Study Result

Apr 29, 2021

Ladies and gentlemen, thank you for standing by and welcome to Fatum Pharmaceuticals Phase 3 Falcon HP Top Line Trial Results Conference Call. At this time, all participants' lines are in a listen only mode. After the speakers' presentation, there will be a question and answer session. I would now like to hand the conference over to Todd Branning, FASM's Chief Financial Officer. Thank you. Please go ahead, sir. Good afternoon, and thank you for joining us. My name is Todd Branning, and I am Fathom's Chief Financial Officer. Today is a very important day for Fathom, and we're excited to discuss the results from our Falcon HP Phase 3 trial that we shared earlier and to answer questions you have regarding the data. 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 presenters Terry Curran, our President and Chief Executive Officer and Osmani Nabulsi, our Chief Operating Officer as well as other members of our leadership team, Martin Gilligan, our Chief Commercial Officer Tom Harris, Senior Vice President, Regulatory Affairs and me. 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. Good afternoon, everyone, and thank you for joining us today on what represents not only a significant milestone for Fathom Pharmaceuticals, but also for those who suffer from acid related disorders. Fathom was founded almost 2 years ago when we licensed and offered them to the U. S, Europe and Canada, and we embarked upon the mission of improving the lives of people suffering with acid related gastrointestinal disorders. Binoprazan, a potassium competitive acid blocker, or PKAB, has the potential to be the 1st in class best in class gastric antisegradable agent in the United States, where there's not been an innovative acid suppression therapy approved in over 25 years. We believe vinoprazine is not just an incremental innovation, but instead holds the potential to be a major breakthrough in the treatment of acid related disease. This is due to vinoprazine's PKANs provide rapid, potent and durable acid suppression that we believe translates to a differentiated clinical profile. This profile has already been seen in Japan where vinoprazem was extensively studied, launched and rapidly reached market leadership with annual sales exceeding $800,000,000 Pelicobacter pylori is a chronic bacterial infection of the GI tract, which impacts more than 200,000,000 people in the United States and Europe. Falcon HP is our Phase 3 program in this disease area, investigating venoprazan versus the current standard of care with a PPI based triple regimen. The study was designed to investigate venoprazan when combined with antibiotics in 2 regimens, both JUUL therapy with venoprazan and amoxicillin and also with triple therapy with the addition of clarithromycin. Today, I'm very pleased to announce the results of this FALCON HP trial and report that the study met all of the primary and secondary endpoints with an ultrasound delivering superior H. Pylori eradication rates versus the comparative PTI based regimen. As you'll see from today's presentation, Falcon HP has highlighted the large unmet need in this disease and the promise of the not present to so many patients. Before turning the call over to ASME to discuss the data in more detail, I'd like to thank our entire FASM team and the clinicians and clinical staff who worked incredibly hard to ensure continuity of operations for the trial during the pandemic. Most importantly, I'd like to thank the patients who participated in the FALCON HP trial. We look forward to working with the FDA to submit new drug applications for both phenoprazan based regimens before the end of the year and are hopeful that today's positive results will lead to a better future for H. Pylori patients. I'd now like to introduce Asmi. Thank you, Terry. I too would like to thank all Talcan team members, all the clinicians, their staff and all the patients who participated in the TRICON HP trial. We hope that today's results will enable us to advance a much needed new treatment to combat and eradicate H. Pylori. H. Pylori is the most common bacterial infection worldwide. In the United States alone, 115,000,000 people are estimated to be infected with H. Pylori and annually approximately 2,500,000 patients in the United States are treated for H. Pylori. Globally over the last 2 decades, H. Pylori eradication rates have steadily declined to unacceptable lower levels. Our hypothesis for TITAN HP trial was that when it presents potent and durable asset suppression profile would allow for better antibiotic efficacy in eradicating a final rate. It is notable that following lenabirzan's launch in Japan in 2015, this declining trend has reversed and itch pylori eradication rate has now steadily increased since the introduction of vinoprazine to the marketplace. I'm happy to report that the FALCON HP trial results support our hypothesis and may offer the same opportunity to address this unmet need as it did in Japan. Now we