Conference Transcript - AMLX 2026-09-15

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Perfect. So, welcome, everybody. I'm Kaylin McGurk. I'm a member of the investment banking team at Morgan Stanley. It is my pleasure, my absolute pleasure, to welcome Josh Cohen and Justin Klee, co-founders of Amalex, to the stage today. Just a very brief disclaimer before we get started. You've been to many of these before. Please visit the Morgan Stanley Research Disclosure website www.morganstanney.com forward slash research disclosures for important information about this and other presentations. So without further ado, fantastic to have you at our conference. It's been a highly eventful and highly successful summer at Amaleks with the amazing data you had on Avexatide in PBH over August. Let's start there because obviously it's the burning question. Let's talk a little bit about the data, you know, firstly in terms of the headline results, what you saw, what you were expecting, and then obviously a lot of follow-up questions on this topic.

Joshua Cohen, CEO

Sure, yeah, so first I'd say we had high expectations given all of the prior trials of the vexatide, but I'd say this exceeded our expectations. The data, just to kind of highlight our pre-specified primary outcome, which was the rate of level 2 and level 3 hypoglycemia in people living with PBH. These are events that are extremely debilitating. Any one of these events is considered a medical emergency. We saw a 55% reduction with the active versus placebo with a p-value of 0.00003. We hit all of our secondary outcomes also with high statistical significance, similar effect sizes as well. And I'll note what's nice about the secondaries too, those include looking at level two individually by finger stick or by CGM, both of which were met, as well as looking at level three hypoglycemia, which is a clinical event. That's when basically people have become so hypoglycemic that they're incapacitated, you know, basically warranting rescue from another person. Safety profile was also consistent with prior studies with a very favorable safety profile. So overall, we were thrilled and I think maybe most so, we've gotten to know a number of physicians that treat PBH, patients living with PBH over the last years. And for many people with PBH, this is a completely disabling condition. There was a survey recently where 90% of people with PBH interviewed described themselves as having a disability, you know, due to the condition. So it's just been incredibly gratifying, incredibly exciting. It's really our mission as a company to be able to deliver therapies to diseases that have either nothing or completely inadequate options, and that's certainly the case in PBH. So, you know, coming off this, we're planning to submit our NDA by the end of the year and then, you know, already prepping to launch in 2027 if approved.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Maybe just a follow-up question. So this was a 78-patient study with a crossover design. You saw very impressive statistical significance on the primary endpoint. What does that, you know, tell you about the targets, the underlying biology in an era where everyone is trying to agonize GLP-1 and you're antagonizing? So how should we sort of see the result relative to the underlying biology in the disease?

Justin Klee, CEO

Well, I think that I'd start with the prior work that had been done in post-bariatric hypoglycemia. So post-bariatric hypoglycemia, PBH, doesn't occur in most people. It happens to about, we estimate about 8% of people who get bariatric surgery. In the years following, it takes years to... What appears to occur is that nutrient transit has been increased because, you know, a significant portion of the GI tract has been resected. In some individuals, this causes a very significant increase in their body's own production of GLP-1. So this is a condition that is driven by this excessive, exaggerated GLP-1 response. So people have 10 times, 15 times, sometimes 20 times normal levels of GLP-1 in response, often to nutrients, but it can be for other triggers as well. GLP-1 is a very strong potentiator of the insulin response. And so what occurs in people with PBH is that their GLP-1 has this inappropriate production and secretion, which causes this exaggerated insulin response, which causes, of course, blood sugar to drop significantly. In these cases, this sort of drop in low blood sugar is, by definition, a medical emergency because, of course, our bodies, particularly our brains, need glucose to function to do all of our sort of daily activities to fuel all of the cells in our bodies. So when your blood sugar gets to this very significant low, essentially, the brain starts shutting down its functioning. So that's why we see these essentially neurological complications. So people get severe dizziness, confusion, even loss of consciousness, seizures. So this biology had been known for a long time, actually going back to the 80s, some really elegant work showing that in response to various gastric surgeries, people could develop this very debilitating chronic condition. A group, particularly at Stanford, who reasoned that, well, then if we have an antagonist of the GLP-1 receptor, then we would block that GLP-1 response, and maybe that would then block the downstream hyperinsulinemic hypoglycemia. That is what they saw in five consistent studies. The lucidity trial, which we just read out, was the longest, largest duration study that had been run to date. in a real-world setting, when people are at home, you know, their dietary guidance and the sorts of things to control their PBH, if you inhibit this GLP-1 response, these hypoglycemic events from occurring. And that's indeed what we saw with the clinical data. So I think this is really exciting because, to your point, not only are the results very promising for PBH, but we really feel like we're getting at the heart of what's causing this very debilitating condition. and I think that's why we've seen such strong results of the vexatide now consistently through six studies.

