Phathom Pharmaceuticals, Inc. (PHAT)

Investor Day 2020

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Dec 14, 2020

Good afternoon, and welcome to Fathom Pharmaceuticals Virtual Investor Day. Thank you for joining us. My name is Todd Branning, and I am Fathom's Chief Financial Officer. We have a very exciting and robust agenda today. As a housekeeping item before we begin the meeting, I want to make you aware that at the end of today's presentations, we will hold a Q and A session with our meeting presenters, including both our key opinion leaders and select members of Fathom's management team. You may submit questions at any time using the text box below your webcast window. We will try our best to answer as many questions as we can during the Q and A portion of the meeting. If you have questions after the meeting concludes, please send them to irfathompharma.com. As a reminder, matters covered in today's presentation, including the accompanying slides, include forward looking statements. Such statements involve risks and uncertainties that may cause actual results to differ materially. A discussion of these statements and risk factors is available on the Safe Harbor statement slide as well as under the heading Risk Factors in our SEC filings. All forward looking statements speak as of the date of this presentation, and we undertake no obligation to update such statements. Now to begin the meeting, I would like to turn the webcast over to Teri Curran, Fathom's President and Chief Executive Officer. Teri? Thank you, Todd, and welcome to Fathom's 1st Virtual Investor Day. Thanks for joining us. I'm absolutely thrilled to have with me today several members of the senior management team at SABL. Admit of all who came to us from Takeda has deep gastrointestinal experience. Martin Gilligan joined us from Celgene where he was fundamental and instrumental to the launch of OTEZLA and also has extensive launch experience in both primary care and other specialty categories and Todd Branning, our CFO, who has extensive financial experience, most recently from Amneal. We also have several distinguished KOLs that have joined us today, Doctor. Stuart Spector, Doctor. Colin Howden and Doctor. Ronnie Fass. Thank you for joining us. I'd now like to talk a little bit about our lead asset at Satnam, a potassium competitive acid blocker, one of the holy grails in the acid secreuniary category, the first innovative therapies for acid related disorders in more than 25 years. We have licensed phenoprazan for the U. S, Europe and Canada from Takeda. This is a largely derisked asset having been approved in 14 countries across Asia and Latin America and most recently in Mexico. It's on the market in Japan generating revenue of more than $725,000,000 and most recently became the market leader in Japan overtaking Nexium and has more than 90% of the h. Pylori market. Importantly, it continues to grow up more than 17% year on year, that's in the 6th year in the marketplace there. The company went public in October of 2019 and raised capital of $209,000,000 This provides you an overview of our promising late stage opportunities in our pipeline. We have 2 large Phase 3 programs, specifically in GERD in the healing of erosive esophagitis and the release of heartburn and also the maintenance of healing of erosive esophagitis and release of heartburn. And as we reported out most recently, we've completed enrollment for that study and we expect top line results in the second half of twenty twenty one. The second program in H. Pylori, we're studying both dual therapies in oprazan and amoxicillin amoxicillin as well as triple therapy with the addition of flustamatin. That program is accelerating and we expect to complete enrollment in January of 2021 and read out the top line results in the second in the Q2 of 2021. I'm thrilled to announce today that we will be embarking upon a Phase 2 program in mid-twenty 1 for the treatment of heartburn associated with non erosive reflux disease or NERD, a major category within GERD, which the team will talk about a little later in the program. The team has really made great progress for a young company in building a leading biopharma company. I want to address the pipeline that I just discussed. We have received FDA Fast Track and QIDP designation in the combination with certain antibiotics we've been uprisen for the h. Pylori indication and target NDA submission in the second half of 'twenty one for HT and to 2022 for erosive esophagitis. We've also received agreement from the FDA on the proposed initial pediatric study plan. Importantly, the team has made outstanding progress in preparing for the launch. We've assembled an experienced and proven executive management team and recently made key leadership appointments in commercial, medical, market access and finance, and importantly, who established commercial supply from multiple manufacturing sources. We're also well capitalized with $209,000,000 from the proceeds of our IPO. We recently filed our S3 shelf registration and have initiated ATM facility in November of 2020. Over the next 2 hours, we have a program that will cover as we move into the clinical profile of the discuss the Phase 3 trial design and the planned indication expansion. Doctor. Spekler will discuss the GERD classification and the prevalence of the disease, importantly, the impact that it has on the quality of life, acid control and healing. Doctor. Hallum will discuss H. Pylori treatment limitations and then I'll present potential to deliver a superior therapy. And Doctor. Sacks will address NURD, the unmet needs in the marketplace and why we believe the OpRegen profile can address some of that unmet need. Martin will then cover the market opportunity and focus on the commercialization strategy, and then Todd will provide a financial update. With that, I'd like to now hand over to Agni Zbulsi. Agni? Thank you, Terry. So I'd like to start the story with rimebrzan by describing the mechanism of action. As the story of rimebrzan really comes down to its distinct mechanism of action in relation to PPIs. Although both target proton pumps, they do it differently. A key point to highlight is that the proton pumps are tricky target because they are constantly switching between active and inactive states in response to stimuli like food. And also they have a high rate of turnover with new pumps coming online each day. PPIs covalently bind to and inhibit only the active pumps and have a short half life of 1 to 2 hours. And thus, they are not present to inhibit the new pumps that come online later in the day. As such, PPIs have slow onset, takes about 3 to 5 days for them to start, limited potency, limited duration of action. On the other hand, vinoprazan, a PCAP, unlike PPIs, it is a competitive enzyme inhibitor and it has been the Holy Grail for the type of inhibitor sought after for a while now. Hence, unlike PPIs, vinobrazan inhibits both active and inactive pumps, stable in acid and has long plasma half life with a very slow dissociation rate. So it can cover the full 24 hour dosing interval regardless of which states the pumps are in. Because of all of that, veniprazem reduces rapid, potent and durable effects on the pumps. These mechanistic differences are best demonstrated in this head to head study that compared venoprazan to Nexium. This is a BKPD study. On day 1, Nexium barely moves the pH above 4, while veniprazan rapidly moved the pH to 7. Now going to look at day 7 on the right hand side of the slide, Nexium, which is a steady state at this point, it never gets the PH to 7 and allows the pH to spend a fair amount of dosing of the dosing interval, especially at night below 4 below PH4. On the other hand, vinobrazan almost always gets the PH above 4, significant portion actually in the 6 to 7 range and is 1 to 2 pH points higher at any given time point compared to Nexium. Now to point out this is a log scale, so viniprazine translates actually to being 10 to 100 times more potent than Nexium in this study. These results are great PKPD demonstration of how vanabrisen is more rapid, potent and durable than a PBI. Now before moving to the efficacy element, let me point make a point or 2 on safety. We are in a very unique situation that at this stage of running Phase 3 trials, we have significant amount of safety data. We have over 7,000 patients exposed to vinibrisan in clinical trials and over 25,000,000 patients receive vinibrisan in the marketplace. So we have very well characterized safety profile. Overall, phenobrazan safety profile is very similar to that of PPIs. Now moving to talk specifically about our programming GERD. As a brief high level background and Doctor. Spekler will speak to this in a lot more detail, But what I want to highlight here that GERD is very highly prevalent disease and its treatment represents one of the largest drug categories. In the U. S. Alone, about 6,800,000,000 doses of PPIs were prescribed last year, and this does not even include OTC. Despite the availability of PPIs and other anti secretory agents, there is still significant unmet need, as about 30% of patients remain inadequately treated with PPIs. Now GERD patients typically present with GERD like symptoms and are treated empirically without undergoing endoscopy. And for those patients who undergo endoscopy, typically due to persistent symptoms, they are diagnosed with either having EE, erosive vasosagitis or non erosive disease, which is NERD. Regardless of which path the patients undergo, the unmet needs remain high. And we'll go over that in more details throughout the presentation. To specifically speak of erosapos sevagitis, more rapid, more potent and durable healing and symptom relief is needed. And for patients with this disease, we are currently running a registration program to address the unmet needs in both healing and maintenance parts of that disease. Before describing our study, I will review data that we have from Japan showing how vinabrizan fares in relation to those unmet needs I just described. This is the data from Phase III study that was done in Japan in a row of esophagitis healing, comparing vanebrzan to lansoprazole, which is brevacid. Vanebrzan was clearly superior to lansoprazole, in particular, the 2 weeks data on the left hand side of the slide. This data showed that vinabrazine heal patients faster than lansoprazole. Also, on the right hand side of the slide, higher potency was demonstrated by vinobrazan with a clear differentiation even further differentiation from lansoprazole in those patients with more severe disease, grades LA, CNT. So this study demonstrated the faster onset of effect and the more potent effect of vinibrisan. Now what is even more remarkable are the data from the Erosophus sepsis maintenance study. On this slide are the data from Phase 3 maintenance study done in Japan. This is in patients who have healed lesions and then given continuous therapy to measure how many of them will have their lesions recur while on treatment for 6 months. And as you can see in this study, veniprazem patients had recurrent had recurrence rates in the low single digits, while those in lanceprasol had recurrence rates as high as 39% in patients with more severe disease. Such low recurrence rates seen with venoprazan actually have not been seen with any other agent. This is a testament to the durability of effect that vinubrisen provides. Such data promises significant positive clinical impact and potentially very positive economic impact. Now in a smaller study done in Japan as well that specifically looked at heartburn symptom relief, veniprazan convert to lansoprazole in the study as well showed that it relieves symptoms better and faster than lansoprazole as it started doing so on the 1st day versus the 3 to 5 days lansoprazole needed to start showing effect, which is very consistent with other PPIs. Also, PPIs do not adequately control nighttime symptom. And as you can see in this study, vinoprazan did a much better job of controlling nighttime symptoms compared to lansoprazole as seen on the right hand side of the slide. Now based on the data I just shared from you from the yeast study in healing, the yeast study in maintenance and this symptom relief study, you can see when a present ticked every box of what is currently needed in the treatment, more rapid, more potent and more durable effect on healing as well as 24 hour symptom relief. And this is what we aim to show in our program. So this is on this slide is the study that we are currently running. This is