designed FASCAL in HP as a 3 arm study, as you see here on this slide. Comparing vinoprazan in combination with clarispromatin and amoxicillin and vinabrizan in combination with amoxicillin alone versus lanceobrazole in combination with clarisiromitin and amoxicillin. I will refer to these as vinoprazole therapy, vinoprazole therapy and lansoprazole triple therapy. The primary endpoint for each vinoprazole base regimen in this trial is non inferiority versus lansoprazole triple therapy. Now based on FDA feedback during the design phase of the trial, it was agreed that non inferiority comparison would exclude patients with amoxicillin or crathromycin resistant strains of H. Pylori. Now to meet the secondary endpoints in the 5 1HB trial, the phenoprazan regimens were required to achieve superiority. The 2 key secondary endpoints of superiority are to be performed on 2 patient population subsets. First, the subset of patients with clerestromicin resistant strain of H. Pylori and then all randomized patients confirmed with H. Pylori infection. And the approach of the sharing the data will be as such. I will first refresh you on our statistical approach for controlling for Type 1 error. We were where we set the alpha, testing the triple therapy at 0.04 level and the dual therapy at 0.1 level. The reasons for testing the dual at a lower 0.1 level is that since this was the 1st Phase 3 study testing the dual therapy, we set the statistical bar higher. Based on the hierarchy for each and for each therapy, if the primary endpoint of non inferiority was met, we were to assess the secondary endpoint of superiority in the order shown on the slide for a total of 6 key tests in the study. Now I'll move to the actual results. Here are the statistical outcomes of each of these tests, which as you can see are very impressive. We essentially hit and achieved significance on all of the 6 endpoints. Not only was the primary endpoint of non inferior death for both vinobrazan regimens, but also we passed all of the superiority tests, hence demonstrating clear differentiation for both veniprazan regimen versus the lancevrazole standard of care arm. Now I'll move to more detail on each of the endpoints. 1st, for the primary endpoint, 1st starting with the triple therapy and first for the primary endpoint of pneuprazan triple therapy that excludes patients with resistant strain to clarithromycin or amoxicillin. For both the MITT population on the left and the paired protocol population on the right, we met non inferiority with high statistical significance. In the MICT population, the veniprazine regimen achieved 84.7 percent eradication rates compared to the LASAP result triple arm of 78.8% for a delta of 5.9%. In the per protocol population, this delta further improved to 8.3%, where the venabresan triple therapy eradication rate reached 90%. I want to point out that the per protocol population is a standard pylori guidance that considers key parameters of protocol compliance. Now one very important finding to highlight here is that in addition to achieving non inferiority in this subset of population, a pre planned test for superiority was also performed as an exploratory analysis. This test was also significant the superiority test was also significant in both MITT and PIR protocol datasets. Moving on to the secondary endpoint where the primary objectives were to test for superiority of anuprozan regimen to lensoprosulf triple therapy. Now the first superiority test, as you see here on this slide, was in patients who had clarithromycin resistant strain of H. Pylori. Overall, we had 20% of the patients in the trial that qualify in this subset. In MITT population, we see 33.8% delta between vinoprazole lansoprazole cirvulotherapy. And as you can see, the lansoprazole regimen eradication rate in this subpopulation was only 31.9%. Now furthermore, when we compare the per protocol population, the delta actually increases to 38 point 2% in favor of the veniprazine regimen. These results are highly significant underscoring the ability of veniprazine to drive better efficacy from the combination regimen even in the resistant population. Now going into the second secondary endpoint, this is in the all randomized patient population. We also see VENERGYN triple therapy with a very strong separation from lenzeprazole triple therapy. The delta in the MITT population was 12.3%. And in the Pervertacol population, vinabrazine achieved 85.7 percent eradication rate versus 70% for lansoprazole regimen, giving us a delta of 15.7%. Now this is the data on the triple therapy. Now I will move to the dual therapy data. The results are also impressive. On this slide, the primary endpoints were non inferiority, which was achieved. Essentially, no difference was observed between the two arms. However, I want to underscore the importance of these results. What we essentially what this finding suggests is that patients that are not resistant to clarithromycin, you can get the same