Joshua Cohen, CEO

Yeah, very minor correction too also, parallel group studies as well. Parallel group, sorry, yes, correct.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Maybe we should just think about, you know, patients have this condition chronically. How should we be thinking about the durability of the benefit beyond 16 weeks and sort of any thoughts on that?

Joshua Cohen, CEO

Yeah, one with the vexatide, we start seeing a benefit at a single dose. You know, in our prior studies, there were studies where people basically took a single dose of ivexatide, had a meal test, and you could see a significant difference from placebo with just the single dose. As we've looked out further, that benefit seems to be persistent. We don't see any difference over the 16 weeks. And we wouldn't really expect to. You know, this pathway doesn't really have any, you know, it doesn't kind of have any feedback loop that would sort of prevent that. So we would expect kind of persistent effect. PBH itself is also a chronic disease. Once you have PBH, you have it for life. Once you have the surgery, the surgery doesn't go away. You have it for life. So we do expect that to continue deriving the benefit that this would be a kind of chronic treatment, chronic therapy.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

And just one last question around the other observations. obviously in this population that have been through bariatric surgery, the concern around weight regain with GLP-1 antagonism. You did, Justin, talk about the GLP-1 levels being supra-physiological, but just comment on what you saw in the study.

Justin Klee, CEO

Yeah, I think that was encouraging as well. Given that this is the longest study duration, would we see the GLP-1 antagonist? And the answer is no. There was no avexatide-related weight gain. There was no avexatide-related medical hyperglycemia. You know, the safety tolerability was consistent with the prior studies, even over this longer time period. So we're very pleased with that. But I'd say it was not surprising to us. We are trying to bring back the GLP-1 response to a more physiologic level. These are people who have very exaggerated. We're trying to dampen that response. It appears like that's what we're able to do with the vaccine side for people with DBH.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Obviously, from the disclosure so far, we've seen, obviously, the hit in terms of, you know, clearly, clearly meeting the primary endpoint, the consistency. What can you tell the audience, if anything, at this point around publication and presentation of the full data set?

Joshua Cohen, CEO

So, one, I think we tried to share, you know, all of the relevant, you know, data, met the pre-specified primary, high statistical significance, met all of the secondaries, good safety profile. We will be looking to publish this in kind of high-profile format, also to present it, hopefully in high-profile format as well. I think that's very important. One of the most important audiences here will be those physicians who are looking to learn more about Ovexotide and understand it better, and so we do think it's important to publish data in that way. But, again, I think we've shared kind of the key data, so I don't think there's going to be anything, you know, new really there, just more details around the edges.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Thank you, Josh. I wanted to come back to the point you made around the sort of the impact on patients. And you had Dr. Marilyn Tan, your PI for the lucidity study, on the call, and she had made some sort of interesting observations, one of them being that even presenting a single severe hypoglycemic event in her mind was clinically meaningful. Clearly, your results suggest you've achieved far more than that. But, I don't know, just Justin, if you want to just dwell a little bit more on that in terms of the feedback that you've had from physicians, patients, what impacts them the most, and as they look at potentially embarking on treatment with a vexatide once approved, what aspects of the profile are going to be most compelling from your standpoint?

