with a full unblinded analysis to guide phase three trial decisions.

AMX114 (ALS - LUMINA trial):

• The first patient was dosed recently, with early cohort data expected this year.

Future Outlook

• Amelix is focused on completing Avexatide's phase three trial recruitment and preparing for commercialization.
• The company is preparing to release AMX thirty five HELIOS trial data and design the phase three trial.
• The interim analysis of the Orion trial will determine the next steps for AMX thirty five in PSP.
• AMX114's early cohort data will focus on safety and biomarkers, particularly neurofilament levels.

Q&A Highlights

• The LUMINA trial aims to gather safety and biomarker data, including neurofilament levels.
• The phase three Avexatide trial design features a parallel group placebo-controlled trial with conservative powering assumptions.
• AMX0035's interim analysis in PSP will assess safety and efficacy with a high threshold for phase three progression.
• The HELIOS study in Wolfram syndrome has shown improvements in outcomes, particularly c-peptide levels, suggesting pancreatic beta cell rescue.

Readers are encouraged to refer to the full transcript for a detailed discussion of Amelix Pharmaceuticals' strategic initiatives and future plans.

Full transcript - 24th Annual Needham Virtual Healthcare Conference:

Poonakanan, Associate, Needham: Good morning, everyone. Welcome to day three of Needham's twenty fourth annual conference. My name is Poonakanan, and I'm an associate here at Needham. And I'm really excited to have with us here today Josh Cohen and Justin Klee. They're the cofounders and co CEOs of Amelix Pharmaceuticals.

They'll be providing us with a corporate presentation. Following that, we'll open up the floor for any questions. Just as a reminder, please send any questions that you may have on the dashboard. Josh and Justin, if you're ready, please take it away. Thank you.

Justin Klee, Co-CEO and Co-founder, Amelix Pharmaceuticals: Excellent. Thank you so much, Pourna, and thank you, Needham, for hosting us. So as Pourna mentioned, I'm Justin. With me is Josh. We're two co CEOs and cofounders at Amlex.

So we're very excited to share a bit more about Amlex and our exciting, clinical pipeline today. So but before we, get into the presentation, just a brief disclaimer. We will be making, forward looking statements, and, I would advise you to please review this disclaimer as well as look for more information on our investor website. So brief overview of our clinical pipeline. So we have three assets in four ongoing clinical trials.

Our lead asset is Avexatide. Avexatide is a first in class GLP one receptor antagonist. So it lowers insulin and raises glucose. Avexatide has FDA breakthrough therapy and orphan drug designation, and we are enrolling in a pivotal study in post bariatric hypoglycemia or PBH right now. We expect top line results from that study in the first half of next year, and PBH is really a significant unmet need.

There are no treatments available for people with PBH today, and we estimate there's about a hundred sixty thousand people in The United States who have, PBH. So I'll share a bit more on that in in a moment, but, we're very excited about the prospects of Avexatide to help people with PBH. Next is our combination small molecule, AMX thirty five, targeting ER stress and mitochondrial dysfunction. So we have AMX five in two clinical trials, both in diseases characterized by ER stress and mitochondrial dysfunction. The first is Wolfrum syndrome.

We announced, the first results from our first clinical trial last year in Wolfram syndrome. Quite exciting. We are continuing to follow those participants now longer term, as well as planning for our pivotal study in Wolfram syndrome. We also have an ongoing study of AMX thirty five and PSP. PSP is a really devastating neurodegenerative disease affecting about twenty thousand people in The United States.

There are no treatments available. We are running a phase 2b three clinical trial right now, and we will have an unblinded interim efficacy analysis of that trial, in the third quarter. So that will be the go no go point for if we then enroll for a phase three trial. And then last, AMX114 is our first in house developed antisense oligonucleotide targeting CALPN2. Calpane two is a key effector in axon degeneration.

Now we think that that has, potential promise in multiple, disease areas. We're first evaluating in ALS. We just announced this morning that we have dosed the first participant in our study in people with ALS with one hundred fourteen, and we should have our first early cohort data by the end of this year. So across our, clinical assets, we have milestones, in each program over the next twelve to fifteen months. Very excited about each of them.