efficacy with the venoprazan JOL survey as you do with the lenoxoprazole triple therapy and venobrazan does not need clear stromatin as such. We believe this is meaningful, especially when we consider the importance of antibiotic stewardship. Now I'll move to the superiority endpoints, starting with the clarithromycin resistant subset. The severity of the dual therapy is clearly seen on the slide. We see 37% delta in favor of anuprozan dual therapy versus the lansoprazole triple therapy in the MICT population, over 50% separation in the per protocol population. Crilifenibirsen dual therapy is not encumbered by clarithromycin resistance as you see here. Now to the next slide. This superior improvement that we've seen in the prior slide carries through to all randomized population as seen here. 8.7% delta in MITT and 11.1% delta in the group protocol analysis. Now taking all this data I shared with you together, the results speak to vena present potential place in the treatment paradigm for H. Pylori. Now you have to remember, because patients are not typically tested for crystallomycin resistance in advance of their treatment, the resistance state of patients is not known before selection of their therapy. This is why the efficacy results observed in the clarithromycin resistant subset in addition to the results in the all randomized subject is so important. Now I will describe a summary of the safety data. This is very important to also report that the safety profile of vinobrazan arms were comparable to the profile of lansoprazole. On this slide, you can see the adverse events reported with over 2% frequency. But nuprazan was very well tolerated with an acceptable safety profile that is in line with what we know from the Japan data. We have fast data from Japan on safety to represent. The 3 arms in this study essentially were comparable. Now before turning it back to Terje, I once again would like to thank everyone for their work and involvement in this trial, especially during a year of pandemic. Having been familiar with this molecule for a long time and understanding its potential, it's very exciting and gratifying to see such results as we are sharing with you today. PIPEN HPE provided a contemporary evaluation of efficacy of a common PPI based triple therapy. And what we have observed in our large registration trial is how eradication rates of such therapy has truly declined. We also now see the potential of how viniprazan may help address this problem. We see the potential of vinabrisan that vinabrisan may provide through substitution of lansoprazole in a standard triple therapy regimen, but we also see its potential and the potential opportunity for dual therapy to change the treatment paradigm H. Pylori. That is until today, has not seen advancements through adding other than through adding more agents and creating more complex regimen to deal with this problem. We are looking forward to working with the authorities to submit NDAs for both regimens before the end of the year. With that, I'll pass it back to Teri. Thank you, Anthony, for that overview. As I said at the outset, today is an important day for Fathom and 2021 is a pivotal year for our company. We continue to execute on all of our key milestones. In addition to today's announcement, earlier in the month, we initiated our Phase 2 trial in non erosive reflux disease. In quarter 4, we plan to submit our NDA application to both phenoprazem based regimens in H. Pylori and we also look forward to sharing the top line results of our FALCON EE trial evaluating venoprazan in neurosis esophagitis, which is completed enrollment in November. Thank you again for our entire FASM family and to all of the clinicians, clinical staff partners, but most importantly patients involved in the FALCON HP study. With that, we'll open it up for questions. Thank you. Our first question comes from Gary Meckman from BMO Capital. Please go ahead. Your line is now open. Sorry, we have Umer Raffat from Evercore. Please go ahead. Hi, guys. Thanks so much for taking my question. Congrats on the data. I have 3 if I may, perhaps one for each of you. First, would you confirm that everything you're seeing today is broadly consistent with the Japanese data? And perhaps how would you characterize the results relative to a bismuth based quad technology that has bismuth in there? It's not a fair competitor, but would love to hear from you on that one. Secondly, maybe a little more data specific question. I noticed if you look at the clarithromycin resistant subgroup, there appears to be at least in the non compliant patients, so this is again teasing out the protocol from the MIT. In the non compliant patients in particular, it's odd that the comparator arm's eradication rate goes up meaningfully, but the doublet arm's eradication rate goes down dramatically. And I just wanted to understand better why that is in the non compliant Carythromycin resistance? And finally, if you could remind us what your expectations