Good morning and welcome to the Cinclus Pharma Virtual KOL event. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. As a reminder, this call is being recorded and a replay will be made available on the Cinclus website following the conclusion of the event. I'd now like to turn the call over to Christer Ahlberg, Chief Executive Officer and President at Cinclus Pharma. Please go ahead, Christer. Thank you very much, everyone, for joining us today. We are excited to host this session focused on linaprazan glurate, our unique next-generation potassium competitive acid blocker, our PCAB. We will begin with an expert overview from our key opinion leader, KOL, who will walk through GERD, the disease, the limitation of current therapies, and how PCABs, through their novel mechanism of action, rapid onset, food-independent dosing, and limited interactions, may help address persistent unmet needs, particularly for patients with severe erosive GERD. We will also review real-world patient cases that illustrate the everyday challenges clinicians face in managing these patients. I refer you to the fact that we may be providing forward-looking statements in this presentation. I ask you to refer to our documents on file. So, and after the KOL segment, Peter Wallich, our Commercial Director at Cinclus Pharma, will discuss the commercial landscape. Peter has a long background within the PPI field and, as former Vice President of AstraZeneca, and responsible for Nexium and Prilosec launch globally, and the huge success of both the products and also switching from Prilosec to Nexium. As he will highlight, erosive GERD represents a large underserved market with significant unmet needs, and we believe linaprazan glurate has the potential to become best in class and to meaningfully differentiate in this space. It's now with my great pleasure to introduce our KOL speaker, Dr. Prateek Sharma. Dr. Sharma is a Professor of Medicine and the M.J. Blaylock & E.T. Underwood Professor at Cancer Center in Kansas City, and is internationally recognized for his leadership in advancing the diagnosis and management of GI diseases and cancer. His pioneering work across esophageal diseases, GERD, Barrett's esophagus, imaging technologies, digital health, sustainable healthcare, and advanced endoscopic treatments has helped shape clinical practice worldwide. With over 550 publications, including guidelines, book chapters, and several major textbooks, his research has appeared in top-tier journals such as NEJM, JAMA, Gastroenterology, AJG, and Gastrointestinal Endoscopy. He's also a frequent invited speaker at major national and international scientific meetings. We are honored to have him with us today. With that, Dr. Sharma, please take it away. Okay, thank you very much, Christer, and good morning to everyone. So what I'll do is just set the stage and talk about where we stand with the management or approach to gastroesophageal reflux disease, what's the current landscape, and despite our advances, what are some of the unmet needs that will still persist for this huge patient population, so first of all, it's important for us to understand what is gastroesophageal reflux disease, because I bet you that all of us who are on the call today have at some point had some heartburn or epigastric burning, et cetera, and so when does that turn into a disease from just a simple symptom? This is the Montreal definition from 2006, which defines this: that when the reflux of stomach contents starts causing troublesome symptoms, meaning that the patient starts getting impacted by it, quality of life, and/or complications occur, which is from the physician's perspective. This is how we define gastroesophageal reflux disease. The other thing to recognize is what's the global impact of this condition. It was assumed to be a condition of just the West, but now we know that this is something which impacts, you know, people in the East as well. If we look at the population prevalence, this is a more recent survey which was done in the U.S., close to 70,000 respondents. This is in the general population surveys that were sent out, and you can see the demographic breakdown of this population. If you look at any reflux symptoms, close to half of the population of the U.S. will have any reflux symptoms. Now, if you go to the definition, which is troublesome symptoms, that's about 20% of the U.S. population. So one in five in the general U.S. population will have gastroesophageal reflux disease. And if you look at any symptoms in the past seven days, it's about a third of the population. So no matter how you slice and dice it, it still tells you that a huge proportion of the U.S. population suffers from gastroesophageal reflux disease. Now, coming to the global, you know, distribution of gastroesophageal reflux disease, it tells you it's a worldwide prevalence. The colors shaded in red and maroon are high prevalence, and those with green are less prevalence. If you were to just look at an average, roughly about 14% of the global population also suffers from gastroesophageal reflux symptoms. This is, of course, a disease which started in the West, but now it has become, unfortunately, a global issue which we all have to deal with in different parts of the world. With that in mind, let's look at why is it just not symptoms, but something beyond symptoms as well. This is looking at disruptive reflux symptoms, which are frequent versus what I just told you is just like symptoms which the patient is not really concerned about. If you look at disruptive reflux in which the patient has frequent