Phathom Pharmaceuticals, Inc. (PHAT) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to Phathom Pharmaceuticals Phase III PHALCON-HP Top Line Trial Results Conference Call. [Operator Instructions] I would now like to hand the conference over to Todd Branning, Phathom'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 Phathom's Chief Financial Officer. Today is a very important day for Phathom, and we're excited to discuss the results from our PHALCON-HP Phase III 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&A session with our presenters, Terrie Curran, our President and Chief Executive Officer; and Azmi 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&A portion of the meeting. If you have questions after the meeting concludes, please send them to [email protected]. 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 Terrie Curran, Phathom's President and Chief Executive Officer. Terrie?

Thank you, Todd. Good afternoon, everyone, and thank you for joining us today on what represents not only a significant milestone for Phathom Pharmaceuticals, but also for those who suffer from acid-related disorders. Phathom was founded almost 2 years ago when we licensed vonoprazan for the U.S., Europe and Canada, and we embarked upon the mission of improving the lives of people suffering with acid-related gastrointestinal disorders. Vonoprazan, a potassium-competitive acid blocker, or P-CAB, has the potential to be with first-in-class, best-in-class gastric anti-secretory agent in the United States, where there's not been an innovative acid depression therapy approved in over 25 years. We believe vonoprazan 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 vonoprazan's distinct mechanism of action, which provides 10 to 100x greater acid control than proton pump inhibitors. P-CAB provides rapid, potent and durable acid suppression that we believe translates to a differentiated clinical profile. This profile has already been seen in Japan, where vonoprazan was extensively studied, launched and rapidly reached market leadership with annual sales exceeding $800 million. Helicobacter pylori is a chronic bacterial infection of the GI tract, which impacts more than 200 million people in the United States and Europe. PHALCON-HP is our Phase III program in this disease area, investigating vonoprazan versus the current standard of care with a PPI-based triple regimen. The study was designed to investigate vonoprazan when combined with antibiotics in 2 regimens, both dual therapy with vonoprazan and amoxicillin and also a triple therapy with the addition of clarithromycin. Today, I'm very pleased to announce the results of this PHALCON-HP trial and report that the study met all of the primary and secondary endpoints, with vonoprazan delivering superior H. pylori eradication rates versus the comparative PPI-based regimen. As you'll see from today's presentation, PHALCON-HP has highlighted the large unmet need in this disease and the promise of vonoprazan's so many patients. Before turning the call over to Azmi to discuss the data in more detail, I'd like to thank our entire Phathom 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 PHALCON-HP trial. We look forward to working with the FDA to submit New Drug Application for both vonoprazan-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 Azmi.