are on the peak sales potential of this specific indication? Is it sub $100,000,000 or is it materially north of that? Thank you very much. Okay. Thank you all for your questions. Firstly, perhaps I'll make some comments regarding the comparison to the Japanese data and our expectations around the trial. I think while it's difficult to make cross trial comparisons, I think if you look importantly at the effect size between the venoprazem triple regimen and the lensopprazole triple therapy, they're quite comparable to the results in Japan and you see lower education rates in both arms of the study. Importantly, I think if you think look at the assumptions heading into the study and the expectations for the triple therapy arm, which was what we based our assumptions on. The dual therapy arm was included in our study, but was not the basis for our assumptions. The primary endpoint, we expected that we wouldn't see a difference in non inferiority. And what we saw there as you heard from Magne in the preplanned exploratory analysis, we actually reached statistical significance. For the second endpoint, we expected to see a 10% difference in the secondary endpoint for all patients and we saw 12.5%. And then in the secondary endpoint for clary resistant patients, we expected to see a 30% improvement in eradication rate and we actually observed 33.8%. So I think we could summarize by saying that in terms of the observed results from the FALCON program, we met or exceeded our expectations. I think, Asmi, perhaps would you like to discuss the quad portion of Umer's question? Yes. Hi, Amrita, it's Rami. So the quad data range across different trials, different regimen, including business in the 80% to 85%, 87%. So we clearly our data shows that we are in that range. And now I'm comparing generality because we're not doing head to head trial here, as you're obviously clear. But clearly, vinabrisan actually surpasses that to 90% in the triple therapy. I would say what is key here is to focus on a couple of things. One is that this trial converts to a very utilized and efficacious therapy in the marketplace, which is the lensoverazole PPI based therapy. And the separation that we see is very healthy and significant separation. So it's hard to tell till we do a head to head with a bismuth based treatment, which by the way Takeda will be doing a trial with phenoprazan and bismuth. We'll see the results and what that will do. So I don't want to venture into comparing TOKWAD across study and across database that of past data that's collected over time, I would like us to focus on the delta that we see in this trial. Now that said, from a convenience perspective and safety perspective, I think moving to a very efficacious triple and more so JUUL and for some patients will be more optimal path than going to more cumbersome, more or less antibiotic friendly kind of regimen. Umer, this is Todd. I'll take the last question you asked around revenue projections for HP. So I think it'd be premature for us to talk about that today. We've been doing a lot of scenario planning across a whole range of outcomes for what we could possibly see on this trial. Now that we have the results and we know which outcome we've received, we'll do work on sharpening our pencils and refining that analysis. But frankly, we've got further work to do on that before we're in a position to really communicate about expectations. Thank you, Adam. And to your last question to your other question about the observation you had on the data, I cannot explain it today because this is top line results that we just got and we communicated very quickly. So there's more we need to do more to appreciate each element of the data on subset analysis. So hopefully on a subsequent discussion, we can explain to you in more depth other layers of the data. Thank you, guys, and congrats again. Operator, I think we're ready to take the next question. Your next question comes from the line of David Steinberg from Jefferies. Please go ahead. Your line is now open. Okay, great. Thank you. Good afternoon. So I have a couple of questions. The first one is, if I recall you have a QIDP designation as it's an antibiotic. And I think in that designation, you're entitled to priority review. Is that still the case? And if so, what sort of timeline do you expect the FDA will act on? Secondly, as it relates to QIDP, as I understand it, you get an additional 5 or 6 years of duration beyond the 5 year NCE and then you throw in a 6 month pediatric exclusivity. So does that correct? And does that imply that you'd have it a minimum of 11 years duration, obviously assuming FDA approval? And then the next question is, I know that H. Pylori is very broad infection. I think it's estimated over 100,000,000 Americans have it. But because it's asymptomatic, they have the diagnosis rates are really low, I think in the range of $2,000,000 Is there anything in your data or the fact that you used a broader group of patients in