Guggenheim 3rd Annual Healthcare Innovation Conference - AMYLYX PHARMACEUTICALS INC

I'll just talk louder. Well, good morning, everybody, and thanks for joining us for today's another fireside discussion here at Guggenheim's Healthcare Innovations Conference. Really pleased to have the team from Amelix here with us today, co-CEOs Josh Cohen and Justin Klee. So that went sequentially to my left. But, you know, really thrilled. Amilex has actually been a really gratifying story for the Guggenheim team. We picked up coverage, I think, in June of last year before kind of an epic run of successes. So I'll turn it over to Josh and Justin, you know, to really give us a little bit of the lay of the land of where you see Amelix headed from here in the wake of the very positive Lucidity data. Sure. So, yes, we had a really exciting year. We had the phase three readout from Lucidity where we met our pre-specified primary endpoint with a p-value of 0.00003, which we were incredibly excited about. That measured the rate of level two and level three hypoglycemia. These are severe hypoglycemic events. Level three is basically when somebody is rendered so incapacitated that they need kind of third-party assistance. Level two is a level that's been picked by the ADA, where your brain is at a severe lack of sugar, and you start to have major problems. So we met that pre-specified primary endpoint. We also met all of the secondary endpoints with a kind of consistent and highly statistically significant result across those two, with a favorable safety profile as well. So with that in hand, we're now working towards our NDA submission by the end of the year, planning for a launch, if approved, in 2027. And I think just the more we've dug into the PBH market, the more excited we've gotten. About 90% of people who have PBH describe themselves as disabled. So when you have this condition, it really takes over your whole life. It's really hard to live with and manage. And I in line with that, both from physicians and patients, we hear an incredible excitement for the potential of a therapy. As we've continued to do claims-based work and dig into the market, we estimate there about 160,000 people living with PBH, and today there's no therapy for them. So we're very excited about this. We had a big year this year, but I hope we have an even bigger year next year. Yeah, and, you know, maybe before we drill, you Know, more deeply into kind of lucidity and what's coming next week at Obesity Week, which I'm sure you'll have limited ability to talk about specifics. But from a commercial perspective, Amalix has a history of having launched a product previously. That always is one of the big questions for any biotech. What are you doing from a Commercial Prep perspective to really land in this market effectively? Yeah, well, thanks. And I appreciate the nod to our prior launch. We're very proud of of the work we did there. But of course, there are always lessons learned, so we hope to do even better this time. That being said, each market is different, and so we're approaching this with the right level of diligence. I think first and foremost, it always starts with people. I think you really need the right leadership on down, especially as you're building a new market, as we are with PBH. Huge unmet need, but there's never been an FDA-approved treatment for people with PBh. And so this is new. there's a lot of education needed. I think on the people side, given the strength of the prior results going into Lucidity, we started to build that leadership team both on the medical affairs and commercial side. We have a really strong leadership in medical affairs and commercial in place. They've been doing great work. I think this past year we spent a lot of time really understanding the market, understanding the patient journey, going through multiple different claims analysis, analyses to recognize where people are, how are they treated, who's treating them, figuring out what, you know, future call points and those things will be, so really getting a sense of the landscape. I think right now there's a lot of focus on disease education. We have an ongoing campaign both for people with PBH as well as for healthcare professionals, And those efforts will continue to ramp up as we go into anticipated launch next year. I think overall the way we're approaching this is a rare disease, but of course it's a large rare disease. We estimate there are about 160,000 people in the United States. And so I think generally what we've seen so far is that the concentration in the market is similar to what you might see in other rare diseases, but the overall numbers are or just higher, given the size of the population. We're doing a lot of payer preparation work now. We're starting to work on our various campaigns that we'll have. So we're in full launch preparation mode. But I think it's going to be really important that while this is a high unmet need, there are well-educated centers, and we need to make sure we're partnering with them, there's also a market to build. And so I think we're really trying to make we get both of those aspects right. Perfect. So let's talk about lucidity and, you know, just kind of what you're excited to educate the market on next week in particular. We have the August top line results, but, you know what would you just sort of want investors and patients and, and physicians to really focus on, you know, kind of coming out of the meeting. Yeah, I think I touched on a little bit, but I think first just the meaningfulness of these outcomes. When you think of level two and level three hypoglycemia, these are severe, dramatic events for patients, and being able to reduce them is just a very, very big deal for this disease. I'd also add just the consistency of data, the consistency of data between this trial and the previous trials, as well as the consistency of the data within this trial. Not only did we hit our composite of level two and level three, but we hit level two, and level three individually. We also hit level two, whether you measured it by finger stick or by continuous glucose monitoring. So I think it's just, you know, the kind of strength