Good morning, everyone. Thank you for joining the session with Amylyx. I'm Ami Fadia, Biotech Analyst here at Needham, and it's my pleasure to be hosting Jim Frates, CFO of the company. Jim, thank you so much for taking out the time to do this today. I will turn it over to you to take us through the presentation. Just for our listeners, if you have any questions, please send it to me through the dashboard and we will take it from there.
Well, thanks, Ami. I really appreciate everybody taking time on Tax Day. Hopefully, everybody's already filed. It is a lovely spring day here in Boston where we are. Thank you for spending a half an hour, 45 minutes with us learning about Amylyx. We have a very exciting year ahead of us with phase III clinical data coming in Q3 and hopefully being able to market the first-in-class drug to treat what is really a difficult and insidious disease. Our focus has been on developing diseases for unmet needs in rare disease markets. This year, the focus has squarely been on avexitide for post-bariatric hypoglycemia. Before we delve into the whole presentation, though, I always like to center it on people. This is a picture of Maggie, who's a mom and an advocate living with post-bariatric hypoglycemia.
As you delve into this work, it's one of the things we liked about avexitide from the start. We like to say the more work you do on avexitide in this condition, the more important a solution becomes, and I think the more evident that we have an opportunity to provide one for these patients. It's a very difficult reactive disease that causes people to have very severe hypoglycemia, which is one of the most dangerous conditions out there, right? Because when your brain is not getting glucose, and it's called neuroglycopenia, and we'll get into the details of that a little bit more and how we're measuring in our phase III, et cetera. It's very difficult for folks to live with this condition, and we try and keep people like Maggie, who are so committed to finding a cure. They're really our true North Star.
We will make forward-looking statements. I will make forward-looking statements in this presentation, of course. It's hard not to when you're talking about a biotechnology company and developing drugs for new and as yet maybe fully understood conditions. Please refer to our SEC filings. We take a great deal of care outlining not only the details of our business, but the details of the risks associated with that. We make those filings periodically, and you should be familiar with those because they are quite comprehensive. Amylyx, just at a high level, right? We are, as I said, focused on rare diseases. The vast focus this year and into next year and beyond is on avexitide, which has FDA Breakthrough designation for this disease called post-bariatric hypoglycemia. After bariatric surgery, it's a reactive hypoglycemia. It's also called hyperinsulinemic hypoglycemia or HH.
You might recognize why we don't go around saying hyperinsulinemic hypoglycemia at every turn. What does that mean? That means it's a hypoglycemia that's basically driven by the overproduction of insulin, right? Of course, I'm not an endocrinologist, but I do think we all understand that diabetic pathway, that weight gain pathway where insulin is produced in response to meals, in response to exercise, stress, other things that we go through as humans, a finely tuned system. If you're producing too much insulin, well, then there's not enough sugar in the bloodstream or in the body to be taken up by insulin. Therefore, more sugar is taken out than is normal, and you have this hypoglycemia. Particularly with HH and PBH, post-bariatric hypoglycemia, it is so quick and so fast, the insulin overproduction, that it can be quite serious. We've all felt hypoglycemia generally.
Many of us have experience with diabetics in our homes or in our lives. This reactive post-bariatric hypoglycemia is more dramatic, more quick, more fast, and that's what makes it so dangerous, frankly, and the opportunity for us. We also have programs with AMX0035 in Wolfram syndrome, with our calpain-2 targeted antisense oligonucleotide, our 114 program for ALS. We have a longer-acting GLP-1 antagonist, our 318 program in collaboration with Gubra, which we're super excited about. Let's jump into avexitide now. At the start, too, I should say we're well capitalized. We had over $300 million at the end of last year. Our expectations is that should take us in, even as we prepare for commercial launch, in the idea that we have planning for success, that should take us into calendar year 2028 with the resources that we have.
We're still a small focused company, under 150 people at this stage, and very focused on the development of avexitide. Again, first-in-class, GLP-1 receptor antagonist, right? We always care and appreciate when people focus on the GLP-1 agonist. A lot of times people just say, "Oh, that's a GLP for short." Well, we all know the details. There's many different GLP agonists, which you all I'm sure are familiar with and getting more familiar with. There's dozens of those and many companies trying to go public and follow in that pathway. We say, "Great, keep going.