your studies, I think, HP infections plus dyspeptic sufferers versus I think in Japan it was just HP infection to those patients with a history of gastric ulcers that would allow for potentially a broader use? And is there anything in the works diagnostically that will help expand the very small group of patients who are currently diagnosed versus the $100,000,000 plus who actually have H. Pylori? Thanks. Thanks, David, and thanks for those questions. I'll take the first couple on QIDP. Yes, so we expect to QIDP was granted for the H. Pylori indication in 2019 and we were also granted Fast Track. So assuming that we submit both of the NDAs by year end, we would expect to have an 8 month review period for that Fast Track. And you're correct with the assumption regarding the additional 5 years regulatory exclusivity. With QIDP, we would get 5 years for NCE exclusivity with an additional 5 years for QIDP. And then we plan to conduct a pediatric study with which is an additional 6 months. So that brings us to at least 10.5 years post the launch of an oprazan. Okay. And then the second question and actually a follow-up to the first one. Does that mean a generic couldn't file until 10.5 years because with a 5 year NC exclusivity, unlike the 3 year Waxman Hacks, you can file immediately, but with the 5 year you can't? Okay, got it. Yes. That's correct. Yes. And I think the second component of the question regarding the diagnosis rates of HB, I think you're absolutely right. A very prevalent infection in the U. S. And Europe and is largely undiagnosed as a latent infection. And I think there are opportunities for us to expand the market in terms of diagnosis rates and treatment rates as we enter into the market or particularly in the U. S. Where the treatment diagnosis and treatment rates are particularly low. I think I'll also ask Martin Gilligan, who is our Chief Commercial Officer to make a comment. Yes. What we find is that the patients who are diagnosed treated are those that present the symptoms and it's an onset of symptoms within probably a couple of months that they actually reach a physician. So compared to some other diseases, they move rather quickly, but it's clearly symptomatic driven, but there's a lot of activity in the marketplace. Physicians are becoming aware of declining eradication rates and antibiotic resistance. So there's a heightened awareness to the infection overall. And just one quick follow-up. I think you said that the product in Japan is close to $800,000,000 in annual sales, something like that. What market share does it have in H. Pylori? And of that $800,000,000 sales, roughly how much would you tease out that are actually in H. Pylori currently? Yes. We don't have visibility into that data by indication, but conversations with the Japanese team would expect it to be around 10% market share of their revenue. Thanks. Operator, we're ready for the next question, I think. Yes, sir. Your next question in queue comes from Gary Meckman from BMO Capital. Please go ahead and ask your question. Your line is now open. Hi, this is Evan filling up in for Gary. Congrats on the data again. So I had a couple of questions. One, it seems like the clari resistant data for the triple therapy and the dual therapy for the intent to treat population were pretty similar. Would you be able to kind of give a little more color around that? And in terms of commercializing, would you be focusing on one over the other? And would you also remind us on how many sales reps would you need to actually commercialize both of the products? Thanks. Maybe, Azmi, if you take the first question? Yes. So I was saying for the dual and triple therapy, it looks like the clary resistant intent to treat population were pretty similar, it was 65.8% for triple therapy and the 69.6% for the dual therapy. What would you be able are you planning on focusing on one of the treatment options over other more so the triple therapy since you saw pretty equivalent data? And also, what is the actual of H. Pylori population actually have clear resistant strains of H. Pylori? Do you happen to know? Yes. I can address the resistance. Sorry, I can address the resistance quickly, sorry. And then on the commercial implication of the data, I'll leave that to you. So there's not really good resistance data available in the U. S. Or worldwide. But we know from multiple studies and multiple sources, more recent sources, that the U. S. Range from about 14%, 15% to about 25%, even 30% in some regions. So it depends around the region. And Europe has even wider range. And we can see from our study, we were spot on at 20%. So that's what's in the environment. And then as I mentioned, physicians don't really test before treatment. So that's why our data is very relevant and multiple dimension to that. Now as to the data and potential positioning, I'll leave to Terry and Martin. So we intend to take both the JUUL therapy as well as the triple therapy for and we believe that with the