Conference Transcript - EPRX 2026-06-03

James Halliwell, CEO

Good afternoon, and thank you very much for being here. My name is James Halliwell. I'm the CEO and co-founder of Upraxy Pharmaceuticals. Really appreciate everybody here in person and those who are listening not live with us here. So really appreciate you taking the time. I'll give you a little bit of background on myself while you're reading the really fine print there of the forward-looking statements. So physician by background, cardiothoracic anesthesiologist, spent my career doing cardiac transplantation, which really required a lot of precision. And why does that matter? Well, it matters because you need to be very, very precise with the drugs that you deliver. So it's about where those drugs go and also how they deliver when they're there. What you're seeing on the screen in front of you here is the diffuse fear technology. So this is something that we created in-house. It's covered by five different patent families for a very long period of time. What it allows us to do is to actually give an injection directly into wherever it is we want to be. In this case it's the esophagus and so we'll be talking more about this indication as we go. Once we inject in there we have the ability to actually deliver the drug directly into that tissue and deliver for a long period of time up to a year so the drug is going where you want it and not where you don't want it. So let's talk a little bit about esophageal disease and here we're going to talk about EOE or eosinophilic esophagitis. I think of this sometimes a little bit simply as asthma of the esophagus. So this is an inflammatory condition, and the thing that's really interesting about EOE is that a lot of us don't know about it, yet it's actually become incredibly common. And so the prevalence has grown very rapidly. Several years ago, in 2020, this was an orphan disease. The last orphan indication last orphan designation was actually given out in 2022. Right now it's gone way past those numbers and they're estimating by 2030 a million patients are going to have EOE. So it means you probably know someone that has this disease you just haven't talked to them. It's incredibly difficult to eat food gets stuck you can end up in the emergency room and there are not a lot of treatment options available today. In the United States the only long-term treatment treatment option is a biologic, which is delivered once a week via injection. So there's a lot of need for patients here, and we're going to be talking about what we hope we're going to be able to offer to these patients. This is a very complex disease, so you can't target just one thing, and we've seen quite a few failures in this space where people have targeted, for example, just IL-5, just mast cells. What we are using is actually our API is fluticasone propionate. It's a very well-known steroid, well-characterized, been around for a long period of time, but we're delivering it in just the right way into the tissues. What this allows us to be able to do is to target not just one of the inflammatory mediators that are involved here, but many of them. So eosinophils directly, lots of inflammatory cytokines to really get control of this disease. We're going to walk you through the data that we're seeing from our phase 2A trial. So how do we actually deliver this? Actually gets delivered during endoscopy. So patients are already going for that endoscopy and we give the physicians able to give injections directly delivering the medicine into the esophagus and here you can see the pattern of these injections. When we look at this, this sounds like you think, oh injections into the esophagus, it sounds complicated, it sounds difficult, it sounds painful. Patients actually can't feel these injections. It doesn't take very long, it takes four or five minutes for physicians to do, and it's a very small amount of time relative to the amount of time they have booked for these procedures in their endoscopy suite. And so there's a lot of advantages for the physician as well as for the patient in actually having the drug delivered this way. So patients, once they are diagnosed with eosinophilic esophagitis, they actually have to show up once a year and to be able to go for an endoscopy. Why? This is actually a progressive fibrostrenotic disease. So once you have it it's going to continue to get worse. And so 60% of patients right now are showing up for their annual endoscopy, 20% it's about every two years, and 20% don't show up that often. So we're really piggybacking on the back of a procedure patients already going for, they're already having, and being able to add a few minutes to that to be able to deliver a therapy for a very long period of time. This also really fits the gastroenterologist's practice, which is they like to do endoscopies. It is a big, important part of their practice, and it fits their compensation model and the way that they work, as well as for a patient. This is very different than having to take an oral medicine once a day, twice a day, or an injection once a week. This is just simply a once-a-year therapy for patients. It also represents a really high-value commercial opportunity. When we look at the pricing that's available today for products that are already on the market, the pricing is, there's a lot of premium pricing that is there. And so when we look at this and we'll