Amylix at TD Cowen Conference: Strategic Pipeline Insights

On Tuesday, March 4, 2025, Amylix Pharmaceuticals (NYSE: AMLX) presented a comprehensive update at the TD Cowen 45th Annual Healthcare Conference. The company provided a strategic overview of its drug development pipeline, highlighting significant progress and challenges. The discussion, led by co-CEOs Justin Cleave and Josh Cohen, focused on the advancement of key treatments for rare conditions, supported by a strong financial outlook.

Key Takeaways

• Amylix is advancing Avexitide into a pivotal Phase 3 study for post-bariatric hypoglycemia (PBH), with data expected in early 2026.
• AMX35 showed promising results in Phase 2 trials for Wolfram syndrome and is progressing with a Phase 3 trial design.
• AMX-114, targeting ALS, is in Phase 1 trials with early data expected by year-end.
• The company’s cash position is robust, extending through 2026, supported by recent financing.
• The Q&A session highlighted the unmet medical needs in PBH and Wolfram syndrome, where no current treatments exist.

Financial Results

• Amylix’s cash runway is projected to last until the end of 2026.
• Additional financing was secured earlier this year to support the development of key programs.

Operational Updates

Avexitide (PBH)

• Phase 3 trial is actively recruiting, with initial dosing expected soon.
• Recruitment is anticipated to complete by year-end, with a data readout in the first half of 2026.

AMX35 (Wolfram Syndrome)

• Week 48 data from the HELIOS trial is expected in the coming months.
• Phase 3 trial design is underway, informed by HELIOS data and regulatory guidance.

AMX35 (PSP)

• Phase 2b study has enrolled 139 participants, with an unblinded interim analysis expected in Q3.

AMX-114 (ALS)

• The LUNA trial is actively recruiting, with early cohort data anticipated before year-end.

Future Outlook

• Avexitide could potentially launch commercially in 2027.
• AMX35’s Phase 3 program for Wolfram syndrome will be updated later this year.
• Interim analysis in Q3 for AMX35 (PSP) will guide future steps.
• Early cohort data for AMX-114 will inform further ALS treatment development.

Q&A Highlights

PBH Treatment Expectations

• Any reduction in hypoglycemic events is considered beneficial by patients and physicians.

Wolfram Syndrome Management

• No approved treatments exist; symptoms are managed as they arise.
• The HELIOS trial’s increase in C-peptide levels is promising for potential disease modification.

Wolfram Syndrome Diagnosis

• Diagnosis involves clinical suspicion and genetic confirmation, focusing on early-onset diabetes and vision loss.

For further details, please refer to the full transcript below.

Full transcript - TD Cowen 45th Annual Healthcare Conference:

Operator: I think let’s get started. Welcome, everyone. Econ forty fifth annual health care conference. I’m just here to present the team from Emily’s who has a couple of slides that they wanna show you. And then after that, we’ll do a Q and A session.

So here we have, Justin, Josh Cove Josh Cohen, right, and Justin Cleave and, co CEOs of Amylix. And we, and I’ll also get you over to you all. And then at the end, we’ll do a quick q and a session.

Justin Cleave, Co-CEO and Co-founder, Amylix: Excellent. Thank you. Yeah. Thanks for coming to our presentation. Thanks to the, TD Cowan team for inviting us to present.

So as mentioned, I’m Justin, one of the two co CEOs and co founders of Amlex. And with me is Josh, my fellow co CEO and cofounder. So, first, before getting started, I think all of you know this, but we will be making forward looking statements during this presentation. So I’d please refer you to this slide as well as what’s on our investor website. Going through our pipeline, so first, we have three assets in four clinical trials, and we have significant milestones in each of our programs over the next twelve to fifteen months.