of the data comes from the fact that no matter how you look at it, sort of no matter how you slice it, you see a strong and consistent benefit that also matches what we've seen in prior trials. I'd add too, I think, is we've had a few opportunities have ad boards show the data to different key opinion leaders the totality of the data I think has has been really important for physicians both from an efficacy perspective as Josh was talking about but the safety and tolerability as well the profile is very consistent with what we've seen in prior trials we did not see any evidence of weight gain or sort of things that people could be concerned about mechanistically we never thought that that that might be a concern. But again, nice to see the 16-week data to support that. So I really think it's that totality of data that physicians have found very encouraging because, again, there's never been an FDA-approved treatment for people with PBH before. And I think it is that totality data that has physicians very excited that they may finally have something to offer their patients. Great. And then just without obviously going into specifics, just what you observed in the placebo arm. I know there's still some confusion around that, but it seems like the primary emphasis is to kind of go back to the official phase two data and utilize that as a point of education. But how consistent would you say those data were as you went from four weeks to 16 weeks? That was probably one of the sort of uncertainties that we had heading into the phase three data. Yeah, I'd say data, as we've said, were quite consistent. It was really an incredible thing to see just how consistent the data has been, um, trial to trial. You know, obviously I can't give specific data from obesity week before obesity week, but I just mentioned as we've presented this data at advisory boards, as we've shared it with some of our, you know, clinician advisors, um. There's just great excitement. And, and really it's the type of data, the more we dig into it, just the more excited we get. Great. Um. You know we don't again no specifics but uh in terms of just this perception of level three events having more value to prevent than the level two event can you talk a little bit more about that and you know sort of uh the dynamics of or maybe the wrongness of that mentality yeah i i'd say when you talk to endocrinologists they're very familiar with level two hypoglycemic events They're very familiar with level 3 hypoglycemic events. And I think they're both telling you really important things about what's going on with the individual as well as, of course, the population. Level 2 is telling you what's happening in the blood. The level of hypoglycemia we're talking about with level 2, this is not your run-of-the-mill sort of low blood sugar. This is a medical emergency. This means that your brain is starved for glucose. The medical term is neuroglycopenia. Physicians are very, very worried about that. If someone in the hospital, for example, for any indication, has blood glucose less than 54 milligrams per deciliter, it's like all hands on deck. I mean, it is a big, big deal because people know the consequences that can occur with that level of hypoglycemia. So that is a really important measure. Level three, as Josh was indicating, means that the person cannot help themselves. They need independent rescue. So it means you've had the manifestation of that neuroglycopenia. You need help. So both are really important. And, again, I think the strength of the data set here is you can look at either. Avexetide clearly showed very strong reductions on both. And I think, again. That's why the physicians we've shared the data with are very excited. Because whichever way you look at it, it's telling you the same story. Got it. And, you know, experts like Marilyn Tan, who've been sort of leading the space from, you know, 2016 on, are outliers, I think, to some degree in terms of that level of expertise. But, you know, as you look at the awareness from endocrinologists, where does that sit today, and how do you sort of see obesity week as kind of a starting opportunity for building that awareness? Yeah, I'd say there's decent awareness among the endocrinology community. It's not uncommon you hear from endocrineologists, even the ones that are not the Maryland Tans of the world, that they see a number of these patients, that have a number these patients under their care. I think what they really struggle with, though, is in most endocrinal logical conditions, we have drugs, we have treatment pathways. We have ways to manage. This is a condition we really don't today. So you hear from a lot of physicians this sense of kind of helplessness, that I really, I have these patients, but I have sort of nothing for them. I really want to have a therapy for them, so I think you know we observed at Endo earlier this year just an incredible interest of people kind of coming to our booth, speaking with our team, wanting to learn more about Avexotide. I anticipate that continuing, you know, at Obesity Week as well. And I'd say for our team, it's also a great opportunity to do a bunch of one-on-ones, to meet with a bunch of the physicians, just to give them kind of more information, answer their questions, etc. But I think there's a tremendous excitement. There's really been nothing in this space, and I think the endocrinologists really recognize that they need something. I will say as well, we're also working right now with our disease state education campaign, Uncover the Mystery of PBH, and what we've seen there is also a lot of engagement directly with sort of the materials we're putting out to help educate people on how to recognize and observe PBH. We've actually even heard directly stories of people being diagnosed through the campaign, you know, as well. So I think there's good awareness. I think there could still be even better awareness, and that's what we're working to do. Great. Um, you know, in terms of the participation in the, uh, open label extension, you know, the strong roller is the strong rollover. Can you talk a little bit about that? Um, and you know how the expanded access program