talk about where this belongs, when we talk to key opinion leaders, when we look at how this data is being received, It's really viewed as sort of the second-line therapy after proton pump inhibitors, which are really the first-line therapy. So avoiding and bypassing the daily oral medications and the weekly medications that are currently being taken, but not really leaving patients with a full satisfaction. And also compliance in this disease is a real issue. Digestive diseases week was just a few short weeks ago. physicians were continually talking about compliance with existing medication and how poor it was. There are some published studies that say compliance with daily oral medications in this disease is only 30%. So in other words 70% of people are discontinuing because they dislike it so much, partly because of side effects and partly because of convenience. So let's now talk about some data. So the RESOLVE trial is a two-part trial. The first part of the trial is what we're going to walk through in data but first I want to level set a little bit. What does success actually look like for a product in eosinophilic esophagitis and particularly for this product? So number one is durability. So we know very clearly in talking to patients and talking to physicians and in talking to payers the durability lasting between nine and twelve months from a single injection is actually incredibly important because it aligns with a convenient time for the patient and in alliance with the physician's practice. Symptoms. What we know is that actually symptom control has been very difficult in this disease, and so achieving a 40% rate of clinical remission is actually a bar that leads to a lot of uptake by KOLs in terms of prescribing and high volume prescribers, as well as would ideally reach a lot of satisfaction for patients. Tissue health. We want to see improvement in a meaningful degree in both inflammation and histology. And it's interesting, you'll notice I haven't really talked about eosinophils here. This disease is really shifting from chasing reducing eosinophils to actually reducing fibrosis and improving patient symptoms. And so that's why these are the focus here. And obviously something that is very safe, and we'll talk all about that. So let's look here at what we see with our 1B2 trial. So this is the first part of the trial, the part A. This is a dose escalation trial. So this is all about testing how many injections do we need, what dose do we need, in order to be able to get the kind of efficacy that we just talked about really generates to success here. So here what you'll see is at the beginning we only followed patients for six months. As we got to higher doses and more coverage we followed patients all the way out to one year. And we've been releasing data as this has been going. We're going to talk about pharmacokinetics, safety, and also all of the outcome measures that are here so you can see this data. So first let's talk about pharmacokinetics. I showed you that little diffusphere molecule which is how we deliver drugs. Flutigazone, if you were to give it by itself, only lasts a few hours. And here what you're seeing from a single injection that we are delivering across a whole bunch of doses here all the way out to the one-year time point. So we're getting very strong durability from a single injection given in a five-minute procedure along with your endoscopy. You only see a very small peak in the first 24 hours. After that is a zero-order kinetics for 52 weeks. So how does that pharmacokinetic profile translate into efficacy? So here what you see is across a variety of cohorts. You'll also notice the numbers decrease over time. That's just because all the patients haven't reached out to the final time point yet. That data will all be concluded as this trial is concluded in Q3 of this year. So lots more data to come. What you'll notice is that by two weeks, we've achieved 40% clinical remission. And then patients are seen close to 60% clinical remission by week eight. And at six months, it's 80% of patients in clinical remission. and then actually maintaining and holding that about all the way out to 52 weeks. So demonstrating that durability, demonstrating that patient symptom response, and the Straumann Dysphagia Index is looking at multiple measures of discomfort with swallowing. So one of the interesting things is why the difference between two weeks and six weeks. We often think when we give a medication that we get its peak effect early and not late. And the answer to that is this drug fluticasone propionate is doing a couple of different things and we see that here demonstrated when we look at EREFs. So EREFs are basically a visual guide to be able to tell us about both inflammation and also structural abnormalities. There's a lot going on in this slide. I'll distill it right down. Essentially what it is saying is that the more coverage we give and the more drug we give, the more impact we have on EREFs, meaning that things like inflammation, exudate rings and strictures are improving over time as we give this drug in higher doses and more coverage through the esophagus. If you do not deliver it evenly throughout the esophagus and don't give enough drug, you don't get the results that you want, which when we think about a daily oral medicine or a twice daily oral medicine where compliance is an issue. What this is telling