data as it's read out, we've clearly shown differentiation versus the standard of care with PPI triple therapy in both regimens. And in conversations with physicians, both with GIs and PCPs, that they really like the flexibility to be able to utilize either a JUUL therapy, reducing the antibiotic load or triple therapy. Perhaps Martin could also add to that. Yes. One of the things that we as Terry just said that we hear from physicians is that they like the flexibility of having the choice and with the dual therapy, Also part of your question was the sales force sizing. We're taking that work on right now. I mean our ongoing hypothesis based upon data is that there's about 16,000 what we would call high volume or high potential prescribers for H. Pylori. And that represents those 20% of the physicians represent 70% of the scripts. So as we go through a sizing exercise, we're looking somewhere in a range of 80 to 90 sales representatives, but we have a lot more work to do before we finalize any numbers. But given the state that we're moving forward with our commercial planning and we'll start to dig down even deeper in the numbers. Great. Thank you. Thanks, Martin. I just wanted to clarify as well just a comment that I made earlier. The market share for vinoprazine in Japan in the H. Pylori segment of the market is more than 85% market share and the revenue in Japan of that $800,000,000 about 10% of that is from the h. Pylori indication. Just wanted to clarify that. Operator, we can take the next question please. Yes, sir. Your next question comes from Yatin Suneja from Guggenheim Partners. Your line is open. Congrats on good results. Just two questions for me. So the first question is actually if you look at the data, specifically on the primary endpoint population, which excludes the antibiotic resistant patient population, Can you just frame for us the benefit or perhaps the value proposition of using WANO, whether it's a triple regimen or a dual regimen given that Lonza is also driving similar eradication rate? I can't speak that clinically. So, hi, it's been the admin I will speak. So, when you look in that population, which are sensitive, if I heard you right, sensitive to the antibiotics, So they're not encumbered by the resistance. Clearly, veniprazan truciliterbi chimes and outperforms the triple therapy with lansoprazole and also is more optimal than the dual therapy based on the data. The reason I highlighted that we have an exploratory superiority test that we ran and that's pre specified, but pre specified as exploratory and we show superiority in the triple lenabresen versus triple nansoprazole. And I think that's significant because they're not equal triple to triple even in that population based on the data we've seen. And as Martin said, we need to understand the data more and also that will help us in how to position this. But that's an important finding that I think will be able to drive forward and discuss with the FDA. Hopefully, we'll be able to get on the label as well. Got it. Yes. I think, Justin, from a clinical perspective, physicians are not testing. And so this is going to be really important message for us as we're launching this product that they can start prescribing this product and without knowing whether a patient is clair resistant or not, they're starting with the therapy that's most effectively superior than the standard of care from the beginning. So it's going to be a very important differentiation for us in the marketplace. Got it. Got it. That's very helpful. I think another question on a similar line. Just trying to get a sense of what is a clinical meaningful superiority margin? We understand, I think, from a regulatory standpoint, the hurdles might be different than what is clinically meaningful. So just trying to get a sense of what your market research and what KOL feedback you have gotten on the delta that you should be showing? Yes. I think we can say that we tested the profile of both the triple therapy as well as the dual therapy in market research with PCPs as well as GIs and showed them the profile of an oprazem. We showed them the Japanese data and they found it very compelling. In fact, more than 67% of them said that they would utilize that as their first line therapy. I think what's really important is the delta between the standard of care and the triple therapy arm as well as the dual therapy. And I think when they see this data, it's going to be very compelling. I don't know, Martin, if you wanted to add anything. Yes. I would just add in, earlier on in the call, Asmi gave what our expectations were of the study and the differences, not only did we hit them, but in some cases, we actually exceeded them. And as Terry said, we did bring those to market research. So the response was really high. And I think what they correlate that with is the differentiator here would be the acid suppression really matters. And so when we see the superiority for the all patients that were in the