Starting with our lead asset Avexitide. Avexitide is a potential first in class GLP one receptor antagonist. So it lowers insulin, it raises glucose. Avexetide has FDA breakthrough therapy designation as well as orphan drug designation. The first indication that we’re focused on is post bariatric hypoglycemia or PBH, which we’ll share a bit more about, but high unmet need, about 160,000 people in The U.

S. Who have this and no therapies approved. We are starting our sixth and now pivotal study in people with PBH following two very strong Phase II trials, and we expect data readout in the first half of next year. Moving to AMX thirty five, which a combination, small molecule that targets ER stress and mitochondrial dysfunction, We’re testing in two diseases characterized by ER stress and mitochondrial dysfunction being Wolfram syndrome and progressive supranuclear palsy. We had positive data from our first Wolfram study last year, looking at measures of both diabetic impact, as measured particularly by c peptide as well as the neurodegeneration that characterizes the disease.

We’ll go through that data a bit more later. And then in PSP, we will have an unblinded interim analysis in the third quarter of this year. We just shared this morning on our earnings call that we enrolled about 139 participants in the study. And with that we’ll have about 80% power to see a 30% effect in our analysis in the third quarter. And then, last are AMX-one hundred and fourteen, it’s an antisense oligonucleotide targeting CALPANE2, one of the key actors in axon degeneration.

We are starting enrolling a study in people with ALS. We expect to dose the first participants in the next couple of months and we should have our first early cohort data by the end of this year. So really exciting pipeline and events over the next, twelve to fifteen months. So as I was mentioning, Avexetide is a GLP-one receptor antagonist, and we are very excited about the potential of a GLP one receptor antagonist. Starting with post bariatric hypoglycemia or PBH, which is our our first primary indication.

PBH is a rare condition that happens in the years following bariatric surgery. Doesn’t happen to everyone. It’s pretty rare. But, it is caused because the body potentiates the GLP one response. So the body produces, secretes too much GLP one often in response to a meal, but it can be due to a variety of different triggers, which causes a precipitous blood glucose drop.

So, what happens when our bodies don’t have enough blood glucose, the brain can’t function the way it’s supposed to. The technical term is called neuroglycopenia. And as you might imagine, this is a highly debilitating condition because people have these very precipitous drops. They may get very severely confused. They may lose consciousness.

They may have a seizure. So eight percent of the roughly two million people who have had bariatric procedures over the past decade get to a population about a hundred sixty thousand people. Now this, population has been well studied in the literature in both prospective and retrospective studies that, suggest you look at some of the studies that we have here on the slide and you can see on our investor website. We started to look at claims based analysis as well and found very similar numbers. So this is a high unmet need.

There are no treatments approved in orphan, but a very large orphan condition. Should mention also it’s persistent. So, unfortunately, once people have this condition, it doesn’t go away. We’re working with someone, for example, who’s had PDAs for eighteen years. So we think that this is a population we expect to continue to grow.

We’re going into our pivotal study now. This is off the off February 1 very strong Phase two trials. Our goal with this trial really is to, of course, have a trial that would support an approval, but also be as consistent with the phase two trials as possible. So we’re using, substantially similar inclusion criteria. Particularly, we’re looking at people who will have at least one hypoglycemic event per week.

That’s the same as what was done in the phase two trials. I’ll note that we’re looking at people who have who had Roux en Y gastric bypass PBH. We don’t think physiologically there’s any difference between you know, I think PBH is PBH, but what’s been studied the most with the dexatide is people have ruined y gastric bypass and then PBH. So again, trying to be as consistent with the phase twos as possible. We’re using the ninety mg dose, which was seen to be highly effective and safe in the prior trial, and will be sixteen week placebo controlled.

As I mentioned, there have been five prior trials of of exotide in PDH. Shown here are the two phase two trials, the phase two and the phase two b study. I hope you can appreciate this is looking at reduction in hypoglycemic events. These are well known, well characterized outcomes for several decades now. Hypoglycemic event level two means that the blood glucose is below 54 mgs per deciliter.