symptoms, absenteeism from work is close to two and a half fold higher. Sleep quality goes down by about 1.5 folds. Psychological and general well-being also is impacted, and the physical and mental health is impacted as well. So it's not just a symptom, but it can start impacting other parameters of patient or population quality of life as well. So it becomes an important condition. So that's from the patient perspective. Now, from a physician perspective, these are things that we are very concerned about, which is the complications. Erosive esophagitis is found in about 30%-40% of patients who undergo endoscopy for gastroesophageal reflux disease. Now, this is a condition in which you see, if you can see my mouse here, the arrow, these are ulcers or erosions, mucosal breaks in the esophagus. This is a patient who has the severest form of gastroesophageal reflux erosions, which is grade D esophagitis. We classify this from A through B, with A being mild and D being the severest. This is what it looks like on endoscopy. These are things where you get concerned about. Also, if this doesn't heal properly, it can lead to narrowing of the lumen of the esophagus, causing dysphagia or difficulty swallowing in which the food can get stuck in the esophagus of the patient. These are called esophageal strictures, which happen in about 10% of untreated reflux patients. Barrett's esophagus, this is the precancerous condition for esophageal cancer. This is found in about 5%-15% of patients with gastroesophageal reflux disease. Again, if you follow my mouse, the normal esophagus is lined with this white squamous mucosa, but in Barrett's, that white squamous mucosa is replaced by this red lining, which is the columnar-type epithelium, and this is the precancerous condition. And of course, because it's a precancerous condition, what we are concerned about is the development of esophageal adenocarcinoma. And this is the mass in the distal esophagus, and it's been well documented that reflux disease is a risk factor for Barrett's esophagus as well as a risk factor for esophageal adenocarcinoma in its severest form. So these are the potential complications of gastroesophageal reflux disease. So in clinical practice, we typically classify reflux as erosive GERD or non-erosive GERD. What is erosive GERD? This is when you have findings on endoscopy which are abnormal, just as I showed you in the endoscopic picture before. On the other hand, non-erosive GERD is one in which the patient has symptoms, but when you perform the endoscopy, there are no findings of erosions or pathologic evidence there on endoscopy. Of course, you can see that the erosions and the erosive GERD look bad on endoscopy, and it is a more severe form of disease. These are some studies which have looked at the risk of progression in erosive GERD versus non-erosive GERD. And you can see that both Barrett's esophagus and esophageal adenocarcinoma are more common in patients with erosive GERD, which is a risk factor for these as compared to the non-erosive GERD. So erosive GERD is the bad form of the disease, both from a physician perspective as well as a patient perspective and from a complication perspective as well. So let's talk about PPIs or proton pump inhibitors, which all of us are familiar with because they've been around for decades and really changed the landscape of reflux disease or GERD management. Now, this is in the era of H2 blockers in which PPIs provided the most effective healing as compared to H2 RAs, so cimetidine, famotidine, ranitidine type medications in red. And of course, over placebo, this is how PPIs performed in patients with erosive GERD. So this has now become the standard of treatment for these patients in this situation. But if you look at the efficacy in severe erosive GERD, when we start talking about Los Angeles grade C and D, which by the way, I forgot to mention to you that the way we classify it is by the LA classification or the Los Angeles classification developed by the IWGCO, which is one of the premier groups evaluating reflux disease globally. And they are the ones that association came up with the Los Angeles classification, which is now the standard way of grading erosive GERD. So if you look at erosive GERD severity, C or D. You look at healing of esophagitis. Incomplete healing occurs in 33% of the patients, even with twice daily BID PPI therapy. And in these severe erosive GERD patients with C and D, close to half of them did not even demonstrate improvement to a lower grade of esophagitis with PPI treatment. These are studies that have looked at six-month healing, 12-month maintenance of healing, all across the board of the different PPIs which are available. You can read them on the right with different colors. Again, the colors are not meant to confuse you, but what it just tells you is that the relapse rates with different PPIs, different doses of PPIs within six months vary a lot, within 12 months also vary a lot depending on the PPI, the type of study, and the dose of the PPI that was used. But what is very clear is anywhere from 20%-30% as an average of patients are difficult to maintain of erosive GERD with PPI. How about patient symptoms and what do patients think of these medications? This is going back to that same survey that I showed you, which was published in 2020 in the U.S. population. During that survey, it was determined that these U.S., I wouldn't call them patients, but population persons because it's the general public, 40% of them were on medications. Of course, the vast majority were on PPI therapy. Some were taking antacids or H2 blockers. When these persons were surveyed about their symptoms while on taking that PPI therapy, 60% had persistent reflux symptoms despite the fact that they had been prescribed the PPI by their provider. 