trial and specifically as we discussed earlier, the clarithromycin resistant patients and the fact that physicians do not test for clarithromycin resistance, to 67% or upwards of 70% of preference to use binoprazan will certainly shine through now that we have actual data to share. So Ian, just to highlight on that, this is Rodney. We aim to show 10% separation in the overall population. And we've shown with the triple, we've shown 12% 15% over 12% over 15%, respectively, in the MYTT and per protocol. And we knew those that difference 10% is very healthy separation and we showed more than that. In the resistant population, we aim to show 30%. That's the design of the study was to ensure 30%. And we knew that a very healthy and even more than acceptable separation. We showed 33 over 33% 38% in the MITT per protocol, respectively. So as Martin said, we exceeded naturally those estimates that we moved into the design with. Thank you very much. Thank you. Operator, we'll take the next question please. Your next question comes from Paul Choi from Goldman Sachs. Your line is now open. Hi, good afternoon and let me add my congratulations as well on the data. My first question is with regard to as we think about what's been discussed with regard to the delta for the primary endpoint versus the secondary endpoint in all comers and the FDA's guidance for you to in terms of your primary endpoint to exclude the antibiotic resistant populations. Can you maybe help frame for us how you're going to approach the agency given that you've had have a stronger wider delta on that secondary endpoint with regard to your filing strategy and just given the fact that as it has been mentioned several times on this call that people are not scanned for diagnosed antibiotic resistance. Is that sort of your the angle you would push or given just help us contextualize this given the agency did emphasize identifying patients with antibiotic resistance for the primary endpoint? Yes. Let me ask Tom Curtis, who's data protection from the call here. Tom, can you help? Sure. Yes, sure. Hi, can you hear me? I'm happy to answer that. So, yes, I think, so look, to be clear, the non inferiority test excluding the resistant patients, the reason that the agency requested that we do that is for a non inferiority test, they wanted to do an apples to apples comparison. The timeframe with the lanzoprazole therapy when there wasn't resistance. So that's really the purpose for why this primary analysis was in this particular subset of patients. But really the agency is going to be interested in the whole data set and in particular they're going to be interested in the all comers population because as it's been repeatedly stated here, there really is no practical way that you can test these patients prior to choosing a therapy. So we think the agency is going to be very pleased with the results and interested in these results. And so we're looking forward to getting in front of them and getting their feedback. Yes. And just to add to that, Paul, typically what you like to see that the data, especially when you're looking at superiority, not driven by one factor or one subset of a population. So if all of the efficacy we're getting and the superiority we're getting from the resistance, then the agency may look and say, well, wait a minute, but you're not showing that in the old comers. But we show it in the old comers and we show it in the non resistant population. So that consistency in the data is seldom seen in trials. So I think that will help the discussion with the FDA because it has that public health implication for better utilization of SERAV4 patients the way treatments are delivered to them today with ignoring the or not identifying the resistance a priority. So I think importantly that superiority data will the expectation is that will be in our label for both JUUL and triple therapy. So from a differentiation perspective, it's very compelling. Thanks, Terry. That's helpful context. And then in terms of my follow-up, just with regard to manufacturing and sourcing, can you maybe just sort of comment on where you are with regard to manufacturing capacity with your partners? And just to confirm, you would be including it in the blister pack for the H. Pylori, the antibiotics as well? Yes, that's correct. So we plan to include the antibiotics in what we're calling a convenience pack for both presentations for both the JUUL and the triple. As we hear from physicians that's something that really encourages compliance with patients. From a manufacturing perspective, we're in a really good position. As you know, we have sourced from Takeda. We also have a second source from a local company that we have entered into a Okay. Thank you very much for taking our questions. Thanks, Paul. Operator, we'll take the next question, please. Your next question comes from Joseph Springer from Needham. Your line is now open. Hi, everyone. Thanks for taking our questions and congrats on the