Amplify at Citi’s Biopharma Conference: Strategic Insights on Avexitide

On Tuesday, 02 September 2025, Amplify (NYSE:AMLX) presented its strategic vision at Citi’s Biopharma Back to School Conference. The company discussed the potential of avexitide (AMX0035) in treating post-bariatric hypoglycemia (PBH) and Wolfram syndrome. While highlighting the promising Phase 3 LUCIDITY study, Amplify also acknowledged the challenges in meeting the unmet needs in these rare disease markets.

Key Takeaways

• Amplify is conducting a Phase 3 trial for avexitide in PBH, with top-line data expected in early 2026.
• The company estimates 160,000 people in the U.S. are affected by PBH.
• Avexitide aims to reduce hypoglycemic events, with no direct competitors in the pipeline.
• Collaboration with Gubra is underway to develop a long-acting GLP-1 receptor antagonist.
• Initial studies show potential for AMX0035 in treating Wolfram syndrome.

Operational Updates

Amplify is advancing its Phase 3 LUCIDITY study for avexitide, targeting the reduction of severe hypoglycemic events in PBH patients. Recruitment is anticipated to conclude by year’s end, with results expected in the first half of 2026. The study’s primary endpoint focuses on reducing composite level two and three hypoglycemic events, with secondary goals including quality of life and healthcare utilization improvements.

For Wolfram syndrome, AMX0035 has shown promise in early studies, with observed stabilization in key symptoms. Amplify is actively engaging with regulators to chart a course for a pivotal study in this rare genetic disorder, affecting approximately 3,000 individuals in the U.S.

Future Outlook

Amplify’s future strategy involves educating healthcare providers and payers about the significant unmet needs in PBH and Wolfram syndrome. The company aims to leverage its rare disease experience to secure premium pricing and market access for avexitide. Additionally, the collaboration with Gubra seeks to enhance treatment options for PBH through a long-acting GLP-1 receptor antagonist.

Q&A Highlights

• PBH Market Opportunity: With an estimated 160,000 U.S. patients, the PBH market is poised for growth. Amplify aims to address the limitations of existing treatments like medical nutrition therapy.
• Competitive Landscape: Avexitide stands out with no direct competitors in the pipeline, offering a unique therapeutic profile.
• Payer Considerations: Amplify emphasizes the importance of reducing hypoglycemic events to minimize hospitalizations and improve patient safety.

In conclusion, Amplify’s presentation at the conference underscored its commitment to addressing unmet needs in rare diseases. For more details, readers are encouraged to refer to the full transcript.

Full transcript - Citi’s Biopharma Back to School Conference:

Josh: AIDA asset. It’s a GLP-1 receptor antagonist, so it’s a competitive inhibitor of the GLP-1 receptor. This is quite important in diseases of hypoglycemia. Despite the GLP-1 agonists now being very famous for obesity, they were initially used for, and still are, used for diabetes, in part because they can cause the secretion of insulin through activation of the GLP-1 receptor and then the reduction of blood sugar. With our compound, we are able to competitively inhibit the GLP-1 response, which can reduce hypoglycemic events and reduce hypoglycemic lows, or at least that’s what we’ve seen in our prior trials. The compound’s currently in phase 3. The phase 3 is ongoing. We expect to complete recruitment by the end of the year with top-line data in the first half of 2026.

We’re quite excited about that trial, especially coming off of five previous positive studies on the compound, which led to FDA breakthrough therapy designation. We do believe that pending positive results from this trial, this trial would be the pivotal trial to support potential registration of the drug as well. Maybe just touching briefly, as we’ve learned more and more about post-bariatric hypoglycemia, we’ve just been very impressed at the unmet need, at how much of therapy is really needed to address the symptoms these patients are dealing with. These patients will have recurrent blood sugar drops, which most often happen after meals, but can happen at any time. Can happen due to exercise, can happen sometimes out of the blue due to psychological stress, caffeine, alcohol.

If you can imagine if at any time your blood sugar could deeply drop, you start to have to live a very sheltered life. You are unlikely to be able to drive. You may be very nervous when you go up and down stairs and at high risk for falls. It may be hard to go through your day-to-day life where in the middle of a meeting or in the middle of a day, all of a sudden you can’t put together a sentence because your blood sugar has dropped so low. It really limits life quite a bit for people who have this disease. We’d be really excited to bring a therapy forward.