42% were having that burning sensation of heartburn. Close to 50% were having both the burning as well as bringing the contents back up, which we call regurgitation. PPIs, it appears that although good medications have a problem with healing, erosive GERD, specifically the severe erosive GERD, can also have a problem that patients or persons in the general population, despite therapy, still continue to have symptoms in that situation. The question comes up is that they're good, but what else is available today or will be available in the near future for looking at it? So for this, let's just step back because again, they're currently being used PPIs, but they probably have some issues which affect their overall efficacy. So first of all, we need to understand that they have an enteric coating because the naked molecule would be vulnerable to degradation by the gastric acid. But of course, this delays the absorption. They require activation by the gastric acid. So that's important. They only impact the actively secreting parietal cells. So you have to understand is that in the stomach, we have parietal cells which secrete acid, but in fasting, only 5% of these cells are actively secreting, whereas with meals, more of them are actively secreting. And PPIs impact only the actively secreting medication. And that's the reason you take it also before meals. They have a short plasma half-life, about two to three hours. Of course, they undergo degradation in the liver through the CYP2C19 pathway. So for individuals in which there is variability in the rate of how they get broken down because of the CYP2C19 pathway differentiation, patients can have different responses to the same dose and duration of the medication so that individual variability can exist. Now let's talk about the PCABs, which are the new medications for suppressing the parietal cell secretion of acid or PCABs or potassium competitive acid blockers. Now, these are some of the pharmacological features for PCABs which differentiate it from PPIs. They're acid stable, so they do not require that enteric coating, and hence they can be absorbed rapidly. So the mechanism or how they can act is very fast as compared to PPIs. They bind with both the active and the inactive proton pumps within the stomach. And so as PPIs need to be timed along with the medication, along with the meal, we ask patients to take it 30 minutes before their meal. That's not true for the PCABs because of the fact that they can bind to both active as well as inactive proton pumps in the stomach. And also their primary metabolism is not through the CYP2C19 pathway. So individuals who have variations in their CYP2C19 pathway metabolism, that inter-individual variability in response to a medication will be lower with the PCABs as compared to the PPIs. So now let's start and see what the data are for the PCABs. These are showing you some initial PK/PD data. This is using linaprazan glurate, and you can see that control of gastric acid is significantly higher. This is the amount of time that this PCAB can inhibit acid in the stomach, which is more than 90% of the time the pH remains more than 4. If you were to compare this to the PPIs, this is significantly, significantly higher as compared to that. Let's look at least the U.S. studies where we have vonoprazan which is available. These are the pivotal studies done in the U.S. using vonoprazan compared to PPI, which was lansoprazole in this situation. This is the phase three trial, and it's a non-inferiority design and eight weeks of treatment with this medication. On the left, you will see healing, which is the healing of erosive GERD by week eight, as well as comparing heartburn three days between the two medications that the patients were randomized to. This showed that vonoprazan as compared to lansoprazole was non-inferior for healing of erosive gastroesophageal reflux disease. Now, this is the maintenance phase in which the patients who achieved healing for erosive GERD were then randomized to two different doses of vonoprazan or a PPI, and this was continued for 24 weeks or six months, which is again very typical for these drug trials which are done. If you look at the maintenance of healing across the three bars which are presented here for the two doses of vonoprazan and lansoprazole in orange, and then healing of more severe erosive GERD grade C and D erosive esophagitis, you can see that the PCAB now starts outperforming the PPI in this situation. Here it's non-inferior, and here it was statistically significant in healing of erosive grade C and D erosive esophagitis. Now, if you look at other PPIs of vonoprazan from other countries, these were the data from the U.S. There's the systematic review which was published using six studies, again from globally, from specifically Asian countries, and compared to PPI, if you look at it, there's no difference in the adverse events. The overall efficacy was the same, but it's only when you start looking at severe esophagitis grade C and D is when the PCAB starts outperforming the PPI in this situation, so now if you do that same analysis, but you look at other PPIs which are available, not in the U.S., but ex-U.S., so including tegoprazan and keverprazan, these are 24 studies in which a network meta-analysis was possible in which you're able to compare PCABs with different types of PPIs in this network