We have, other preclinical programs as well, such as our potential long acting GLP-one antagonist we're working on with GUBRA. But today, we'll primarily focus on our clinical pipeline. So sharing a bit more about our lead asset, Avexatide. So as I mentioned, Avexatide is a GLP-one receptor antagonist, and GLP-one receptor antagonist, is, potentially important in conditions of hyperinsulinemic hypoglycemia. So when the body secretes too much insulin, which causes very rapid, drops in blood glucose.

So, the primary indication we're studying, of exotide in is called PBH or post bariatric hypoglycemia. So PBH occurs, in a, rare group of people in the years following bariatric surgery. What happens is the body seems to potentiate the GLP-one response. Our bodies will secrete GLP-one in response to a meal, sometimes in response to other triggers. In people with PBH, we don't totally know why, but it seems that the body overproduces and secretes GLP-one, sometimes up to 10 times normal levels.

This causes a very rapid and high secretion of insulin, which then causes a very precipitous drop in blood glucose. So what happens when our bodies don't have enough blood glucose is essentially our brains are starved. The medical term is called neuroglycopenia. So people experience bouts of severe confusion, even loss of consciousness, even seizures sometimes. So this is really an unmet medical need.

There are no treatments available for PBH right now. But given that we think GLP-one has such a, prominent role in PVH, it's why vexatide, a receptor antagonist, makes so much sense in the condition. And as I mentioned, this is a rare complication that happens in the years following bariatric surgery. On average, it takes one to three years after the surgery. It can happen even longer before symptoms manifest.

But there have been millions of bariatric procedures that have been performed in The United States. So we estimate about eight percent of people who get a bariatric surgery will develop PVH With the well over two million bariatric procedures that have been performed, this gets to a overall prevalence in The US of about one hundred and sixty thousand people. It's also a persistent condition. So once people have PBH, it unfortunately does not go away. So this population will only continue to grow.

This has, population has actually been quite well studied, in the literature. And so I would point you to some of the publications that we've listed to in our presentation, both prospective and retrospective studies looking at people in the years following bariatric surgery. But this is quite a challenge and a problem. We started to look at claims based data as well, and it corroborates these numbers. So I think this population will only continue to grow.

And as I mentioned, it's really significantly impacts people's lives. So we think we have a real opportunity to hopefully change that with vexatide. Now, you know, what also makes us very excited about the prospects of Avexatide to potentially help people with PVH is the consistency we've seen in all the prior trials. So there have been five prior trials, of Avexatide in people with PBH. And in each one, Avexatide did what we would expect, which is it raises glucose, and in particular, it raises, postprandial or after a meal glucose nadir, doing quite a significant job at preventing those very significant drops in blood glucose.

So we saw that again and again and again from the phase one to the ascending dose studies and then to the phase twos. So I'll walk through the phase two data in a little more detail, as that is what is substantially informing our phase three pivotal clinical trial design. So in the phase twos, what was particularly looked at was what's called level two or level three hypoglycemic events. So these have been well agreed upon definitions by the American Diabetes Associations and other groups for quite a few decades now. And level two means that the person's blood glucose has dropped below 54 mgs per deciliter.

The reason that's important is because that's when people start to enter the range that is neuroglycopenia. So it's when the range where the brain is no longer getting enough blood glucose and people are at very significant risk for these associated symptoms. Level three means that the person has been so severely impacted, regardless of whatever the blood glucose level is, they need independent rescue. So this is the severe confusion I was talking about as well as a number of other symptoms. So these are very clinically meaningful outcomes.

As I hope you can appreciate in both the phase two and phase 2b, there were substantial reductions in the level two and level three events. So going to the phase two b, there's fifty seven percent, sixty eight percent, fifty three percent, and sixty six percent, reductions in level two and level three events at the two dose groups studied. As we now go into the phase three study, we went with the single daily dose, the highest dose studied, that's ninety mgs once per day. And importantly, the composite of level two and level three hypoglycemic events, so that's that combination of these two here, is an agreed upon primary outcome from FDA. That's both in guidance.

FDA has also reviewed our phase three protocol, so we are starting enrolling that study now. So a little more on the pivotal study design. Given the very strong results in phase two and the unmet need, that's what supported the FDA breakthrough therapy designation. So our goal really with the phase three trial is to try to have as substantially similar population as possible, and keep the design as similar as we can. So, a few things of note.