you is if you are not consistent you will not get results and we see that throughout the data with other mechanisms and delivery and other drugs. What you're looking at here is biopsies. So there we were looking at symptoms, then we were looking at visual signs, and this is now actually looking at the tissue itself. It's looking at inflammation and it's looking at structural abnormality, so actual fibrosis. You'll see our three highest doses here. The red is sort of the bar. That is where the best is today in terms of response in EOEHSS. When you look at the yellow, which is the yellow and the green are the two doses that we're using in our phase 2b trial, what you can see is a 50% better response in the yellow and then 50% better again when you look at the green bars there which is our highest dose. Not just demonstrating improvement in inflammation but also improvement in fibrosis and durability all the way out to nine months. All again from that single injection given at time zero. So very meaningful response and again not something that is placebo responsive in any trial. This is just hard validated data. We also want to be able to look at EOE in the subscores. So I talked about that it's both inflammation and it is also structural. Here what you're looking at is the same thing. The more drug we give, the more coverage that we give, the more we are having an impact on inflammation, but really importantly we're having that impact on fibrosis. We are reversing the scar tissue that is occurring in this disease, why is that important? Because that's what's leading to that symptom improvement at six months where we have 80% of patients in clinical remission versus 40% to two weeks because we're actually altering the underlying state of disease in the esophagus. So not just stopping progression but actually reversing disease. We did talk about eosinophils and that eosinophils have not really correlated well to actually getting symptom improvement? Well, we kind of see the same thing in this trial. We do reduce eosinophils very dramatically. You can see the percent of biopsies in remission here, and again, there is a pretty good dose response here, and you can see our highest dose doing the best. That said, we don't actually see a correlation between eosinophilic reduction and patient symptoms the way we do with when we see an improvement in fibrosis, and we see an improvement in inflammation. There, we really do see that correlation to improvement in patient symptoms. So overall what we're seeing here in our early data is that patients seem to be getting a healthy clinical response. They're also seeing a very good response in terms of their histology, fibrosis, and inflammation. Again from that single injection the other question then becomes what about tolerability and safety? So when we look care, we have over 230 months of patient follow-up. Fluticasone propionate being a corticosteroid, the things that you often worry about in this disease with oropharyngeal candidiasis being the big thing in EOE treatment when you take a corticosteroid. You will see rates on product monographs around the world and in other studies of 25 and greater percent of oropharyngeal candidiasis. We've had a zero percent rate of oropharyngeal candidiasis throughout the entire follow-up period and patients are followed very very closely. There have been no serious drug-related adverse events and no change in cortisol and no change in glucose level. We talk a little bit about procedural adverse events there. So that is talking about people have a sore throat. So we have about 20 percent of our patients that have a sore throat, last for about 24 hours. It turns out that that rate of sore throat and duration of sore throat is exactly the same as if you went for an endoscopy and did not have the procedure of receiving the drug. So again really demonstrating that this has been very safe, well tolerated by patients, and people do not spend time in the endoscopy clinic any longer after their procedure than if they didn't have the procedure. So really not affecting again practice flow through. So let's talk a little bit here about what's upcoming. So this is the phase 2b, so the second part of this trial. So here what we're looking at is a single administration, so randomized controlled trial, double-blinded, and patients are coming in, they're either getting 20 sham injections, so that is injections of just our vehicle, so that's the placebo, or they are getting the six milligrams of drug or the eight milligrams of drug per injection site, and then we follow them all the way out to a year. Now the placebo group actually crosses over at six months. So at the six month time point the patient remains blinded. They show up for what they think is a routine endoscopy to get biopsies and evaluate the medicine. While they're there the physician doing their procedure is unblinded and randomizes them to either dose A or dose B while the patient is under anesthetic and remains unaware that they even got a procedure. We're following pharmacokinetics, safety tolerability, and all of the outcome measures that we just showed you. In addition to SDI for the patient reported outcome, we're also looking at DSQ, which if you follow EOE, you'll know that DSQ is also one of the other validated measures. So we're going to be looking at both. In terms of the sort of catalyst and timing and development path