Avexatide at Cantor Global Healthcare Conference: Strategic Advances in PBH Treatment

On Wednesday, 03 September 2025, Avexatide (NYSE:AMLX) presented at the Cantor Global Healthcare Conference 2025, outlining strategic advancements in addressing post-bariatric hypoglycemia (PBH). The company highlighted the potential of Avexatide, a GLP-one inhibitor, to meet an unmet medical need. While promising data and regulatory progress were discussed, challenges such as market limitations and patient management complexities were also acknowledged.

Key Takeaways

• Avexatide targets PBH, affecting an estimated 160,000 people in the U.S.
• Phase III trials focus on Roux-en-Y patients, with data expected in 2026.
• Avexatide has shown a 64% reduction in severe hypoglycemic events in trials.
• The company is considering premium orphan pricing for Avexatide.
• Recruitment for the trial is expected to complete by the end of the year.

Understanding PBH and GLP-one

• Approximately 8% of bariatric surgery patients develop symptomatic hypoglycemia.
• PBH involves excessive GLP-one production, leading to insulin spikes.
• The condition affects around 160,000 individuals in the U.S., primarily post-Roux-en-Y surgery.

Avexatide Clinical Data and Trial Design

• Phase IIb trials demonstrated a 64% reduction in level II and III hypoglycemia.
• Phase III trials will extend to sixteen weeks, focusing on Roux-en-Y patients.
• The trial design aims to maintain consistency with previous studies.
• The data readout is anticipated in the first half of 2026.

Regulatory and Commercialization Plans

• Avexatide has received Breakthrough Therapy designation from the FDA.
• The company is exploring premium orphan pricing and expects broad insurance coverage.
• Roux-en-Y patients represent a significant portion of the PBH market.

Future Outlook

• Avexatide’s recruitment completion is targeted by year-end, with data expected in 2026.
• Potential expansion into other indications such as gastrectomy and esophagectomy is under consideration.
• Updates on related programs, including ALS research, are expected by year-end.

Q&A Highlights

• Focus remains on Roux-en-Y patients to ensure trial consistency.
• The company is aware of the market limitation risk but plans to generate additional data if needed.
• Discussions included the importance of reducing medical emergencies associated with severe hypoglycemia.

Readers are encouraged to refer to the full transcript for a comprehensive understanding of the conference discussions.

Full transcript - Cantor Global Healthcare Conference 2025:

Unidentified speaker: Three years on average after the bariatric surgery will develop this very persistent symptomatic hypoglycemia. So what does that mean? Well, when we’re talking about this sort of severe hypoglycemia, the medical term is neuroglycopenia. So what it means is that the blood sugar gets to a level where the nervous system stops functioning the way that it’s supposed to. So the first thing that people notice is the typical autonomic symptoms.

They sweat, they shake, basically their body is trying to build up their, their, glucose. The body, when it’s no longer able to do that, essentially, the nervous system starts sort of breaking down. So, people, may have loss of consciousness, they may have seizure, they have bouts of very severe confusion. And the reason this appears to be happening is that, for this eight percent group of people, their bodies overproduce and over secrete GLP-one. And we know that GLP-one controls insulin which controls glucose.

So they have up to 10 times normal GLP-one, their insulin spikes and their glucose plummets. So then how does this present to the doctor? Well, I would say that for, I’d say, you know, these symptoms can appear to be, well, kind of nebulous, right? Oh, I’m very severely confused. Oh, I had a loss of consciousness, I wasn’t sure.

But I’d say if the person gets to an endocrinologist, these are very clear symptoms of hypoglycemia. Hypoglycemia has long been recognized by endocrinologists as a medical emergency, severe hypoglycemia. So I would say if they get to an endocrinologist, and certainly if the endocrinologist recognizes they’ve had bariatric surgery, then it’s quite a straightforward diagnosis. And that’s why today we estimate there are about one hundred and sixty thousand people who have post bariatric hypoglycemia. Given that the rates of bariatric surgery have continued to be quite high, we expect that in the coming years there is going to be more and more people diagnosed.