So in the phase two, what was studied was Roux en Y gastric bypass, PBH. In the phase 2b, a number of different surgeries that can cause PBH were studied. Now we don't think there's anything different about the physiology of these different, of these different, surgeries causing PBH. We think PBH is PBH, but we have the most data in people with Roux en Y gastric bypass causing PBH, and so that is the population we'll be studying in the phase three. Also important in terms of inclusion criteria, in the phase two studies, very key were that people had to have a run-in period where there was at least one event, one hypoglycemic event per week in order to qualify for the study.

We're doing the same thing in the phase three. So that's really to make sure that we are evaluating people who have this very persistent hypoglycemia before entering the study. The dose we are studying again is the highest daily dose studied, is in the phase 2b trial. It'll be a sixteen week placebo controlled study and then with an open label extension. As I mentioned, the FDA has reviewed the protocol, and so, we are actively enrolling for this study.

And, we are, very, excited, as I mentioned, for the prospects and what this might mean for people with post bariatric hypoglycemia. So just, very important as well is the safety profile. So I mentioned the efficacy, but importantly, Avexatide was quite safe and well tolerated in both, phase two trials as well. Injection site reactions were quite comparable to, placebo. When they occurred, they were, the vast majority were mild, very occasionally moderate, and seemed to resolve quickly.

So, strong efficacy from the phase two trials, and a good accompanying safety profile as well. So reviewing the overall timelines, we're very excited about the prospects of this program and what it might mean for people with PBH. We are actively recruiting now. We expect to complete recruitment of this pivotal study by the end of the year and then have data in the first half of next year. Given breakthrough status, which we would mean a priority review, this would mean a commercial launch in 2027.

Again, as I mentioned, for a condition where there are no treatments, and we estimate an overall prevalence of a hundred sixty thousand and, really a substantial unmet need. Our IP rights go out to 02/1937. That's before patent term extension. And we have orphan drug designation as well. So we're very excited about Avexatide as our lead program, but as I mentioned, we also have, two additional assets and three ongoing clinical trials.

So for more on that, will happily pass to Josh.

Josh Cohen, Co-CEO and Co-founder, Amelix Pharmaceuticals: Thanks, Justin. So I'll talk today about the rest of our pipeline. So starting with AMX thirty five, this is our combination of two small molecules targeting ER stress and mitochondrial dysfunction. Maybe just an important step back to that part of the reason why we were so interested from the start in sodium phenylbuterate and terisediol is really decades of literature where these are often used as tool compounds to target ER stress and mitochondrial dysfunction. So that's an effect of these compounds that's been replicated again and again across the literature.

So maybe starting with Wolfram syndrome. We started working in this space, about eight years ago, and I'll describe the disease a little bit. So Wolfram syndrome is a monogenic disease. It's caused by mutations in the WFS one gene, and what the WFS one gene is believed to do is stop, ER stress in cells when it gets excessive. And so what's observed is when patients have mutations and dysfunctional WFS one, the ER stress response can get, you know, can can become over overactive leading to cell death and dysfunction.

And where that particularly happens, is in the beta cell, the pancreatic beta cell, and in neurons. And so that, you know, translates into what you see, from the clinical phenotype, which namely people with Wolfram syndrome will start by looking like type one diabetes, usually at about six years old. So that will progress to, you know, full blown insulin dependent diabetes. But then they'll also see neurodegeneration such as blindness, deafness, eventually speech and swallowing difficulties, and breathing difficulties, and usually people unfortunately pass away in their early thirties. It's a progressive disease, so all these symptoms are getting worse over time, And we estimate there are about three thousand people living with Wolfram in The United States today, and there are no approved therapies, for for Wolfram syndrome.

So touching a bit too on the mechanism, as I said, this is a monogenic disease caused by mutations in WFS one. It's often called in the literature the prototypical disease of ER stress, and that's where our compounds come in, having shown, you know, evidence against ER stress, you know, repeatedly across many different models. You can also see on the QR code on the right a link to some of our preclinical data. As I mentioned, we have been studying this comp this combination of compounds in Wolfram syndrome for about eight years. And in that work, we studied cellular models as well as the mouse model of the condition showing highly statistically significant results in slowing the, progression in the mouse model as well as, ameliorating the phenotype that we see in the cellular models.

So it's that work which ultimately drove us towards, the clinical trial, which we, you know, presented some data on. So, you know, diving into that a little bit, maybe first, what do we what do what is expected in people with Wolferham syndrome? So as I said, Wolferham syndrome is a progressive disease. Over time, the diabetic phenotype gets worse and worse. Vision gets worse and worse until patients become completely blind, and they have progression across all the other symptoms that I described earlier that you can measure with a clinician global impression of change or a patient global impression of change as well.

