Conference Transcript - AMLX 2026-05-13

Jason Gerberry, Analyst — Bank of America

All right, everybody, we're going to get going here with our next company presenter at the B of A Annual Healthcare Conference. My name is Jason Gerber, I cover pharma and biotech, and I'm pleased to be introducing Amlex Pharmaceutical and Joshua Cohen, co-chief executive officer. And this is an interesting time for Amlex on the cusp of pivotal phase three data expected in the third quarter, a transformational event. So I imagine a lot of our discussion is going to be focused on the lead program for PBH. So, Josh, thanks for joining us.

Joshua Cohen, CEO

Yeah, thank you so much for having us.

Jason Gerberry, Analyst — Bank of America

So, you know, fresh off of 3Q and, you know, I guess ahead of the pivotal lucidity trial, maybe you can just talk a little bit about the trial design, some of the questions that it's designed to answer, and if successful, how this could be an advancement for patients with PBH, you know, this sort of frame, and then we'll go from there.

Joshua Cohen, CEO

Sure. So we're very excited about the phase three readout expected next quarter. Avexatide, our lead asset, has been through five prior trials, all of which showed highly statistically significant effects on glucose and insulin. And then in the phase two and phase two B, we studied the rate of level two and level three hypoglycemia, which showed quite a strong effect as well. So under that backdrop for the phase three, our goal was to try to keep as much consistent as we possibly could. So very similar inclusion-exclusion criteria, looking at the endpoints in the same way. You try to replicate that success we saw previously. To your point about meaningfulness as well, this is a patient population that's completely underserved. You know, there are no approved therapies for PBH. The disease, you know, consists of having these frequent, recurrent, dramatic blood sugar drops, sometimes following a meal, but sometimes more out of the blue, you know, maybe after exercise or stress or otherwise. And when these occur, people can become very dizzy, they can lose consciousness. And most patients end up describing themselves as disabled, because, you know, they can't, they can't drive, they may want somebody with them at all times, in case they lose consciousness or otherwise. So, you know, to have potentially the first and only therapy that can impact that disease would be, you know, transformational for these patients. Okay.

Jason Gerberry, Analyst — Bank of America

And I think you framed on your recent earnings call that, you know, a stat sig result would be a win on the primary endpoint. What does that mean relative to treatment options like acarbose that are used by doctors when you talk to them and they cite this as something that they're giving patients? Is there any ability to kind of tease out what sort of benefit patients get from existing modalities, even if they're not FDA approved?

Joshua Cohen, CEO

Yeah, so there have been some small trials of acarbose. And I'd say what happens in PBH is sort of what happens in a number of rare diseases where there's no available options. People try what they can, even if it's not particularly effective. So acarbose is an alpha glycoside inhibitor. It basically makes it harder for your body to break down complex carbs. That doesn't really treat the underlying disease. People continue to have events. And the other thing is when you cannot break down complex carbs, they end up getting broken down by the bacteria very late in your gut so you get severe gas and kind of gastrointestinal side effects not uncommon that people have trouble being on acarbose for more than a couple weeks um but so you know we don't see you know as we've talked to kols and otherwise we really don't see much eagerness excitement it's sort of what they have but you know doesn't really prevent the events and very hard drug um to take this would really be the first drug targeting what we see as the underlying mechanism. In PBH, people have faster nutrient transit, which leads to a dramatically increased GLP-1 response. So after meals, patients with PBH may see 10 times normal, sometimes 20 or 30 times normal GLP-1 responses. So with the vexatide, we have a GLP-1 antagonist. We're going at what we believe is kind of the core of the condition, which is unique. There's nothing else like that.

Jason Gerberry, Analyst — Bank of America

Yeah. So to maybe summarize, it sounds like, hey, we're the first with the positive RCT with the drug where mechanistically there's a lot of sensible rationale in the eyes of HCPs, and that's going to be enough for physicians to want to use this in most of their patients. Is that a fair summary?