Level three is that someone is so severely impaired that they need independent rescue. And so these have been established for some time. They’re also in the, FDA guidance for trials, looking at hypoglycemia. And particularly, that the composite of level two and level three hypoglycemic events, is an acceptable primary outcome. So that’s what we’ll be using, in the phase three trial.

We’re going forward with the ninety mg dose, as I mentioned. I think there is a dose dependent response. But if you look, I think the forty five mg and the ninety mg, dosing, you get to roughly equivalent results. We think that makes sense because with either of those regimens, you’re within the therapeutic range for twenty four hours. So, you’re preventing endogenous GLP one from interacting with the receptor, and therefore, you’re protecting against these hypoglycemic events.

Importantly, the safety profile was also very good. Injection site reactions were virtually the same as placebo in both trials. When there were reactions, they were mostly mild, very occasionally moderate. So, we’re very excited about this program. As I said, it’s our it’s our lead asset and lead program.

We’ve started recruitment. We started that in mid February. We expect to dose the first participants in the study in the next couple of months. We expect to complete recruitment by the end of the year with data readout in the first half of next year. This would support potential commercial launch in 2027 for a significant unmet need and high population.

And I probably don’t have time to go into it, but very strong patent estate as well. Patents go out to 02/1937, not including patent term extension. So that’s our lead program, but we have several other exciting programs as well, and we have milestones in those. And for those, I’ll pass to Josh.

Josh Cohen, Co-CEO and Co-founder, Amylix: Sure. So I’ll talk a little bit about our other pipeline programs. Starting with AMX thirty five, which is our fixed dose combination of sodium phenylbutyrate and terasadiol. We designed this drug originally on the basis of trying to target mitochondrial dysfunction and ER stress. These two compounds have existed for some time, including in the literature, often as tool compounds to target those pathways.

And it’s really those pathways that led to the diseases that we’re focused on at this point, Wolfram syndrome and PSP with AMX thirty five. So starting with Wolfram syndrome, to give a little bit about the wrong direction. To give a little bit about this disease, this is a monogenic disease caused by mutations in the WFS one gene. WFS one is an endogenous regulator of the ER stress response. So when WFS one has a mutation, patients can have an overactive ER stress response that leads to cell dysfunction and death.

And basically, with these mutations, patients see dysfunction in various neuronal populations and beta cells, populations. And how this manifests is initially people look like they have type one diabetes, but as time goes on, they get progressive blindness. They get, you know, walking, speech, and movement, difficulties. And ultimately, this will result in death in early thirties typically, usually due to kind of respiratory failure or aspiration pneumonia from, you know, swallowing difficulties. We estimate there are about three thousand people living with Wolfram in The U.

S. Today, you know, and again, a monogenic disease. So mechanistically, Wolfram is often called a prototypical disease of ER stress, mainly built on the fact that WFS1 is an ER stress regulator protein. So it made a lot of sense to use compounds with strong basis NER stress and mitochondrial dysfunction in this disease. We’ve conducted a number of preclinical experiments over six or seven years, that included patient derived beta cells, patient derived neurons, as well as a mouse model of disease, WFS1 knockout model where we look to see how glycemic control progressed over time and saw a highly statistically significant benefit on glycemic control when dosing with AMX thirty five.

So this is really what led us towards a clinical trial in Wolfram syndrome. So that trial is HELIOS, which is our ongoing Phase two trial, open label trial with 12 people living with Wolfram syndrome. And, you know, what we would expect in people living with Wolfram syndrome is progressive loss of glycemic control, meaning that their diabetes is getting worse and worse over time as the beta cells degenerate and die. We also expect progressive loss in visual acuity. And as you saw earlier, there are a number of other symptoms people with Wolferm Syndrome experience.