data. Just a similar question in terms of where this fits into the treatment paradigm, obviously, based on the data today. How do you see this initially sort of as a first option post first line treatment failure? Or how soon do you think this either dual or triple of enablerazant could be used as a first line option, maybe some additional thoughts on that? And what are the hurdles and dynamics to sort of move it to first line as fast as possible? Yes. I think we're really thrilled with this data in terms of hitting all 6 pre specified primary and secondary endpoints and with superiority data in both the JUUL and in the triple. Our expectation is to be positioned first line for the treatment of H. Pylori eradication. We'll have a broad label, which will enable us to do that. From a payer perspective, in consultation with payers, the dynamics in this category, there's been no new innovation in the last 25 years. And payers really recognize that eradication rates are declining. And clearly, this the Phase III data demonstrates superiority in all patient groups as we've discussed and particularly the more challenging patients. So having an agent that's more potent and durable is something that is very interesting. And I think that the payers as well will be very pleased to see this data. Martin, do you want to add something? Sure. What I'll say is that prescribers recognize that eradication rates are falling and they're seeing it in their own practice and they give us they tell us that information. So when you take a look at the data that ASME reviewed, you can see in the control arm that those rates are lower than they were decades ago and there's been no new novel mechanism of action. So we know that physicians are going to be very interested, something that it's new, the acid suppression that it offers. And we have data with 6 pre specified primary and secondary endpoints that hit across the board. So we think there'll be great receptivity and uptake for first line utilization. Great. Thanks for taking our questions. Thank you, Joe. Operator, we're ready for our next question, please. Your next question comes from Prakhar Agarwal from Jones Trading. Your line is now open. Hi, thanks for taking my question and congratulations on the data. My first question, the QIDP designation for winaprazam in combination with amoxicillin capsules is still under FDA review. Could you provide color on when would you expect to hear back on that combination? And will you wait for the feedback on this QIDP before NDA filing? And secondly, any thoughts on the filing plans in Europe? And any color you could provide on timelines for potential partnerships ex U. S? Thank you. Sure. So I'll give you provide you an update on the QIDP. So we have QIDP status being granted for the tablets. The capsules is still under review. We don't have any additional information as to when we will be hearing additional feedback from the FDA. As a consequence, we're pursuing both parallel paths in terms of manufacturing capsules and tablets. We'll be in a position when we hear from the FDA to move forward with either of those with an NDA by the end of the year. And then in terms of the EU opportunity, I'll talk about the partnership and maybe as Nick can touch upon the strategy. With these terrific results, we're now kind of looking at the sizing of the European opportunity based upon the superiority that we're seeing in this data and looking at sizing the opportunity in the EU. Our base case had been to partner in Europe, but we weren't sure that we really understand the size of the opportunity based upon these data before we make a decision. Yes. On the filing Prakar, this is Admi. So we are, obviously, as I mentioned, pursuing the FDA filing. Now we have discussed with the EMEA the design of the program and all elements with it as we did with the FDA. So this package that we will put together can be geared towards European filing in a straightforward kind of way. From a timing, we will have to we have to make a decision as we come closer to the date, whether we do it on our own or wait if we to work with a partner to work through their reference to certain elements of a file and potential label and so on. So that's the call we'll make later. But from an operational perspective and data perspective, everything is suitable for the PIM filing. Glenn? Thanks, Azmit. Thanks, Bhakar for this question. So I think we just have a couple of minutes remaining here. Operator, if there are any last questions, we will take them. Otherwise, we can wrap up the call. There are no further questions in queue. Please continue. Okay. Bye. Thank you so much for joining us today. Thank you for listening in and please see our website. We'll have the complete deck of slides available there. And if you would like to contact us for additional questions, we're happy to have those calls and engage with you. Thank you very much. Thank you, presenters. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You