Joshua Cohen, CEO

I think it is. And maybe I just add, just characterizing the burden that these patients go through, they're having frequent severe hypoglycemic events. The ADA defines a single level two or level three hypoglycemic event as a medical emergency. And it's true. I mean, we've spoken to endocrinologists who have described patients passing away in their sleep due to severe hypoglycemia. Patients can have falls, car accidents, you know, all manner of things and it also is just dramatic and scary when you suddenly lose consciousness um you may need somebody to rescue you wake up you don't quite know where you are um these are really really severe things for patients and there's nothing available today that's been proven to do you know anything um to these hypoglycemic events so to potentially have a therapeutic that could impact that you know as we've done market research you know the intent to treat does seem high they're really looking for an option for their patients okay can you talk a little bit about phase two to phase three imagine try to keep as many things consistent as possible but what are some of the maybe the the risks of a phase two to phase three effect size compression is it more heterogeneous population which is oftentimes the case in a lot of studies is it the slightly longer end point what are some of the key variables from phase two to phase three translatability yeah i mean maybe highlighting your first point um we are trying to keep as much consistent as we possibly can probably the key inclusion criteria in these studies is the event rate of people come in people coming into the study so we do have a run-in period during the phase two and phase two b people are required to have at least two severe hypoglycemic events in two weeks in the phase three requiring at least three severe hypoglycemic events in three in three weeks so it's an event a week to get into the study you have to be having at least an event a week so we kept that consistent in terms of the elements that are different um the phase two and phase 2b were four weeks um the phase three is 16 weeks um we don't really expect that to change treatment effect or otherwise we haven't seen on the reverse side with the agonists a real attenuation you know over time so we don't think with the antagonist um you'll see an attenuation we don't see ada's um you know of any particular nature with this with this drug either so nothing that would really lead us to believe that the you know effect changes there and then in terms of sites and otherwise too um we've tried to keep the sites quite quite consistent so you know the phase two was five centers the phase uh 2b was was a single center trial the phase three you know includes just about all of those sites and it is a u.s only trial at kind of expert endocrinology centers and expert clinical trial centers so it's all um you know it's all groups that we think were kind of handpicked and you know um we believe can run a quality study okay um some of my correct me if my details are wrong i think lucidity 90 power to detect 35 effect size placebo response 50 percent is sort of the statistical assumptions here um i'd say that we are powered to that i'd say we don't necessarily we tried to be conservative in our statistical assumptions so i'd say we don't um we don't think there'll be a 50 placebo effect um patients with pbh are already doing everything they possibly can not to have these events so we don't think for example they enter a trial and they suddenly become much more successful at not having events um you know so i i'd say we don't anticipate too much in terms of placebo effect um and similarly with effect size we powered to see a 35 relative rate reduction but in phase two we saw 55 and in phase 2b is 64 so i'd say we were conservative in all the statistical assumptions in part because this is the first phase three yeah you know we've conducted with the compound and we believe we have an active compound so we want to make sure we have more than enough power to detect that effect okay yeah because i think the two things that come up most commonly uh with the amlic story is placebo

Jason Gerberry, Analyst — Bank of America

rate risk and market size so maybe if we just dig in a little bit more on placebo i i agree when we talk to physicians they'll tell us that they they wouldn't expect much placebo response in this population so echoing what you said uh i do wonder um you know what you learned from like the run-in period of the uh when you assess that how much can be gleaned from natural history with this population as you you think about that and uh some people talk about resolutes chi study and the placebo response there as a maybe an analog population where there was a higher than expected placebo response so how do you kind of what's the rebuttal on some of those points or or just how would you contextualize that yeah maybe at first underscore your first point from the kols