meta-analysis. You can see is that the failure to heal during the initial part is 6% with PCABs, 21% with PPIs. But with these PCABs, when you go to the maintenance phase, that delta starts actually now coming closer. So even with PCABs, 21% have a relapse of their healed erosive esophagitis at six months. So it tells you again that compared to PPIs, the PCABs are significantly better. There's no doubt about that. But even with the current PCABs, there appears to be some unmet need because these patients are having the relapse there. Let's look at it now going to those individual studies which have been published, and you can see the relapse rates are in gray as compared to when it's on the right-hand side. You will see that the relapse rates with the PCABs on publication which are available, the rate varies anywhere from 10%-20% of the population. So significant improvement over PPIs, but still some relapse persists. So now let's end up with a couple of cases which gives you some real-life scenarios which we see. Here's a patient who is taking PPI therapy and has persistent nighttime heartburn, which is sometimes a very difficult symptom to treat, is when patients lay down, the acid starts bothering them. And this is the patient who is taking the medication appropriately, still drinking some coffee, has a high BMI, but has persistent symptoms. We performed an endoscopy on this patient, and when we go in, what we see is severe erosive reflux disease despite the patient taking PPI therapy. And these circles just point to the area of ulceration and erosion. As clinicians, we are faced with what next? What do we do with this patient who has persistent symptoms and persistent severe erosive GERD in this patient population? So this is a need from both the patient and the physician perspective which still continues. This is another example. Somebody now who has dysphagia to solids, a patient who has reflux symptoms, long-standing GERD on daily PPI, had heartburn and regurgitation which improved, but now has difficulty swallowing in which some of the foods are now getting stuck intermittently in the esophagus. This patient on endoscopy had Barrett's esophagus, which is shown right here. And after some treatment, we saw that also in the distal esophagus, there was a stricture which needs to be endoscopically dilated or stretched. But the question comes up, what is the next medical treatment that we can give to this patient to heal the stricture, to heal the severe GERD which persists in this patient that is having these symptoms? So what I've gone over and shown you is that reflux is defined by symptoms and/or complications, and we currently use the Montreal definition for this condition. It impacts about one in five in the general U.S. population with a global prevalence of about 14%. Besides symptoms, it also impacts sleep, physical, mental health, and productivity, and has a negative impact on patient quality of life. Complications occur, and that's from a physician perspective. Of course, we are very concerned about erosive GERD, specifically the severe erosive GERD, Barrett's esophagus, strictures, and of course, esophageal adenocarcinoma, which GERD is a risk factor, but thankfully it's a low prevalence. Current treatment, PPIs are most effective. I've shown you the data over that. It has challenges with slow onset of action, a short half-life, and relapses which in some studies can be as high as 30%-50%. The current PCABs that are available have been shown to have faster onset of action, longer acid suppression, yet have some relapse rates in studies which can be as high as 20%-30%. With that, I'll stop, and I'll turn it over back to Christer. Thank you very much for your attention. It's Peter Wallich. Thanks, Professor Ahlberg. It was a super presentation. And even though I've worked with PPIs a long time and GERD, there's always new stuff to learn every time you see some new data. So what I'm going to try and do is spend a little bit of time in talking about the commercial side of what we expect with linaprazan glurate, and I'll touch upon some of the things that Prof. Sharma also alluded to. Now, the erosive GERD market is a strong opportunity with large unmet needs. And essentially, if you look at all the grade A and B and C and D patients in the USA and Europe, we're talking about 28 million patients. And if we boil that down to how many patients have severe GERD, C and D, based on the scale that Prof. Sharma talked about the Los Angeles classification, 10 million patients. The market that we're focused on, those severe patients, is about 10 million patients across USA and Europe using the same prevalence numbers that Prof. Sharma talked about. It's a large market. What's really exciting about this from a commercial perspective is also that it's a dynamic market. It's chronic, it's dynamic, and there's many switch possibilities. Essentially, patients come into usually, in most countries, their primary care. The primary care physician doesn't diagnose with endoscopy, but bases their diagnosis on symptoms, patient history, and treats with PPI. Eventually, if they have a patient who is still suffering symptoms or they're concerned about that this patient might have more severe GERD, they refer those patients to the gastroenterologist. In the gastroenterology setting, they do things like endoscopy and pH measurement. The approach to treatment with a specialist, depending on the type of patient they see, is they either use a standard dose of PPI or a high-dose PPI. About 60% of gastroenterologists that we talked to in our research said they're