So again, coming into this study, we would have expected patients to show progressive decline across these measures, and there are some natural history studies. There are published studies out of the WashU registry under Fumihiko Urano, and they're consistent with this finding that people progressively decline who have Wolfram syndrome. We conducted a 12 patient open label study, phase two study with AMX thirty five, And what was so exciting to us about that study is we saw stabilization or improvement across these measures. Particularly in the diabetic phenotype, we saw consistent changes on c peptide, which is a measure of beta cell function, hemoglobin a one c, and time and target glucose range measured by continuous glucose monitoring. We saw stable or improved vision, and patients reported that their, symptom patients and clinicians reported that the symptoms were improving.

And so by and large, you know, really promising data in our view in this initial study. And so in terms of safety as well, just to recall, AMX thirty five through its work in ALS has been in thousands of patients, and I'd say the safety profile we saw in Wolfram was very consistent with that. The most common AE was, you know, mild diarrhea, which again was consistent with what we've seen in the past. So what's next for Wolfram? We're continuing to follow participants in the phase two HELIOS trial that I just described.

We expect to share week 48 data in the coming months. We're also interacting with regulators and working on our phase three program, and so we intend to provide an update on that in, into this year as well. So maybe moving next to our program in progressive supranuclear palsy or PSP, also with AMX thirty five. So similar to Wolfram, I'll start by describing the disease just a little bit. So PSP is often considered, one of the purest tauopathies.

Why is that? There's strong genetic data linking variants in tau, in the, you know, in the gene for tau to the disease. There's clear pathology both in postmortem samples and imaging studies suggesting that tau is instrumental to the disease. So generally considered disease driven by, you know, abnormal tau protein. How does disease manifest?

People present initially looking a little like Parkinson's with gait disturbance, but what makes the disease distinct, patients will have trouble moving their eyes up and down, their arms will be abducted to the side, kind of out to the side. They also have balance difficulties, and ultimately, this disease progresses to a point where patients are fairly locked in, you know, having difficulty moving, speaking, breathing, and usually through respiratory complications, people pass away six to eight years after symptom onset. In The US, we estimate about twenty three thousand people living with this disease and no approved therapies to date. So, you know, I mentioned that PSP is a tauopathy, possibly one of the purest tauopathies. We have seen with AMX thirty five in a randomized trial in Alzheimer's disease a highly significant reduction in both total tau and phosphorylated tau one eighty one in the cerebrospinal fluid.

So this was one of the elements that got us quite excited about studying AMX thirty five in it in, you know, in tauopathy and probably particularly in PSP being one of the purest of tauopathies. So when we think about our work in PSP, we really look at it as we're testing the hypothesis of whether a small molecule that can get across the blood brain barrier can get intracellular and reduce tau will have an attendant clinical effect. And to our knowledge, this is the first time that, you know, a compound that can get intracellular can get across the blood brain barrier and reduce tau is being studied in PSP. So that study randomized a hundred and thirty nine people, living with PSP to active or placebo. We expect data in q three twenty twenty five, so just around the corner, And that data will be a full unblinded analysis, including, you know, the outcomes I show on the right here.

Primary outcome is the PSP rating scale, which is a functional rating scale assessing people's progression with PSP. We estimate that with the 39 sample size, we have about 80% power to detect a 30% effect. And then we also have additional secondary outcomes and biomarkers, which should provide additional data as well. And we're using this, analysis as a go, no go. If the data are strong, we will proceed to, you know, phase three.

If the data are weak, we believe we have many exciting programs in Amelix, and, you know, we'll re reprioritize resources to those. And then maybe lastly, and maybe excitingly today, because we just announced first patient dosed, in this program, I'll describe our AMX one fourteen program, which is our antisense oligonucleotide targeting CALPN two. So CALPN two, you know, over our, over ten years that we've been working in ALS, we've spent a lot of time thinking about, targets that might be particularly interesting to impact the disease. And the target that really came to the top of the list for us was KALPAN two. Why is that?

It's well known in ALS that one of the primary, pathologies is axonal degeneration. Basically, this idea that the axon of the neuron is retracting and degenerating and dying. There's been a lot of research into the pathway called Mullerian degeneration, which is how, axons are believed to self degenerate and die. And some of the you know, one of the proteins that's been most implicated in Mullerian degeneration is calpane and calpane two. Additionally, looking at ALS specifically, there is evidence of calpane two being upregulated.