Joshua Cohen, CEO

this is really a condition where people do everything they possibly can not to have these events um if you think about it you know if if you know having one of these events meant that you're going to become unconscious is going to feel incredibly bad be incredibly confused you really try actively not to have them so patients are already really doing everything they possibly can we don't expect that that's going to change all that much when they enter a trial setting you know additionally there has been other trials in the space including a trial of dasa glucagon and pbh there wasn't a placebo effect observed there either so i'd say again And we were conservative in our powering. We have enough power even if there is a placebo effect. But I think we don't expect too much medically. You also mentioned Resolute and CHI. It may be marked that they're very different conditions. CHI is primarily a fasting hypoglycemia. So you're basically, people with CHI basically bleb out insulin somewhat constantly. So if they don't eat very frequently, their blood sugar will drop, particularly a problem nocturnally. their blood sugar can drop because of course you're not eating during the course of the night but you can prevent most of the hypoglycemia and chi if you just eat frequently and eat very slow burning carbs like cornstarch or otherwise that's very different than pbh pbh is a triggered hypoglycemia so it occurs you know following a meal it gets triggered and sometimes it's triggered out of the blue you know such as from exercise stress um or otherwise so there's not really You can't just eat and not have this hypoglycemia like you may be able to in CHI.

Jason Gerberry, Analyst — Bank of America

Yeah, okay. And if data are positive, what are the outstanding work streams, operational work streams, that are most critical just to enable a rapid NDA submission?

Joshua Cohen, CEO

Yeah, I mean, we have the benefit of having a very experienced team on this. You know, it won't be the first NDA that Amalix has submitted. so we took the action of trying to get as much done as we possibly can ahead of the data so that it's really a process of sort of dropping in the data once the trial reads out compared to starting the NDA after the trial reads out everything's kind of proceeding and lockstep with that too so there's not like a big you know CMC or otherwise thing that we have to wait on you know after the trial reads out, to be able to submit. It is still a big document. NDAs are not infrequently hundreds of thousands or even millions of pages. So it's a big document, and you want to do it right, but our intention will be to submit as fast as possible following data to enable a 2027 launch. And we do have breakthrough therapy designations, so we'd expect the kind of two-month filing period and the six-month priority review that you get with a breakthrough. Yeah.

Jason Gerberry, Analyst — Bank of America

Can you speak to regulatory interactions that you've had so far? You're dealing with the endocrinology division, right? And some investors do flag that division as specifically maybe some more unexpected review outcomes of late. So I don't know, is there anything that you can say to the division and your regulatory interactions?

Joshua Cohen, CEO

So the division we're in is actually sort of a subdivision. It's DDLO that we interact with. Our interactions have been pretty business as usual. And I'd say, you know, one, we have breakthrough therapy, which I think helps in any FDA interactions. And I think we're also just very down the fairway. You know, whereas, you know, I think some of the cases where there have been maybe more contention with FDA have been open-label trials or external controls or novel endpoints. Here, we have a placebo-controlled study with a very well-established endpoint. You know, hypoglycemia, something that's been known for quite some time. And we did have, we did submit our protocol and it was reviewed, you know, prior to initiating our study. So we do believe we're running the study in a way that, you know, could support registration.

Jason Gerberry, Analyst — Bank of America

Maybe let's talk about commercial and market size here. There's not a lot of great predicates out there, right? Can you look to things like ACARBO's utilization or anything in claims data to substantiate? I think you talk about a U.S. 160,000 for epi and then some segmentation factors to that. But anything that we can anchor to to get a little higher degree of comfort around who's in the treatment system, who will be accessible? I mean, ultimately, I understand that this is kind of a market build.

Joshua Cohen, CEO

Yeah, sure. So maybe first starting, we do believe there are about 160,000 people in the U.S. today with PBH. That's based both on a lot of literature. There have been large prospective studies looking at cohorts of people who got bariatric surgery, following them over multiple years, and those cohorts do find about 8% of people in general with bariatric surgery going on to get PBH, and there's been over 2 million procedures in the last decade, which gets you to 160,000. In addition, we've done quite a lot of claims work, and recently we do expect that the IC ICD-10 code will become available for PBH October this year, but what we've done so far in absence of an official ICD-10 code is looked at those people who had bariatric surgery who went on to have claims for hypoglycemia that couldn't be explained otherwise, that couldn't be explained by diabetes or drugs they're taking or otherwise, and that similarly came out to about 160,000 as well we went to sort of further validate that claims work by doing kind of blinded market research with a number of sites we're unaided we ask them you know how many patients do you see with bbh and then we compared that to our claims data to say is our claims data accurately estimating you know what these sites actually have and that came back quite concordant so we do believe that we're successful in our claims data identifying the patients but there's one other element of your question yeah i mean just maybe surround segmentation like what proportion do you think are kind of at the bottom of the funnel and yeah i mean we're trying to target the 160 000 um you know certainly as with any rare disease launch our initial focus is going to be on those centers of highest expertise as well as the centers that are most you know densely serving the patient population but you know severe hypoglycemia is really really bad um you know one you have the kind of the acute complications of you know possibly losing consciousness seizures car crashes falls you also have long-term complications you look in the type 1 diabetes literature people who have regular hypoglycemia are at much increased risk for heart challenges for cognitive challenges etc so these are things that should be treated if they can be treated and so you know our goal is to for every eligible patient you know to try to get them on therapy if our drug is successful.

