Amlex at H.C. Wainwright BioConnect: Strategic Pipeline Progress

On Tuesday, 20 May 2025, Amlex (NYSE:AMLX) presented at the H.C. Wainwright 3rd Annual BioConnect Investor Conference 2025, offering a strategic overview of its promising clinical pipeline. The company highlighted both achievements and challenges, focusing on its lead asset, Avexatide, and other key programs. While optimistic about future prospects, Amlex acknowledged the importance of upcoming clinical data.

Key Takeaways

• Amlex’s lead asset, Avexatide, is in a Phase 3 trial for post-bariatric hypoglycemia (PBH), with results expected in the first half of next year.
• AMX-35 shows promise in Wolfram syndrome, with plans for a Phase 3 program.
• AMX-114 is in early-stage trials for ALS, with initial data anticipated by year-end.
• The company’s cash reserves are projected to support operations through 2026.
• Key data readouts are expected within the next two quarters, potentially shaping future clinical strategies.

Financial Results

• Cash Position: Amlex reported a strong cash position, expected to fund operations through the end of 2026.
• Financial Strategy: The company plans to reach multiple clinical milestones across all programs with existing cash reserves.

Operational Updates

Avexatide (PBH):

• Phase 3 pivotal study is actively recruiting, with completion targeted by year-end.
• Top-line results are expected in the first half of next year, with potential commercialization in 2027.
• Avexatide has shown significant reductions in hypoglycemic events in previous trials.

AMX-35 (Wolfram Syndrome):

• Positive 48-week data supports the continued development of this program.
• Amlex is collaborating with the FDA to plan a Phase 3 program, with design details to be shared soon.

AMX-35 (Progressive Supranuclear Palsy - PSP):

• The Phase 2b study is fully recruited, with results expected in Q3.
• Future investment in the program depends on these upcoming results.

AMX-114 (ALS):

• Phase 1 study is underway, with early cohort data expected by the end of the year.
• The study focuses on safety, tolerability, and biomarker signals.

Future Outlook

• Avexatide: Aiming for commercialization in 2027, with patents extending to 2037.
• AMX-35 (Wolfram Syndrome): Preparing for a Phase 3 program following encouraging Phase 2 results.
• AMX-35 (PSP): The program’s future hinges on the Phase 2b data expected in Q3.
• AMX-114 (ALS): Early data will guide future development, with a focus on biomarker signals.

For a detailed understanding of Amlex’s strategic direction, readers are encouraged to refer to the full transcript below.

Full transcript - H.C. Wainwright 3rd Annual BioConnect Investor Conference 2025:

Justin, Amlex: Thank you. K. Thank you, Andrew. Thank you, Ananda. Thank you, Ain’t you, Wainwright, for letting us present today.

So we’re very excited to share a bit about our pipeline, our upcoming milestones, and, what we’ve been working on. So maybe to start shown here, Maggie, a person living with post bariatric hypoglycemia. She’s also on our patient council, and we really thank her for all of her work in educating us and making sure we’re doing everything we can to serve people with PBH. So before I start, we will be making forward looking statements. For more information on that, I’d refer you to this disclaimer as well as look on our investor relations website for more.

So at Amlex, we have three assets in four ongoing clinical trials. So our lead asset is Avexatide. Avexatide is a first in class GLP one receptor antagonist. It has FDA breakthrough therapy designation as well as orphan drug designation, and we are we have an ongoing pivotal study in post bariatric hypoglycemia, which I’ll talk about in a little bit. We are targeting completion of recruitment of that study at the end of this year with top line results in the first half of next year, which with a positive study would mean commercialization in 2027.

We also have a m x thirty five, our combination small molecule in two diseases targeting ER stress and mitochondrial dysfunction. The first is Wolfram syndrome. We just announced last week more positive results from our first trial in people with Wolfram syndrome. Josh will share a little more on that, but we’re very excited about our the prospects there. We are also testing AMX thirty five in progressive supranuclear palsy, which is a devastating neurodegenerative disease, and we will have the readout of our phase two b portion of the trial next quarter.