Thank you, Terrie. I too would like to thank all Phathom team members, all the clinicians, their staff and all the patients who participated in the PHALCON-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 million people are estimated to be infected with H. pylori, and annually, approximately 2.5 million patients in the United States are treated for H. pylori. Globally, over the last 2 decades, H. pylori eradication rates have steadily declined to unaccessible low level. Our hypothesis for PHALCON-HP trial was that vonoprazan's potent and durable acid suppression profile would allow for better antibiotic efficacy in eradicating H. pylori. It is notable that following vonoprazan's launch in Japan in 2015, this declining trend has reversed and H. pylori eradication rate has now steadily increased since the introduction of vonoprazan to the marketplace. I'm happy to report that the PHALCON-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 PHALCON-HP as a 3-arm study, as you see here on this slide. Comparing vonoprazan in combination with clarithromycin and amoxicillin and vonoprazan in combination with amoxicillin alone versus lansoprazole in combination with clarithromycin and amoxicillin. I will refer to these as vonoprazan triple therapy, vonoprazan dual therapy and lansoprazole triple therapy. The primary endpoint for each vonoprazan-based 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 clarithromycin-resistant strains of H. pylori. Now to meet the secondary endpoints in the PHALCON-HP trial, the vonoprazan regimens will require 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 clarithromycin-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, where we spent the [indiscernible] testing the triple therapy at 0.04 level and the dual therapy at 0.1 level. The reason for testing the dual at a lower 0.1 level is that since this was the first Phase III 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-inferiority met for both vonoprazan regimens, but also we passed all of the superiority tests, hence demonstrating clear differentiation for both vonoprazan regimens versus the lansoprazole standard of care arm. Now I'll move to more detail on each of the endpoints. First, for the primary endpoint, first, starting with the triple therapy, and first, for the primary endpoint of vonoprazan triple therapy, that excludes patients with resistant strain to clarithromycin or amoxicillin. For both the mITT population on the left and the per-protocol population on the right, we met non-inferiority with high statistical significance. In the mITT population, the vonoprazan regimen achieved 84.7% eradication rate compared to the lansoprazole triple arm of 78.8% or a delta of 5.9%. In the per-protocol population, this delta further improved to 8.3%, where the vonoprazan triple therapy eradication rate reached 90%. I want to point out that the per-protocol population is a standard predefined subset based on FDA H. 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 preplanned 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 per-protocol datasets. Moving on to the secondary endpoint, where the primary objectives were to test for superiority of vonoprazan regimen to lansoprazole triple therapy. Now the first superiority test as you see 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 the subset. In mITT population, we see 33.8% delta between vonoprazan triple therapy and lansoprazole triple therapy. And as you can see, the lansoprazole regimen eradication rate in this population was only 31.9%. Now furthermore, when we compare the per-protocol population, the delta actually increased to 38.2% in favor of the vonoprazan regimen. These results are highly significant, underscoring the ability of vonoprazan to drive better efficacy from the combination regimen even in the resistant population. Now going into the second secondary endpoint, this is in the old randomized patient population. We also see vonoprazan triple therapy with a very strong separation from lansoprazole triple therapy. The delta in the mITT population was 12.3% and in the per protocol population vonoprazan achieved 85.7% 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 2 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 vonoprazan dual therapy as you do with the lansoprazole triple therapy. And vonoprazan does not need clarithromycin as such. We believe this is meaningful, especially when we consider the importance of antibiotics portion. Now I'll move to the superiority endpoints, starting with the clarithromycin-resistant subset. The superiority of the dual therapy is clearly seen on the slide. We see 37% delta in favor of vonoprazan dual therapy versus the lansoprazole triple therapy in the mITT population, and over 50% separation in the per-protocol population. Clearly vonoprazan dual therapy is not encumbered by clarithromycin-resistant, as you see here. Now to the next slide. With superior improvement that we see in prior slide carried through to all randomized population as seen here. 8.7% delta in mITT and 11.1% delta in the per-protocol [indiscernible]. Now taking all this data I shared with you together, the results speak to vonoprazan's potential place in the treatment paradigm for H. pylori. Now just to remember, because patients are not typically tested for clarithromycin resistance in advance of the treatment, the resistance phase of patients is not known before selection of their therapy. This is why the efficacy results observed in the clarithromycin-resistant subject in addition to the results in the all randomized subject is so important. Now I will describe summary of the safety data. This is very important to also report that the safety profile of vonoprazan arms were comparable to the profile of lansoprazole. On this slide, you can see the adverse event supported with over 2% frequency. Vonoprazan was very well tolerated with an acceptable safety profile, that is in line with what we know from the Japan data. We have past data from Japan on safety for vonoprazan. The 3 arms in this study essentially were comparable. Now before turning it back to Terrie, I once again would like to thank everyone for their work and involvement in this trial, especially during the 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. PHALCON-HP provided a contemporary evaluation of efficacy of a common PPI-based triple therapy. And what we have observed in a larger patient trial is how eradication rates of such therapy has truly declined. We also now see the potential of how vonoprazan may help address this problem. We see the potential of vonoprazan, that vonoprazan 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 of 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 Terrie.