Keep looking for those incremental benefits in weight loss. We're very focused as the first GLP-1 antagonist focused on what we think is another large opportunity, and again, particularly post-bariatric hypoglycemia in our phase III, which we've dubbed the LUCIDITY study for the clarity, hopefully, that that will bring for folks. What is avexitide, really? Well, first, I'll start with what is PBH, again, so many people necessarily haven't heard of. We all know bariatric surgery, I assume. Down here on the chart in the left is the rate of gastric bypass surgeries by type down below. You can see there's a little dip there in COVID, and then a rebound, and then maybe a little moderation in that growth as we go forward. These are all data from the Bariatric Surgeons National Organization. We feel like this is the best database.
2025 has not been published yet, and I think, in fact, we're still waiting for 2024. As many surveys are done, it takes a while to conclude all this data. We've seen the various types of surgeries continue to grow. There's roughly 250,000-270,000 of these surgeries a year. What post-bariatric hypoglycemia is a result of a small rate of side effects. We peg it around 8%, various papers, and we'll get into that a little bit later. There's been a lot of work in this area. Interestingly, over a dozen sort of prospective studies to find out how many people are living with medically serious post-bariatric hypoglycemia. Again, in a small percent, remember, bariatric surgery is a major gastric surgery where the stomach is either bypassed or dramatically reduced in size.
That means that patients eat less, less nutrients are absorbed, and there's dramatic weight loss. We're talking about people losing 100 lbs, 200 lbs. These are generally people with BMIs that are starting with BMIs over 40. Generally, in the 250, 300, 400 lb range. Not your typical patient who might be using other weight loss strategies. These are people who are very, very seriously affected by their weight. Blood pressure, heart issues, very, very serious. They have a hard choice to make, and it's a brave choice to go through the surgery. They lose a lot of weight. There's like an 80%+ cure rate, I believe, with diabetes that they see after this. Interestingly, it's all connected to the GLP-1 system as well. The nutrients pass through their gastric pathway much quicker. That means it gets to the lower intestine more quickly.
GLP-1 is activated there. That produces the insulin, helps deal with the blood sugar, and we all know the benefits of GLP-1 agonists. More production of that often happens after post-bariatric surgery. Now, the ones that get into trouble with an overproduction of GLP-1 are the ones that we're focused on. We've seen 50- 100 x normal ranges of GLP-1 in response to meals. Again, even small amounts of food and certainly carbohydrates or liquid carbohydrates, all those things we're trying to avoid that spike our blood sugar. When we're healthy, we can deal with that. These folks have an overproduction of insulin, and this kind of takes you through where the GLP-1 receptors are turned on. That downstream produces more insulin. Well, when there's not a lot of food and sugar in the bloodstream, what do you get?
You get hypoglycemia, and it can also happen very, very quickly. That's a hallmark of PBH. avexitide is actually a truncated form of exendin. People will remember exendin from Amylin's in the very first approved GLP-1 agonist. Avexitide is exendin nine through 39, so a truncated form of that well-used and experienced peptide. By truncating the first part, it turns into an antagonist. It doesn't turn the receptor on. It blocks the receptor from the natural cycling of what would turn the GLP-1 receptor on. We have what is a very effective antagonist. What have we learned about that? We've seen that through five different studies. This next study I want to show you in the phase I really demonstrates that. Eight patients were given their own control.
On the left-hand side is their response to insulin, or excuse me, their insulin response after they've taken a Glucola, which is just a pure drink of sugar. This is a single-dose study, and you can see on the left, if you're on placebo to start with, you get your spike in insulin, which you expect. If you look at avexitide, which is the open dotted line, and then the control is the line in the middle, but you can see that the insulin spike doesn't happen when they have avexitide on board after the sugar challenge. The same thing happens in glucose. You can see over here, on the right-hand side. Unfortunately, there's different papers, so the slides are slightly different. In this one, the placebo is in the black line. Avexitide is in the open squares, which is the bottom one.