our Phase 3 study, which have completed enrollment and currently all patients are into treatment phases of this study. Our study has 2 parts, a healing phase and a maintenance phase. And in this study, we are comparing venuprisen to lansoprazole, testing for non inferiority at the end of each phase, which is all what we need for approval, but also we will be testing for superiority at certain key points in the study. And if we achieve those, all of that will be in the label. The study is de risked from a clinical and regulatory perspective, and its design mirrors the studies done in Japan, which I have shared with you a few minutes ago. The study is aimed to give us 3 indications, e healing indication, e maintenance indication as well as heartburn symptom relief indication. And I would like to point out that this study design has been discussed and agreed with the FDA and the EMEA, and they both agreed that this study plus the data generated in Japan can be the basis for the NDA. No additional efficacy or safety data were requested. Now let me zoom a little bit deeper into the statistical element of this study. In the healing phase, the primary endpoint for approval is non inferiority on healing of AE by week 8. Our study has over 90% power for non inferiority with a margin of 10%. If the primary endpoint in this portion of non inferiority is met, we will assess the secondary endpoint in the order as shown on the slide here. 1st, we will assess non inferiority for heartburn relief over the 8 weeks period and we have a 90% power for that. Then we will move to assess superiority at week 2 in grades LA CNT patients and then superiority on onset of heartburn resolution by day 3. Now on the maintenance portion of the study, on the statistical elements of that, the primary endpoint for approval is non inferiority on the percentage of patients that maintain healing as assessed by endoscopy at week 24. For this test, the study has over 90% power for non inferiority at 10% margin. Now if the primary endpoint of non inferiority is met, then we'll move on to assess the veniprazan 20 milligram superiority first, and that's over lansoprazole and we'll assess on healing maintenance for first for patients with grade CNG and then for all commerce. This then will be followed for non inferiority tests on heartburn relief. If we pass those tests, we'll move on to testing the 10 milligram dose in the same order. We have 90% PAR for all these tests as well. Now with this, I will pause and pass the stage to Doctor. Stuur Speckler, who will describe erosive vasovagitis and GERD overall in a lot more details than I did. Doctor. Speckler? Thank you, Azmi. So let's talk a little bit about erosive esophagitis and GERD. Now this slide shows you an endoscopic photograph. This is actually one of the patients in the erosive esophagitis study. And you can see why we call this erosive esophagitis, those whitish areas that you see at about the 3 o'clock area, the 6 o'clock area, those are erosions. We also call those mucosal breaks. And this is very typical of what we find in patients with bad reflux disease, bad GERD. Now GERD is essentially a plumbing problem where there's a leaky valve at the end of the esophagus. That valve, called the lower esophageal sphincter, is supposed to remain tightly closed to prevent the reflux of acid and other noxious material in the stomach from coming back into the esophagus. When that noxious material, the acid from the stomach does come back into the esophagus as it has in the patient in this slide, it causes the typical symptoms of heartburn, which are heart I'm sorry, GERD, which are heartburn at burning sensation behind the breastbone and regurgitation where material actually comes up into the mouth, gastric material actually reflexes all the way back to the mouth. Next slide, please. Now as Asmi just mentioned, this is an extraordinarily common problem in the United States. Survey studies suggest that about 20% of adult Americans have bothersome heartburn at least once each week. And as a nation, it's been estimated that we spend over $12,000,000,000 each year for the evaluation and treatment of GERD. Now when patients with typical GERD symptoms of heartburn and regurgitation go to see a doctor, they're frequently treated just on a symptomatic basis and usually with proton pump inhibitors. So we don't send everybody for endoscopic evaluation. Patients who either don't respond to the proton pump inhibitors or who get symptoms back after they stop the proton pump inhibitors, those will have an endoscopy. And the endoscopy will separate these patients into those with erosive esophagitis or those with non erosive reflux disease. And GERD, by this so called Montreal definition, is a condition that develops when the reflux of stomach contents into the esophagus causes troublesome symptoms and or complications. Now what happens when we do an endoscopy on patients with those typical symptoms of heartburn and regurgitation? Well, only about 30% of the time do we see this reflux esophagitis like you see on the left hand portion of the slide. Again, that's also called erosive esophagitis or those erosions are also called mucosal breaks. But in the large majority, 70% of patients with typical GERD symptoms, we don't see esophagitis, we see what appears to be a normal looking esophagus and those are patients with non erosive reflux disease or NERD is the acronym, and I think Doctor. Foss will be talking a lot more about that in his lecture later today. Now we grade reflux esophagitis using this so called Los Angeles grading system. And this is what we're using in the erosive esophagitis study. I don't think it's critical that you know all the details of the LA grading system, but just know that it scores patients on the basis of mucosal break size and extent, either as LAA, where you see on the left hand panel there that little mucosal break and LAB, the arrows are pointing to a much longer hypnocosal break. LAC shows that those mucosal breaks have now extended between folds in the esophagus. And in LAD esophagitis, more than 75% of the circumference of the esophagus is involved by mucosal breaks. This slide just emphasizes how common these symptoms are. Now this is another Western population. This is a study that was done in Sweden. It's an interesting study because they sent out questionnaires to random people in the population, asked them if they had GERD symptoms and then invited those people to come in and have an endoscopy. So this is something like you would just be sitting in your home and have a open a mail and say, Oh, I'm invited for endoscopy. Well, about 20% of the population had weekly GERD symptoms, very much in accordance with studies that have been done in this country. And the people who accepted the invitation to come in and have an endoscopy, 15% were found to have erosive esophagitis. Now our study is looking specifically at patients with erosive esophagitis. And if you look at the breakdown of the LA classification of patients with erosive esophagitis, you'll see that roughly a third have LA grade A esophagitis, 39% LA Grade B, 20% C and 7% Grade D. Now what happens when you have bad reflux? There's a lot of complications that can develop. Okay? The first panel here on the left shows that that acid that refluxes back up into the esophagus can actually cause an erosion deep enough that we would call it an ulcer. Now that ulcer can heal, and when it does heal, it can sometimes heal with the deposition of scar tissue. Imagine if you had a gash on your hand or something like that, A deep gash can heal with scarring. And if the esophagus scars, it can narrow the passage and give patients a lot of difficulty swallowing food. Now that ulcer also can heal with an abnormal lining. So instead of healing with the normal lining of the esophagus, it heals with an abnormal lining that under the microscope looks more like the intestine than the esophagus. That's the 3rd panel that you see there. That's called Barrett's Esophagus. When the esophagus heals with that abnormal lining. And you can see it, it's very clear that there's a difference in the color of the lining of the esophagus at the end there with a reddish area representing what we call Barrett's Esophagus. And Barrett's Esophagus is a problem because it predisposes to cancer, a specific type of cancer in the esophagus called adenocarcinoma, which has been increasing at a very alarming rate for the past several decades. So GERD is not just heartburn, it can be complicated disease. Now for the past 30 plus years, we've used proton pump inhibitors as our first line treatment for bad reflux esophagitis. You can see that there's 6 available in this country. There's omeprazole, lansoprazole, rimeprazole, pantoprazole, esomeprazole and dexlansoprazole. Again, they were introduced, the first one omeprazole, in 1989 and there's really been no update. This is what we use. This is our go to first line medication for severe GERD, essentially unchanged for the past 30 years. Now, many of these are available over the counter, some are not. Now, you don't always see a complete response of symptoms to patients that you put on proton pump inhibitors. Here is a study that was done to compare 2 proton pump inhibitors, esomeprazole and lansoprazole. And you can see that at 4 weeks, more than 37% of patients in both groups still had incomplete GERD symptom relief. You can see that days with heartburn during the 1st 4 weeks and nights with heartburn, this Dipariton pump inhibitors did not get rid of all of these symptoms. So what are the limitations of the PPIs? Well, we see that there is some endoscopic and symptomatic relapse despite being on maintenance treatment and the dosages for these different agents, by the way, vary fairly widely. There's incomplete symptom control, as I've just shown you. We can have breakthrough of nighttime heartburn. Now as Azimin explained earlier, the PPIs have to be dosed before meals. The reason for that is the PPIs only bind to stomach cells that are actively secreting acid and that happens during meals. When you're fasting, only about 5% of your proton pumps are active, but when you're eating a meal, about 60% to 70% are active. So they really do require dosing around meals with the possible exception of dexlansoprazole. They're also metabolized by this enzyme called CYP2C19. It's an enzyme that metabolizes a lot of different drugs, But there's genetic variance in the population. So some people are slow metabolizers, other people are very rapid metabolizer. If you're a very rapid metabolizer, it means you're getting rid of that proton pump inhibitor very quickly and it may not be around long enough to control acid very well. And as you've seen, there's data on incomplete erosive esophagitis healing, especially with the more severe grades of erosive esophagitis, the LAsCs and Ds. You've seen this slide already that vanoprazine demonstrated faster, more potent more durable acid control than the PPIs. Certainly, that's absolutely the case on day 1. So rapid onset of action is definitely an advantage of this P cab over a PPI. And even by day 7, you're still seeing better acid control with venoprazine than with esomeprazole. This was a study that was done in 20 healthy Japanese men. So in summary, compared to PPIs, vinoprazine seems to exert more rapid and more profound control of stomach acid secretion. It does not have this requirement that it needs to be dosed around meals. It's not subject to the variable metabolism because it's not metabolized primarily by that CYP2C19 enzyme that metabolizes Certainly, the studies from Japan certainly suggest that it does. Certainly, the studies from Japan certainly suggest that it does and that there is superior maintenance of healing. And I thank you for your attention. Thank you. Thank you, Doctor. Speckler. And now we'll shift gears to H. Pylori. So let's talk specifically about H. Pylori. At the high level, and Doctor. Haldim will speak to this in a lot more depth, but at the high level, H. Pylori is very prevalent disease. And if left untreated, it can lead to serious sequelae such as gastric cancer. The challenge with managing H. Pylori is that the eradication rates have been declining over time to where it is today around 80%, which is not acceptable. This is mainly due to increased resistance to antibiotics in particular to clear sromycin. What is needed now is either better antibiotics, but none is in the horizon or an agent that can improve the efficacy of current antibiotics. And that and this is where vinabrasen comes in. Vinabrasen very efficiently and very effectively raises the pH level to above 6. And at that BH level antibiotics are more potent and H. Pylori is more vulnerable. So let's see how this translated in clinical trials. This is the Japan H. Pylori Phase 3 study. Venabrazan triple regimen, which is venabrazan plus clear stromiciplasamaxillin was amoxicillin was compared to lansoprazole plus the same antibiotics. Venabrizan regimen was clearly superior to that of lansoprazole and it achieved a remarkable eradication rate of over 90%. Also, it's worth noting that veniprazan helped Kirizromycin overcome some of the resistance from H. Pylori with even a greater separation from lansoprazole in that sub population as seen on the right hand side of this slide. Now the question was asked, do we even need clear sromycin that is would vinoprazan blossom oxygen alone can be enough? 