Jason Gerberry, Analyst — Bank of America

Yeah. Is there an aspect of this when you launch where, you know, could there be a leakage, a loss of patients in the funnel at the referral stage? I imagine not all these patients are in these higher volume centers, so to speak. And so there's going to be, you know, an education and then, you know, how do you envision that kind of playing out?

Joshua Cohen, CEO

Yeah, I think it goes to your point. There will be a build here as well. We think there's both, you know, a number of patients that are already under very active care who we think will be able to get on therapy quickly, but there will also be some time where we have to educate, continue building the index of suspicion. You know, not for all physicians right now, if somebody's had bariatric surgery and they lose consciousness, do they instantly go to, okay, this is probably a blood sugar problem or this very well might be a blood sugar problem. There's education we can do to kind of keep building this market and expand out from those more expert centers so i think it leads to a dynamic where we can keep growing this market year over year which i think is a nice you know a nice thing to be able to grow into and i'd add with that too um we also want to keep investing in this market um first and foremost we have a vexatide for pbh in the u.s you know that's that's what we want to launch in 2027 um but beyond that one there are a number of other surgical types that can cause hypoglycemia other surgeries that sort of alter the gut and speed nutrient transit for example people who get gastric cancer will sometimes have gastrectomy which can lead to a very similar set of symptoms as what you get in pbh people with esophageal cancer can get you know esophagectomy people with various gastric reflux disorders can get various surgeries so there are quite a lot of ways you can find yourself towards having hypoglycemia so we see that as as sort of an expansion opportunity as well as looking at xos geographies we're working on a long acting version so i'd say first and foremost we want to serve those you know the patients um with pbh in the u.s that we can get to immediately but we also see this as kind of a multi-year expansion beyond that okay is that education both on the patient side and the doctor side um i.e do

Jason Gerberry, Analyst — Bank of America

you feel like a lot of patients might be out there and they need to kind of um elevate what they're at risk of or dealing with or just not aware of what they're dealing with and need a physician interaction? How does that dynamic look to you?

Joshua Cohen, CEO

Yeah, I think it is education on both the patient and the physician side. On the patient side, right now, physicians really don't have much to offer their patients. So there are some patients who have maybe gone to the endocrinologist several times, sort of heard the same advice every time, and maybe less prone to go back to the endocrinologist at this point because they've you know they don't have something new to be told so there there may be some patients we sort of have to reactivate now that there's a um you know now that there may be a new treatment um available for them but there are also those patients who are very actively under care today um so you know i think i think we'll see both you know in the market okay so your expanded access protocol if i understand right is is larger than the lucidity enrollment.

Jason Gerberry, Analyst — Bank of America

What are the criteria to get into the EAP? And I just wonder, is this at all an indicator at all of the market overall, right, a faster enrollment?