using high-dose PPI for especially their C and D patients, but even their grade A patients. That can be twice the labeled dose, up to four times the labeled dose. Of course, in many countries around the world, and now in the U.S.A., we have the first-gen PCABs available. There's a lot of drug switching in the acute healing phase. After that, patients go into maintenance, and Prof. Sharma talked a lot about the big issue, which is relapse rates. Despite being healed, they either go on to no treatment or they go on to maintenance treatment with PPI or PCAB. Within six months, you can see here the relapse rates of between 21% and 40% for PPIs and PCABs. After 12 months, the literature will tell us that it's about 80% or 90% of patients relapsing. In many studies in Europe that have talked about what are the motive, why do patients go back after relapse? It's because they've had symptoms after the treatment. It's because they're having symptoms. Relapse is a key issue. Patients go back into the cycle, and we start the process again. It's dynamic because you have acute phase healing, maintenance, and then back again, all within six to 12 months, many drug switching opportunities in a large population. Obviously, that's great, but it's also important if you're going to launch new drugs that there's unmet medical need. I think we heard a lot about that from Prof. Sharma. What's really interesting is that when we talk to gastroenterologists in Europe and USA, so looking at the left-hand side of this with the bar charts, whether they're treating C and D patients, the severe patients with standard dose PPI or high-dose PPI, about 36% of those remained healed. They had some symptom improvement and remained healed. But even with the grade A and B, the more mild to moderate patients, around 30%-34% remained unhealed despite treatment with normal or high-dose PPI. So as was clear, the PPIs are very good for a lot of patients, but there's still many patients that remain unhealed. And I thought it was really interesting when Prof. Sharma talked about esophagitis and then stricture and Barrett's. And it came back home to me, the need for that. You need to heal because you don't want people to get strictures or Barrett's or develop further complications. And when we talk about symptoms, that's also a key problem for patients. Obviously, that's what patients go to talk to a doctor about. And here on the right, you can see the quality of life. And Prof. Sharma showed a different version of how it impacts daily activities. But here, it's also interesting to see how moderate to severe GERD symptoms actually affect people in the same way as diabetes, mild, moderate to severe COPD, hypertension, or depression. And this is looking at both physical and mental dimensions on the SF-36. And so people do feel worse than the general population. And nocturnal GERD symptoms are closer towards how people feel when they have angina and chronic heart failure. They are things that really impact patients. It's not. We're not talking about a heartburn after having a spicy meal. We're talking about patients with real symptom problems that do impact their quality of life. There's two aspects of symptoms I want to touch upon: that 40% of GERD patients have remaining symptoms despite PPI treatment. Prof. Sharma showed a study there which had a higher number, which was interesting. Also, when we talk to specialists and primary care doctors, 49% of patients have nocturnal symptoms, which are really bad and difficult to treat. Ever since doctors go to medical school, they get taught about GERD, that bringing the pH above 4 is important to managing GERD, especially erosive GERD. Here we have a picture of the evolution of treatments from 1976 with the H2 receptor antagonist onwards. And so we had first Tagamet launched, and then Zantac as a second launched in the H2 receptor antagonist. And Zantac became the leading brand until in 1989, Losec or Prilosec launched. And then the fifth PPI to launch was Nexium, and that became the leading brand. And then we have the first-generation PCAB with vonoprazan, first launching in Japan in 2015 and U.S.A. in 2024. And we're developing linaprazan glurate. And you can see here the percent of time on top that the pH is kept above 4. So linaprazan glurate keeps the pH above 4 for 96% of the time, whilst the first-generation PCABs range between 70% and 85% of the time, depending on the PCAB we're looking at, for example, Tagamet and vonoprazan. The PPIs range between 10-16 hours, and then the H2 receptor antagonist about 8 hours. This is a major impact on patients because you're getting control of the acid in the esophagus during the daytime, but at nighttime, you're losing that control, and that's also leading to nocturnal symptoms. So let me look at this a different way to emphasize what it is like for patients. So this is looking at in the red bars, the time that the acid in the esophagus is less than pH 4. So all that red and pink is basically washing the wall of the esophagus and damaging it and causing symptoms. I kind of equate this to a beach which is being pounded by a storm constantly, while with linaprazan glurate, we have only one hour of time less than pH 4. Linaprazan glurate achieves this all within the first day and first dosing, while the other compounds we have on this page at the moment take several days to reach their steady state. We'll get back to that in a minute. Now, I think that doctors, as I mentioned, have been searching. They've searched for ways to increase the pH above 4. They went from H2 receptor antagonist to PPI, embraced