2 smaller Japanese studies were specifically designed to answer In those studies, we represent dual regimen achieved over 90% eradication, thus giving us a very strong proof of concept that this regimen can work. Accordingly, vinobrazan has the potential. When you look at the triple regimen, dual regimen data, minibrisan has the potential not only to achieve over 90% eradication rate, but potentially do so with 1 antibiotic. If so, this will be a great step forward in the field. Hence, comes the design of our study. This is our ongoing Phase 3 study, which Terry earlier announced that we will complete the recruitment for in January and results will be coming after that. So this study that we're doing has 2 vinabrasan arms, 1 triple and 1 dual regimen. Each is to be compared to venabrazan triple regimen and will be tested for non inferiority, which is the endpoint we need for approval. But we will also test for superiority and if those are achieved, those will be on the label. This design has been agreed with the FDA and DMEA and also they agreed that this study plus the Japan data can be the basis for the NDA. Also, I would like to point out that the FDA has granted us QIDP status, which will give us an additional 5 years of exclusivity on the molecule itself and not just on the indication. Also, we have fast track and we expect priority review for the H. Pylori NDA. Now zoom in a little bit more on the statistical aspects of this study. As I mentioned, the primary endpoint for approval is non inferiority and it is non inferiority on the eradication rate of each of the ropizan regimens compared to lansoprazole triple therapy in patients who have who are not resistant to either colistromycin or amoxicillin. We have over 90% power for this endpoint with a 10% non inferiority margin for testing. If the primary endpoint of non inferiority is met, we will assess certain key secondary endpoints for superiority. First, we will assess superiority in patients with clear stromicin resistance, again, each of the venabrzan arms against the triple LENSO arm. And then we will assess the superiority for all commerce. With that, I will pause here and pass the stage to Doctor. Colin Howden, who will describe the disease and the unmet need in more details. Doctor. Howden? Thank you, Asmi. Good afternoon, everyone. Thank you for joining us. I'd like to update you and appraise you a little bit about H. Pylori infection. So this is probably the most common chronic bacterial infection to afflict mankind. And recent studies in the United States suggest that up to 36%, more than 1 in 3 American adults have H. Pylori infection. Now that's a striking statistic, but to understand it, you need to realize that most H. Pylori infections are asymptomatic. It's also interesting to note, I think, that most infections are acquired in childhood. So when we see adult patients with H. Pylori infection, they often ask us, how did I catch this? The honest answer is, we don't know, but you probably had it for many, many years. Up to a 5th of people with H. Pylori infection can go on to develop serious disease, which includes peptic ulcer disease and its complications and also, as Asmi alluded to, gastric cancer. And in fact, the NIH consensus conference over 2 decades ago and the World Health Organization's International Agency For Research in Cancer have concluded that H. Pylori infection is a definite cause of cancer. And in fact, H. Pylori is responsible for more gastric cancers worldwide than are the hepatitis B viruses hepatitis B and C viruses responsible for liver cancer worldwide. Next slide please. And the evidence for eradication of H. Pylori reducing the risk of gastric cancer is increasing quite dramatically. Summarized in this slide are 2 studies from Choi and colleagues from South Korea, where first in the first study patients with small lesions of gastric cancer were removed endoscopically and then randomized to treatment for H. Pylori infection or control, and you can see that treating the H. Pylori infection dramatically reduced new lesions of gastric cancer. In the CHOICE study this year published in the New England Journal of Medicine, they showed that detecting H. Pylori infection in the first degree relatives of gastric cancer patients and treating the infection in those relatives also reduce the lifetime risk of gastric cancer. And most importantly, perhaps for this audience, the Kumar study at the bottom of this slide is a U. S.-based study conducted by researchers at the University of Pennsylvania and studying the VA health care system. And they were able to show that for veterans who were correctly diagnosed with H. Pylori infection and who were successfully treated for it actually had a statistically significant reduction in the incidence of gastric cancer. And I believe that that is the first time this has been convincingly demonstrated in a U. S. Population. Next please. The trouble is, we're not doing a terribly good job at treating H. Pylori infection. A number of studies have shown that the correct patients or correct individuals are not being tested for H. Pylori infection. When they are tested and found to be infected, not everyone receives treatment and sometimes they don't receive the best treatment. The VA study that I just mentioned from Kumar and colleagues found that the diagnosis of H. Pylori infection was made in a lot of veterans who did not subsequently receive treatment for the infection and that's inexcusable. Also of notice among those who were treated, only about 20% were retested. Now the American College of Gastroenterology, the ACG treatment guideline from 2017 has strongly recommended that all patients be retested for H. Pylori infection treatment. And the main reason for that is that our current treatments are simply not that good. So it's important that we try and determine who has been successfully treated and who hasn't. And also in this slide that there's an additional study from the Cleveland, Ohio area, which essentially shows the same thing, really inadequate performance in testing patients, providing appropriate treatments and providing retesting after treatment. The ACG guideline that was updated in 2017, I've already mentioned there are a number of indications for testing for H. Pylori infection and it should be understood that anyone who tests positive should be offered treatment for the infection and after treatment they should be retested to see whether the infection has been cured. The first four indications on this slide are well established and they were present in the 2,007 version of this guideline. The ones further down the list are additional reasons to consider testing for H. Pylori infection in adults. And the most important one there is dyspepsia, which essentially means a pain or discomfort that's centered in the upper abdomen. That's a very common presentation, both at primary care and at secondary care. And there's increasing evidence that a proportion of patients with dyspepsia will be successfully will have successful improvements in their symptoms with eradication of H. Pylori. And as I've already mentioned, there's increasing evidence that the eradication of H. Pylori from asymptomatic individuals probably reduces their lifetime risk of gastric cancer. Next slide please. Here are some real world data from Brown University in Rhode Island, and this looked at their experience with treating patients for H. Pylori infection. This was not in the context of a randomized controlled trial. This is what we call real world data. So patients with H. Pylori infection attending 2 medical centers in Providence, Rhode Island received a variety of treatments at their physicians' discretion. The only treatment that achieved an eradication rate of close to 90%, which is what we'd like to be able to achieve, The only one that did that was so called bismuth based quadrigal therapy. That means giving bismuth, metronidazole, tetracycline and a proton pump inhibitor together for 14 days. And that's an effective regimen, but a very complicated regimen for patients to adhere to. Unfortunately, one of the most frequently used regimens still in the United States is so called legacy triple therapy, which comprises a proton pump inhibitor, clarithromycin and amoxicillin for 14 days. And you can see that the eradication rate there was below 80%. And some other recent studies have shown it to be even lower than that. And this is largely due to the increasing rates of clarithromycin resistance by H. Pylori. Next please. We have remarkably few reliable recent data on H. Pylori resistance rates in the U. S. And Europe, but what you see on the slide in front of you is the best currently available data. I'd first of all like to draw your attention to the Graham study, which is the 3rd study listed there, and this comes from a recent U. S.-based multicenterrandomized controlled trial. And the patients in this study were treatment naive. They had never received treatment for H. Pylori infection before, and you can see that 17% of them harbored H. Pylori strains that were resistant to clarithromycin and 44% had strains that were resistant to metronidazole. Above that, the study from Kumar and colleagues is also worth a brief mention. Again, this is from the University of Pennsylvania, and it looks at patients from the Delaware and Philadelphia area who were referred to Penn because of persistent H. Pylori infection after unsuccessful treatment. And the numbers are quite alarming. 43% had strains that were resistant to clarithromycin and 69% had strains that were resistant to levofloxacin. Next slide, please. So the life and death of H. Pylori, we know that intragastric pH is a key factor in determining effective eradication of H. Pylori. 2 of the antibiotics that are still frequently used in the treatment of H. Pylori infection are amoxicillin and clarithromycin. We know that they are more stable at higher levels of intragastric pH And also at higher levels of introgastric pH, you've got a more actively replicating population of H. Pylori organisms that are more susceptible to attack by antibiotics. And the table at the bottom of the slide looks at the MIC or the minimum inhibitory concentration values for various antibiotics, not all of which are still used in the treatment of H. Pylori infection, but shows that this is really a function of introgastric pH. And if you look on the 3rd bottom line there for clarithromycin, you can see that just by increasing the introgastric pH from 5.5 to 6, we reduce the MIC by a factor of more than 4 fold. So venoprazan with its ability to elevate intragastric pH rapidly and to sustain a high intragastric pH shows a great deal of promise in more effective treatment for H. Pylori infection. There are a number of unmet needs and there are a number of problems with the current treatment regimens. The most important that I've already alluded to is the growing resistance to a number of antimicrobials, but particularly to clarithromycin. Current regimens are complicated for patients to take. They're difficult for patients to adhere to. We require to prescribe 3 or sometimes 4 different medicines be taken together for 14 days. That involves the intake of a lot of tablets at different times during the day, and it's not surprising that many patients just aren't able to achieve adequate adherence. There are also a number of adverse effects from current treatment regimens. All antibiotics, of course, can cause some diarrhea, clarithromycin and metronidazole can cause taste disturbance and nausea, and there's a risk of C. Difficile infection with antibiotic use. Next slide, please. So let's look at some