So we also expect that on global metrics of symptomology that patients will get worse and worse. But what we actually saw and have seen thus far in this trial is stabilization or improvement across these measures, both the measures of glycemic control, the measures of visual acuity and the kind of global metrics of symptom progression. So we’re continuing to follow those patients. We expect to report on our phase or on our week 48 data in the coming months, but really encouraging to see, you know, in contrast to what we might expect in this disease, stabilization or improvement across multiple measures. And then from a safety perspective, AMX thirty five has been in thousands of people, including through our ALS work.

And generally there, the safety profile has been very good with the most common AEs being some diarrhea, some GI side effects. That’s the same as what we saw in Wolfram with no new notable safety signals. So where do we go from here? As I said, we’re expecting week 48 data in the coming months. And then we’re gonna, we’re with that data as well as talking with regulatory agencies, including the FDA, we’re designing the phase three trial.

So we’ll come back with an update later on, you know, the design and scope of that phase three program. So then moving to progressive supranuclear palsy, second indication that we’re looking at with AMX thirty five. So diving a little, you know, what is PSP? PSP is a tauopathy. Both when you look pathologically, you can see clear, you know, accumulation of tau in brain regions that are affected by the disease.

But also there’s an incredibly strong genetic association with certain variants in the tau gene and PSP. So this has led the field to look at PSP as as strongly as a telepathy. How does the disease present? People start with gait disturbance. This is why it’s often called an atypical Parkinson’s, because people may have, you know, walking or movement disabilities.

But it becomes clear it’s not just Parkinson’s when people don’t respond to dopamine and have a series of other issues such as speech and swallowing, balance, and other movement difficulties that kind of go above and beyond Parkinson’s. With these, patients typically pass away in six to eight years. And while it’s an orphan disease, it’s a fairly large, orphan disease at approximately twenty three thousand people in The United States. So again, building off the fact that PSP is a telepathy, AMX thirty five had previously been studied in a randomized placebo controlled study in people living with Alzheimer’s disease. And what we saw in our CSF biomarkers was a highly statistically significant reduction in tau and phospho tau in the CSF in people with Alzheimer’s disease.

So this got us interested in looking at AMX35 in tau driven disease. I’d also add AMX35 is a small molecule. So while there have been some, you know, interest in tau approaches in PSP, there has not been one that can get intracellular and that can cross the broadband barrier. We do believe that this is the first time that such an approach is being studied. So we’ve recruited 139 people in a Phase 2b study in PSP.

We expect to report an interim analysis in the third quarter of this year and that will be an unwinded interim analysis. So, we’ll have data on the PSPRS as well as several other outcomes. We expect with the sample size that we have about 80% power to detect a 30% effect on the PSPRS based on the published literature. And so maybe lastly, I’ll jump through our AMX one hundred and fourteen program in ALS targeting CALPAN2. So AMX 114 is an antisense oligonucleotide targeting CALPAN2.

So basically, it results in less production and expression of the CALPAN2 protein. CALPAN2 is a protein that’s been intimately linked to the axonal degeneration process. It’s a protease that kind of destroys the cytoskeleton leading to the neuron, you know, pulling back its axon from the muscle and desynapsing from other neurons as well. The connection to ALS is strong. There’s been evidence of significant upregulation in samples from people living with ALS.

Benefits have been seen in, you know, mouse models and other models with inhibition of CALPANE, and it’s been linked to some of the, you know, genetic and other pathological elements of ALS such as TDP 43 and some of the other genes. Also note CALPAN2 as a close link with neurofilament. So in ALS, one interesting observation, we note that neurofilament is much higher in ALS compared to healthy control, but it’s not actually the full length neurofilament. When you look at the western blot on the right of the slide, you see that the neurofilament we observe is actually a fragment. Neurofilaments are 68 kilodalton protein.

One of the primary proteases thought to cleave neurofilament is CALPAN2. So it’s possible when we’re measuring this neurofilament, we’re actually measuring, you know, indirectly CALPAN two activity. And so I’ll say, you know, going through our preclinical data as well, so we have tested with our ASO in multiple preclinical models. In the interest of time, I probably won’t go through them one by one, but both models that are genetic models of ALS as well as models where we chemically induce axonal degeneration. And across those models, we see a reduction in neurofilament, improvement in cellular survival and improvement in axon integrity with AMX-one hundred and fourteen.