Last, certainly not least, is AMX one fourteen, which shows our antisense oligonucleotide targeting calpane two, which is a well known target in neurodegenerative disease. But this is the first antisense oligo targeting it, and that would be for the treatment of ALS. So we have a first in patient study ongoing now, and we expect the first cohort data at the end of this year. So many exciting assets and milestones ahead. I’ll first be focusing on our lead, which is a vexatide for the potential treatment of post bariatric hypoglycemia.

So post bariatric hypoglycemia is is a condition that affects people in the years following bariatric surgery. So not everyone develops it. It’s it’s rare. We estimate about eight percent of people with bariatric surgery may develop post bariatric hypoglycemia. What appears to happen is that the body upregulates the GLP one response.

So the body overproduces GLP one. Blood levels can be as high as 10 times normal. So GLP one is one of the body’s master regulators of insulin and therefore glucose. So with this very high level of g l p one, people experience very precipitous drops in blood glucose. When our bodies don’t have enough glucose, our brains stop functioning the way that they’re supposed to.

The medical term is called neuroglycopenia. We are developing a vexatide, which is a GLP one receptor antagonist. So it blocks endogenous GLP one from interacting with the receptor, thereby raising the glucose nadir back to normal levels. Now I mentioned that PBH is rare. It happens, we estimate, about eight percent of people who get bariatric surgery.

But there have been millions of bariatric procedures in just the last decade in The United States alone. So shown here are some of the studies that have been done looking at the population in the years following bariatric surgery who will develop this persistent and symptomatic hypoglycemia. There are very good retrospective and prospective studies. And what really characterizes the disease is that they get these very persistent and symptomatic drops in glucose that cause people to have severe bouts of confusion, loss of consciousness, even seizures. So as you might imagine, this is a very severe and debilitating condition.

We estimate there are about a hundred sixty thousand people in The United States today who have PBH. Once someone has PBH, it appears to be persistent. In fact, it can even be progressive. So we expect the population to only go up. We’ve also done our own claims based work looking at medical claims providers, and we get to very similar estimates as what’s been shown in the literature.

So orphan disease, but large orphan disease. Now avexatide has been studied in five trials already in people with PDH, three phase one trials, and two phase two trials. In each of those trials, what was really dramatically shown was a change in the post meal glucose nadir. So the glucose nadir is the lowest point of someone’s glucose. That’s where they’re in the hypoglycemic range.

And what I hope you can appreciate is that in each study, very significant increases in the postprandial glucose nadir and thereby helping with PBH. This is what helped support the FDA breakthrough therapy designation. In the two phase twos, avexatide cut the rates of level two and level three hypoglycemic events very significantly as well, with the highest dose tested, about fifty three percent reduction in level two events, and sixty six percent reduction in level three events. Now level two events are defined as a blood glucose less than 54 milligrams per deciliter. That is the range at which people become neuroglycopenic.

They become at risk of having these very severe symptoms. Level three is that someone is so significantly incapacitated, they need independent help. They need somebody to rescue them. So these are very meaningful events, and these have long been defined by the American Diabetes Association and other groups. So now as we go into this pivotal study, we will be testing the ninety milligram once daily dose, looking at the composite of level two and level three hypoglycemic events.

This is an outcome that FDA has reviewed in our protocol. It’s also in FDA guidance when drugs are looking at treating hypoglycemia. Importantly, avexatide was also well tolerated. So looking at AEs, injection site reactions, it was quite similar to placebo in the phase two and phase two b studies, and so we look forward to now continuing to look at that in the phase three. So the goal of the phase three pivotal study is really to try to be as consistent as possible with the phase twos.

The phase twos were showed very strong reductions in level two and level three hypoglycemic events. The phase two trials, probably the key differences, the phase twos were both twenty eight day studies, so four weeks. The pivotal study is a sixteen week placebo controlled trial. The key inclusion criteria are, first, looking at the event rate, so how many level two or level three events someone needs in order to qualify for the study. In the phase twos, it was two events in two weeks.

We’re doing three events in three weeks. So same event rate. Notably as well, we are studying in people who have Roux en Y gastric bypass, post bariatric hypoglycemia. While we do not believe that there is a difference in surgery leading to PBH, we believe PBH is PBH. We have the most data in people who had Roux en Y gastric bypass and then PBH.

So that’s what we’re studying in the trial. So as I mentioned, the study is up and running. We dosed our first participant in the study last month, and we’re seeking to complete recruitment at the end of the year with top line results in the first half of next year. So we’re very excited about the program. PBH is a significant unmet need, 160,000 people and growing.