data now in which venoprazan based regimens were compared with PPI based regimens in H. Pylori infection. So this is a meta analysis of 3 randomized controlled trials where venoprazan amoxicillin clarithromycin was compared with PPIamoxicillinclarithromycin. Note that treatment in these studies was for 7 days here in the U. S. Treatment would ordinarily be for 14 days and that is how Fathom's pivotal Phase 3 trial is being conducted. But if you look at eradication rates by ITT, that's intention to treat analysis or PP per protocol analysis, you can see that there were higher eradication rates for the venoprazan based triple regimen than the PPI based triple regimen. And interestingly, on the right hand side of the slide, you can see that the venoprazan based triple regimen in double blinded randomized controlled trials was associated with fewer adverse events than the PPI based triple regimens. Asme has also alluded to the problem of clarithromycin sensitivity or susceptibility. Here is a meta analysis of 5 different studies, 2 randomized and 3 non randomized, where venoprazan triple therapy was compared with PPI based triple therapy. And we're looking here in terms of eradication rates based on clarithromycin resistance or susceptibility. So on the left hand side of the slide, you can see the success rates with the different treatments in clarithromycin susceptible strains, and you can see that the results with vanoprazan were numerically higher than with PPI based triple therapies. But on the left hand side of the slide, you can see the results for clarithromycin resistant strains, and you can see that there is a dramatic difference in success rates between venoprazan and PPI based triple regimens with venoprazan being almost as successful in clarithromycin resistant strains as in clarithromycin susceptible strains. Next slide. As Asme alluded to, however, we're also quite excited that the prospect of a dual regimen with venoprazan, that would include venoprazan and a high dose of amoxicillin. And we feel that the potent acid inhibition that PKABS, potassium competitive acid blockers, including venoprazan can achieve may allow for successful treatment with PKAB amoxicillin dual regimen. There are a number of obvious potential advantages to that. First of all, we because the regimen would not contain clarithromycin, we don't have to have any concerns about possible clarithromycin resistance. As a clinician, I know that there is a great deal of antibiotic overuse for all indications. If we had a reliable dual regimen, we would be able to reduce the number of antibiotics that we were prescribing. It would be a simpler regimen for patients to take and it's obviously good antibiotic stewardship. Next slide please. So here are some data with the benoprazan based dual therapies. On the left hand side of the slide, you can see the venoprazan dual regimen, that's venoprazan amoxicillin compared with the PPI based triple regimen of PPI clarithromycin amoxicillin. In treatment naive patients, the JUUL therapy was superior and in patients who were treated second line, they were similar, but there was a numerical advantage to venoprazan JUUL therapy. And interestingly, on the right hand side of the slide, a small study from Japan, where the venoprazan dual regimen was compared with the vinoprazan triple regimen. And you can see that the eradication rates were identical. They were 94% in both arms and that shows a great deal of promise for vinoprazan based dual therapy. Next slide please. So in summary, H. Pylori infection is highly prevalent throughout the world and here in North America that recent meta analysis of prevalence studies suggesting a 36% pooled prevalence rate among U. S. Adults. We know that current treatments are suboptimal. Most of the regimens that are prescribed in this country are still dependent on clarithromycin and clarithromycin resistance rates are increasing in this country and in Europe also. We have very few contemporary reliable data on resistance rates. I've showed you the best data that we can put together on that. And our current regimens are complicated, requiring 3 or 4 different drugs. So with venoprazan, we have the prospect of simpler, more efficacious based regimens. The triple therapy, benoprazine, amoxicillin, clarithromycin has shown high eradication rates in populations with high levels of clarithromycin resistance and we also have the very promising possibility of an effective dual regimen comprising venoprazan and high dose amoxicillin. So I will end there. I thank you for your attention. Thank you, Doctor. Howden. So before moving to the next section, I just want to remind everyone online to since we're going through a lot of data and a lot of information very quickly, we will have time at the end to answer questions. So please put your questions on the website in the space for questions and we will get to those towards the end. Now going back to GERD, but specifically to talk about our new program in non erosive disease, NERD, which we're very excited about. So we've shown this slide before. As I mentioned before, we have a great opportunity to address the unmet medical needs, not only in the ROSA subcitanic space, but NERB and thus GERD disease state as a whole. In NERB, faster and more durable symptom relief is needed. In addition, there is a need for flexible dosing to manage symptoms on demand for some patients as those patients desire. There is a clear rationale for further expanding our clinical research effort into NERD. First start to describe again that there is significant patients need for better symptom relief and there is a clear need for greater flexibility and convenience in the management of those symptoms. That is why non continuous regimens are widely used by U. S. Patients. And Doctor. Faz will describe the unmet need and the disease in a lot more detail when his presentation comes after mine. Now this is the current state of high level and since pharmacological profile of vinibirsen supports the potential for success in meeting those needs, we are initiating our NERD program, starting with a Phase 2 on demand study and also plan to pursue both continuous and on demand dosing regimens in Phase 3. When we look at what's available today for NURIC patients, again, like Faraz will speak to this more, the treatment options are that are available are known to have limitations, especially for on demand use. PPIs, which are mostly heavily used in this space, have slow onset of action take about 3 to 5 days to start working properly. Hence, they do not offer the patients with dosing flexibility. H2RAs, although they have rapid onset, they do lack durability. So looking at vinabrisan and its characteristics, we believe it has the potential to overcome those limitations on both ends of the spectrum and provide NERD patients with fast durable relief with increased flexibility with respect to dosing regimen, continuous and on demand. So we can have the best of all worlds in one molecule. So back to the slide which we showed earlier, I just want to illustrate that point. As you see on the left hand side, this is the data really that illustrates the potential very well. As you can see, veniprazan rapidly raised the pH to 7 within few hours on day 1 on day 1 of its administration, which is very strong indicator of the potential of vanuprisen in this space of fast symptom relief in neuro patients. Now before describing our GLAN Phase 2, I want to point out that we are taking key steps working with our advisors on the call and others, key steps to optimize the design of our studies, Phase 2 and beyond. As you may know, Takeda ran 2 classical continuous dosing nurse studies in Japan. And although the results were directionally in favor of 1 of our end, they did not achieve statistical significance. Now historically, Japan NERR trials have observed small effect size because the patient reported outcome in symptom based studies have reported smaller effect size and were not as consistent compared to the S counterparts. We believe these Takeda trials enrolled very heterogenic patient population not properly selecting for asset driven disease and they did not employ optimal heartburn data collection. In our program, we are utilizing the learnings from those studies. And hindsight is very important in this case and have plans to enhance the probability of success by maximizing steps to enrolling patients who are most likely to have asset driven disease, excluding those who most likely have functional disease and we plan to enroll patients in the U. S. Only. Essentially, all pass continuous dosing nurse studies in the U. S. Were successful and Doctor. Faz will speak to that more. Also, we are increasing the testing sensitivity by utilizing modern eDiRC data collection. Now this is on this slide is our Phase 2 study design. And this study we plan to initiate mid next year. So we're starting with a run-in period and responders during this run-in period will be randomized into 1 of 3 doses of vanaprazan. Remember, this is a Phase 2 dose ranging study. So we run 3 doses of vanaprazan and also we'll have a placebo arm. And patients will go through a treatment period of 6 weeks and then we assess the endpoint. The primary endpoint will be the proportion of heartburn episodes with complete relief. This is very practical endpoint to how we expect patients to be using the product if it is to become available post the proper clinical trials. In addition, I would point out that in this study, we have a number of secondary endpoints to further assess speed of onset of symptoms, symptom relief and the durability of relief. Now this study we discussed with the FDA and we have received advice from the FDA regarding this program and now we are moving forward with our plans to initiate the Phase study as stated mid next year. With that, I will pause and pass the stage to Doctor. Ronny Fass, who will describe the disease state and the unmet need in more details. Doctor. Fass? Hi. Thank you very much, Yasmeen. So I will cover the topic of the on demand therapeutic strategy for non erosive reflux disease. And non erosive reflux disease is the most common presentation of gastroesophageal reflux disease. Studies have shown that in this country between 60% to 70% of the patient with gastroesophageal reflux disease, they have non erosive reflux disease. In fact, in some countries in Asia, non erosive reflux disease accounts for up to 90% of the patient with gastroesophageal reflux disease. Now how do we define non erosive reflux disease? These are patients that have typical symptoms of gastroesophageal reflux disease like heartburn and regurgitation, but they don't have esophageal inflammation in the form of erosive esophagitis like was discussed by my colleague, Doctor. Speckler. These patients experience episodic heartburn and regurgitation. But despite the fact that these are episodic, they do profoundly affect these patients' quality of life, especially if these symptoms occur during nighttime. Now because we are not dealing with erosive esophagitis, the focus of our treatment in patient with non erosive reflux disease is the relief and prevention of symptoms. Thus, on demand regimen is best suited in this patient population. Now this is a recent study. It's an epidemiological study that looked at the prevalence of gastroesophageal reflux disease in the adult patient population in the United States. The study has shown that 2 out of the 5 adults that participated in this survey, and more than 71,000 of them participated and filled this survey, So 2 out of 5 reported of having GERD related symptoms at least once during their lifetime. 1 out of 3 reported having GERD symptoms in the past week. But most disconcerting from the results of this study was that 54% of the GERD patients experienced persistent symptoms despite daily PPI use. So the study has 2 important findings. 