And maybe the last point I’d say on the diagnosis is on the endocrine boards this past cycle there are actually two questions on post bariatric hypoglycemia. I think it all speaks to the fact that this is a growing challenge, there are no current treatments available, and as Josh was mentioning, it’s a very significant medical need.

Unidentified speaker: So is it an estimate of one hundred and sixty thousand diagnosed today?

Josh: So we don’t have an exact number of diagnosed today. It is something we’re working on as well. What I would say is, in talking to endocrinologists, it’s not hard to find a number who have well over 100 diagnosed patients under their care. So there’s clearly quite a large cohort of people diagnosed today. I think there’s also opportunity, though, to continue making this diagnostic pathway better.

Testing blood sugar is not a hard thing to do. So after somebody’s had bariatric surgery, particularly if they have some symptoms, it makes a lot of sense to evaluate blood sugar as one of the possible causes of those symptoms. That’s done sometimes today. That might be done by an endocrinologist, but that’s not necessarily routine or standard of care in bariatric surgery yet, and that’s something that I think is an opportunity for leverage for us as we kind of continue forward into the commercial space, pending good data.

Unidentified speaker: Because until the patient gets to the endocrinologist, right, presumably they’re not being followed by the surgeon anymore. That’s long in the past. And they’re presentable with these vague symptoms. And as a clinician, I could envision someone saying, well, that’s sort of a fasting blood test. You’re like, your blood sugar’s normal.

So is that likely occurring at any meaningful degree? And if so, how do you find those patients and get them into the endo setting?

Unidentified speaker: Yeah, I think you’re right. I mean, I think that, what we hear from patients is definitely that it’s a bit of a journey to get the diagnosis. So on average, the diagnosis is one to three years after the surgery. But to your point, those symptoms probably start significantly earlier. So I think that for us, as we start to think towards commercialization, the first is that we have, at least thousands of people who are currently diagnosed with PVH at the top centers.

And then how do we raise the suspicion? Well, I think in some ways it’s quite straightforward. The person’s had bariatric surgery, they’re one or more years out from the surgery, and they’re experiencing these signs and symptoms of hypoglycemia. And I think what’s nice, too, is that we can leverage a lot of the work that’s been done in the diabetes world because severe hypoglycemia is one of the more significant complications of too much insulin or of other reasons that the body can have too much insulin. So I think there’s a lot of awareness and literature we can leverage from the diabetes world to raise the suspicion, let’s say, if the person goes to the emergency room or they go to their primary care doctor and, hey, you’ve had bariatric surgery, you had unexplained loss of consciousness, you should probably go talk to an endocrinologist.

Unidentified speaker: Got it. So you’re taking a once a day approach with the delivery profile. I guess presumably different patients are kind of spiking different levels of GLP-one and might need different levels of GLP-one coverage. So why take the approach you took as opposed to more of a rapid insulin kind of approach and treat prior to meals and titrate that way?

Josh: Yes, it’s a great question. Pharmacologically, as you said, this is a competitive inhibitor of GLP-one, and we do see in these patients that they can have 10, sometimes even 20 times normal circulating GLP-one levels. However, their events don’t just come after meals. The meals is probably the most typical, most classic presentation, but you also see patients having events during exercise, during psychological stress. We’ve heard them describe after caffeine.

We’ve heard patients who have said they have an event out of the blue and can’t assign a cause, that just seemingly comes out of the blue for them as well. So our view is that you do want the drug on board, certainly at meals, but also at other times as well, where they might have another trigger that causes it. In terms of dose, I think one of the things that was quite impressive for us is taking the ninety mg dose in the Phase IIb, the average effect was a 64% reduction in the composite of level II and level III hypoglycemia, but the median effect the median patient actually was brought down to zero events during that four week period. So it does seem that you can get quite deep responses at the dose we’re studying. So anyway, I think it’s an opportunity for kind of continued work, continued research as we keep going forward, but we think we’re already seeing quite a meaningful effect.