So where do we stand now? We’re actively recruiting in LUNA, which is a placebo controlled multiple ascending dose trial. We’re actively enrolling the first cohort and this will look at both safety and tolerability as it is a first in human. So of course, safety is very, very important. But additionally, we’ll be looking at pharmacodynamics such as neurofilament levels and other biomarkers relevant to ALS and relevant to the CALPANE pathway.

So, you know, summing up with all of this, one, we have cash that gets us through the end of twenty twenty six. We just raised additional financing at the start of the year. So that will get us through milestones in all of these key programs. And just recapping some of those milestones for Avexatide, we’re actively recruiting our Phase three program, expect to finish recruitment by the end of the year and have data in the first half of twenty twenty six. With AMX35, we’ll have additional data from the HELIOS trial, the forty eight week data in the coming months, and that will help inform along with our regulatory interactions or Phase three program with in PSP with AMX35, we expect to have data from an unblinded interim analysis on 139 participants in the third quarter of this year.

And then with 114, we’re actively recruiting for Illumina, and we expect to have early cohort data before the end of the year as well. So with that, thank you all so much. We’re quite excited about the pipeline we’re advancing to hopefully help many patients with significant unmet need. And I think there’s Q and A, so I’d open up for questions as well. Maybe there’s not Q and A.

Operator: I have a couple quick ones. Sure. Just on the Abexotide phase three program, it’s the level of improvement in hypoglycemic events do you think physicians are gonna look for when they kind of evaluate new treatments in in the space, you know? And does it does it matter that you see a similar level of improvement on the level two and the level three events or just one matter more than the other?

Justin Cleave, Co-CEO and Co-founder, Amylix: Great question. So I’d say right now, there are no treatments approved for PBH. And so, right now, unfortunately, the bar is low. I think maybe starting from the patient perspective, talking with patients, they’ll say, my gosh, anything would help because these are just incredibly debilitating. And it’s also not just that they have these events.

Their set point is off. So they’re kinda always flirting with hypoglycemia, which we all know the feelings of being you know, you you skipped a meal and you feel really bad. Imagine that times, like, 10, and that’s just your stable level. So it’s so I think for for patients, really, any relief would be would be helpful. For doctors, I think the way they think about it is they wanna keep their patients safe.

Level two is a physiological measure that means that it’s at the range where your brain stops functioning the way it’s supposed to. Level three means you’ve had one of these events where you’re so incapacitated, you need someone to help you. And so I think for physicians, both matter because level two means that you’re in danger. Level three means it already happened. Now I think going to your question on what percent would be meaningful, certainly, the results that we’re seeing in phase two are very strong.

I mean, I think those those you know, it’s what supported FDA breakthrough therapy designation. Based on the powering, we are powered to see, you know, even half of that effect, in in in the in the Phase three trial. But, you know, I I think going back to, you know, what’s meaningful, right now, there’s nothing for people with PBH. So I I think the, the bar is unfortunately low.

Josh Cohen, Co-CEO and Co-founder, Amylix: And just to add, oh, I should probably should talk to that. To add one additional, comment as well. In the past trials, there were patient interviews. So after the trial, a subset of the patients were interviewed to ask how their experience was on trial. And one of the questions was how would you rate the efficacy you experienced on a scale of one to 10?

Every patient but one rated at 10, the other rated at nine. And in their kind of verbal description of why they gave it that rating, it was that, one, they felt protected from these significant hypoglycemic drops, but also even on the, you know, maybe less deep hypoglycemia, they felt more energy, they felt more focus, things like that that, you know, when your blood sugar is consistently low, you just don’t, you just don’t function well.