Justin Klee, CEO

Sure. Happy to. And, yeah, Josh, please add in as well. So going back to your question on sort of what were the expectations for the study, what we heard very consistently from adult endocrinologists is that right now, Now, PBH is among the most severe conditions they see in their practice. They have no treatments for people right now. The mainstay is medical nutrition therapy. And even with medical nutrition therapy, people continue to have these events. And these are potentially traumatic for people to go to the hospital because of one of these hypoglycemic events. If you look at the American Diabetes Association and other endocrinology resources, they say very clearly severe hypoglycemia is a medical emergency. and it's because as I mentioned you get neurological complications when you're not keeping up your blood glucose to these levels so I think that's why we heard such consistent feedback that in the phase 3 study any reduction, even preventing a single event as you were mentioning, would be clinically meaningful and so we kind of interpreted that to mean statistical significance is really the bar for success I'll say when we share the results with our steering committee they were over the moon. I think that this was statistically significant. But also, I think it was the totality of the results. It was all of the secondary outcomes, highly significant results as well. So it was kind of like, whichever which way you looked at it, you get a very clear picture that this is truly impacting PBH. And again, in the backdrop of currently there are no FDA-approved treatments for PBH. So I think just the feedback we've heard so far is people are very, very excited. And it's, you know, part of the reason we're so excited to both get the results out but then submit our NDA.

Joshua Cohen, CEO

Yeah, and I wouldn't add too much to that, but maybe I'd just share maybe a couple of the stories, you know, or the types of stories we hear from physicians that really probably define sort of why Marilyn or Dr. Tan is sort of sharing that as well. We've heard stories about people, you know, getting into car accidents. We've heard stories of people falling down the stairs, you know, having fractures, you know, you know, going to the hospital, potentially even broken hips, things like that. Most extreme story I've heard as well is somebody dying in their sleep from hypoglycemia. So I think these are the reasons why the physicians say, I want to prevent as many of these as they possibly can, because they've all seen how bad it can get if hypoglycemia gets deep enough. And so they really want to do what they can to try to prevent that.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Perfect. Maybe just coming back to, you know, the population and the market opportunity for Avexatide following the filing and launch. I think you've said in the U.S. there's approximately 160,000 patients, which is actually pretty sizable. you know how have you defined that patient population are these patients easy to find you know the sort of obvious questions when you're the first in an area around you know patient identification and you know building a new franchise yeah maybe happen to start if you want to add so I'd start with there are great literature to start in this disease there have been large prospective studies following the outcomes of people who have had bariatric surgery And it's really from those that we derive this approximately 8% who continue to have, you know, unacceptable chronic symptoms following bariatric surgery.

Joshua Cohen, CEO

We followed up that work with claims-based analysis. So we've looked in the claims to try to find those patients who have had bariatric surgery, who go on to have hypoglycemic events that can't be explained by any other cause. And we similarly get to the approximately 160,000 that the literature would support as well. subsequent to that as well we've done kind of both survey based work and now work with our MSL team in the field as well to talk to the sites individually and for example survey them and ask about their patient populations who do you see, what is the nature of these patients what are their symptoms, etc and that's been quite consistent with the claims data as well, for example if our claims data predicts that a site has 73 patients, our survey results will often come back very concordant with that that they, you know, have that number of patients as well, which I think all comes to using kind of the claims-based analysis, which, you know, is down to the level of individual sites, individual doctors. It does allow us to, you know, be very strategic in our kind of deployment model to know, you know, which are the most important sites to talk to, how should we sort of divide this market. But I'll say, you know, anecdotally, even maybe to describe endo earlier this year, we're at a disease state education booth. it was full the whole time, really overfilling the whole time with endocrinologists who were coming to ask about ivexatide. It really is not hard to find physicians with sizable numbers of these patients that they would be quite interested in treating if there was a therapy available.