And maybe last thing I’ll say there is in the ADA guidelines, level II and level III hypoglycemia, so called severe hypoglycemia, is considered a medical emergency. So when we’ve talked to doctors about clinical meaningfulness, the answer is usually, If I can reduce the risk of a medical emergency at all, that’s meaningful. So we’ve heard even things like even reducing one level two or level three event is meaningful. And so reducing by 64% or more clearly crosses their meaningfulness threshold.

Unidentified speaker: So I was going to ask, like, data is quite impressive, but not 100%. So it’s interesting that the median is 100%. For those who are maybe dragging that average down, is the presumption that they might need a higher dose? Is that a population that you’d plan to address with Avexatide? Do you kind of reserve that for your next gen program to tackle?

Unidentified speaker: Yeah. So I would say we definitely think that GLP-one is at the heart of this. So whether that’s trying a different dose or regimen, those are things we’d definitely like to explore in the future. I think right now going into the Phase III trial, very strong data, good safety profile as well, and that’s what supported the FDA breakthrough status. So that’s why we went with the dose that we have now.

But based on our tox data, we could go up in the dose. We think there’s a lot more to explore here. And the other thing I would say is that I think what we’re able to leverage, quite a lot of the learnings of GLP-one and the GLP-one receptor, which at least I think of a little more like a thermostat, rather than, you know, you want on or off, you know, you want really stable. And so, for weight loss, the GLP-one receptor agonists are very effective because people have, too much glucose, and so it’s dialing your glucose back. In this case, people have up to 10 times GLP-one levels, and so we’re dialing it back the other way to try to bring it back to glycemic control.

Unidentified speaker: Got it. I know other companies, maybe in the insulin space, who tried to get hypoglycemia labels always ran into challenges with the FDA. Maybe kind of a good segue from the Level two and three categorization that you emphasized to explain why it’s different for abexatide, why there is a path to a hypoglycemia addressing product label?

Josh: Yes. Good question. So yes, I think kind of maybe in the early 2000s, 2010s, there were some discussion with some diabetic medications that maybe saw a reduction in hypoglycemia, whether that would be in their label or not. The FDA, I think, since then has clarified pretty clearly what they expect. Hypoglycemia label claims, they have in their guidance specifically that level two and level three hypoglycemia are what they’re looking for to support label claims.

And in our case as well, this is the primary endpoint. In a lot of those cases, it was like a safety endpoint or a secondary endpoint. And I’d also add, we have breakthrough therapy. We’ve quite specifically sent our protocol, gotten it reviewed by FDA. So we do feel pretty confident that we’re conducting this in the right way to get the appropriate claims.

Unidentified speaker: What is level three, two, and one then?

Unidentified speaker: Yeah. No, it’s a great point. I think that was the first thing, which I give a ton of credit to the ADA and other endocrinology groups. I think the first thing was, you know, let’s define this, in the right way. So, level one hypoglycemia is defined by blood glucose less than 70 milligrams per deciliter.

So that’s where you’re hypoglycemic and you should start to sort of take notice, because, that’s important. The next threshold is level two, which is less than 54 migs per deciliter. That’s called medically significant or clinically significant hypoglycemia. And the reason that that blood level of glucose is important is that’s where the body starts to enter the range of neuroglycopenia. So, that’s where the, you know, our brains are the highest glucose utilizers in the body.

When you get to that level of hypoglycemia, your brain slows down and really stops functioning. That’s why some people may lose consciousness because your brain basically is trying to shut down what it can to sort of preserve itself. Level three, is independent of blood glucose. It’s that someone is so significantly impaired they need independent rescue they need someone to help them. And so those are very clearly defined, events.

Obvious ones would be like loss of consciousness and you need help, but there are several others. So I would say when we talk about severe hypoglycemia, from the ADA and other groups and now from FDA, we’re talking about those level two and level three. Level two meaning your blood glucose is so low that this is a medical emergency level three, you’ve already had the event where somebody needed to help you.