actually operates. I think there may be a little bit of confusion there that, you know, this is just an unlock and patients are just going to be piling right into it. Um, I may be guilty of thinking that way also, but, um, you Help us understand how the EAP is sort of structured. So probably a few things there. So first are the open label extensions. So greater than 90% of people completed the study, and then all the eligible people went into the open-label extension. Eligible meaning they made it into the study with compliance and then went intothe open-labels extension. So very, very good continuation. And I think that presents us further data presentation opportunities as well, which we're really excited about. On the expanded access program, particularly, I'd say, first, at a high level, FDA has made it very clear that these programs are about access. And so I think that's very much where we're focused as well. And there are different types of EAPs, but this is the type where you have something that's promising, has phase three data, looks like it's headed toward a near-term approval marketing authorization, and so this is to provide access. Now, the way that actually works is that you have a protocol and then different physician centers are sort of reach out to ask about, you know, they have, you know people they'd like to enroll in the expanded access program and sort of that starts the whole cascade. So it's unlike a clinical trial where it's very prescribed and you have these set number of centers and you sort of get the whole enrollment engine going, expanded access is much more driven by the physicians. Now we have the protocol, we have to set up, etc. But again, it has to do, the operations has to deal with the access side. That being said, there's been such excitement around Avexatide, both from the physician standpoint as well as people with PBH. I'd say generally as a company, we're enthusiastic about expanded access programs because I think they provide a great humanitarian benefit for people and has long term follow up as well. So that's why we initiated the program even ahead of the phase three trial, and we'll continue. Great. Yeah, and I just add to your point of, like, is it just turning a key, so to speak? You still need to do budgets. There are still IRBs. There are Still Protocols. So there's still work that goes into setting up and standing up an EAP at every individual site that you do that. But exactly as Justin said, there's been a lot of excitement about this program. Hopefully it doesn't take the seven months that we keep hearing it takes to, like, establish a phase one program in the United States. So anyway, outside of that, you know, beyond the EAP, you've got your regulatory path. I think one of the things that we've talked about is just frustration to some degree is to watch large pharma companies, you know, execute a program from phase three data, you know, and within six months you've got the product filed and ready to go. You are absolute outliers in that regard with the rest of biotech in my experience. So how are you doing it? And how far along are you? And it seems like you still have very high conviction to be able to execute and deliver. Yeah. So we're on track to submit by year end. And I think it's a lot of pre-planning and work at risk. You know, even ahead of the phase three readout, we were already doing, you know, tremendous work to prepare the NDA. And I Think that started from having a lot Of confidence in the drug with five prior trials gave us a lot OF confidence going into the phase Three. You know it is still hard work. These are big documents. All that being said, we did all the kind of forward planning. We mapped everything out so that we would be able to submit by the year end. And I'd add, too, as I mentioned with commercial, the same goes for regulatory medical. I mean, we have just a world-class team. Our regulatory team, whether at Amlex or at other organizations, have overseen multiple NDAs, BLAs, marketing authorizations, not even just in the U.S., but globally. Same with our clinical team, our CMC team, et cetera. So we have a really experienced team that's been working on these things. So I think that's the other advantage we have is that this is not their first rodeo. They've done this a lot, and so that's why I think we're in the very strong position we're in today. And from a manufacturing perspective, can you just help us understand what needs to be completed, executed to initiate the NDA, or are you pretty far down that path at this point? Yeah, we're on track, so we don't see any issues there in terms of submission or otherwise. And I'd say, similarly to everything else, we believe this is a big market, so tried to get quite ahead of things on the manufacturing side as well. Got it. And I think, what will the commercial dose be, and what's being used in the OLE? So the commercial dose, the intention is to have the 90-milligram dose single injection. And to your point, so to be just very, very specific, in the 16-week lucidity trial, the dose was the same as was done in the phase 2B, which was a back-to-back injection of 245-milligram doses. So total 90 back-to-back, you know, two injections. In the open label extension, we manufactured our own material, single 90 milligram dose, and that's what we intend to use commercially. We don't believe there should be any difference between doing back-TO-back injections or a single injection. And, of course, far more convenient for people to have that single injection." Perfect. The ICD-10 code, can you maybe talk a little bit about how that can benefit the company and really sort of benefit patients in the disease state? Yeah, so just to kind of level set to, ICD to N codes are more tracking codes. They're not reimbursement codes, so not something we need for reimbursement. But we are quite excited that there's now a dedicated ICD 10 code for PBH. there was not prior, and I think it, you know, it represents kind of the increasing knowledge, interest, excitement about PBH as well. These things take a little bit to kind of flow through the healthcare system and into people's epics and CERNers and everything like