Unidentified speaker: Super, super helpful, Josh. Let’s talk about the market opportunity, though. When you think about as the trials are rolling, is there anything that you learned about this patient population and a lot of your KOL discussions? Do you think ultimately the incidence rates are going to be higher than you think? Should we look at bariatric surgery procedures as sort of an indicator maybe of the potential of the market? Related to all this, like what I know GLP-1s don’t play a direct role in what you’re talking about. Maybe you talk about that. I think in investors’ minds, like that’s kind of the, you know, people view that as competitive, which it’s not.

Justin: Yeah, very important question. Let me take it a little bit in reverse. Right now, we estimate there are about 160,000 people in the United States who have PBH or post-bariatric hypoglycemia. That sounds like a really high number, but it’s actually quite rare. The reason that there are so many people who have PBH is there have been so many bariatric procedures over the past couple of decades, particularly in the past 10 years. The estimate is only about 8% of people who get bariatric surgery will develop PBH, but 8% of millions of people, you get to very high numbers. It’s really a rare complication in the years following bariatric surgery that someone gets PBH. The unfortunate thing for people with PBH is it seems to be very persistent. Once someone has PBH, once whatever in their body potentiates the GLP-1 response, it stays.

For example, in the prior studies, the average time people had had PBH was about 10 years. They had had PBH for a decade. That’s despite having medical or particularly dietary intervention, they’re still having these very frequent hypoglycemic events. I think in our estimates, the numbers, the population will only grow. It’ll grow based off of the number of bariatric procedures. To start, though, 160,000 is already quite a substantial, it’s orphan, but it’s quite a substantial orphan market with no treatments currently. So far, there have been about the same number of bariatric procedures year over year over the past several years. That does not seem to be impacted by the new weight loss drugs. No one can, of course, perfectly predict what’s going to happen in the future.

What we’ve heard from weight management clinics is that these are really not the same populations of people they’re talking about. Someone who gets a bariatric surgery is looking to lose 100 pounds, 150 pounds. These are people who have severe obesity. That’s very different than your typical person who’s looking for a weight loss therapy. In fact, even if you look at the trials, while oftentimes they’re talking about % weight loss, they’re very different populations of people. In the bariatric surgery trials, these are generally people who are 300 pounds and above. In the weight loss studies, these are people who are generally around 200 pounds. These are very, very different populations. I think that’s why hearing from weight management clinics, these are not the same populations that we’re looking at.

In terms of what we’ve learned about the PBH market, I think the more we learn, the more the unmet need comes through and the more we’re excited about an opportunity to help people. These are people who have really a debilitating condition. If you think, if at any time you’re afraid that you may lose consciousness, you may become so severely confused that you don’t know where you are. Some people have seizures. People are in and out of the hospital quite frequently. These are often typically women in their 40s, often caring for children as well. They’re afraid to be alone. They are afraid to leave their homes. What we hear from endocrinologists is this is a population who really, really need treatment. As Josh said, we’re excited about the potential to be able to help them.

Unidentified speaker: Great, thanks guys. Maybe, as you highlighted the high unmet need in the space, could you help paint the picture of what is currently available as a treatment for patients and why there is such an unmet need for avexitide and what is the competitive landscape for PBH, and how would avexitide differentiate itself from existing or other pipeline therapies?

Josh: Sure. Unfortunately, there really isn’t much today for PBH. The mainstay treatment, as Justin mentioned as well, is what’s called medical nutrition therapy. This in and of itself is a very unpleasant thing to have to go through. Basically, it’s avoiding all or as many as possible simple carbs, never eating large meals. That means you’re basically never having, you know, a full dinner for the rest of your life. You’re having very, very small, you know, kind of, you know, snacks and never eating kind of a full meal for the rest of your life. Even with that, patients still report having frequent events. You can have events both from meals, but also from other triggers, whether exercise, stress, caffeine, all the manner of other things can drive these events.