Unidentified speaker: Is there a glucose threshold for level three?

Josh: There isn’t, and it varies a little bit person to person, but level three is defined clinically. To give you a picture of it, it’s defined by needing independent rescue. And to give you a picture, you can imagine loss of consciousness. You can imagine somebody being so confused they don’t know where they are, not speaking sensically, becoming so weak that they’re maybe still conscious but barely moving. That’s kind of a picture of Level three, if that makes sense.

Unidentified speaker: Right.

Unidentified speaker: And so, in theory, Level three could have a higher glucose than Level two?

Josh: It could in theory. I’d say it rarely does, but it could in theory.

Unidentified speaker: And I think to your point, too, these were originally defined in the diabetes space. And the ADA and others very clearly say severe hypoglycemia is a medical emergency. PBH people are persistently having these hypoglycemic events. So, for example, in the prior trials of Avexatide, people were having one or more events per week before getting treatment. So this is, you know, I think highlights the really unmet medical need here.

When we talk with endocrinologists who, you know, see a wide variety of patients, they often will say, these are some of the most fragile patients I have in my care. You know, they’re often afraid to leave their homes because you can imagine if at any time you might suddenly be so severely confused you don’t know where you are, You know, you’d be afraid to, be alone. You want to have a very limited life, as Josh was saying. So I think, it speaks to, the unmet need here and what we think is the potential of Avexatide to help them.

Unidentified speaker: Maybe we can frame the Phase III program. And one question I’ve heard investors ask or lament over is, well, it’s only the Roux en Y gastric bypass patient population. So as we think about the hundreds of thousands of patients out there to treat, it may only represent 60 or 70 and maybe you can help us with the percent that Roux en Y represents. So maybe kind of take us through the Phase III and touch upon that question in particular.

Josh: Sure. Maybe I’ll start with that question, and I can kind of run through the Phase III as well. So first of all, I think, overall, with the Phase III, our goal was to keep as much consistent as possible with our prior trials. The prior trials had really strong data, so we want to leverage that as much as possible, not test new hypotheses, confirm the hypotheses we’ve already seen in the previous studies. So when you look through the previous studies, the vast majority of patients had Roux en Y.

There were a handful of people with other surgeries tested, and the effects did look similar across them. But again, the vast majority of data we have thus far is in Ruin Y. So again, along with that philosophy of confirming and not testing new hypotheses in the Phase III, that’s why we chose to do Ruin Y in it. I’d say we also felt that, one, biologically, there should be good argument that across these surgeries, very similar things are happening. You see a very similar GLP-one elevation across all of these surgeries.

Ultimately, from a label perspective, we, of course, don’t know yet. That depends on the FDA review. I think it is a risk, given that we are running it specifically in the Phase But I think that risk can be mitigated. Ultimately, if we do need to generate additional data, we’ll have run this study. We dosed our first patient April 30, expecting data first half of next year, took about a year or will have taken about a year.

If we do need to generate additional data, that’s not a hard thing to do. And from a market perspective as well, recent data published by Doctor. Colleen Craig, she estimated about seventy percent of the currently prevalent PBH patients had Roux en Y, whereas about thirty percent had vertical sleeve. So the Roux en Y does seem to be quite a big portion of the market as well. And then I think kind of framing the Phase III more broadly, as you asked as well, again, it all goes with that same theme of trying to keep as much consistent as possible.

So the inclusionexclusion criteria are nearly identical as it relates to the previous studies. The main differences are that the study is sixteen weeks in duration instead of four weeks in duration. That’s mainly because it’s a Phase III, and you kind of need that slightly longer use. There’s no kind of reason to expect that any there would be any particular difference as you go out longer or any change in the drug’s efficacy as you go out longer. And then it’s also parallel group instead of crossover design.

But again, that shouldn’t really change the biological effect of the drug.

