Amylyx Pharmaceuticals, Inc. Common Stock Stifel 2026 Virtual Cardiometabolic Forum

Sure. So maybe just to start for those possibly newer to the story, we are focused with avexitide on treating post-bariatric hypoglycemia. Post-bariatric hypoglycemia, or PBH, is a disease that people get in the years following bariatric surgery. We estimate about 8% of people following bariatric surgery, or roughly 160,000 people in the U.S. And when people get PBH, it sort of takes over their whole life. It is characterized by frequent recurrent hypoglycemic episodes, often after meals, but not only after meals. Sometimes people will experience these during stress. They will experience these during exercise. Sometimes they will experience them out of the blue, with no precipitating cause. And they can get very deep very fast, with people potentially losing consciousness, having seizures, becoming very dizzy, confused, et cetera, resulting in about 90% of people describing themselves as disabled due to PBH.

We just recently completed a phase III trial of avexitide in PBH. I would say we had high expectations, but it even exceeded those, meeting the pre-specified primary outcome, which was tracking people's level 2 and level 3 hypoglycemia. These are basically really significant hypoglycemic events characterized by the American Diabetes Association. Each event characterized as a medical emergency. But we showed a 55% reduction with a P value of 0.000003. We had consistent results across the secondary outcomes. We met every secondary outcome also all with high statistical significance. And those included looking at level 2 events individually, looking at level 3 events, which are basically when people have had the severe loss of consciousness or severe confusion or otherwise. And then also looking by CGM as well, also met with high statistical significance. Drug was safe and well-tolerated, generally consistent with the prior trials as well.

We are quite excited. Disease with significant unmet need, and our team had already been hard at work on the NDA prior to receiving the study results, given our excitement about avexitide overall. So we expect to submit before the end of the year, and are already hard at work prepping for a potential launch in 2027. And maybe last thing I will say, and then maybe pass it over as well, is I think the more time we have spent in this space, we have just seen what a significant unmet need it is. I was pretty struck at this year's ENDO conference, where we had a disease state education booth educating on the signs and symptoms that might trigger a physician to know that what they are seeing is PBH.

Our booth was just constantly incredibly well-attended by different physicians telling us a really consistent story, that they have many of these patients, that despite their best efforts to manage them, these patients remain incredibly debilitated by this condition, and really their excitement for any potential new science, new approaches that might come out. We're all systems go, and excited to talk today.

Yeah. I think the beauty of this data set is that it all looks good, right? It hit with similar effect size and significance across all of those outcomes. I think that's what so far we presented to our steering committee. We're working hard on the medical presentation publication as well. I think, again, speaking to the steering committee reaction, I think their first thought was, "Wow, that primary outcome tells you everything." I think also is the totality of the data. The fact that each secondary outcome tells you something slightly different. Level 2 events by self-monitored blood glucose is the most accurate, but CGM is continuous, right? Both hit with high significance. Level 3 events, which of course is someone's had the clinical manifestations of hypoglycemia such that they need rescue. That hit. Each component is telling you something slightly different, but each way you look at it's a very strong signal.

I think that's really the feedback that we've gotten from physicians, that the primary speaks for itself, but it's really the totality of the data, of course, combined with the safety profile that is so encouraging.

Yeah, I don't think anything specific to keep an eye out for. We tried to get the most important data out, the primary endpoint, the secondary endpoints, the safety. Our team's hard at work to try to get a presentation, and potentially a publication, as quickly as possible. I think we'd love to do it before the end of the year. The reason for that is, we think when there's important medical data, it's really good to get it in front of the medical community as quickly as possible. That's certainly what we attempt to do here. Certainly trying to get it in as high profile a setting as we possibly can, which I think is, again, really important when you have, in our view, hopefully practice-changing types of data.

Yeah, I really appreciate that. Just to back up for people who are maybe less familiar, seemingly any gastric surgery, certainly bariatric surgery for weight loss can lead to this condition. As we're defining it, post-bariatric hypoglycemia, we're so far talking about bariatric surgery for weight loss leading to this chronic severe hypoglycemic condition. There historically have been two major surgeries that surgeons perform for weight loss. The first is Roux-en-Y gastric bypass. The second is sleeve gastrectomy. Roux-en-Y gastric bypass historically was what was used most. Probably in the last maybe 15 years, 10, 15 years, sleeve gastrectomy has become the more prevalent surgery.

That being said, I'd say we've heard from many surgeons and weight management clinics that I think Roux-en-Y gastric bypass is starting to be used more frequently again, just given that it has a higher degree of weight loss than a sleeve gastrectomy, but both are very effective. I think it depends a lot on the clinic. Each of these surgeries can lead to the same condition, post-bariatric hypoglycemia. Again, it's pretty rare. Most people do not develop this condition. I think the question is, when we ultimately get to the indication statement from FDA, will the label say Roux-en-Y gastric bypass PBH? Because that's the population that we studied in the Phase 3 trial. Or will it say PBH, meaning for any surgery that led to this hypoglycemic condition? Obviously, it's early. We don't know yet. We're far from those discussions.

I'd say to your point, we think there's a strong rationale that we believe the pathophysiology is the same, regardless of the surgery that led to PBH. I think most endocrinologists would say, "Look, PBH is PBH. The surgery that led to it happened some time ago." I think, again, there are no treatments today for PBH, and I think endocrinologists want a treatment for PBH. So we think there's a strong, rational argument from our earlier Phase 2b trial. Avexitide was also studied in people with a variety of different surgeries leading to this condition, and avexitide appeared to work just as well, regardless of the surgery that led to PBH. All that being said, the Phase 3 trial inclusion criteria was Roux-en-Y gastric bypass leading to PBH. That's why I think we really don't know yet.