Justin Klee, CEO

Yeah, and I would say, too, that we've tried to encourage people to do their own doctor calls, and I think that's what first encouraged us so much. It did not take long to find adult endocrinologists who have quite a few patients under their care and pretty consistently said, you know, these are some of the most fragile patients I have under my care. And I think doctors feel a bit helpless right now that they don't have better options for their patients. And so that's just been very, very consistent for us. And so I think, and again, in any rare disease, triangulating exactly how large is the population and how many people are diagnosed and who are they cared for is a bit art and a bit science. I'd say in this case, every single piece of art research, and even research that wasn't done by us, for example, by the team at Stanford, has come back to this about 160,000 current population of people with CVH. The percentage of the bariatric surgery annual numbers will only continue to grow over time. Now, at what growth rate? We, of course, don't know yet, but even 160,000 is foundation.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Justin, maybe just on that, in light of, obviously, newer, higher efficacy weight loss options, the propensity or the sort of funnel in terms of bariatric surgery going forward, What have you seen in recent years, and is that slowing down in any meaningful way, or what are your views there?

Justin Klee, CEO

Yeah, I think, you know, first I'd say in terms of the overall population, because I think sometimes the math can get a little confusing. So we're starting from a current population of about 160,000. We work with people who have had PBH for 15-plus years, 20 years. It appears that, sadly, once someone has PBH, it doesn't go away. So I think the question is then, what's the growth rate of the population over time? And is that 15,000 new people per year? Is it 12,000? Is it 17,000? Of course, we don't totally know, but it's some percentage of the bariatric surgery volume. We've talked to many clinics, weight management clinics, bariatric surgeons, and I'd say generally they're not having trouble filling their OR time. And, you know, I think what we've seen in terms of the dynamic is I think early on there's this sense of, oh, well, now we have these weight loss drugs and maybe there won't be a need for bariatric surgery anymore. I think what we've seen now happen is actually because weight management is more in the public discourse that more people are having conversations about bariatric surgery. And they're very different populations. Bariatric surgery is often for someone who might have a BMI 40 or greater. so that's somebody who may need to lose 100 pounds, 150 pounds. They're not going to achieve that with the current weight loss drugs. That's very different than if somebody needs to lose 20, 30, 40 pounds. And so they're very different parts of the population. If we just look at the U.S. population as a BMI 40 or greater, that's about 30 million people, substantial group still. And even at this last year's endo, I really pressed many of the endocrinologists I met with, Do you see a use for bariatric surgery still? And to a physician, they said, absolutely. They said, if somebody has severe obesity, I'm thinking about bariatric surgery. If somebody has diabetes, I'm thinking about bariatric surgery because they're very, very good diabetes remission rates. If somebody just doesn't want to take something chronically, I'm thinking about bariatric surgery. So I think the physicians absolutely still see it as a mainstay of weight management. And, of course, this is a rare side effect. Hopefully now, though, as we do our work and look for hopeful approval next year, they'll have an answer to this rare side effect.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Coming back onto the, Justin, the approval, the filing timeline, I think you've stated your intention to fill the NDA by the end of this year, which is pretty fast. what sort of would you need to chop between now and then what is important that you need to do in order to get that filing that submission in on time

Justin Klee, CEO

well I give our team a ton of credit they've been working hard on the NDA all year we had high confidence going into the lucidity trial based on the first five trials of Vexitide and so we thought hey this is an unmet need we need to be ready and the team did just that

Justin Klee, CEO

So I just give them tremendous credit. So the last wood to chop, as you were saying, is everything around the CSR and the associated work around the phase three trial. But that's why we've set quite a tight timeline for the NDA submission is because our team has really done such great preparatory work, and now the bulk of what's left is around the phase three. So sort of walking through the timelines a bit more, So the goal is to submit by year-end with Avexatide, and so with the potential launch alongside our NDA preparation work, we are also doing all of our launch preparation work as well.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

On the commercial side, as you ramp up there, what are the most important elements to have in place? What do you have now? What do you need to build between now and the launch?