Unidentified speaker: Maybe just to put some fine numbers to what Josh was saying. So, Doctor. Colleen Craig, who is one of the, inventors of Avexatide at Stanford, and, one of the world experts in, in PPH, at Endo she presented work she’s done looking over the past thirty years of bariatric surgery and categorizing people who have clinically significant post bariatric hypoglycemia, meaning really needing treatment. And she found that about one hundred and sixty seven thousand people actively have PBH in The United States today, and of those, one hundred and nineteen thousand had Roux en Y gastric bypass surgery. So, again, as I sort of started with, actually any upper GI surgery can lead to this same persistent symptomatic hypoglycemia, and we would definitely like to study that in the future, including gastrectomy for gastric cancer, esophagectomy for esophageal cancer, and other upper GI surgeries.

But if you just look at the Roux en Y gastric bypass PBH population, you’re still well over one hundred thousand people. It’s a very significant unmet need.

Unidentified speaker: If and when you do decide to explore the other indications, can you move right into Phase III? If not, would you consider getting Phase II underway sooner rather than later so you can kind of move quickly?

Josh: Yes. I mean I probably won’t give precise clinical development for the other indications quite yet. But maybe I’ll say I think we could move quite efficiently. The ultimate endpoints we’re looking at here are going to be similar across these different studies, both looking at the kind of glycemic control as well as looking at the hypoglycemic events. And I’d add, too, in the Phase IIb, the study was open to multiple surgical types, and the effector looked very similar across Roux en Y, VSG, and in that case, also gastrectomy for gastric cancer and Nissen fundoplication, which is done for severe, basically, acid reflux GERD.

If it gets severe enough, it can burn holes, and it’s better to surgically repair it.

Unidentified speaker: For the Phase III, how do you think about the potential for patients to kind of self liberalize their own diet so that the event rate doesn’t fall as much, but on the other hand, they’re just eating far more liberally?

Unidentified speaker: Yeah. So I think with any intervention where diet can influence things, it’s certainly something you want to pay attention to. But I would say I think there are a few reasons that we feel confident that that shouldn’t significantly change things. I think the first is the strength of the prior data. We’re going into the sixth trial now of Avexitide in PBH.

In the phase two in particular, the investigators noted that there was some diet liberalization and yet the drug still had very substantial reductions in hypoglycemic events. So I think it speaks to the fact that we believe GLP-one is really at the center of this. And so, you know, the other thing I sort of remind everyone is that people with PBH are already very carefully managing their lifestyles. As you might imagine, if they have slight excursions let’s say they decide, you know what, today I’m going to go eat a Snickers they have a very, negative consequence, right? People may lose consciousness, they may end up in the hospital.

So people are very careful, not to deviate, from their lifestyles. The other thing I would say is in the trial, we are monitoring, I think, much more closely, than had done previously. At every study visit, the investigators remind people to stay consistent with their diet. We also have a run-in period, a three week run-in period of the trial, where these sort of baseline, habits and event rates are set. And so the idea is then to maintain consistency, throughout the study.

So it’s something we’re paying very close attention to. But again, going back to the strength of the prior data and the fact that I think people are already very carefully controlling their lives gives us confidence now in the phase three.

Unidentified speaker: And if they are so carefully controlling, why is the placebo arm having event rates at the way they’ve had in the Phase II and you would expect in the Phase III?

Josh: Yes. So even when you carefully control your diet, patients will still have events. The diet is, I would say, partially effective in this indication. But for many patients, particularly the patients we’re enrolling in the study, they’ve not achieved success even despite best attempts with the diet as well. And just maybe adding as well a couple of other things.

One, we also do retrain the patients on the diet at every interaction with the clinic, so they’re getting that reinforcement again and again of that training. And the other thing I’d say is I think any liberalization, if it occurs and again, our hope and what we’re training for is that it doesn’t occur. But if it occurs, it should also be self limiting. If you’re a patient who liberalizes and then has an event, you’re probably not going to do that again. So we really don’t anticipate that a patient would consistently liberalize and just drive themselves into events unnecessarily.