The control is the dotted one. You see in the control and the placebo, you get that spike in glucose, which corresponds with the spike in insulin. You can see that dramatic drop in glucose, though, right? As insulin spikes on the left, people are going down below that blue line, and they're in a clinic, and so now they're rescued, right? This is if their glucose is crashing, the physician gives them more glucose to rescue them from really getting into the dangerous zone of hypoglycemia, which is below 50. You can see with the avexitide group in the middle there, that flat line on the right, they don't need rescue. It's not seeing the insulin spike, and so therefore you don't have a glucose spike. Your insulin's dealt with, we'll call it normally in the normal course.
You produce insulin, you deal with the glucose spike that you have, and you don't go into that reactive hypoglycemia, which is what happens to the placebo and the control group here. That's very nice. We saw that, again, single study, single dose, you're seeing an effect of this drug. We think it's on target. Of course, not just us, but these were done by folks at Stanford before we acquired the product last year. Not only that one study, we've done five studies. The group, Stanford, and then Eiger Pharmaceuticals that had it before us, have done five studies over time. That phase I IV infusion of avexitide that I just described, they then did a subcutaneous injection again, small numbers. You can see the postprandial glucose nadir, right?
Where is that bottom of the glucose curve, which is really what you're trying to protect in these people, right? Because if glucose goes too low, that causes hypoglycemia. Measuring the glucose nadir is shown in this bottom column here, or row, excuse me. A single ascending dose study, multiple ascending dose study, and then two different phase II studies that we'll go into a little bit more detail with really the kind of more real-world, let people go home, let them have their meals, let them live their lives, and yet we still saw quite dramatic p-values with relatively small numbers, which shows you there's quite a dramatic drug effect here, which is one of the reasons why this, of course, allowed Eiger to get Breakthrough designation for PBH.
That's obviously another important part of this development program, and it allowed us to really have confidence in trying to replicate these studies in our LUCIDITY study in phase III. With the next slide, I'll show you some of the results from the phase III. Reducing these rates of hypoglycemia in two different clinical studies. We have the phase II PREVENT study on the left, the phase II-B study on the right. There's a further slide that explains exactly the differences there, mainly around doses. You can see in the phase II study on the left-hand side, they tried avexitide twice daily with 30 mg injections. Again, it's a peptide, so it's an injectable. We'll be aiming for a daily injection of 90 mg. Again, really nice dose finding that they did 30 mg twice a day, 60 mg once a day.
Let's look at the differences there in level two and level three hypoglycemic events. All very significant. Obviously, the higher the dose, we get more coverage through the day, and we've determined that we're going to be using 90 mg once a day in the morning before a meal, and that coverage lasts really through the day quite nicely. You're seeing that avexitide's cutting rates of hypoglycemic events by greater than 50%. The really nice thing, too, here, the median patient in the phase II-B study, the median patient had zero events. Again, that means more than half the patients had zero events, which is really quite dramatic and shows, again, we think, on target delivery, very consistent p-values here. Just to touch on level two and level three hypoglycemic events. What are those? There's actually three levels.
This has been defined by the American Diabetes Association, accepted as endpoints in FDA guidance for many years, kind of used ubiquitously throughout endocrinology. A level one event is when your measured blood glucose via a finger stick, you use a glucometer, you take a little drop of blood, you put it in your little reader. I actually have one here. I use one myself. It measures your glucose. Normal range of glucose at sort of fasting would be probably 90-115. When you eat, your glucose spikes up, and then your body produces insulin, and you come back down again. Hypoglycemia, most of us are worried about hyperglycemia with type two diabetes, et cetera. You're worried that your blood sugar's not coming down to that range, and you might measure HbA1c, which measures blood glucose over months at a time.
An individual glucose level is what we're talking about here. You're in level one hypoglycemia when your blood glucose is below 70, okay? That's where you'll start to feel, you might feel some dizziness. You might feel some lethargy. You might feel some brain fog. You'll certainly feel maybe hungry. That is the body's signal saying to you, "Hey, you need to eat." My dad always used to say with little kids, they don't have very big livers. They don't have a lot of glycogen stores. When they're hungry, their behavior goes haywire because they're probably hypoglycemic, he would always say. Give them some food, and we all know that giving kids a little bit of food can really deal with issues, right? We all face that hypoglycemia maybe in the afternoon, maybe after exercise, et cetera. Level one is 70.