Joshua Cohen, CEO

Yeah, we had already started building ahead of the data. Really, our focus ahead of the data was getting all kind of the leadership elements in place, beginning to make kind of the key decisions we would have to make or at least getting the work started, whether that's in channel or, you know, or otherwise. You know, I'd say I think with any launch, it comes down to, you know, working very hard to have, you know, the right and kind of most important messages for the physicians and the community and making sure they're able to get those messages and get them in, you know, the appropriate fashion, as well as making sure that they can access the drug and that that's as frictionless a process as it possibly can be. So I'd say we're, you know, continuing to hire that team, continuing to kind of build out towards that, you know, making decisions such as, you know, what is our channel strategy going to look like? What are our patient services, you know, going to look like? But, you know, I think kind of a reflection from, you know, past launches or past launches as well is really, you know, it comes down to great people and great teamwork. And I think that's, you know, with a great leader in Dan as well, I think that's, you know, one of the main things we're focused on as we're, you know, getting towards launching again.

Justin Klee, CEO

And I'll say something that we did in advance is we built out, started to build out our field medical team. And so for a number of months now, we've had a really great team out in the field who has the experience and have been meeting with physicians in different offices to understand their. And I think now with these very strong Phase III results, again, working toward presentation, publication of those results, we're very pleased to have that team out in the field because, again, there's a really high unmet need here. I think the best way to do that is, of course, to have people out in the field. But I'd say we'll continue the build both in terms of people as well as all of the associated operations over the course of this year and next.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

I could easily spend the last 10 minutes or so talking about lucidity and obviously the opportunity in PBH, but maybe whilst we have you, obviously and rightly so, there's a huge opportunity just in front of you, which is around PBH. As you think about the biology of the vexatide, the mechanism where receptor antagonism may be appropriate and attractive? How are you thinking about other indications? What's the most interesting or compelling for you?

Justin Klee, CEO

I think there are a number. So I'd start with as one surgeon put it to us, the body doesn't know that the gut is resected for weight loss or for cancer or for whatever indication. It's just that the nutrient transit has now been increased. What that means is that there are any number of upper gastric surgeries that can cause the same condition. Commonly used ones include, there are a number of other reasons people get gastric surgery as well. Each of these has the potential to cause the same condition. So we think that that's certainly something that we're very excited about. We have data from a prior study or a couple investigator studies as well of ibexatide in those other surgery-induced type of glycemias. So it's something we're very eager for. I think that's particularly important when we look at most major countries in Asia, including Japan and others, very high rates of gastric cancer, one of the leading causes of death. And so in reaction to that countries have had very, very strong ME initiatives. In fact, probably foremost in Japan, they have nationwide screening to prevent people from having gastric cancer. And Japan alone does on the order of about 100,000 gastrectomies each year. People with those surgeries end up with this condition at, if anything, higher rates than what we see with bariatric surgery. So very significant unmet need there, and I think one nice thing about Japan, particularly as a country as well, is a great regulatory agency from products and, of course, a single country, single language as well. So I think that's of high interest to us. We get compassionate use requests, though, from all over the world, order of magnitude prevalence of PBHs there is in the U.S., in South America, Middle East. So I think there's a lot more to do and many, many more people to help. There are other causes of hyperinsulinemic hypoglycemia. For example, there are genetic causes, congenital hyperinsulinism. Avexatide actually has a separate breakthrough status for congenital hyperinsulinism based on three very strong trials supporting that indication. And then we have a long-acting program in IND-enabling studies right now. A vexatide is a once-daily subcutaneous injection that PBH people with PBH are very used to, for example, pricking their fingers multiple times a day and have expressed generally no concerns with a daily injection. However, if we could get to a long-acting, our goal is to have our IND next year in 2020 Mix 318. So I'd say with this whole opportunity around a GLP-1 receptor antagonist, we see so much to do. Obviously, first and foremost, we have to focus on our NDA and our launch preparations in the U.S., but there's really a lot more to do here. We think the biology is so exciting. We see a long road ahead here.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

We have just under five minutes. Maybe in the last couple of minutes, I don't know if you call it 114 or 01. Yeah, that's what I gathered. Maybe just talk a little bit about that program, obviously a different indication and sort of what we should expect over the next 12 to 18 months.