Inhibition has shown benefit in most models. It has linkage to various ALS substrates, and I'll touch on too the link that it has to neurofilament. You know, as folks may know, in ALS, there's been a lot of evidence that neurofilament is significantly higher than in healthy control and potentially correlates with disease progression. But interestingly, if you look at the western blot on the right, what we see in ALS is actually cleaved neurofilament. Neurofilament is a 68 kilodalton protein, which you'll notice is absent.

What you're actually seeing is a cleavage product of neurofilament. And what the literature suggests is that the primary protease cleaving neurofilament is calpane and calpane two. So we believe that it's, you know, it's possible that that neurofilament signal you're seeing in ALS is really a result of excess calpain activity. So in terms of our preclinical work as well, we've seen highly significant reductions in neurofilament in different insult models designed to induce external degeneration. We've seen rescues in models of oxidative stress.

We've also studied in, genetic ALS specific models and shown rescues in mortality. And, you know, more of that data is published and presented and and can be found on our website and through the QR code here. So we're now enrolling in our first clinical trial with AMX one fourteen. This is a randomized placebo controlled multiple ascending dose study in people living with ALS. So I know that was a mouthful, but to kind of go through it, it will study four cohorts.

In each cohort, nine people will receive active drug, three people will receive placebo, and these are people living with ALS. And, of course, in this study, we're gonna be very interested in safety and tolerability as it's our first in human study with one fourteen, but additionally, we're quite interested in the biomarker results probably with a particular focus on neurofilament given the linkage to CALPIN two and to ALS. And we expect that we'll have early cohort data, this year. So maybe kinda zooming out, you know, all of our programs through the company. So we raised money at the start of this year, and one of the main intentions in raising that money was to ensure that we would be able to get through our lead asset readout, the Avexitide readout without, you know, explicit need to, you know, retap the capital markets.

And so that is how we're managing the business. We expect cash through the end of twenty twenty six, and, you know, the cash we had on hand at the end of last year was a hundred and 76,500,000.0, but we did also do the offering right at the start of the year, which brought us to, you know, about pro form a 240,000,000. And so maybe just to highlight some of the upcoming events for Amelix. With Avexatide, we are, you know, actively recruiting our phase three trial. We expect to complete recruitment by the end of the year.

Data readout in the first half of twenty twenty six. That's our lead program. With Amex thirty five, we expect to release week 48 data from the HELIOS trial in the coming months. We're also interacting with regulators and designing our phase two trial, which we'll share in this year as well. With the Orion trial and PSP, we expect data in q three, so just around the corner.

And then with AMX one fourteen, we just dosed our first participant, and we expect early cohort data this year. So with that, we're really excited about, you know, our programs, all of which we believe have the potential to help patients who have significant unmet needs. And, thank you so much for having us, and I'll I'll pass it over for questions.

Poonakanan, Associate, Needham: Thank you so much, Josh and Justin, for the wonderful presentation. We have a few questions here, so I can just start. Can we start with the press release that came out today? Could you talk a little bit about the LUMINA trial and what can we expect from the early cohort data this year?

Josh Cohen, Co-CEO and Co-founder, Amelix Pharmaceuticals: Sure. So as we shared this morning, we dosed our first participant in the LUMINA trial. As a reminder, this is an antisense oligonucleotide delivered intrathecally, in people living with ALS. It's a randomized placebo controlled multiple ascending dose study. You know, as I said, a bit of a mouthful, but that that is the design that we're that we're working on.

For the early cohort data this year, that will be data, you know, both on safety, and, we expect to also have, you know, biomarkers both we're looking both at, calpane specific biomarkers as well as biomarkers such as neurofilament, which have garnered a lot of interest in the field. So that's that's kind of the data that we expect to have later this year.

Poonakanan, Associate, Needham: Okay. Thank you so much. Could you walk us through the phase three lucidity design and your confidence in what you observed in the prior phase two trials? In addition, what are your powering assumptions for this phase three design? Like, it is the design is slightly different from your phase two study design.

Right? I just wanna confirm that.

Justin Klee, Co-CEO and Co-founder, Amelix Pharmaceuticals: Yeah. So very happy to walk through that. So maybe I'll I'll I'll go a bit in reverse order. So the the phase two trials were both crossover designs. The phase two was it had a a screening period, a placebo period, and then crossover to one of two dose groups.