Level two is where we start to see neuroglycopenia. Again, your brain uses 30% of the glucose in your body, and if your brain's not getting enough glucose, we start to lose important functions, again, concentration. You'll faint. You'll get dizzy. You won't be able to remember things. Literally, we've heard patients report that they were playing the violin at church, and they got through the whole service, and nobody noticed. They were still playing, but afterwards, the person said, "Hey, when are we going on?" They completely missed the hour-long church service that they lived through because they were hypoglycemic and their blood sugar was so low. They just weren't understanding and processing with their brain the things that we normally do.
Blood glucose below 54, which is a level two event, is very serious and is called a medical emergency, actually, because it needs to be dealt with. If you don't deal with it now, you're going to continue on and have the risk of much more serious medical complications. Obviously, if your brain doesn't get enough glucose over time, you'll have permanent brain damage. People can faint. They need to be rescued. That's what a level three event is. If they can't rescue themselves and deal with this medical emergency themselves, it's deemed a level three event. This is, again, when someone passes out or, worse, has a fall, and then is so disoriented that they can't manage to get their blood glucose higher again. That's level two and level three, and that's what we're measuring.
Those are the long agreed upon endpoints with FDA for measuring hypoglycemia events. What we're measuring in the phase III, our specific outcome, again, this is part of the guidance, is a composite of level two and level three events. Both of them are important, and really the composite is just counting both of them, and you can't have two events in an hour. If you have a level two and a level three, and like you say, they do travel together if you're really having a blood glucose drop, you could have both. You only count one for the purposes of the primary endpoint, but you do count them both. You add them up, and we're comparing the number of hypoglycemic events, level two and level three in the placebo group to the number of events in the active group.
Hopefully, we're seeing a difference there where people on drug over the course of 16 weeks, and maybe we go to the next slide. Well, of course, before we do that, we always have to talk about safety, and that's another thing that we quite appreciate about this program. The side effects have been really mild to moderate and transient. We didn't see any serious treatment-related AEs. The most common AEs really sort of have to do with, again, similar diet thing, diarrhea, maybe headache, things that might be associated with hypoglycemia. We saw in relatively short studies, I say we, but Eiger and Stanford, the groups that ran these studies, saw no discontinuations. They were relatively short.
As we compare, there's a nice slide that we have that's worth taking a look at. This is the three studies lined up on top of each other, so you can really see how they worked. What's changing, what's different, we have another slide. The phase IIs were admittedly shorter. Looking at 28-day durations, crossover to different doses or crossover between placebo, things like that. The duration is relatively short. Let's call it a month. We're doing 16 weeks study, the double-blind period, so it's a longer part of the study. Most other things we're trying to keep exactly the same as we've done. Another important point to note is we're also studying just one particular type of bariatric surgery, which is Roux-en-Y, or RYGB, Roux-en-Y gastric bypass, it's so called. The other major type is called sleeve gastrectomy.
We have had a few patients with sleeve gastrectomy in the phase IIs, on the order of 10% or 15%. Again, being a small company and wanting to make sure that we made as few changes as possible, we decided to focus on Roux-en-Y. That's where we had the most data. We think there's a very good argument for, and of course, we'll have to see the data, because this is not a surgical, we don't believe it's a surgically driven outcome. It's a GLP-1 response outcome. Hopefully we'll get a broad label. We obviously have a long way to go before we're in label discussions. It should be noted that we're just doing Roux-en-Y gastric bypass. Here are some of the other differences in the studies. Again, we're using the same study population, very important, the same run-in criteria.
We have a run-in period. In the previous phase IIs, it was a 14-day run-in period where to be entered into the study or to be randomized, you had to have at least an event a week, one of these serious events a week that's tracked the same way we're going to track it in the study. In the phase III, it's a three-week run-in period. We want to get people more comfortable with using the continuous glucose monitor that's blinded, so it acts as an alarm if blood glucose goes below 50, again, same thing that was done in the phase IIs. We want people to get used to the technology, get used to tracking the events on their phones with the dropdown menus, et cetera, and then also having an event a week.
Our run-in for LUCIDITY, our ongoing phase III, was a three-week run-in period, but the same event rate, an event a week over three weeks. That's a little tighter. To get your coin flipped three in a row is a little tighter than getting two in a row, obviously, if we all remember our probabilities. Really trying to aim for the same thing, which is making sure that people have a baseline set of events that we can then track once they're on drug versus placebo, again, over the 16 weeks. There's a 32-week open label extension period after the 16-week treatment period. We'll be reporting the 16-week primary endpoint.