those. They started using double dose or triple dose or higher dose of PPI because they were looking for better pH control. Unfortunately, the mechanism doesn't work in that way to increase the pH very much. I think that search for time above pH 4 is why PCABs have had such a great traction in the marketplace. We now see PCABs, the first generation, available in more than 25 markets. In most of the countries, we see premium pricing above PPIs. We were very excited to see the performance of vonoprazan in the USA with Phathom. It's really exciting to see now that it really seems to be taking off. The prescriptions, this slide says 580,000. It's actually 740,000 based on their last report. They have, in their first full year of sales, they expect to be close to $175 million net revenue. In Asia, we've seen the PCABs on the market in Japan. So from 2015, has about 44% of the market. Korea has four approved with about 23% of the market with double-digit growth. In other countries, you see PCABs being updated in the latest guidelines as being important for these patients. Even in Latin America, for example, in Mexico, we see the PCAB has achieved a third position in the marketplace. They're really being accepted in the marketplace because doctors are looking for time above pH 4. Now, this graph here is a classic graph which has been developed over many, many years. The green line represents the linearity from all the studies of looking at what% of time above pH 4 equates to healing of erosive GERD. It's based on all the data from the H2 receptor antagonist onwards, and it's produced a linear curve. What we did is we thought, let's plot the U.S. vonoprazan studies against lansoprazole in blue and purple. Vonoprazan has a pH above 4 of 85%. That's in the FDA label. If we track that up to the graph with the blue dot, that's the healing rate, 91.7, which is what we had for the C and Ds in their studies. That linked up very nicely. We looked at the lansoprazole in the same study, same situation, 66% above pH 4. Looked at the C and D healing rate, 72%. It matches. So we know that Tagamet is around 70-something%, but we haven't seen the healing rates, but we've heard it's close to 80% for that drug. Things seem to be matching. If you look at the linaprazan glurate with 96% above pH 4, you take that line up, it's getting close to 100%. Usually, you don't get 100% in the studies, but I'm looking forward to our phase three study where I think we'll be in the high 90% based on the biomarker for pH control and the fact that we have such a strong pH control. So in terms of what that means for linaprazan glurate, in terms of when we launch and what we expect and how we will differentiate. First, in the left-hand side of this table where we compare against PPIs, vonoprazan, vonoprazan's FDA label, and linaprazan glurate, we're talking about pH control, the time that pH is above 4. We already have best-in-class pH control. That's been demonstrated. It's already studied. It's published. We have 96% on day one already for time above pH 4, while vonoprazan takes about several days to get from 63% only up to 85%. And PPIs are around up to 70% after three to five days. So we've already achieved best-in-class pH control. Now, when we talk about the clinical side of things, we can base a lot of our thinking about what happened and what we saw in the phase two study where we had excellent results and very good data, so we know that in terms of the healing effect, we had 55 percentage points compared to lansoprazole at the four-week stage compared to vonoprazan's U.S. study, which was 18-20 percentage point difference between lansoprazole two to eight weeks. We are expecting a high healing rate at four weeks, and so time to healing at four weeks compared to eight weeks with the PPIs and vonoprazan, the first generation, and as well, we're looking very closely at the symptoms. So you can imagine with us covering the pH above 4 for 96% of the time, day and night, how we will have a very strong potential effect on symptoms already from day one. So we're looking very closely in our phase three study. We have organized it so that we can look at the total day symptoms as well as the day and nighttime symptoms. And so we expect to have very strong data in the symptomology as well. So with that, we expect to be launching with the best-in-class into a market which is very large, dynamic, lots of switching opportunities, and where we believe we'll have a strong basis for success. So with that, Christer and team, I'll hand over to questions and answers. Great. Thank you, Peter. So at this time, we will be taking questions from the audience. To our analysts that have joined us live, please use the raise hand feature to indicate you have a question. To our audience on the webcast, please use the written text box at the bottom of the webcast player. Please hold for a brief moment while we poll for questions. Our first question comes from Oscar Haffen Lamm from Stifel. Please go ahead, Oscar. Hi, thank you. Thank you, Dr. Sharma, for this presentation and also to the Cinclus team for organizing this event. My question would be, looking ahead to the data that will be generated by the phase III trial of linaprazan glurate, I was wondering, Dr. Sharma, what in the dataset will you be particularly interested to see? I mean, for example, will it be the nighttime symptom relief? Will it be the percentage of time above pH 4 and the acid control? I'm just curious to hear about what in the end will be driving your decision to prescribe one drug over another. Thank you. Okay. Thank you, Oscar. I