of this, again, we're going to have more data through Q3 from the 2A portion of this trial. And the 2B dose optimization, we're going to have interim data in Q4, so we will not have reached the 52-week time point. Instead we're gonna have a very meaningful data cut of patients out to six months, as well as we will have patients that are out to nine months in a year, as well as quite a few crossover patients. So that'll occur before the end of the year, so really looking forward to having that data. On the back of that data, we anticipate an end of Phase 2 meeting in the first half of 2027, setting us up to begin our phase three trial where our hope and expectation is a single registrational phase three trial likely to be sized around the 300 patient mark in order to meet the safety database and obviously be very well powered there. So we anticipate probably just picking a single dose as we go forward into that phase three trial. One of the really interesting things about the data that we've just described. So we talked a lot about the fact that this was being injected by the physician exactly where they wanted it, that we're seeing really good safety and tolerability thus far in this trial, and in addition to that, that we're reversing fibrosis. So one of the things that the physicians have noted, we see it on the EREF score and we see it in the EOHSS, is that patients are entering this trial with strictures and those strictures are resolving. So if you imagine taking a scar tissue and actually reversing that scar tissue. That was really important to the physicians and they came to us with two things. Number one was there are a lot of patients with benign esophageal strictures. So 5% of those patients have EOE, 95% of those patients do not have EOE. Most of them are coming from having reflux disease, Barrett's esophagus, and procedures that have happened in their esophagus. The therapy today is a balloon dilation and an injection of triamcinolone, so a short-acting steroid. So they're already doing the procedure of injecting the steroid, and they've shown in prospective randomized controlled trials that that works. It extends the duration of time between the balloons that they have to do. So the physicians have really come to us and said, we see your drug working in EOE, and we would like to explore it in this disease. This is a disease with a million patients in the United States, no current therapy available, and really not much in the way of development happening there right now. And 500,000 of those patients are actually going for balloon endoscopies on a fairly regular basis. We anticipate beginning that towards the end of this year, early part of next year. The next thing that physicians came to us was actually lower GI physicians. It was fibrostenosing Crohn's. So the difficult thing for physicians is they are doing colonoscopies and seeing in the proximal colon and terminal ileum that patients are actually developing these lesions that are fibro stenosing. So what that means is they're going to get longer, bigger, and the lumen is going to get narrower and narrower of the colon that often then leads to bowel obstructions and surgery. The problem is there are not great therapies for that disease today and so what they've suggested to us is because they can see the lesion and they watch it just simply grow over the years, that to actually be able to inject the fluticasone directly into that lesion to try and stop its growth and prevent a stenotic lesion and a bowel obstruction would be very, very appealing. So we're busy working with KOLs now on a trial design for fibrostenosynchrons, which would be a program we would look to begin in 2027. There are other things that we can look at in gastroenterology and then obviously expansion beyond that. If you start to use your imagination of what you could do with a technology where you can deliver directly into a tissue bed, be able to deliver a medicine there and not off target and be able to do that for a long period of time, a lot of things are going to come to mind and we're busy working on quite a few of those things early in our labs as as most of our efforts though are focused on gastroenterology and expanding that there. A little bit of sort of where we are from a runway perspective, so at present we have just over a hundred and forty million dollars in in essentially cash and in short-term GICs. You'll also notice that we have a lot of insider ownership board and management on a fully diluted basis on 21%, 11% on an issue, an outstanding basis, a market capitalization of close to $500 million. And so this gives us the ability to deliver everything that we talked about in EOE, so through Phase 2b to the launch of the Phase 3 program, allows us to do fibrous to no-synchronous, benign esophageal strictures, and takes us through till mid-2028. So really giving us the capability to be able to to really drive forward deliver on these programs deliver on a lot of catalysts for shareholders and and really backed by by a great group of investors so I will I will leave a little bit of time here for for questions and so so if there are any questions in the packed room here happy to take them I stand between everybody in a cocktail hour so So with that, thank you very much, everybody, for taking the time to be here at the end of a very long day. I really appreciate it, and enjoy the rest of the conference.