There are some off-label therapies that are tried, generally kind of hormonal therapies, including somatostatin analogs and alpha-glucosidase inhibitors like acarbose. These show pretty limited efficacy with quite significant side effects. They really are not particularly helpful in the treatment of PBH. I’d say probably won’t spend much time commenting on others, but there really is no other drug in the pipeline with a profile like avexitide. We see ourselves in a very strong position competitively.

Unidentified speaker: Gotcha. That makes sense. Maybe speaking of the phase 3 LUCIDITY study, you mentioned the rarity of PBH, but given the overall number of bariatric surgeries, there are a decent number of patients out there. Could you provide some early color on how patient recruitment and retention for the study is coming along? How is the enrollment timing looking? Is it still a year-end 2025? I know earlier you said the readout is still targeted for the first half of 2026.

Justin: Yep. I’ll take it in reverse. Yes, target still a year-end to complete enrollment and then data in the first half of next year. There’s been a lot of enthusiasm and excitement from the centers. If you imagine, this is a highly debilitating condition. There are 160,000 people in the country and there are no treatments available. I think what we’ve heard very consistently from endocrinologists is these are some of the most fragile patients they have under their care. There’s tremendous excitement. Of course, given that there were five prior trials of AMX0035 in PBH showing very strong reductions in hypoglycemia and hypoglycemic events, people are very excited that there may be a therapeutic on the horizon for their patients.

Unidentified speaker: Awesome. Thank you. Maybe let’s talk a bit more about the LUCIDITY study. You know, the reduction in the composite level two and level three hypoglycemic events obviously is a primary endpoint. What are some other key secondary endpoints that might help influence your data assessment of avexitide?

Josh: I mean, maybe I might start with hypoglycemic events are already quite significant. The ADA defines level two and level three hypoglycemic events as a medical emergency. When you’re talking about reducing those types of events, you’re talking about reducing something really significant and important for patients. We are also looking at a number of kind of quality of life scales, including scale specific to how hypoglycemia can affect your life. We’ll certainly be looking at healthcare utilization as well, including hospitalizations, things like that. I think our primary endpoint is already quite a clinically meaningful endpoint. That’s certainly going to be the main driver here, I think, as well.

Unidentified speaker: One of the questions, I guess, we can wrap on this program with more of a commercial question. I know you have a rare disease model. This is you guys’ wheelhouse. You know this, you know the rare disease structurally, the market, but maybe not this indication. What work have you guys done in advance to try to maybe prime the pump in terms of how payers may view this, how the cost-benefit, is there sort of a magnitude of effect that you think would be reasonable from a cost-benefit and a risk-benefit? Questions like that.

Justin: Yeah, very important. Work that we’re doing now, and of course we’ll continue next year as well. I’ll talk a little bit and invite Josh and Jim to join in too. I think the first thing that we’ve heard is that as considering that endocrinologists consider a single hypoglycemic event as a medical emergency, really doctors are feared for their patients having these events. The number of doctors who tell us a story about a patient who had an event and crashed a car, or they were shopping and fell and hit their head and ended up with a concussion, it’s really frightening. I think the first thing that’s really come out in the research is that doctors want to keep their patients safe. Even just a single one of these events is very dangerous.

While there are people who have more frequent events and people who have less frequent events, I think generally what we’ve heard is we don’t want our patients having any events, regardless of how frequent they are currently. I think that’s the first thing that’s really come out. The second, I think, is the sort of burden of disease. We’re going to work to present and publish on this more. The amount of hospitalizations and visits and just what people with PBH go through is really challenging. On a population level, we have looked at a number of different claims databases now, all of which corroborate the numbers that we saw based on the literature estimates. About 160,000 people actively have PBH in the United States.

As we continue to do our research, we’ll think about segmentation, based on how many patients a doctor may have under their care. There are some doctors who have hundreds of patients under their care. There are some who have 10 patients under their care. We’ll continue to do that work. I think in terms of the rare disease model, we very much think that this has the same sort of characteristics as one would look at in other rare diseases. It’s a big population. 160,000 is a kind of big rare disease, if I can say that. It’s got the same hallmarks as one would see in these other areas. To your point, with our first launch in ALS, I think we were quite successful at understanding how do you target centers in the right way, how do you educate people in the right way?