mean, and probably I'll start off first, and Peter, if you can add on to it. I mean, so first of all, in this, because it's phase three, we won't be measuring, I think, the acid part, but we'll definitely be looking at the symptoms, as you've mentioned, and of course, the healing of the severe erosive GERD. So compared to baseline endoscopy, what is the healing rate of severe erosive GERD with this medication? Peter? Yeah, I think that's absolutely right. I mean, the study is designed to show superiority in healing as well as symptom control. All those parts are important. But the healing is the it is called the healing one study, so it is a main part of it. But we're also excited about the symptoms. I don't know, Christer, if you have anything else to say. No, I think that's fine. Okay. All right. Thank you. Thanks for the questions, Oscar. Our next question comes from Arvid Necander at Carnegie. Please go ahead, Arvid. Good afternoon, and thanks for taking my questions. So a couple of questions for Professor Sharma, if I may. So as you said, the patients with erosive esophagitis continue to relapse on PCABs, 21% in vonoprazan phase III program. But what proportion of these patients, roughly, do you see coming back to seek care? Do you see most of them coming back to their physicians to change the treatment plan, essentially? I'll start there. Yeah, no, good question. Yes, you're right. I mean, because of, and of course, the relapse leads to the symptoms as well as findings on endoscopy. So it's basically symptom-driven. So what we see is because these patients are probably under the care of a gastroenterologist, these patients do come back to us seeking additional treatment. Many of them, by the time they come to us, they've already started some therapy at home, OTC, whether they're taking a bunch of Tums or antacids along with it by the time they come to see us. So yes, we do get to see these patients. Okay. Then I was just wondering, how meaningful is the benefit of also having the NERD indication on the label, I guess, in the case of vonoprazan? Does this make it easier for physicians to prescribe, I guess, when the disease severity is somewhat uncertain, lowering the diagnostic burden when it would otherwise be higher? Yeah, so good question. I mean, so you're talking about, would PCABs be the one even in otherwise symptomatic patients that you would start them off of even in the NERD population? And currently, we do in the NERD population start off with PPIs as the first treatment option. And then if they're failing, again, I mean, different insurance plans, different institutions have different algorithms for the NERD population as to what you can or cannot do in that situation. So I would say that yes, I mean, in a subgroup of patients, it is important. But the vast majority that we start the PCABs on are still patients with erosive GERD. Okay. Great. Thank you, Professor Sharma. I had a couple of questions for Mr. Wallich as well, if I'm not taking up too much time here, so I'll give it a shot. I guess, as you said, Peter, vonoprazan is getting really good traction in the U.S., but two years into the launch, coverage outside the commercial setting seems to be very limited. Does this in any way surprise you, and is it any cause for concern? Do you mean outside the commercial setting? Do you mean Medicaid? Private insurance. Okay. Unfortunately, I don't know enough about that, so I apologize. But I think the anecdote I will use is that obviously, coverage is something they've been going for. They've been getting more coverage, and they've got, I think, 80% in the commercial setting for coverage. But I think what really is the turnaround point for Phathom was that they went away from just wanting to talk to gastroenterologists and primary care and doing direct-to-consumer and spending time on NERD to focusing on gastroenterologists because they realized that that's where those are the doctors who are prescribing PCABs because they have the severe patients. And so I think that, to me, was more important in their strategy recently, which has turned them around. But I don't have enough information about the coverage with Medicare to be able to comment on that side of the question. I apologize. Yeah, don't worry at all. Thank you so much, guys. Thanks for a good presentation. Can I just ask also to add on to the question Arvid just mentioned? When we're talking about relapse in the clinical studies now, for instance, for vonoprazan with 20-plus% relapse within six months, that's with erosions. Do you have any view on relapse on symptoms within six months? I mean, since that is what patients are coming back for. Yeah, no, good question, Christer. I mean, the symptom relapse is much higher always as compared to the relapse of the erosions. And you're right. I mean, the patient will come to us with symptoms. In this situation, I mean, because the original disease was typically erosive GERD, we want to make sure that that is healed, right? I mean, and that's the way we will definitely find out. And these are the patients who typically do undergo endoscopy because they had erosive GERD to begin with. And we will find that the symptomatic patients will have erosions. But overall, the symptom relapse is higher than the relapse of the erosions. Okay. Thank you. Great. So our next question comes from Kevin Sule at Redeye. Please go ahead, Kevin. T hank you. And thank you for a great presentation as well. So my question is regarding the high willingness to switch drugs or treatments within erosive GERD. Like you mentioned in the presentation, do