Operator: Then I guess on on the Wolfram program, is how do you just given that there are no approved treatments, how do physicians kind of manage their patients with with this condition? And I guess, what have what what has seemed to resonate the most with these physicians when you show them the L. O. Three, five profile?

Justin Cleave, Co-CEO and Co-founder, Amylix: So great question. So again and, you know, you maybe notice the theme. There are no treatments for Wolfram syndrome right now. So right now, if you think about it, Wolfram starts as early onset diabetes, so people very quickly get on insulin. They’re often on, on, you know, closed loop systems and stuff because, they have because the beta cells are degenerating, they actually get periods of hypo and hyperglycemia.

And then over time, it degenerates further and further. And so they constantly need, sort of, you know, different different, levels of insulin and and, you know, more insulin over time. Then with the, it becomes a whole body system disease. And so physicians just try, you know, in in in each domain to do therapy. You know, for example, progressive blind progressive progressive vision loss leads to blindness.

So kids have to learn braille and, you know, learn how to use a walking stick and and the like, as well as, as you might imagine, there can be quite significant depression. So they try to help with that. So it’s really, people try to help with a variety of different symptoms, but there’s nothing that changes the progression. I think the, you know, I think there’s probably two things that we’ve heard the most. One is, I think, the totality of the data, every outcome went in the right direction, which given that this is a whole body disease, I think that’s very exciting.

I’d particularly highlight though the C peptide. C peptide is a direct measure of the body’s insulin production and secretion. We’re not aware of another study in any diabetic indication where C peptide is increased. And so when we’ve talked with endocrinologists or specifically diabetologists, they kind of say, like, wow, I don’t think I’ve I don’t think I’ve ever seen a trial where C peptide actually increases. So not only would you expect a decrease over time, but we’re actually seeing, it go in the opposite direction.

So I think that’s what’s gotten people particularly excited. And we think it’s because we’re getting at the heart of the disease. We know that the disease caused by the WFS one mutations causes the ER stress and mitochondrial dysfunction. That’s what we’re trying to target, with AMX thirty five.

Operator: How important is the diagnosis? They’re just like clinical diagnosis and how heterogeneous is the presentation?

Josh Cohen, Co-CEO and Co-founder, Amylix: Yes. Great question. So I’d say today, it mostly is clinically suspected and then genetically confirmed. So there are genetic panels, there are commercial genetic tests where you can quickly test and, you know, confirm Wolfram syndrome. But what we hear most often talking to people is that, when a type one diabetic starts to show progressive vision loss, it becomes suspected.

So it’s usually that combination, and particularly if it’s optic atrophy compared to diabetic retinopathy, you know, leads people to think that this may be potentially Wolferam syndrome. You could imagine though a future state where people do some screening of type one diabetics or otherwise, possibly not just for Wilfraham. There are a number of monogenic diabetes, and people have started making commercial panels with multiple of the different genes for genetic diabetes. So you could imagine a world where when somebody has a early onset diabetes diagnosed that they check if if there’s a particular genetic cause.

Justin Cleave, Co-CEO and Co-founder, Amylix: I’d say to your question on, on heterogeneity, the natural history is is pretty good, and, there’s one US based study, we’re now working to get. There’s a UK based study as well. I’d say, as you might expect, there is some heterogeneity, but the pattern is pretty consistent. Kids typically typically get, early onset diabetes, six, seven, eight. Then it’s usually the vision loss, and then sort of the neurodegeneration, the other diabetic, implications sort of show.

But there is some heterogeneity. But I guess going back to Josh’s point, clinical suspicion, genetic confirmation, you get you know, it it it I think it lessens a lot of the variability you might see.

Operator: Then with that, I think that we’re just at time. So I think that we’ll probably end it here. But thank you all for coming, and I hope we’ll have a great rest of the conference.

Justin Cleave, Co-CEO and Co-founder, Amylix: Excellent. Thank you all.

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