How do you educate payers in the right way? At the end of the day, I think we view it as education. One, this is a significant unmet need. I think it’s telling that story. What does it mean to have PBH? Why is it important? The second is the data supporting the treatment. I think we’re fortunate that hypoglycemic events are very well recognized, particularly from the diabetes world. These have been defined for some time. I think it’s really just about education again and again, whether that’s in a physician’s office or at payers as well.

Josh: Yeah, and maybe the only thing I’ll add that maybe goes back to your question as well about endpoints in the trial. One thing we’re also doing in the trial is structured patient interviews, where we kind of interview the patient post-trial. This was also done for a number of the patients in the previous trials. One thing that was striking is that patients described feeling quite a bit different while on drug. This makes sense given that hypoglycemia, you feel terrible when you’re hypoglycemic. It’s not just that your blood sugar’s low, but it also causes a huge stress hormone release. Quite often you become quite nauseous. You can be quite dizzy. You’re not thinking clearly. It’s just a very, very unpleasant thing.

I think one other thing we’re excited about potentially commercially is, with many drugs, you take a Lipitor or otherwise, maybe you can get a blood test and you can see the difference, but you can’t feel the difference. I think it’s something we’re quite hopeful for that we continue to see that as we get through our structured interviews and otherwise, that this is a drug hopefully that makes people feel better when they’re on it. I’d say overall commercially as well, echoing what Justin said, physicians describe that any reduction in significant hypoglycemic events is meaningful. We’re quite excited about that. Again, in the phase 2b, we saw a 64% reduction, which is obviously quite meaningful for people living with this disease. I think we do view this as a rare disease launch. There’s quite a number of physicians we’ve spoken to who have over 100 patients.

Those are certainly going to be some of the mainstays as we start the launch, hopefully pending good data as well.

Justin: I’m happy to add maybe just one last piece too. I think certainly, when you’re buying your home, the advice is that you want to be in a great neighborhood. I think we’re fortunate to have a great house in a great neighborhood. What I mean by that is I think there have been a number of rare endocrine launches recently that support premium pricing, that support access, and show that in these areas where there’s high unmet need, physicians are willing to prescribe and payers are willing to pay because they recognize the challenges and treatments that are needed here.

Unidentified speaker: Maybe just to add a little perspective, you know, an investor asked the other day, you know, is this a difficult disease to diagnose? It’s interesting because in many ways you could answer that both yes and no, right? From the yes side, you say, if you’re not looking for it, it can take some time for a patient on their patient journey, right? Also, too, interesting fact, most of the people who get bariatric surgery around the world are female, tends to be in their 40s. It’s about 70-30. It really is a difference from a male-female perspective, female-male. A lot of times it’s misdiagnosed as menopause or other things when they’re struggling to find these symptoms.

If you’re looking for it, if you know that you ought to be on the lookout for this, someone’s had bariatric surgery, it’s pretty easy actually to see the causes of the manifestations of this persistent hypoglycemia. I think we have an opportunity here when we start commercialization to be very focused and very targeted on that group of people who’ve been suffering with this disease for a long time and have sorted their way to the adult endocrinologist centers that we’ve talked about, and we can find a lot of folks there. At the same time, we can begin to do some education and start to make sure that it’s a thing that physicians start to think about when they see patients that fit a certain pattern.

Another interesting fact, nothing to do with us, but we’ve just heard recently a number of questions are starting to appear on the endocrinology board exams about post-bariatric hypoglycemia. As the number of bariatric surgeries grow over time and this small, you know, 5% to 8% side effect, but again, in a population of now over two million people that have had surgeries in the last two years in the United States, it’s starting to be something that endocrinologists are thinking a bit more in, even as they train for their boards. It’s quite an interesting market when you look at it from being able to stage the growth, which is something a small company can do.

Justin: Makes sense, guys. Yeah, I think everyone’s all looking forward to the first half of next year when LUCIDITY reads out and see, you know, how data will be impactful for patients and that have PBH. Maybe let’s move on to AMX0035. You know, just briefly, can you talk about the molecule, its mechanism, and perhaps why it makes sense in Wolfram syndrome?