Joshua Cohen, CEO

Sure. So AMX-114 is an ASO targeting Calpain-2. So Calpain-2 is a protease that's involved in basically breaking down the cytoskeleton when a nerve's axon degenerates and dies. It's been shown to be associated and activated in multiple neurodegenerative diseases. There's genetic data linking it to ALS, and we've seen preclinically, as well as other groups have seen preclinically, really for decades, of evidence of this being a very important protein in the axonal degeneration process. I deal with an ASO. There are multiple calpains, and we wanted to sort of exquisitely target just calpain 2, and we wanted to be targeted in the CNS as much as possible. That's nice about an ASO that you can target that particular genetic sequence, and with intrathecal dosing, you can, you know, primarily target, you know, the nervous system, so to speak. So trial ongoing, a multiple ascending dose placebo-controlled study in people living with ALS. Because it's a protease, there are known things that Calpain-2 cleaves, some of which can be measured in the CSF. So we'll be measuring those and tracking biomarkers, both to look at biologic target engagement, but there are also some biomarkers such as neurofilament light we will look at for kind of disease engagement as well. So we're, you know, quite excited about that program, and we should have more biomarker data, you know, in the coming months and quarters.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

And you've been busy, so you struck a second collaboration with Gubra out of Denmark. I will be hosting their fireside at around the same time tomorrow for anyone in the audience. What attracted you to the company, the partnership? You've obviously worked together before. You know, what are you looking to do?

Justin Klee, CEO

Yeah, we were so pleased with our first collaboration, and so that's why we started a second around another rare endocrine target, as you mentioned. So, you know, we acquired Avexatide in July of 2024, and we're looking at, you know, the peptide space generally, and I think there's been just tremendous advancements and the logical understanding of how do you develop peptides and including how do you develop long-acting peptides. And so we did what we tend to do with as many people as possible. And I'll say several people, including some of the academic leaders, said Gubra is the company you want to talk to. So we met with Gubra, I'll say in particular their scientific founder, and we were just so impressed by the depth and breadth of Naha that they have peptide drug development, their experience on multiple programs translating from preclinic to clinic. And I also think we just had a really nice, I'll say, collaboration from the start, both in terms of expertise. I think we brought different expertise to the table, which is always a great place to start, as well as just sort of cultural values. I think we and they have a genuine curiosity about the science and also an interest in trying to develop meaningful treatments for people. So just a great collaboration from the start. So at the end of December in 2024, so, you know, just six months or so after we acquired of Exotide, we started our collaboration with Guubra to develop the long-acting GLP-1 receptor antagonist. We were so pleased with the collaboration. You know, in just about a year's time, we came up with molecules that met our, you know, very strict. And so we're looking for opportunities to partner again and to leverage their great experience with peptide drug development and our own with rare endocrine clinical and now soon-to-be commercial development as well. So we, you know, identified a target and started the, you know, we're starting the collaboration now. So we're very, very excited. And I think that's how we generally want to view it. I certainly think we have great ideas. We have exciting things in our pipeline. but we're always looking for other people or groups who can bring complementary expertise. So this is another nice such example. And again, with the goal of delivering treatments that are for really areas of high...

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Thank you. We actually are bang on time. So I did have one more, but I think you actually addressed it in the last response, Jasmine. Again, congratulations to all of you, the broader company as well. Super exciting time. I'm great to have you here, and obviously thank you, everybody, for attending today.

Justin Klee, CEO

Thanks so much for having us.

Kaylin McGurk, Analyst — Morgan Stanley Investment Banking

Thank you so much.