Same total daily dose, but one was once a day, one was twice a day. The phase two b study had a screening period and then two different dose groups. Again, same total daily dose once a day versus twice a day, although the phase two b dose was 50% higher than in the phase two. So I'd I'd say that now going into the phase three, most of the details are substantially similar. So the way that we're collecting data is the same.

We're getting blood glucose measures via finger stick. All study participants will also have a continuous glucose monitor. Level three events are being adjudicated by an independent, committee as was done in the phase two trials. The, dose that we are studying is the same as was, studied in the phase two b. So and then the run-in period too is the same.

So one one event per week. The in the phase twos, we had a two week run-in period. The phase three, we have a three week run-in period. It's basically just to allow for a little more training, but same event rate. So it's still at least one per week.

The the difference really is that the phase three is a parallel group placebo controlled trial instead of a crossover, and then also that it's sixteen week instead of twenty eight day dosing. Now that being said, we don't have any reason to believe that the efficacy should wane over time. There's nothing in the nonclinical studies that suggests neutralizing antibodies or or anything of the sort, But that is the key difference as we go into the phase three trial. In terms of powering, I'd go back to the phase two trial. So as you can see, the results on lowering level two and level three hypoglycemic events were very statistically significant and with far fewer participants.

So in the phase three trial, we have more participants and more time, which means that we only have more power, than we did in the phase two trials. Even if we show half of the effect size, that was observed in the phase two trial, we still will be over 90% powered. So even using quite, conservative assumptions going into the phase three study, this is still greater than 90% power. And I think that's because of the very highly significant results that were observed in the phase two.

Poonakanan, Associate, Needham: Okay. That that's really helpful. You mentioned that it's a slightly longer duration study, right, in phase three. Are there any potential safety concerns that might be, like might be a risk with, like, the longer term study versus, like, what you saw in phase two?

Josh Cohen, Co-CEO and Co-founder, Amelix Pharmaceuticals: Yeah. I'd say by and large, we've seen a very strong safety profile with vexatide, both clinically thus far as well as nonclinically. You know, in our preclinical studies in, you know, animals, we've dosed to many fold higher than the human equivalent dose that we're studying here, and we've seen, frankly, very, very strong safety profile, and in all of our clinical studies, a strong safety profile as well. So there's no particular concerns. You know, it is the first time we'll be studying the drug out to sixteen weeks, but we have, you know, no particular reason to be concerned.

Poonakanan, Associate, Needham: Okay. That that makes sense. Could you go a little bit into detail on your prevalence estimates for PBH? And, also, within the PBH, is there a particular patient segment you see benefiting the most from therapy like Avexatide? And lastly, what what are your expectations from the duration of treatment?

Would it be given chronically?

Justin Klee, Co-CEO and Co-founder, Amelix Pharmaceuticals: Yeah. Those are great questions. So maybe starting with the population a bit. So if we look at first the the number of people who've had a bariatric procedure over the past decade, it's well over two million people. Of that group, actually quite a high number will have some hypoglycemia, some hypoglycemic events.

That's more like thirty or forty percent of the overall population. The population that we're talking about with what we call PBH are the people who have particularly persistent symptomatic treatment resistant hypoglycemia. So that hundred sixty thousand, that is the, you know, so called more severe group, the group who really have persistent hypoglycemic events. So when we're talking about where do we think of vexatide could be a meaningful treatment, it's particularly in that population. Now that being said, this year, we're doing a lot of commercial preparations, market insights, to really understand where should we focus our efforts first.

I think that a hundred sixty thousand is quite a substantial prevalence, and, you know, we want to make sure that we're very targeted and thoughtful in our commercial approach. So again, we think it's a large unmet medical need, but, you know, I think often in rare disease, particular in areas of where there haven't been prior treatments, it's it's, you know, it's very prudent to have a targeted approach. So that that's that's our plans, but we'll get more of those market insights as as we go forward this year.

Poonakanan, Associate, Needham: Okay. That makes sense. And like you mentioned, you're preparing for the commercialization. So, I guess, can you talk a little bit more about that? This would be the first drug that you're taking to market.

So what are you doing to build build the commercialization team and everything?