Josh: Sure. So AMX0035 is a combination of sodium phenylbutyrate and taurursodiol. These are two compounds that have been around for some time, including in the literature, studied in many models and also in our hands, in part due to, you know, strong effects on stress. They can even be used as tool compounds in different stress models because their ability to hit that pathway, you know, is so clear. That’s part of what led us, you know, into Wolfram syndrome. About eight years ago, we started speaking to a physician named Dr. Fumihiko Yurano, who asked if we might want to collaborate to study the compounds in Wolfram syndrome. His rationale was that Wolfram syndrome is often considered in the literature as the prototypical disease of stress.

It’s generally a monogenic disease caused by mutations in the WFS1 gene, which is a gene, you know, in a protein that helps basically to shut off the stress response. If that protein’s not functioning, you end up with this kind of runaway stress response that leads to cell dysfunction and death. We did a number of years of preclinical work. They all looked, you know, quite good. A number of that’s published, or a good amount of that’s published in the Journal of Clinical Investigation Insight. Ultimately that’s what led into our clinical work with AMX0035 and Wolfram as well. To talk a bit about the disease, it’s quite a rare disease, estimated about 3,000 people in the U.S. who have Wolfram syndrome. It manifests initially looking like juvenile diabetes, like type 1 diabetes. As patients progress, they’ll also see diabetes insipidus with some hypothalamic, you know, dysfunction.

They tend to go blind, ultimately fully blind, you know, as they get into late adolescence and adulthood. Ultimately they’ll see other neurodegeneration, including brainstem degeneration, which leads to breathing, respiratory, you know, type problems as well. Usually these patients pass away in their early 30s. We ran a trial, you know, initially open-label study in 12 people living with Wolfram syndrome. We tried to track some of those cardinal symptoms of Wolfram syndrome. The one that changes the most over time is the diabetic outcomes. Those were our primary endpoint in the study. Namely, we tracked C-peptide, hemoglobin A1C, blood glucose using continuous glucose monitoring, as well as vision and kind of a general symptom score as well. Across all of those, we saw stabilization or improvement in our initial study, which was consistent with what we had seen in the preclinic as well.

Limitation that it’s an initial 12-patient open label, but we really did see what we would hope to see in that study. Now we’re interacting with regulators. Our thought is that the next step would be a pivotal study in this disease, especially given that it is a rare disease. It would also be the first pivotal study conducted in Wolfram. We’re working with the agency to determine the best path for that and endpoints. Certainly our goal is for that to be as efficient as possible. I think when you’re going after a disease with 3,000 patients, you don’t want to run too large or too long of a study ultimately to enable getting into that commercial space ideally.

Justin: Yeah, that makes sense. I think you guys really hit the nail on the head with just how the rarity of a disease it is and the urgency to get something to market. AMX0035 did have a recent, I would say, data readout from PSP that perhaps wasn’t quite as anticipated. Might there be any read-throughs from those results to your ongoing discussions with the FDA regarding the phase 3 design for Wolfram? I appreciate you asking. No, I don’t think there’s any read-through, different divisions and different supporting mechanisms. To cover that, we ran a phase 2b trial in progressive supranuclear palsy, PSP, with the same drug, AMX0035. The rationale was that in a prior Alzheimer’s study, AMX0035 had lowered tau, which is the key pathological protein we see in PSP. That being said, sadly, no drugs ever worked for PSP.

It was the first study of AMX0035 in people with PSP. We had that data readout very recently, and unfortunately, there was no difference between active and placebo. What I think is very different with Wolfram syndrome is, first, Wolfram syndrome is a monogenic disease. We understand the pathophysiology much better. What we see in cells is what we saw in mice is what we see in people. The second is that our first clinical study in Wolfram syndrome, every outcome went in the right direction. In fact, we saw improvement across many of the measures, including the measures of glycemic control, which is very exciting. I’d say, whereas our first trial in PSP with AMX0035, unfortunately, there wasn’t a clear benefit, our first trial in Wolfram syndrome, there was a very clear benefit. That’s why we’re working on the phase 3 program now.

Unidentified speaker: Maybe the same type of questions on Wolfram, just from a commercial kind of context. I mean, what work have you guys done looking at the unmet need and, obviously a rare disease, but I wasn’t sure how active the patient community is and what visibility maybe the study has among other drugs. There’s not a lot out there in the pipeline for Wolfram, fortunately for you guys.