1, that gastroesophageal reflux disease is very common in the United States and 2, that about half of the patients that are taking PPI continue to have persistent symptoms. Now that brings us to a discussion about on demand therapy. Now patients, when they get treatment, for example, with a PPI for gastroesophageal reflux disease, they're asked by their physician to take it on a daily basis. So this is a physician driven therapeutic strategy and it's called continuous therapy because the patients have to take the medication on a daily basis. On demand therapy, on the other hand, is an example of a non continuous therapy. It is patient driven, meaning the patient decide whenever they need to take the medication and for the duration they desire. The only rule here of course is that the patients can take the medication only once a day. Now this is a study that was done in Japan, and this is an on demand study of venaprazone versus daily PPI. It's a relatively small study. It included 30 patients with non erosive reflux disease. Now all these patients were treated with daily PPI and before they entered the study, all of them in a questionnaire pointed out that they were satisfied or very satisfied with their continuous daily PPI therapy. Then patients were converted to vinoprazone 20 mg on demand for a period of 8 weeks. At the end of the 8 weeks of treatment, subjects were asked about their preference to remain with the on demand vinaprazine approach versus converting back to the daily PPI. And as you can see on the left side, the vast majority preferred to stay on vinoprazone on demand, 77%, clearly suggesting that patients are content with such a non continuous therapeutic strategy. Now when we go back to the epidemiological study that I just showed you, it's very interesting that one of the important findings was the fact that about 31% of the patients with GERD were using their PPI in a non continuous fashion from 4 to 6 days a week to few times a month, again, clearly supporting the concept that on demand therapy is highly desired by a subset of patients with gastroesophageal reflux disease. Now why PPIs cannot serve as a good on demand treatment? Here are 2 studies that are available on the FDA database and there were 2 independent randomized trials that looked at omeprazole in 2 doses versus placebo in patients with episodic harbor. The objective of the study was to evaluate the efficacy of omeprazole once a day in an on demand approach versus placebo, meaning that patients will take the omeprazole on demand, but can take only one pill at a time on a daily basis. The primary endpoint in this study was the percentage of 1st episodes with sustained complete relief. The design is on the left side. There was a 1 week run-in period with placebo and then patients were randomized to omeprazone magnesium 20 20 milligram, omeprazole magnesium 10 milligram and placebo. All of them were given in an on demand approach, as I previously described. When you look at the two studies, you can find out that there were no differences that were observed among the different arms of the two studies, clearly suggesting that PPI on demand, at least in these two studies, did not do better than placebo. So what kind of pharmacologic attributes an anti reflux medication needs in order to be a good on demand therapy? Well, there are 4 of them. The medication has to demonstrate rapid effect, potent acid suppression, durability of the effect and then flexibility of administration. For example, PPIs have to be taken about half an hour before a meal, while for example, venaprazone is not dependent on a meal. So it's much more flexible. Now the colors represent how much this attribute is being satisfied by the medication, where the more darker the circle, then the more satisfied is the attribute, and when the circle is lighter, then the attribute is less satisfied. And you can see that in all four important attributes, vinoprazone leads PPIs. And if you compare vinoprazone to 2 anti reflux medications that are commonly used as on demand therapy like antacids and H2 blockers, winaprazone also performs better in all four attributes as comparison to these 2 anti reflux medications. For example, antacids, many times, one has to take them multiple times in order to deal with an episodic heartburn in an on demand approach, and it's primarily because they're not providing potent acid suppressant. The same thing is about H2 blockers. Here is a pharmacodynamic study showing the advantage of PCCAPs over PPIs. For PPIs, it takes 5 doses in order to reach maximum effect. Now knowing that you're taking a PPI once a day, that means it takes about 5 days for PPIs to reach maximum effect. Now this is not the case when it comes to PKABS and you can clearly see that within the first dose, the PKABS already reach maximum effect and they reach it relatively rapidly, clearly showing again the advantage of PKABS over PPIs, which can serve them very well as an on demand therapeutic strategy. Next slide. So I'd like to summarize here about the potential of venaprazone for the treatment of non erosive reflux disease. So currently available options for on demand treatment of non erosive reflux disease, as I already mentioned, the 4 important attributes for a medication in order to serve as an effective on demand therapy. On demand treatment with PPIs is not FDA approved, but studies have consistently shown and we've known already for the last 3 decades that an on demand approach is an important area of unmet need and the venoprazone at this point provides a unique opportunity for positioning this medication in an area of an unmet need. The pharmacology of PPIs does not support an adequate on demand treatment profile, as we discussed, and venoprazone pharmacology supports potential development as an effective on demand treatment option for non erosive reflux disease patients. Thank you very much. Thank you, Doctor. Fest. So on this slide, this is our program, which Therese showed earlier. And today in the R and D portion of today's call, you have heard from Doctor. Speckler, Haugen and Pfas about GERD, both EE and NERD and about H. Pylori. You heard about that the current state in managing those diseases and how that current state and related outcome clearly highlight the significant unmet needs, which we are working very hard to bring vinabrisan through the clinical program to address those needs. We described veniprazan data in our program and the excellent progress we make to date, especially during an exceptionally challenging year worldwide. And we are extremely excited about our progress and about today's announcement of enhancing vinoprazem potential by pursuing non erosive disease indication as this promises to further advance the field and better meet patients' need and cover the whole spectrum essentially of GERD diseases in addition to H. Pylori. With that, I would like to pass the stage to my colleague, Martin Culligan. Martin is our Chief Commercial Officer, and he will describe the marketplace, the commercial opportunity and the potential for veneprisma. Martin? Great. Thank you, Azmi. What I'd like to do over the time together is share with you why we think this is these markets are a unique opportunity. There's certainly a big opportunity and how we plan to realize that for the Oprazant. So what I would like to start with are just a few numbers. What you're going to see here in the slide is, as you're well aware, we're going to be entering markets that are very large revenue markets. The ACE2 antagonist reached over $3,000,000,000 sales in the U. S. At its peak and the PPIs were at $12,500,000,000 But what makes this opportunity so unique is that for 25 years, there's been an innovation drought. There's been nothing that's been developed, no new mechanisms that have been introduced. So what we've heard is that most GERD patients believe that they can get better control over their symptoms. And I think we saw some of that data previously in the last hour. We also know that GERD patients try 2 or more therapies to control their symptoms. So there's switching going on and there's additions going on. And we also know that from a physician perspective, 2 out of 3 physicians are concerned about the long term use of PPIs. So as you think about it, the standard of care is something that's 25 years old and there's a lot of dissatisfaction in the marketplace. So then comes the year 2015 when Takeda introduced tachycap or venoprazan into Japan and that's where the treatment of these diseases began to change. And it's our intention to change treatment of these diseases as we enter the U. S. Market. So let's talk a little bit about Japan. Our goal is to equal and to exceed the success that Takeda has had in Japan with the introduction of Enoprazan here in the U. S. So we're often asked what's similar between the Japanese market and the U. S. Market. Well, both of them are highly generic sized markets, that's for certain. We also know that prior to the introduction of an OPRAZAN in Japan and still currently and definitely in the U. S, there's a lot of dissatisfaction with PPIs. Patients could feel better, there's a lot of switching going on And that H. Pylori rates were declining in Japan prior to the introduction of phenoprazan and they're currently declining below 80% here in the U. S. So when you think about that, the other unique thing is that both markets in anticipation of this launch, we're very excited about the introduction. So what did Takeda achieve? They became the market leader in Japan with revenue with a 38% market share. And that's quite amazing given the high genericized marketplace. They also documented cost effectiveness of using vinoprazan and they did all this with a premium branded price and achieved $725,000,000 in sales last year, very large for Japan. We also know that in Japan, venoprazan, the majority of the sales are made up of GERD and was only 2 years before they achieved an 80% market share in the marketplace specific to H. Bylori. So you've heard some of these numbers and I just want to recap a few of them for you. The first one is on the left regarding H. Pylori, 2,500,000 patients are treated annually. I have just mentioned to you the eradication rate has fallen below 80%. In GERD, there's 6,800,000,000 PPI doses prescribed annually. Now that's for everything for PPIs, but the majority of that is in GERD market. So it's very large. And the dissatisfaction rate again with the standard of care is 15% to 45%. So what strikes me here is the quote that says, people want to get better fast and they want instant results. And that's the promise that we hope to bring with vinoprazan. We hope to see superior eradication rates, faster healing and superior maintenance. Now I just described to you that the opportunity is very large, but it's also wide open. There's no products in late stage development in these categories. We also know that other products introduced in the U. S. Have been variations of old regimens. And in the U. S. There's no PKABs in development, but they are in Asia. And what we know about them is that the profile looks very similar to PPIs, they have shorter half lives or they have a different chemical structure compared to vinoprazan. So what's it mean? It means that we're looking at a promotionally sensitive market with little to no branded competition, which gives us the ability to have a commanding share of voice. And as I said before, it's an innovation starved market. There's just been nothing going on here for 25 years, No introductions. So how do physicians feel about vinoprazan? As you can imagine, we've been very active this past year talking to physicians about their impressions. I can tell you that I worked on many launches in my career and never have I seen preference share rates of around 60%. When you present the profile for these indications to physicians, both gastroenterologists and primary care, there is a high desire to use enoprazan. What's interesting here on the GERD data is that it's very similar results for both primary care physicians and gastroenterologists. And that's not so common to see when you introduce a product that covers both the specialty and the primary care area. And then in H. Pylori, what you're going to see is that these numbers are approaching 70% in terms of preference to prescribe. Those are incredibly high numbers. And the other thing that these respondents picked up on is that they enjoy the flexibility that we could potentially have with a triple therapy and a dual therapy. So, it provides not only high eradication rates, but the potential to have different dosing regimens. Now during this year, we started to do our work and started to look at the target audience or the customer base. And what we know as it's a really large TRx market, we also know that it's a highly concentrated group of prescribers. 