Josh Cohen, Co-CEO and Co-founder, Amelix Pharmaceuticals: Yeah. Great question. So so, actually, you know, as you may recall as well, this actually will be our our second drug that we'll take into market. Sorry to correct. But the you know so so we are, one, taking all the experiences we took from our Relivria launch, where we did about, you know, just under 400,000,000 in year one sales.

You know? And and I think we took a lot of learnings from that as well and certainly are applying them as we move into this launch. We're hiring a great team. We just, announced at the start of this year. Dan Monahan is our chief commercial officer who has tremendous experience and is really strong, in the role, and, you know, we've been hiring the leadership underneath him as well, and think we have some great people there, also.

You know, I'd say as we think about this market, as Justin said, you know, it is a new market. You know, we will be the first, you know, potentially be the first drug that is launched in PBH. So we do think that education will be important. We think there's a lot. You know, there's certainly a set of, KOLs and people who are very aware of this disease and, you know, will will speak broadly about how significant of an unmet need it is, but there's also a large cohort of people who will, you know, require education and otherwise, you know, kinda as we get out there.

But, you know, as Justin said, this year is really a year where we're doing a tremendous amount of market research and insights so that as we get into '26, we're ready to start putting those into action and then, you know, launch in in 2027.

Poonakanan, Associate, Needham: Okay. That that makes a lot of sense. I guess for the last few minutes, we can we'll move on to the So the for AMX0035, what can we expect to see from the interim analysis? And could you give us additional color on the specifics behind the go and no go decision that you might have?

Justin Klee, Co-CEO and Co-founder, Amelix Pharmaceuticals: Yeah. Very, very happy to. So so in our our progressive supranuclear palsy trial, we enrolled, randomized a 39 participants. We will be looking at everyone who through at least twenty four weeks of treatment. For the people who have been on treatment longer, you know, we'll use all available data.

When we do the interim analysis in the third quarter, it will be unblinded. So we'll be looking not just at safety, but efficacy as well. Probably the most important outcome we'll be looking at is the PSP rating scale. That's the most widely used scale in PSP. It's been quite consistent trial to trial.

So, unfortunately, no treatments have worked in PSP. But, looking trial to trial, the progression rate has been quite consistent on the PSPRS. We'll be looking into a number of other clinical scales as well as biomarkers as well. When we do that analysis, we'll really be looking at the totality of the data. So for the gono go, you know, I think it's very important as we go into a potential phase three, we wanna have high confidence.

Right? That that's that's a significant undertaking. So the you know, we wanna really make sure that we have a high probability of success before we enroll in that study. So I think I'd I'd really orient people towards the PSPRS, the associated outcomes, the totality of the data, but we're gonna have a pretty high bar to to enroll for that phase three part of the trial.

Poonakanan, Associate, Needham: Okay. Thank you. That makes a lot of sense. And in terms of your Wolfram syndrome study, the HELIOS study, what insights have you gained from that study, and how are you leveraging that to inform your potential phase three design?

Josh Cohen, Co-CEO and Co-founder, Amelix Pharmaceuticals: Yeah. It's an excellent question. So I think we've learned, you know, one, we we certainly learned a lot just in in conducting the study about some of the outcome assessments. Some of them can be, you know, somewhat burdensome as well, and so we're definitely taking those learnings as we go into phase three. But I think the other thing is, you know, we saw something very surprising here.

You know, we did not expect you know, we were hoping for, you know, slowing the disease or stabilizing the disease, but we actually saw on, you know, many of our outcomes was improvement. You know, on the c peptide particularly, which is our primary outcome, we showed, you know, a numerical improvement, which is, you know, not really been seen, you know, all that often in diabetic conditions and really suggests some degree of, you know, rescue of the pancreatic beta cells. So as we go into the phase three, I think we have a lot of, you know, I think really well understood, well validated type outcomes that that we can use, and we're trying to run effectively the most efficient study. You know, I think we want we believe that this is potentially a very important drug for warfarin, and, you know, we wanna, you know, cut the most rapid path we can, you know, to to people in in in need.

Poonakanan, Associate, Needham: Great. Awesome. Thank you for providing all of that additional color. And with that, we're actually at time. So I just wanna thank everyone for joining us today, and thank you to Josh and Justin for providing this wonderful presentation.

And with that, hope you all have a rest like, good rest of your day. Thank you.

Justin Klee, Co-CEO and Co-founder, Amelix Pharmaceuticals: Excellent. Thank you, Pourna. Thank you all.

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