Josh: Yeah, great question. One, similar to some other rare disease spaces, the advocacy is a lot driven by mothers. There are a number of mothers who have really made a mission to see a difference in this disease. They’re quite well organized, quite impressive individuals who are advocating for Wolfram as well. The top clinic in the country is definitely a clinic out of Washington University run by Dr. Fumihiko Yurano. He personally maintains a registry of people living with Wolfram syndrome that’s over 400 patients. This is definitely the type of rare disease where we expect it to be rather concentrated, approximately 3,000 patients overall, but already 400 of those in Dr. Yurano’s registry. From a diagnostic path, monogenic disease, so you can diagnose it using a genetic test. Genetic testing is not often conducted in diabetes.

You could imagine a path where if you have somebody with juvenile diabetes or type 1, particularly if they’re antibody negative, which would suggest a somewhat atypical presentation of type 1, potentially conducting a genetic test and being able to pick up these patients, particularly if you see any optic or otherwise disturbances or diabetes insipidus in them as well. Clearly this could be better diagnosed. When we’ve seen and talked to patients and otherwise, there’s usually quite a diagnostic delay. Encouraging even with that, that we see at least 400 patients in a registry at a single site also. Lastly, since we’ve started the trial, we have heard from Dr. Yurano and from the patient advocacy groups as well. They have seen a major uptick in awareness and interest. Dr.

Yurano often says, "I’ve been getting a referral every week," which again suggests that there’s a lot more people considering this when they see juvenile diabetes, particularly with an atypical presentation or other symptoms coming at the same time as well.

Unidentified speaker: Okay, that’s super helpful. Maybe talk a little about, just to round out the pipeline, maybe the collaborations, the Gubra deal. Maybe just give us a little bit of context for that, the strategy there, maybe how you got there, selection of it, and then we can go from there.

Justin: Yeah, we’re very excited about that collaboration. Thank you. I think we, as I’ve said, the more work we’ve done with avexitide, the more work we’ve done with PBH, the more excited we get. In fact, something else entirely that we didn’t get to talk about is it turns out that other upper GI surgeries, basically any upper GI surgery, can cause the same persistent hypoglycemia as well. I think that’s an opportunity for future work. Whether that’s gastrectomy for gastric cancer or esophagectomy for esophageal cancer, there are many other surgeries that can cause the same persistent hypoglycemia, and there are no treatments available. We think there’s really a lot of work to do now and in the future. Currently, avexitide is taken as a daily subcutaneous injection. For a population high on that need, no treatments available, I think that’s very appropriate for market.

I think there are other good examples of that even recently in the endocrine space. When patient interviews have been conducted, patients say, "Look, I’m pricking my finger multiple times a day to test my blood glucose. That’s a lot more bothersome than having to take a, you know, injection in the morning." We feel very confident in going to market with avexitide as it exists today. That being said, all else being equal, and that’s the important point, efficacy and safety being equal, longer acting would be better. The technology to take peptides and make them long acting, I think, has been really nicely developed over the past couple of decades.

We did what we try to do in various spaces, which is talk to the experts, and several of the kind of brain trusts who have developed these peptides over the years are in Denmark, as people may be very well aware of. They pointed us to this company called Gubra, who are a Danish biotech who had built this really robust peptide platform. We started discussing the potential of developing a long-acting inhibitor of the GLP-1 receptor with Gubra. They and we felt like it was just a great partnership opportunity. They, as you might imagine, have been working on the GLP-1 receptor for a long time. They have all of those assays up and running already. They have a very robust library and platform for developing peptides. We signed a research agreement at the end of last year, and now we’re off to the races.

We haven’t given explicit timelines yet, but I’ll say we’ve been very impressed with the work they’ve done so far. I think as we get a little further in development, we’ll give more details on the timelines. That’s a program we’re very excited about.

Josh: Maybe just a small add there, we did show at earnings as well that we already have seen compounds with strong in vitro and in vivo potency, as well as extended half-lives as well. More work to be done, but it does seem that the project’s progressing as we would like to see.

Unidentified speaker: Fantastic. We’re out of time, guys. Thank you very much. Really appreciate the conversation.

Justin: Great. Thanks so much for listening to us.

Josh: Thank you so much.

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