20% of the physicians write 70% of the scripts in both H. Pylori as well as incurred. So when you think about that for H. Pilari that's about 16,000 high volume writers and for GERD it's about 40,000. And we know the overlap is about 30%. So what we think at launch at this current time is that we could launch with in the range of about 90 sales representatives. And then as we look forward to GERD because of the high overlap in terms of prescribers, we'll then take a look and see what our breadth and depth goals are, determine how much further we need to go higher than that. But we know we'll be able to leverage all of those 90 heads right from the beginning. Now to have a successful launch, you have to have the right people. And it begins with having leaders and experience in our organization. So I am going to take a little bit of time on this slide to virtually introduce you on paper to our leading commercial team. First, we have Joe Jones, who recently joined us and he's going to be the Vice President of Sales. Joe comes with broad GI experience and most recently, excuse me, has been working on LINZESS, both in sales as well as in marketing. So he's going to bring a wealth of experience, category knowledge and also relationships with many gastroenterologists. Christine Fisher has joined us from Regeneron. She's going to lead our insights group. And what's really great about Christine is not only is she able to deliver insights, but she connects the different insights and we're able to turn them into actions. Beginning in January will be Susan Kim. She's going to be Vice President of Marketing. Susan comes from Amgen via Celgene. And Susan has built a blockbuster. Susan was there to build the launch of Otezla, prepare for it, launch Otezla and has seen it all the way through to this point. So, she's had the ability to conceptualize prior to being in the market all the way through the lifecycle and seeing double digit growth. Susan also has GI experience in her background and actually she began her career in health outcomes. Philippe Rudy has joined us as Vice President of Medical Affairs. Philippe has 2 things that are really valuable to us. 1, he's worked at very small pharma coming from Liquidia as well as large. And then he's also worked in therapeutic areas that cover both primary care and specialty. And then last, I'll introduce you to Mark Devlin. Mark is our Vice President of Market Access. He's joining us from Allergan. And as you know, Allergan had a very broad portfolio. They certainly had some therapeutic areas that I'm certain represent challenges. Mark brings the experiences of negotiating contracts as well as bringing to us relationships within the payer community. So as we speak about the payer community, let me say that we clearly recognize that access is going to be critical to our success. And we have some early insight from the payers and they recognize the unmet need that you heard from our the 3 physicians who joined us today. They're not blind to it. So they do have interest in having discussions to see where vinoprazan would fit. So let's talk about the 3 areas for payers. The first one is, we know that this is a large population in need. There's 65,000,000 people with GERD. And of those, we know 50% of them progress in their line of therapy annually. So that means there's a lot of movement in the marketplace. We also know, as I mentioned before, that there's a declining H. Fibrillation rate with the current regimens. These things result in healthcare system utilization. So what happens when someone fails in their erosive esophagitis or they have a recurrence? That means they have another lesion, which means they're backing up to the treatment phase, which means they're taking up more resources of endoscopy and physician visits, as well as more drug utilization. And when there's in a failed eradication cycle, what that means is that patients being retested yet again and they're being treated over again. So in this area, there is a lot of healthcare system utilization when there's failed treatments. And as I mentioned already, I think once or twice is there's lack of alternatives. 25 years with nothing introduced into the marketplace. And what we know is that the majority of patients when we come to market will have already passed through PPIs as their standard of treatment. So what will the drivers be? We know that health plans have objectives to meet unmet needs for all of their patients, all of the lies, the terminology that they use. We know that we'll have some clinical well, we hope we'll have clinical superiority from our clinical trials versus PPIs. Lowerosive esophagitis recurrence rates, faster healing and greater eradication rates. You heard from our speakers that we, our pharmacology, delivers a rapid, potent and durable asset control. And bringing in a new mechanism of action when there's been nothing to turn to for all of these years for these patients once they've had a PPI or even before the PPI is different from all the other approaches. So our intention is to deliver this with a potential branded premium price commensurate with the value. So we'll be working on a value proposition that matches the unmet need to what we deliver in our clinical trials. Now as we look at pricing and access, we're looking at various market analogs, but we believe that we can achieve broad access and we can do it with a branded premium price. If you simply look at DeXcellent, which was the last PPI to market with minimal to no differentiation at all, they had very good access and they currently have a lack of $9.69 a dose. So we know that the payer market is going to be really critical for us, but we think we're equipped and ready to be prepared for it. So it all begins with opportunity. I'll back up a little bit and talk about that opportunity. And when you ask physicians why do patients fail H. Pylori eradication? We hear 2 things mainly. The first one is the resistance to antibiotics and that's what Doctor. Houghton commented on. But we hope to address that. As you saw in our clinical data from Japan is that we have high eradication rates in all patients and those who are clarithromycin resistant. So this one key issue that's faced in terms of eradication failures, we hope we address to our clinical profile. The second one is the lack of drug therapy and compliance excuse me, the lack of compliance to drug therapy. There's a lot of pills to take in this regimen over a couple of weeks period and it can get confusing. And so our intention to deliver a convenience pack where we really clearly lay out the noprazan, the antibiotics, when to take them and how to take them together. That's another solve. So what I'd like to share with you is a patient's perspective. This is Lisa and Lisa will tell you a little bit about her journey. Thank you. The symptoms started in my late teens, early 20s. I always had stomach pain. I was always tired. So I first decided to make an appointment with my GP. No one did any real testing or anything like that. So it was frustrating and it was miserable. The one specific moment that I knew that I had to visit a doctor and find out what was wrong with me was when I was laying on the couch one of the nights thinking that I'm going to die this way and that I won't be able to ever enjoy life with my children. I got an endoscopy and my diagnosis for H. Pylori came within 3 days. My GI doctor also let me know that I had an ulcer that had been probably caused by H. Pylori for letting it go for so long. I had multiple rounds of antibiotics and they all failed in the long run and clarithromycin was in all of those rounds. I felt better for about a year. The symptoms slowly crept back in. My ideal treatment would be fewer doses, packaging that had all the pills in together and what time to take it, that would be hugely helpful for me. It would have to be something that would eradicate H. Pylori, so I don't have to go through the pain, go through the testing, go through the rounds of medication. I want it to just be I just want to be done with it. That would be life changing. I would tell h. Pylori to please leave me alone because my family and I are tired of it, and I'm tired of being in pain all the time. So I had the good fortune of being able to meet Lisa. And I think what you probably heard from her journey is while we all think of this condition as an acute condition for her, this is actually very chronic and she's not alone in that. What we've learned in speaking to patients is that most patients contact the physician within a few months of their symptoms. And we know that from Lisa's story, it's just because they contacted their physician in her case of primary care, it doesn't mean that it's immediately diagnosed and taken care of or eradicated. We also know that about half of the patients found that their drug regimen confusing. I already mentioned to you that we plan to offer convenience back. And that they enter this treatment as we all would is that their infection would be eradicated and they would be treated effectively. And then once again, we know from Lisa that that's not necessarily the story for everyone. So we hope that we have the potential to deliver a superior eradication rate that solves this condition for so many patients. And then interestingly, we found that about a quarter of the patients continue to use PPIs. So how would I summarize what we intend to do with H. Pylori? Most importantly and for the purpose of the patient, we want to reverse the curve of the declining eradication rates. We also from a business perspective want to set a strong launch foundation in RAM for erosive esophagitis. So let's talk about erosive esophagitis. And speaking to physicians, we asked them about their interest in a new product. And specifically they told us they want something that works quickly, provides durability of response and provides potency. And when you see this quote down here at the bottom, what stands to me is the clinical urgency. They have a clinical urgency and what we're hoping is that venoprazan is the puzzle piece that meets the gap in these unmet needs. Now you heard about you heard Lisa's story for H. Pylori. Let's talk about the patient journey for ROSA vasophagitis. It's a little bit complicated. Their journey looks a little bit different. The first one is when they begin, they typically start over the counter drugs before they get to a physician's office. But when they get there, what they want is they want to shed themselves of the OTCs and they want immediate relief, they want immediate healing. And we hope that phenoprazine can deliver this potential speed of not only symptom relief, but also in healing. When they do go to the physician's office, what we know is unlike many categories, they do not request a specific product. So it's our goal to awaken this therapeutic area and drive patients in through DTC when we get later in our lifecycle to activate them to ask for venoprazan. Now for any therapy, what everyone's looking for is something that's efficient and convenient for dosing. And you heard earlier from Doctor. Fast that you really need to take KPIs with food to get the maximum effect to make it effective. And that's not the case with vinoprazan. We hope to offer the flexibility because vinoprazan is not dependent on food to achieve asset suppression. And then in their journey, when they reflect back upon it, we ask them their experience. What we tell what we hear is that basically it takes a while to get any relief up to 3 weeks before they start to see any partial or fulsome to relief. Many of them are moving to a BID dosing or what they're doing is they're continuing on with OTCs. And we have the potential for both rapid and improved symptom relief and healing. The journey is the same for both erosive esophagitis and NERD. As both ASME and Doctor. Bass talk to us about NERD. And when we hear about NERD from the physicians, we get equal enthusiasm for the opportunity that epinephrine brings forth. When we ask them, what we get back is that 60% of their NERD patients are treated long term with the PPI. So we know that this is a market when you enter into the market, you have the opportunity to have an ongoing relationship with patients because there's a long term commitment. We also know that 39% of the physicians have patients supplement due to OTCs because they're not getting that immediate belief. Again, that dissatisfaction carries over from a rose of esophagitis over into NERD. And then what's very exciting in terms of our ability to disrupt this marketplace is when asked, 65% of physicians tell us they'd be interested in a new class of therapy that works fast, provides durability of response and is indicated for an on demand use. And further, when you ask this group of physicians, would they prescribe enoprazan? We get very high intentions. And here's the