When we announced at the end of March on track in Q1 of this year, full enrollment, you can add your 16 weeks from that with obviously time that it's going to take to bring the data in-house, make sure it's all clean, run the statistics, et cetera. You're looking at the sort of the tail end of Q3 for data, which again is what we've been saying, Q3, but with the March date, we'll probably get a little bit more, I don't know. Who knows? Maybe we'll get more precise on that when we get through and get closer to the timeframe. We've seen the differences. Just maybe a last thing on the market. How we doing on time? I only have a few minutes left here. I want to make sure Ami has some time for comments and questions.
This is a really nice slide that pulled together both from our own research. One of the questions people have, obviously, you might imagine, people spend time, they want to learn about the disease. That's fairly straightforward. Learn about the clinical program. Obviously, that's very important because we want to replicate what we've seen in those five previous studies. Though the question quickly moves to, well, where's the market? What's the market like? There's not a drug already on the market for this, so that obviously has opportunities as well as some potential risks because we can't look sideways and say, "Oh, well, I know BMW sells a lot of cars. That must be a nice car market for German-designed automobiles." What of PBH? As I said, so let's orient you.
Over the last 10 years, there's been a little over 2 million bariatric surgeries in the United States alone. Okay? If you take 8% prevalence, and we'll get into how we get that through the literature and some of our own work, that leaves you with a target market of 160,000 PBH patients. Now, people say, "Oh, what part of those are serious and would want to take the drug?" As we've been learning about this market, and it is a large opportunity, but only because there's so many people who've had bariatric surgery quietly over the last decade because it's so effective. It is a small side effect of bariatric surgery, but because there are so many, it makes it a really, I'll say, a larger orphan market than otherwise.
We went through and you can see, like I said, these 12 or so studies on the right. Many of them prospective, right, where they'd actually have people come in with thousands of people. The Ns on these are pretty interesting. It did occur to me after we pulled all this literature together, it can't be a small market if so many people are spending their time trying to figure out how many people have hypoglycemia, right? If it were a small market, there wouldn't be any papers. People want to do papers about things that are important, and they want to do papers about things where they can find data.
Some of these are prospective, and so they literally had people come in after bariatric surgery, and they would do an insulin challenge test and say, "Are they hypoglycemic or not?" This is where you get this 20%-50% of people after bariatric surgery are hypoglycemic, but they can manage it with their diet. They don't eat heavy carbohydrates, right? They don't eat liquid sugars. They spend a lot of time. They don't eat large meals. They're very, very careful with their diets. Those aren't the people we're talking about for avexitide. Again, we're talking about the people who doing all the diet work possible, controlling their lives as much as possible. Because again, remember, it's not just diet that drives blood glucose. It's stress, it's exercise.
What we've heard from people, they can't walk around a track because literally that amount of exercise will, again, logic, right? Your body's starting to exercise, your body produces sugar. Unfortunately in this disease, your body sees sugar, it overproduces insulin, and you have this massive drop. We're trying to get people back into a normal functioning range here. Further, and this is the last point I'll make about the avexitide market, the group at Stanford has done a much more detailed three or four-year, bottom-up study looking at various codes. There are codes for hypoglycemia. There are not yet codes, ICD-10 codes, for post-bariatric hypoglycemia.
The work Stanford did, and the work we've done on claims data, and you can see the Stanford work published here, and interestingly, using different methodologies, Stanford gets to about the same number we do, which is medically important PBH, that's affecting people's lives. We're excited. We feel like we've found an important drug in an important area. We acquired this asset only in the middle of 2024. Our first participant was dosed in April of 2025. We anticipate data in Q3 of this year. We hope, again, with Breakthrough Designation, we hope we can turn around the NDA as well as the review relatively quickly and are planning for a 2027 launch. We have Orphan Designation here, too. Strong patents that go out through 2037. That's without Patent Term Extension, so there's a potential there.