There are no FDA approved treatments for PBH. Current standard of care is medical nutrition therapy with a positive study next year that would support commercialization in 2027. And our patents go out through base case 2037, and that’s before patent term extension. So we’re very excited about avexatide as our lead asset. But as I mentioned, we have three other ongoing clinical studies.

And for more on that, I will pass to Josh.

Josh, Amlex: Thanks, Justin. Sorry. So I’ll talk through some of our additional assets that are advancing through the clinic as well. So I’m gonna start with AMX thirty five. This is a fixed dose combination of sodium phenyl phenylbuterate and terarsediol.

We designed this working in Wolfram syndrome about eight years ago when a physician contacted us raising the point that Wolfram syndrome is often considered a prototypical disease of ER stress. And he was quite interested in studying our compounds in it given the link the disease to ER stress. So what is Wolfram syndrome? It’s a progressive neurodegenerative and endocrine disease. It starts by looking like type one diabetes.

So patients will present with early onset diabetes, usually in childhood. And then as the disease progresses, they go on to have blindness, deafness, difficulty swallowing, breathing, walking, and ultimately generally pass away in their early 30s. So you can think about it primarily as starting with diabetes, having vision loss, and then a number of other neurodegenerative symptoms. We estimate that there are about three thousand people living in The United States with the disease. That’s really building off of some of the genetic data and prevalence work that has been done in the disease.

And it is a monogenic disease. It’s caused by mutations in the WFS1 gene, which as I said is thought to be critical in how the cell resolves endoplasmic reticulum stress. So AMX thirty five is a combination of sodium phenylbuterate and terisediol. Both of the compounds have been extensively, you know, studied in the literature and also by us showing, you know, clear ability to mitigate ER stress. We also, over those eight years that we’ve been working in Wolfram, studied quite a number of cell models, including patient derived cells from people living with Wolfram syndrome, as well as a mouse model of Wolfram syndrome where we showed highly significant resolution in some of the symptoms that are important in Wolfram syndrome, including preventing the neurons from dying in the neuronal cell models and preventing some of the glycemic and diabetic phenotypes in the mouse model and in patient derived beta cells as well.

That led us into our clinical program. So we started with a clinical trial in 12 people living with Wolfram syndrome, open label study, initial study to get a sense of the biological activity of the drug. What we would expect given that this is a progressive disease is for patients to show progression on diabetic outcomes including C peptide, hemoglobin A1C, and time and target range by continuous glucose monitoring as well as visual outcomes, visual acuity being the main one, and also in their general symptoms which we’re assessing with a clinician global impression of change and a patient global impression patient global impression of change. What we saw instead was actually stabilization or improvement across these outcomes. Probably just to highlight on all of the diabetic outcomes we’re looking at, C peptide being the primary outcome in the study, but also looking at hemoglobin A1C time and range, we saw improvements over time.

And just recently, we presented our forty eight week data and we saw continued improvement. So it seemed that the improvements we were seeing at twenty four weeks in many cases nearly doubled as we went out to forty eight weeks. Here’s our primary outcome, the mixed meal tolerance test. There’s a QR code here to see all of the other outcomes of the study. But as you can see, we see a kind of improvement over time in C peptide, which is a measure of beta cell function.

And that moved in lockstep with the other glycemic measures that we were looking at in the study. And AMX-thirty five has been in many, many patients. Safety profile here was consistent with everything we’ve seen thus far, generally some mild diarrhea, but not much else in terms of safety events. So where do we stand now? We’ve just released the week 48 data, which we’re excited about, continues to show that sustained benefit.

We’re right now working with the FDA and planning out a Phase III program to hopefully advance this drug to patients as quickly as we possibly can. So moving to our next program, progressive supranuclear palsy, also with AMX thirty five. So I’ll start with a little background on PSP. PSP is often considered Parkinson’s. It’s often seen by movement disorder specialists.

But what distinguishes it from Parkinson’s is that patients do not respond to dopamine therapy. So they’ll be given dopamine therapy. They’re not responding. And then they also have a certain cardinal symptoms that makes it clear it’s PSP. For example, they have trouble looking up and down.