opportunity to open up new market segments for us. In NERD, it gave them a reason to use it in new patients. And then they started to think about switches, non or partial PPI responders and keep in mind that the majority of the patients in the category have already been on PPIs and up to almost half of them are not satisfied. And then there's a lot of patients who have long term PPI that physicians just don't think are appropriate for that and are interested in menoprazant on demand. So I started out by telling you that it was a unique opportunity and a big opportunity and hopefully that little bit of that came to light. What we know is the customer see the value or potential value of fast action, superior efficacy and durability. The markets are very large, 115,000,000 patients are adults walking around with H. Vollary, 65,000,000 nerd patients. The unmet need is very clear. There's been nothing in this marketplace and it's been a real drought in terms of introductions of anything exciting in terms of mechanisms. Physicians have a strong preference and desire to use vinoprazan and we know that that target base is highly concentrated. There's little activity in the marketplace and again it's our goal to awaken it and bring new life. We want we plan to have a high and dominating share of voice. The profile is very exciting. As you can see, we heard from our customers already. And we have the opportunity for a potential for a premium branded price. So, we truly believe we have something that's going to deliver something different for patients, for payers, as well as physicians. Thank you. Todd? Thank you, Martin. I'll provide a brief review of Fathom's financial position. Fathom is really well capitalized company with over $200,000,000 of cash on our balance sheet as of the end of September. That's a level of cash that puts us in a really good position to fund the completion of the Phase 3 clinical trials as well as to support the investments we're making to prepare for commercial readiness and to build out the administrative functions that will support the organization in the coming years. We were also pleased that last month we were able to file our initial shelf registration statement, including an at the market program, which gives us really good flexibility and optionality to fund our company as our needs increase and to further support the build out of the organization. So in summary, we're exiting 2020 in a really strong financial position and we have the tools in place to be able to maintain that in 2021 beyond. So with that, that concludes the prepared content of today's program. We can see questions have been coming in from the website. So we thank you for that. We'll take a moment now to pause to review the queue of questions that have been submitted. And our first question relates to the ongoing global pandemic. And the question is, how has COVID-nineteen impacted your clinical development? And what are you doing to prepare for ongoing effects of the pandemic? Teri and Osmi, would you like to respond to that, please? Thanks, Todd. We've been highly encouraged by the work that clinical team has executed during the pandemic and despite the 3 month pause that we took earlier in the year in response to the society's recommendations to cause elective endoscopy, when we began re randomization, the both of the HD and EE trial really accelerated. In fact, the team was able to exceed patient enrollment of our SOUTHEN EE program with over 1,000 participants enrolled, and we remain very encouraged regarding our ongoing enrollment in the HP trial. In fact, we expect that we will complete enrollment for HP in January of 2021. And I think this really underscores a couple of things. Firstly, the outstanding execution and engagement of our clinical team. But secondly, the great unmet need that exists for new treatment options for patients with erosive esophagitis and the commitment and enthusiasm of the collisions that we see that are investigating these compounds. We do not expect to have any impact to the integrity of our studies and look forward to seeing the top line results next year. Like everyone, we continue to monitor the COVID situation closely. And from an operational perspective, we've been scenario planning throughout for 2021, which is really a key or critical year for us to continue our engagement with physicians, payers and patients with our medical team and planning engagements at medical conferences. I have to say that the team has been adapting very well to the virtual world right now. In fact, we just recently ran our first virtual CME, which went really well, was exceptionally well attended. The positive experience that we're having with GIs and engagement has really been because, as Martin outlined, there just is such a lack of innovation in say that say that recruitment from a recruitment perspective, we've been able to build a phenomenal team in the midst of pandemic, and we'll continue to do that throughout 2021 with no negative impact. Thank you, Terry. Next question, and Martin, maybe this is a good one for you because it relates to commercial, is around our plans for establishing commercial infrastructure. So if you could speak to the structure of our sales force and how many reps we'll need in the context of our overall commercial infrastructure plan. Sure. So before I get into the details of the sales force, I think I'll just back up for a minute and talk a little bit about 2020 because I we entered this year thinking it was going to be a very foundational year to get us to get all the bricks in place to get ready to move. And we weren't very far into it before we found out we needed to move rather fast. So part of that planning was bringing on the right people, as I mentioned, in the commercial team. So what will happen is in second half of twenty twenty one, we'll start to look to build out that sales leadership infrastructure. As I mentioned, that will have probably about 90 in the range of 90 representatives, who will call and book high volume gastroenterologists and primary care physicians in these 2 therapeutic areas. What we also see is that in those you're probably talking it's somewhere around 16,000 physicians at launch and that we'll be able to cover them with a good amount of high frequency be the right target base. But that comes later. I think in 2020, what we've also identified is that we've learned a lot. So we've done really robust market research. We started to refine our go to market strategy. We've begun our segmentation work. And as I just mentioned, about the targets, we've begun the targeting process. The other thing I should comment on in the field that we've done this year with the introduction of Philippe joining us is the build out of the MSLs or medical scientific liaisons. This is the group that's actively calling on the thought leaders or in the area and having those scientific dialogues. That footprint is set and we've had people in place and that will continue to grow next year. So that was 2020. You asked about the sales force, so that's about 2021. Just a few other thoughts regarding 2021. It's only December or it is December 14, and our heads are already thinking about January. We'll be completing more market research. We need to dig deeper into our potential positioning, the messages and connecting that unmet need that we see in the marketplace to the benefits that anoperzan delivers. We'll do that with payers, understand more of the differences between primary care and GI as well as patients. You can expect to see that we're going to launch a corporate campaign in the Q1. This will be about introducing Fathom and all the things we're doing here, so the medical community starts to get to know us a little bit better. And then as we finish that and we move on in the year and we approach launch, we'll be looking at an unbranded campaign. And this is where I used the terminology earlier about awakening the therapeutic area. We're going to introduce a campaign that really speaks to the unmet need. It's been very interesting in speaking to customers. When you have the dialogue, they all recognize the unmet need, but no one really talks about it because there's been nothing going on for so long. So it's our intention to raise that dialogue up. And I should also comment then on the payer front. What our objective to do is we've hired someone to lead our HUR efforts. We've begun some outcomes work this year in terms of understanding the marketplace. We'll do more work next year, some studies coming up. And then that will all be ready to hand something to the account group that we want to build out in 2021, so we can start having those individual conversations with payers. So we accomplished a lot in 2020. 2021, we've already begun 2021. And I hope that answered your question regarding the sales force structure. Yes. I think that was good, Martin. Thank you very much. Our next question is around the readout of our Phase III trials and whether there is any going to be any read through from the HP readout, which will be in the Q2 of next year to the EE readout, which will be in the second half of next year. So perhaps, Osmead, that's a good one for you to take? Yes. I'll do that. So although mechanistically both disease state efficacy of going to present both disease states relies on asset suppression and the pH elevation, they're really different disease states. H. Pylori relies on that vinabrizant really improves the efficacy of antibiotics and it's a shorter duration treatment. It was also a sepsisitis, it's healing the lesions. So they're very different in the way they go about the efficacy Fenoprazine goes about the efficacy. So H. Pylori is not predictable of erosophagitis. That's the short answer. Okay, great. Thank you, Azmi for that. Our next question is around the prevalence of H. Pylori and why so many people are actually have H. Pylori infection, but so few are actually treated and what the screening process is for H. Pylori. So, Osmi, maybe I can direct that one back to you and then ask you to have Colin, Doctor. Houghton support with his comments as well, please? Yes. The disease is primarily now empirically treated. The testing for resistance is not a priority. And that's why the dilemma that exists in the field and that's what leads to increase in the resistance actually. But I'll pass it to Doctor. Howden, who can speak more to that. Okay. Thank you, Asmi. Well, the recent meta analysis of prevalent studies suggested a pooled rate of 36% among U. S. Adults. Now that's higher than I perhaps would have anticipated, but nonetheless, that's what the data show. The majority of those people are probably asymptomatic and they may or may not have access to health care. We know that the prevalence of the infection varies widely related to socioeconomic status and also to racial and ethnic groups. So a number of socially disadvantaged or economically disadvantaged people in this country have H. Pylori infection and don't know about it. They're as I said, they're likely to be asymptomatic. And those are the people who are probably at the most risk of developing gastric cancer. And as I pointed out in my talk, there's increasing evidence that detecting the infection in these people and successfully treating it is likely to lead to in the lifetime risk of gastric cancer. So that begs the question, why aren't we doing routine screening in this country? And I don't think I can answer that. We're not quite at the stage of offering universal screening or recommending universal screening in this country, although that is done in parts of Asia where there's an even higher incidence of prevalence, I should say, of H. Pylori infection and incidence of gastric cancer. So I think the study from Kumar and colleagues at University of Pennsylvania is a landmark study. It's likely to change opinion in this country and we may be moving to a more progressive attitude towards screening. But certainly, people would need to realize that the prevalence of the infection is high among adults in this country, particularly among certain racial and ethnic groups. Yes. And one of the things, Doctor. Howden, just maybe you can comment on more. How if you once you identify a patient through symptoms or screening, it's likely that the rest of the family and even maybe the neighborhood that this is the infection rate is very high. Can you comment on that as well? Yes, that's true. One of the biggest risk factors for acquiring H. Pylori infection in childhood is having an H. Pylori affected parent, particularly