you expect the clinical data for linaprazan glurate to speak for itself when it comes to the marketing of the product, or do you still expect a significant need for a marketing effort when commercializing? Do you want me to start, Christer? Yes, please. Yeah. Kevin, that's an interesting question because I remember in the days of when I joined AstraZeneca at the launch of Losec, and people used to think Losec was just so brilliant compared to what was available. People, especially the scientists at AstraZeneca, didn't know why we needed marketing people because it should sell itself. I think we will have really good data. The way our phase 3s are designed and the data, I believe fully that the data is going to come out just based on what we've seen so far in the right way. We'll have great data, but you always need marketing. You can't get away from it. I think our strategy has always been a focus on we talk about severe patients, and we talk about gastroenterologists. We're not looking at a broad approach to all primary care doctors or anything, maybe high-tier primary care doctors. You can launch very successfully with a focus on gastroenterologists with marketing, but obviously not as big as doing a primary care reach out. Christer, I don't know if you want to add on to that. No, I mean, I think that's clear. And I mean, looking into benchmark to other companies in the field, especially GI specialty pharma company in the US, I mean, you're talking about approximately between 60 to 100 sales reps in the US for a specialty strategy. So that is possible. And of course, in Europe, it could differ a little bit depending on where you are. But I mean, it's definitely sizable and okay sizes from a specialist treatment launch. Perfect. Thank you. I think that's very interesting, your answers, because especially within this particular field, the GERD, where we have seen historically that the products with the highest clinical efficacy have typically reached blockbuster potential. So building on that question, I was also wondering, how do you expect the competition from vonoprazan and other PCABs to differ between the US and Europe? You want me to take a - Yeah, sure. Sure. Yeah, Europe, I think competition. I think the way we're seeing it now, we don't see any activity of any other PCAB regulatory-wise or study-wise in Europe. So at the moment, we still have a belief that we might be first in Europe, first to launch, and not even sure if anything will come in after us. In the USA, we will either be probably number three. Tegoprazan is submitting their NDA, I think, shortly. So we're expecting to launch within the next year. So we should be number three, in essence. I don't think - so how would they react to us? I don't think when we launch, I don't think that they'll react. I mean, everyone reacts. We'll have a very strong profile, and they'll try to obviously put up the walls around their own profile. What I find is interesting because we get this question about how much market, how big is the market big enough to sustain a number of products? At the current pricing in the USA, and you only looked at the USA, to reach blockbuster, you need about 400,000 C and D patients out of the 4 million. So there are so many patients in this market space that even if when we launch and we're going to have a bit of competition from vonoprazan and tegoprazan, there's so much opportunity available for us with the PPI patients, plus switching from vonoprazan and tegoprazan failures. Plus, I think, like I said, we've come out with best-in-class pH data at the moment. We have that in hand. We'll be coming out with, I believe, much stronger data than the other PCABs have. So Christer, I don't know if you want to add on to that. No, I think, I mean, this is. I mean, of course, we can learn from the history and how it looks in this market. And each new substance that has been launched with at least a differentiated product compared to the previous one, some incremental effect as well, that would have. I mean, that product has become a blockbuster. But of course, it's important that you have an incremental effect or a differentiation in position in one or another way. And I think that still is the case. And that still is the case since this market has such a big level of high number of patients and very dynamic with many switch opportunities. That has been our aim all the time to actually go focus on the unmet medical needs, the severe patients, and to find the best suited acid control ever possible to actually help these patients. That is, I think we are coming closer to that now. Definitely, we will have a possibility to have an incremental effect compared to the rest existing on the market. Why? I mean, that is the view we have. That, of course, looks very promising. I understand. Thank you for taking my questions and for a great presentation. Great. Thank you for the questions, Kevin. I'll now turn it back to Christer for closing remarks. Yes, time is running here. We are 4:00 P.M. here in Europe in Central European Time. We would like to thank you for your interest and that you actually participated in this call and also many interesting questions. I would like to thank you, Peter, but especially I would like to thank Professor Sharma for a brilliant presentation and a very interesting presentation. Thank you very much for this. I would like to invite you for the next meeting we will have in the future. We will come back with more information about the next event that we will arrange. Thank you for now, and I wish you great holidays in a couple of weeks.