Joshua Cohen, CEO

Yeah, I wouldn't say it's an indicator of the market. We do expanded access programs, mainly to provide, you know, free early access to drug, particularly in diseases that are very severe. You know, if we're able to, do we like to get drug to people sooner? Initially, we're enrolling people who have completed lucidity or who are in some of the past of Exotide trials. Those patients have, many of them have reached out to Amalix. They're very eager to get back on therapy. So that's kind of the initial cohort. And then we do envision kind of expanding beyond that as we get kind of up to the 250. But I think, you know, as expanded accesses go, I think it's actually a fairly large one. um you know there's only so large you want to go prior to launch as well okay uh so vexacide's daily subcut uh you talk about i don't know from any observations with with past trials that have been done how you think uh patients are going to adhere to a daily injection yeah um i think we well when we look at the past trials to start adherence was very good and the phase two and phase 2b we didn't have dropouts treatment compliance was was very strong and i think it starts from how severe this disease is patients are really looking for treatment in the 2 and 2b there were structured interviews of a number of the patients and you could hear in the interviews you know they described feeling a difference as well when you you know when you get severe hypoglycemia you feel terrible and and you know patients know that. And so when you have a treatment that potentially is reducing the rate of that or helping that, you know, you hope patients can feel that as well. See, this is also not a particularly needle phobic population, just to manage their disease, they're doing regular finger sticks for blood glucose. So when we've done market research and asked about, you know, what do you think about a daily sub cube, particularly with a super thin needle and all that, patients really don't describe that much anxiety or fear about that. So we don't think that's going to have a significant impact, you know, in this market.

Jason Gerberry, Analyst — Bank of America

So I'm going to preface by saying I'm not asking you what you're going to price the drug at because I know you won't answer that question. But do you at least know in your mind where you'll price it if you produce, you know, the data, that that could have an impact on pricing power here?

Joshua Cohen, CEO

So, you know, we do a lot of research as we kind of, you know, approach the pricing. And included in that research, we bring our data in front of sometimes retired payers, you know, sometimes different KOLs, patients, et cetera, to try to get kind of a multi-stakeholder view and to learn as much as we can. So, yeah, a little early on the price. What I will say has been encouraging for us is looking at various other launches in the rare endocrine space, some with, you know, healthy price points as well. We've seen generally good coverage. I think there's general recognition among payers and really among the medical community more broadly that hypoglycemia is a severe and can be a very bad thing, can even lead to death. um and so you know i think there's there's an appreciation i think that if you have a drug that impacts that that you know that's really bringing value what do you think one of these patients you know cost the system right uh in terms of these these attacks like how many hospitalizations or er visits are we talking about that could be money saved i'm just trying to think through the pharmacoeconomic arguments yeah i'd say um stay tuned you know we'll probably have more of that data as time goes on. Certainly, you know, our kind of HUR team is working hard on kind of getting more exact numbers. But I do believe these are high healthcare utilizers. You know, even as we've gone through our claims data, you see a much higher than normal hospitalization rate in these patients. You see a lot of complications. You see a lot of drug use, you know, to treat various, you know, comorbidities in this population. So I do think that this is a pharmacoeconomically you know expensive you know population as well okay um on the competitive front some some data from recordati i believe recently your your thoughts on that yeah so um you know probably don't comment too much on on competitors but i'll say um you know uh unfortunately trial from recordati did not see differences on level 2 or level 3 hypoglycemia um this is with passereotide which is you know approved drug has an approved label um so you know i think overall i think we see ourselves as very well positioned um breakthrough status phase three i think there's there's nothing else out there that has a profile like of exotide yep okay and you you framed cash runway uh into 2028 right so that's getting you through early launch so you it's fair to say you won't be resource constrained uh in in 2027 go to market yeah um so we tried to put ourselves in a very strong financial position we raised um last september um so as you said cash into 2028 um we also did not um include revenue in our cash modeling um just to be conservative so you know when you add revenue in and cash might even go longer than that um you know as well um so yeah I think we'll, well, in Q3, when we have our data, we'll be in a very strong financial position.

Jason Gerberry, Analyst — Bank of America

Yep. Okay. And, you know, what does the timeline look like for your follow-on once weekly? I don't want to call it once weekly of Exotide, but it's effectively the same API, just in different delivery technology?