that, but we do believe it will provide kind of another tool to continue tracking people with PBH, both for us but also for sites. You know, if they want to call all their patients with PBh, for example, it's nice if they can track in their system with an ICD-10 code. So on balance, I think beneficial, not something we required, but beneficial as we build this market. And maybe just to talk about the label itself and the sort of opportunities for the label. One big question is, I don't think there's any reason to believe that a ruin-wide PBH would be different from gastric sleeve, which would be different from gastrectomy or gastric surgery. But the agency may take a different view. Can you just help us understand what are you putting in front of the agency? And what's the focus of the breakthrough designation in particular? Yeah, it's a great question. So I'll try to give the lay of the land. So starting with your point, which we very much agree with, We believe that PBH is PBH, meaning post-bariatric hypoglycemia, and even further, any gastric surgery can lead to the same condition, and the pathophysiology is the same. This has been studied for many decades now. You talk to surgeons who do gastric surgeries, they'll say, yeah, we've seen this for a long time. We believe it's the same pathway, which is you have this increased nutrient transit, which causes a GLP-1 sort of exaggerated response, which causes hyperinsulinemic hypoglycemia. So we think the pathophysiology is the same. In terms of what we will be putting forward in our submission, the prior five trials leading up to lucidity were mostly in people who had PBH-following RU and Y gastric bypass surgery. In the phase 2b, they allowed any gastric surgery, including sleeve gastrectomy, leading to hypoglycemia, and avexatide appeared to work regardless of the surgery that led to the condition. Lucidity was in people who had PBH following Roux-en-Y gastric bypass. So the agency, we will make the case that we believe the pathophysiology is the same here. we believe a vexatide appears to work regardless of the surgery leading to the condition, the agency could take the stance that the phase three trial was in people with runo-y gastric bypass and who now have PBH. So I think it's very much a sort of, you know, education question, right? This will be the first time there's an application for post-bariatric hypoglycemia before the agency. If we find ourselves in the situation where the indication statement is for just people who had PBH following Roux-en-Y gastric bypass surgery, first, that's about 120,000 out of the estimated 160,000 people in the U.S. today. So still, you know, the majority of the population, very sizable population. And it would just mean that we have some additional clinical work to do to show these things are comparable. So I think we'll be prepared for whatever the scenario is, but in the long term, we don't think it should make much of an impact. Great. And I think, you know, one of the things that investors kind of struggle with to some degree is how do you launch into a market opportunity that is, you know, rare disease pricing, rare diseased state, but not so rare patient population. Is there kind of a low-hanging fruit approach that makes sense? Or is this kind of an all-comers type launch opportunity as you see it? Yeah, I probably wouldn't draw too stark of a line between low-hanging fruit, as you said, or others. I think certainly the intensity of our efforts will differ at the sites that, for example, have more patients as compared to the sites that have less, but we do believe if people have PBH, we want to serve them. We want to help them, so we won't necessarily have no efforts, let's say, for those who maybe are at less-dense sites or otherwise. I think that's where you can also really lean on things like digital tools, ways to reach many people without necessarily having a rep physically in the door. I think where reps can have a really high leverage is in those sites that have quite a number of patients. And not just to meet the doctor, but we often call it a total office call, to meet to doctor, the nurse, the back office, et cetera, all the care team that come together to help in an endocrinology clinic, to help with somebody living with PBH. So I'd say I probably wouldn't starkly divide a kind of low-hanging fruit compared to a broader group, but definitely at launch we will put extra efforts towards those sites that have quite a number of patients. I'll underscore, too, this is, of course, informed by our market research. And one of the things we looked at early on and subsequently as well is if you try to segment the population based on severity of their condition? Does the endocrinologist see it differently? For example, if someone is frequently going to the ER, going to The Hospital, versus someone who's not, who's having these events, but they're having them at home, endocrineologists really view these as both are, we need treatments for, because the type of hypoglycemia we're talking about is very dangerous. And so while, yes, of course, a physician is very worried about the person going to the hospital, they're still very worried About the person having hypoglycemia at home because that next event could land them in the hospital. So just generally there's a very high intent to treat in this population. And, of coarse, today there has not been a treatment for people with PBH. So we really do think this may be an opportunity to fundamentally change the practice of PBH. Great. Maybe just as a final comment, maybe remind everybody there's a lot of education to go on here. Twenty-five minutes is never really enough. Just the timing of your event and the availability on Sunday. Yes. So we will have both a presentation, kind of live onstage presentation at Obesity Week, as well as an investor event. I should know the exact time of day, but it is posted kind of on our website and we put it up. And please reach out to our investor relations team as well for further information on that. Great. Thanks so much. And good luck this weekend and look forward to a very eventful December in 2027. Excellent. Thank you so much, guys. Thanks.