Unidentified speaker: What are you thinking in terms of pricing analogs and benchmarks that we’ve seen from some of the recent endocrine, rare disease products, quite high pricing?

Unidentified speaker: Yeah, I think, you know, of course, you know, we have yet to price the drug. But exactly to your point, I think we’re entering into, quite an era for rare endocrine drugs. And I think that gives us nice benchmarks to look at. So, you know, I won’t name names, probably many of the folks here know these stories well. But I think what we’ve seen recently is that for rare endocrine drugs, these are premium, orphan priced drugs, and they’re getting pretty good coverage.

And I think it speaks to, one, I think the unmet need. And I might argue that I think with PVH, it’s probably a particularly significant unmet need even compared to some of these other, rare endocrine disorders. I think the mechanisms make a lot of sense. I think often in endocrine you’re replacing something or you have a pretty good handle on the mechanism. In this case we think this is really driven by excess GLP-one.

And I think going back to our prior experience, with our first launch, you know, I think we have a team that brings that payer experience as well. And, with our first product we were able to get over 90 covered lives very quickly in our launch. So that’s what we would intend to do here as well. So long way of saying, I think we’re definitely in this sort of orphan, premium pricing sort of ballpark. And I think we have nice analogs to look at that have gotten very good coverage in that area as well.

Unidentified speaker: Now is this a market that you feel like you can tackle entirely on your own commercially, including not just trying to find the diagnosed patients but go out there and find the undiagnosed patients? And then beyond The U. S, is there an unmet need out there as well? And if so, is it within your commercial grasp? Or would that be an area for a partnership?

Josh: Yes. I’d say we always look at options, consider different options and everything like that. I do think we have the capabilities, though. We did launch in ALS and certainly have taken learnings from that launch. During our first full year of that launch, we did about $400,000,000 in kind of first full year sales.

So we do think we have quite a capability to launch. And I’d also say that we do view this as an orphan market. As I was referencing to, we’ve spoken to a number of endocrinologists who have over 100 patients under their care. I think, pretty logically, those are going to be some of the most important ones to educate on the product and otherwise, again, pending good data and approval. Yes, there is probably true in any market.

There is a tale of patients that maybe are seen in slightly less dense and slightly lower volume, but you can utilize other tactics potentially versus sending a literal sales rep out to them. There are other tactics, such as digital or so called non personal promotion tactics there as well. So I think, overall, we view it as an orphan launch with kind of the size and scope of investment and otherwise that you might expect for an orphan indication.

Unidentified speaker: And I think to your point, too, on international. One, yes, bariatric surgeries are used globally. There’s actually quite international registry looking at bariatric surgeries. We’ve gotten compassionate use requests from all over the world from both doctors and people with PBH alike, highlighting the unmet need there exists globally. And then as I, you know, was talking about other surgeries, you know, gastric cancer, esophageal cancer, these are some of the leading causes of death globally, particularly in major countries in Asia.

So very high unmet need of these surgery induced hypoglycemia conditions as well. So I think we feel like in The United States we have a heck of a lot to do right now. There’s even more to build into, as you were mentioning, and then globally as well. So we think it’s a really nice opportunity that we have quite a lot on our hands already, but then we can continue to build over time.

Unidentified speaker: Lots left to do maybe in the last seconds here, just a quick overview of what we should expect over the next twelve to eighteen months.

Josh: Sure. So I think Avexatide is probably where most people are quite focused. We expect to complete recruitment by the end of the year for vexatide with data in the 2026. And in terms of our pipeline programs, we’ll have an we’re working towards an update on our Wolfram program, which will be talking about the Phase III plans based on regulatory interactions. We expect that this year.

We also should have data from our AMX-one hundred fourteen program in ALS by the end of the year as well. But as probably we discussed today, I think most of the focus is on Avexatod.

Unidentified speaker: All right. And just getting started on that program, too. Thanks, everyone, Justin and Josh. Thank you. Great to see you again.

Thanks so much, Jeff.

Josh: Thank you so much.

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