Joshua Cohen, CEO

So it is a novel molecule. We did work with Gubra, who are excellent, to develop basically as optimized the long-acting GLP-1 antagonists as we possibly could. so basically goober's sort of secret sauce is they can screen quite a large number of peptides very quickly so they screened all manner of different um you know variants peptides to try to find ones with long acting a long acting profile but also good potency manufacturability lack of immunogenicity good in vitro and in vivo data um so you know we uh designed it to be at least um once weekly if not better um we'll know the profile more accurately once we're in clinic you know we don't want to promise the exact pk curve in humans and until we have a pk curve in humans um but right now we're going through ind enabling studies um we'll expect to submit an ind in 2027 um and you know i do believe um this disease sort of lends itself to rapid development as well um we haven't outlined the exact um you know clinical studies we might do um but i think the main questions to answer will be optimal dose and then you know confirming that um that we're having the effect that we want in you know in a larger group okay maybe we'll just uh a few on the earlier stage pipeline the phase two wolfram syndrome program what in the phase two is sort of the the bar for advancing into phase three from your perspective what are you what are you focusing in on here yeah so um we've um presented a week 48 data from the phase two we'll be presenting week 96 data this is for amx 35 in wolfram syndrome wolfram syndrome is a monogenic disease of a protein called wolframin coded for the gene wfs1 um it's a um autosomal recessive disease so it's you know basically complete loss of function of this wolframin gene and it's considered a prototypical disease of error stress which amx 35 is thought to address um in our trial thus far up to 48 weeks we've generally seen stabilization or improvement across the outcomes we've measured so we've been quite excited and wolfram syndrome is a disease where people pass away on average in their early 30s it starts by looking like juvenile diabetes but it becomes clear it's not just juvenile diabetes when people start getting vision loss hearing loss eventually kind of walking difficulties speech and swallowing difficulties breathing difficulties these are what eventually lead to death for people with wolfram so our trial was really focused on the diabetic outcomes as well as the visual outcomes because those move a little quicker as well as kind of a global outcome of you know global impression of change both from the patient and the clinician all of those moved in the direction of stabilization or improvement in a disease where you'd expect them to progress that was for the one-year data that 48-week data you know we'll be excited to have the 96-week data I think we see that data as, you know, as good to kind of, you know, progress to the next study. What we're still working on, you know, with FDA is what exactly does a phase three look like in Wolfram syndrome. It is a disease that has multiple systems involved. So the exact primary endpoint and the exact design, you know, takes a little time to kind of work through.

Jason Gerberry, Analyst — Bank of America

Yeah.

Joshua Cohen, CEO

And does this asset, you know, if it developed through AMLEX, make sense to keep in-house? is this a partnership candidate yeah i'd say we always consider our options um but we don't see that this will be an overwhelmingly um you know we would it's a it's quite a rare disease you know about 3 000 people we estimate have wolfram in the u.s we don't estimate we're running a unduly larger long trial here um so we don't think that this will be much of a you know financial strain if you want to put it that way yeah yeah i guess it's do you see strategically you know some rare orphan-focused companies, there's a core competency in patient finding commercially in the organization, and does it fit from that perspective with an asset like

Jason Gerberry, Analyst — Bank of America

a vexatide and your ALS pipeline that you have as well?

Joshua Cohen, CEO

Yeah, I mean, I think it does. I mean, Wolfram has components of both an endocrine disease and components of a neurodegenerative disease, generally treated by pediatric endocrinologists who are often in a, you know, similar center as, you know, adult endocrinologists and otherwise, so I do think there's an overlap in competency. We look at similar outcomes as well on the kind of glycemic side for Wolfram. But overall, first and foremost, you know, our focus is on, you know, Avexatide. I think we see if we're successful with lucidity and hopefully a very strong launch that enables us to do more things. But from a kind of capital and human resources perspective, our main focus is make sure we keep our eyes on the prize with Avexatide and, you know, try to get it as best as we possibly can.

Jason Gerberry, Analyst — Bank of America

All right, great. Well, we're out of time. So thank you for joining us at the conference.

Joshua Cohen, CEO

Thank you so much. Really appreciate you having us.

Jason Gerberry, Analyst — Bank of America

All right. Have a good one.