We're working on 318, which is a longer acting form. Again, why we think avexitide is a great drug, but a daily injection in a large market, right? We want to be the first ones to make that market even easier for people to use. That's why we're investigating a more longer-acting peptide with our Gubra collaboration. I'll just wrap and say, as I mentioned earlier, maybe we'll go to the slide that talks about 114, which is our calpain-2 targeted, or this is a good one. We're running our study in 114 that's ongoing. We ought to have biomarker data this year. It's in kind of a classic dose escalating study. We'll be reporting out. We're already in cohort 2. We'll be reporting out the cohort 1, the lowest dose biomarker data.
We know that there are calpain-associated biomarkers and other things like NfL that people are very interested in in ALS, and we ought to be able to see those biomarkers. Now, whether we'll see it at the lowest dose, obviously you want to start, particularly with a targeted ASO like this, with a dose that all the regulators feel comfortable with. We do think that we're going to need to escalate here some, but we've seen a really nice safety margin in animals, and so far, we're very happy with how that study is going. Stay tuned for more work in ALS. The vast focus is on avexitide, and with that, I'll thank you for the attention. We'll remember Maggie in our hearts, and all the folks suffering in silence with this disease, PBH.
Hopefully, we'll have positive data so we can help them get back to leading normal lives. Ami , over to you. Sorry, I went on. I get excited about it. There's a lot of detail here that I only covered very quickly.
Yeah, no.
We're always happy to fill in more if people are interested.
Sure. Jim, I think this was really helpful to go over the story, and the detail was necessary. In the time that we have, just a quick reminder for listeners, if you have any questions, feel free to send it to me through the dashboard. I wanted to spend a couple of minutes just talking about the phase III LUCIDITY study. You mentioned that the primary endpoint is a composite of level two and level three, and this is the first time you're sort of studying this drug for a longer duration compared to the phase II work that was done. Help me understand whether you anticipate any change in the efficacy profile with longer duration of treatment. As we think about the composite endpoint, is there a requirement from the FDA standpoint in terms of the effect size that they would want you to demonstrate?
Yeah.
Is the bar statistical significance?
Yeah. Well, thank you. All good questions. Let's see. Of course, the duration, right? This is going to be a drug that we do expect is used chronically. People will be on this for a long time. Interestingly, the average age of a bariatric surgery is the early 40s. Another important note, you'll see kind of an imbalance in our studies between men and women, and that's because there's an imbalance in people who have bariatric surgeries. It's almost 70% of the people who have bariatric surgery are female. Obviously you'd expect that carries through to the people who have post-bariatric hypoglycemia. The other thing, and one of the other criteria is you have to have sort of diagnosed PBH for over a year before you enter into the study.
Some of our patients, I believe in the phase II, the average duration of living with PBH for folks was seven years. We can have people, again, and that's only in your early 50s. Again, we expect people to be on this drug, if it works, for a long period of time. What we do know about the GLP-1 system, right, millions of people have been on the agonist. There doesn't seem to be any waning of effect. Now, obviously, if you come off the drug, they don't act any longer, but I suppose that's the hallmark of an effective drug. If you go back to what was the problem, you're not necessarily curing the disease, right? We haven't gotten there yet with all our wonderful pharmaceuticals. Some, but most you still have to take them to have the effect, so that's not a surprise.
We think that the target, the GLP-1 receptor is one that can be blocked and again we're not. It's a competitive binder we're not removing at [an intresting later or knocked out minds], without the GLP-1 receptor without the GLP production and they survived just fine, right? Again, because the body's insulin response is so critical, GLP-1 is a modulator, and it seems to fine-tune the response and maybe helps in lots of other ways, but it's not like you're completely removing insulin, right? If like you removed insulin from people, they won't be able to survive. So, were hopeful. The other part is I think that, so ṭhe only treatment that people have for this is again, this very very strict medically managed diet .
We feel like if people have been living with a very medically meaningful case of post-bariatric hypoglycemia, they're on that diet every day, and they're doing everything they can to avoid events. Because literally, the ADA says, and you can pop it up on Google, a single event of hypoglycemia is a medical emergency, and so you never know when that next one is going to happen. It's very hard. You hear from people like Maggie, they don't live alone. They rarely drive their car. They frequently don't leave the house. It's very hard for them to work. In one of the studies, 85% of the people with PBH characterized themselves as disabled, so it's a very debilitating condition.