They can look side to side but have more trouble looking up and down. They’ll often walk with a pose with abjected arms out to the side. They have particular balance difficulties. And the progressiveness of it is distinct as well. Patients will often lose the ability to speak, swallow, breathe, and survival is generally pretty short at six to eight years with PSP.

There’s estimated to be about twenty three thousand people in The United States living with PSP. And one thing really important to say and partly why we were so excited to go into PSP with AMX thirty five is that PSP is a tauopathy. There’s incredibly strong genetic data linking certain variants and tau to the disease. And you can also see by PET scan and also in postmortem brain samples significant deposition of tau in the exact brain regions where you also see progression of the disease. So I mentioned this before but we had run a kind of investigator collaborated study with AMX35 in Alzheimer’s disease where we saw a highly significant reduction in total tau and phosphorylated tau in the cerebrospinal fluid in a placebo controlled study.

Having got those results we thought about where were the what might be the purest tauopathy where we might study this drug and PSP came to the top of the list. So where do we stand with that? We’ve completed recruitment of a phase 2b study in PSP with 139 participants. We’re going to have the data from them in Q3 of this year. That will be a full unblinded analysis looking at outcomes including the PSPRS and several secondary outcomes.

We expect we’ll have about 80% power to detect a 30% effect on the PSPRS. So this initial analysis should give us a sense if the drug is having a benefit in this disease. This will also be the go no go for us in this program. As a company with four, in our view, exciting programs, if the data is quite strong, it will encourage us to keep investing and keep moving forward. But if the data is weaker, we’ll reprioritize into our other programs.

So lastly, I’ll touch on our AMX114 program. This is our antisense oligonucleotide targeting CALPIN-two for the treatment of ALS. I won’t spend an immense amount of time on what ALS is, but in very brief progressively paralytic disease where people typically pass away in about two years. So why CALPIN-two? It’s been widely recognized in ALS that axonal degeneration is one of the key pathologies.

People often describe it as dying back. This idea that neurons disconnect from the muscle and slowly die back, retract to the spinal cord and to the motor cortex for the upper motor neurons. One of the proteins most associated with axonal degeneration is CALPIN-two and makes sense as a target in that sense. Additionally, it’s been knocked out and it’s been studied in various ALS disease models where inhibiting CALPN-two shows a benefit. One other interesting element about CALPN-two, neurofilament has come to a lot of attention as a biomarker in ALS.

But what’s interesting, if you look at the Western blot on the right of the slide, neurofilament is a 68 kilodalton protein. You’ll notice in ALS, there’s not really a 68 kilodalton band. The neurofilament that we’re observing in ALS is a cleaved fragment of neurofilament. And one of the things that CALPANE is known to do is cleave neurofilament into fragments of about this size. So one of the hypothesis also that has us quite interested in CALPIN and ALS is that it may be causing a lot of the neurofilament increase that we see in the disease.

We run our CALPIN ASO in a number of relevant disease models. We’ve shown knockdown of neurofilament and neurotoxic insult models. We’ve seen benefit in ALS specific models. All of this has led us into our clinical trial, which is right now recruiting. We have dosed the first patient.

And this is a randomized placebo controlled multiple ascending dose study. So we will there’s both an active group and a placebo group and it is in people living with ALS. We expect to have early cohort data by the end of the year, which will include safety and tolerability, but also early signals on biomarkers and otherwise. So maybe lastly, overall for the company, we have cash through all of these milestones. We expect our cash to take us through the end of twenty twenty six.

And maybe just reviewing through the various milestones with With Avexatide, we’re actively recruiting. We dosed our first patient last month. We expect to complete recruitment by the end of the year, have data from the Phase III pivotal study in the first half of next year, which if positive we expect to support the filing for approval in PBH. With AMX-thirty five, we’ve just reported our forty eight week Wolfram data. We are now working towards finalizing the Phase III design, which we expect to share before the end of this year.

We are also expecting to present data from our randomized controlled trial in PSP in Q3 of this year. And then lastly with AMX114, we’re actively recruiting for the study. We expect to have early cohort data in ALS, which will include safety, also biomarkers by the end of the year. So we’re quite excited for everything going on in Amelix. We focus only on diseases of substantial unmet need, and we believe we have therapies that have the potential to serve these patients.

Thank you.

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