an H. Pylori infected mother. So H. Pylori does tend to cluster in households and families. Now at the moment, we don't recommend our practice screening asymptomatic family members for H. Pylori infection because we know that once the infection is successfully treated in an adult, even if that adult lives in a household where there's other H. Pylori infected family members, the risk of reinfection is very low. So at the moment, we're not recommending, we're not practicing the testing of family members, but that may change as evidence continues to grow. Okay. Thank you, Beth. I think that was really helpful. So I can see we've got several questions dealing with the same topic. So perhaps I'll just try to consolidate them into one question. And that is around how payers might be willing to treat or whether they would be willing to treat vinoprazan differently to PPIs. So Martin, maybe I'll start with you on that and then perhaps Doctor. Speckler can lean in from more the clinical side of things. Sure. So I think what might be rooted in that question is what we see in the marketplace before. And I know in many categories there's a lot of step edits, there's delisting, non access. And I think what we've seen over the past couple of years and the majority of therapeutic areas is there's just been a constant influx of new mechanisms. Even in the GI space, when you look at IBD or you look at rheumatoid arthritis or some other areas, it seems like every 10 to 18 months, there's a new mechanism of action. And then following that new mechanism of action are 1 or 2 molecules within that mechanism of action. And it creates a real reimbursement challenge because what a lot of those companies are doing is they're really splitting hairs to find their differentiation to find their space to get reimbursement. And this market and vinoprazan just appears to be very differently over 2 decades. And there's no alternatives. It's really just a PPI and nowhere to go beyond there and with no other mechanisms on the horizon. So it just says that here's an area with tremendous unmet need. And as I mentioned before in early feedback from payers is that they recognize that. So it offers a potential solution for increased eradication rates and for the payer what that might mean is you have less cycling through for H. Pylori cycles. You have less testing, less office visits, less drug treatment. And then for erosive esophagitis in the broader GERD market, it was specifically for erosive esophagitis is when people fail their treatment and they're in maintenance, they're backing all the way up to the treatment phase. And with a compound that could potentially have faster healing and superior maintenance, you're looking at potentially again less visits, less endoscopies and less drug treatment. So there's clearly a need and there's also an opportunity in here for the payers. And Doctor. Speckler, do you have anything to add? No, I agree with what you just said, Martin. And physicians really are starved for something new here. Understand that there are 6 different PPIs and they have differences in dosages and administration and that sort of thing. However, for clinical purposes, they're all considered essentially the same. One doesn't have a clear advantage over another. And this is a drug that you have that at least in Japan is showing some clear clinical advantages. I think physicians will be very anxious to adopt this. And barring any major insurance problems with it, which I wouldn't anticipate, I think it would be adapted very quickly. Okay. Thank you, Martin and Stuart for that. So our next question is around the NERD program and the on demand regimen inside of that. And it's a question around, would patients that would potentially go on to an on demand treatment regimen be looking to simply avoid chronic use of PPIs? And would this potentially be a first line or a second line therapy with the on demand regimen? So perhaps, Teri and Martin, I could ask you to speak to that. Yes, sure. So our intention would be to have a very broad label for that indication. So it could be used both as a first line as well as an on demand therapy. Martin? Yes. I think I would also add to that is, I would imagine there's going to be 2 groups of patients, one that will be start out as continual and then maybe transfer. But then also what we heard in evaluating to move forward is that there's a lot of patients who need just to start out at on demand. So from our perspective, and from a business perspective, it really is going to open up new growth drivers for us. We know already there's a large population that's taking PPIs on demand. And we also know that another growth driver is just the entire nerd population whatsoever. So, it's clearly it offers different areas for us to exceed both new starts, as well as potential, if appropriate, switches. Okay. Thank you, both. We have another question on neurodegenerative development program. Maybe, Ozmi, I'll direct this one to you. The question is, why the decision to start with a Phase 2 program and on demand rather than proceeding directly to a Phase 3. So perhaps you could talk about our approach relative to the development program and on demand? Sure. As we mentioned, none of the PTIs are brewed in this space. And the FDA has not really cemented their approach to the endpoint. Now we discussed our program with the FDA and we wanted to do things. 1 is fine tune the endpoint to be sure that we have something meaningful, measurable in a producer kind of way and above all meaningful to patients. But also we wanted to do a dose ranging study. This gives us not only a regulatory path that's based with the FDA because they said they not really gave that approval before to BBIs or the PCAPs for sure. But also because that gives us the creativity and the flexibility to design a very efficient Phase 3 programs to give us, as Terry mentioned, the broad label we desire for continuous on demand. And that evaluation stage is very prudent to do as we are progressing with our current program, the program. Perfect. Thank you, Ozmi for that. Our next question is actually on the rights we have to commercialize vinoprazine in Europe and our approach and thinking around that. So, Terri, if I could direct that one to you, please? Sure. Yes. So, we do have the rights in both Europe as well as Canada. So, it's currently finalizing some market research that we're doing in Europe in the core five markets to really size the opportunity there. Our base case is that we will most likely partner in Europe, But we really want to have the answer to the question on the size of the opportunity before we move forward with those discussions. Okay. Thank you for that, Terry. Our next question is just around the projected costs related to the neuro clinical program and how that would impact cash position of the company. So I'll take that one. So as we've talked about the first step in the neurodevelopment program will be the Phase 2 on demand trial and we'll begin to incur those costs in 2021. We expect the cost to be on average what you would expect to incur on a Phase 2 trial. So the commencement of that program and the occurrence of those costs in 2021 are going to have a significant impact on our cash position and aren't going to have any impact on our ability to continue to be able to fund the completion of our Phase 3 clinical programs as well as to further build out and make the investments that we're making in the organization to prepare for commercial readiness. So, and as a reminder, as I mentioned during my comments, we do have the shelf registration statement as well as the ATM program in place, which would allow us to raise some capital in the event that we need to. So let me take a look here at the next question. Perhaps, Martin, I'll push this one to you and any of the KOLs as you deem fit. So in terms of the clinical and the commercial opportunity, can you provide more color around how physicians may practically use the regimen? And how do you think patients will have access to vinoprazine upon launch? Sure. So, I would think from H. Pylori, our trials deliver what we've seen in Japan, I would imagine it would be the primary go to given the high eradication rates. The fact that we would be offering a dual or triple therapy options, so it provides more flexibility to the prescriber. And then for the patient, clearly in a convenience package is going to make things a little bit better. And I think if we hit those Phase 3 trial, I would imagine that the payers would also be very open to that. In terms of the physician experience, and I think that was the base of the question for erosive esophagitis, again, I mean, there's no reason really why not if you have good safety to want faster healing and superior maintenance. So again, we believe in the response back in terms of their intention for preference share to be in the 60% plus range would tell us that it would quickly become something that they would go to rather fast. I don't know if any of our other speakers have comments, any of our I don't know, Ronny, Doctor. Fass, do you have any comment on that? No, I do think that in the case of on demand therapy, because we don't have any medication at this point that is approved for on demand, any PPI, I mean, then I see a great opportunity. I mean, basically, there will be the sole medication that will be available to people to provide something that is specifically approved for on demand. Okay. Thank you, both. Our next question relates to the regulatory exclusivity that we expect for vinoprazan and in particular the QIPP designation we have and what that means in terms of that exclusivity. So, Terri, can I ask you to speak to that? Sure. So we expect to have at least 10 years of market exclusivity from the date of our HP approval. And so for a little color on that, the HP approval will give or grant us qualified infectious diseases product designation QIDP. And that adds 5 years of regulatory exclusivity to our already 5 years of an NCA exclusivity. So that's at least 10 years. And we expect that there's a strong potential for an additional 6 months for pediatric exclusivity. So that's 10.5 years from the time we launch. Okay. Thank you, Terry, for that. I think maybe we have time for one more question here, and that again relates to our neurodevelopment program. And just what are the criteria we'll be examining in the trial program and how those compare to the experience in Japan in studying NERDS. So, Osmi, could I ask you to answer that one, please? Sure. As I mentioned, in Japan, they only studied continuous therapy. So they have not studied on demand. So demand is very unique program than what was done for 100% and anything else. That's why the novel approach it's a very novel approach. So regardless of on demand or continuous, the key criteria for us is to include patients who most likely have acid related disease and we're working with Doctor. Faz to zoom in on the right selection criteria. The data collection and using eDiaries and more modern techniques and zooming in on the right symptomatology for inclusion and follow-up, as well as something that's really different. In Japan, they included subjects who are light in their symptoms, 2 symptom Ipsen over 2 weeks, over a short period of time. We will be more consistent with what was traditionally done in the U. S. So we will select patients with at least 4 episodes over 2 weeks and over a longer period of time. So these were the key elements. Again, I want to emphasize that on demand is very unique with very unique endpoint compared to what was done in Japan. But even for the continuous patient selection criteria and data collection would be very different than Japan. That. Okay. Thank you for that, call today. As in the call today. As you've heard, 2021 is a catalyst rich year for Fathom, including completing enrollment of our Phase III HRO trial, sharing top line results of both Phase 3 clinical trials as well as initiating our Phase 2 trial in Merd and the NDA submission for H. Pylori. We're really excited at Faizan, moving vinoprazine forward. And the team here is really focused on identifying that unmet need and moving the numbers then forward. Clearly, we have a differentiated MOA and product profile, moving into an innovation style category that hasn't had a product, a new product available for more than 20 years that has the potential to be a blockbuster. Thank you for joining us today and thank you for your attention.

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