We think that, of course, it's the experiment, we'll have to see, but that the management of that diet is going to be consistent because they really don't want the consequences of going off and having a pizza are so terrible that, one, you'll probably only do it once if you do it because you'll realize that you're overtaxing your system. Again, this is why you run a placebo-controlled study, and this is one of the reasons why we have 78 people in the study and not just 20. Even though 20 drove a p-value with three zeros in front. We're obviously making it a much bigger study because there'll be more variability, and I believe we're in 12 centers all around the United States. No international sites, which again, should help with variability. Experienced clinical sites. No one dominating the clinical outcomes.
That was I think the answer to a couple of your questions. I might not have gotten to everyone, though.
Yeah. No, I think maybe just sort of honing down on the primary endpoint in the study. Maybe if you could sort of talk about the powering of.
Mm-hmm
The endpoint.
That's right.
Composite endpoint of level two and three.
Yeah
Maybe sort of define for us the amount of difference you saw in the phase II. What do you need to see in phase III to be successful?
Yeah. Thank you. If we went back and looked at the phase II-B study, which is the one that used 90 mg, which is the one where the dose that we're using. Just pulling up, it's on slide 10 for people following along at home or if you want to look. Yeah, there we go. Thank you. Again, a very robust p-value, and we saw a 64% reduction in the composite, so looking at level two and level three. Again, I would say this is why we got Breakthrough Therapy designation. Obviously, bigger study, more variability. I think if we saw this, and again, this is the data where more than half of the patients, the median patient, had zero events. That's pretty extraordinary. We literally took people to zero events.
That would be something that I think the medical community and the patient community would be very excited about, obviously, as would we. Now, we're powered to see a 35% difference because we're wanting to be more conservative, right? We saw a 64% difference. We're powered to see a 35% difference, and including a larger placebo effect than we saw. Again, the question is, well, what happens with people? Is being in a study going to change their hypoglycemic events? There's arguments that it might improve. There's been cases. Another company studied dasiglucagon in both CHI and PBH. Again, smaller studies, 12 or 14 people. They did not see a placebo effect in PBH. They did see a placebo effect in CHI. They're kind of different diseases. We don't have the time to get into them here.
Mm-hmm
CHI, you have an overproduction of insulin, so you want to eat more to give the insulin something to do. Here, you're eating food, and it's more reactive, and then you have the overproduction of insulin in the absence of sugar. Actually eating causes the hypoglycemia rather than the other way around in CHI. There's many other differences as well. Suffice it to say, we tried to power conservatively. The last thing is, there's no bogey that the FDA says, "Oh, you have to see an effect of X." They're obviously going to want to see something that's safe and efficacious. We've powered the study, like I said. This is a very clear endpoint for them. Our expectation is there'll be little debate on the endpoint, right? You lower the events of hypoglycemia with tried-and-true measures.
Again, we're using the gold standard that they want to see, which is finger sticks, so the patients are taking finger sticks each time they feel symptomatic or the alarm goes off, et cetera. We don't think anything beyond stat sig versus placebo is really what's required. Obviously, we're going to hope for better than that, right?
Yeah.
If we can replicate what we've seen in the previous studies, that's why we're so excited about this development program, as it has shown. Again, as I started off with this morning, it is a very important pathway. Antagonizing an important hormonal or incretin pathway is a tried and true approach to drug making. We think we've shown that we have an antagonist, and now we're doing the hard work of biology and then testing it, 78 people.
Yeah
At home over 16 weeks.
Yep. Yeah. No.
Yeah.
I think you've sort of thought through what you need to demonstrate in the clinical study, so it's about executing on the study and seeing the data readout.
Yeah. Obviously, I want to thank you for the time. I think we're at time.
Yeah.
Thank people for their attention. They can certainly find us through Needham or through our own IR team, to follow up. Again, it's fairly dense. Depending on where you want to drill down, there's a lot more information that's out there. We're obviously more than happy to get people educated as we try and replicate this clinical study, and then hopefully deliver a therapy for folks who are living with a very, very difficult disease. Ami, thank you so much.
All right.
We'll see you soon.
Thank you. Thank you, Jim. See you soon.
Happy Tax Day. Bye.