Thank you, Azmi, for that overview. As I said at the outset, today is an important day for Phathom, 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 II trial in non-erosive reflux disease. In quarter 4, we plan to submit our NDA applications of both vonoprazan-based regimens in H. pylori, and we also look forward to sharing the top line results of our PHALCON-EE trial, evaluating vonoprazan in erosive esophagitis, which has completed enrollment in November. Thank you again to our entire Phathom family and to all of the clinicians, clinical staff partners, but most importantly, patients involved in the PHALCON-HP study. With that, we'll open it up for questions. Thank you.

[Operator Instructions] Our first question comes from Gary Nachman from BMO Capital. Sorry, we have Umer Raffat from Evercore.

Congrats on the data. I have 3, if I may, perhaps 1 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 business-based quad technology and that has business in there, it's not a fair competitor, but I 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 noncompliant patients. So this is again, teasing out the per-protocol from the mITT. In the noncompliant patients, in particular, it's odd that the competitor arm's eradication rate goes up meaningfully. But the doublet arm's eradication rate goes down dramatically. I just wanted to understand better why that is in the noncompliant clarithromycin resistant? And finally, if you could remind us what your expectations are on the peak sales potential of this specific indication? Is it sub-$100 million? Or is it materially north of that?

Okay. Thank you for your 3 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 looked importantly of the effect size between the vonoprazan triple regimen and the lansoprazole triple therapy, they're quite comparable to the results in Japan, and you see some lower eradication rates in both arms of the study. Importantly, I think if you think -- look at the assumptions, heading into the study and the expectations of the triple therapy arm, which was what we based our assumptions on, the dual therapy arm was included in that study, but was not the basis for our assumption. The primary endpoint, we expected that we wouldn't see a difference in non-inferiority. And what we saw there, as you heard from Azmi, 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 clari-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 PHALCON program, we've met or exceeded our expectations. I think Azmi, perhaps would you like to discuss the quad portion of -- in this question?

Yes, Umer, this is Azmi. So the quad data range across different trials, different regimen, including [indiscernible] in the 80% to 85%, 87%. So we clearly -- clearly our data shows that we are in that range. Now I'm comparing generally here because we're not doing head-to-head trial here, it is obviously clear. But clearly, vonoprazan actually surpasses that to 90% in the triple therapy. I would say what is key here is to focus on -- on a couple of things. One is that this trial converts to a very utilized and efficacious therapy in the marketplace, which is the lansoprazole PPI-based therapy. And the separation that we see is very healthy and significant separation. So it's hard to tell until we do a head-to-head with bismuth-based treatment, which, by the way, Takeda will be doing a trial with vonoprazan and bismuth. So we'll see the results and what that will do. So I don't want to venture into comparing drug [indiscernible] a cross study and a cross database that's -- that 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 dual 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 would 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.

And Umer, to your last question -- to your other question about the observation you had on the data, I cannot explain it today because this is -- 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 and subset analyses. So hopefully, on a subsequent discussion, we can explain to you in more depth other layers of the data.

Your next question comes from the line of David Steinberg from Jefferies.

Okay. Great. 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 time line 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 -- is that correct? And does that imply that you'd have at 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 million Americans have it. But because it's asymptomatic, the diagnosis rates are really low, I think, in the range of 2 million. 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 suffers versus, I think, in Japan, it was just HP infection in 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 million plus who actually have H. pylori?

Thanks, David. Thanks for those questions. I'll take the first couple on QIDP. Yes. So we expect -- 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 that the additional 5 years' regulatory exclusivity with QIDP, we'll get 5 years for NCE exclusivity with an additional 5 years for QIDP. And then we plan to conduct a pediatric study, which is an additional 6 months. So that brings us to at least 10.5 years post the launch of vonoprazan.

Okay. And then the second question. And actually, a follow-up to the first one. Does that mean a generic could file until 10.5 years because with the 5-year NCE exclusivity, unlike the 3-year [indiscernible] you can file immediately, but with the 5-year you can. Okay, got it. Okay.

Yes. That's correct. Yes. And I think also with the second component of the question regarding the diagnosis rates of HP, yes, I think you're absolutely right. It's a very prevalent infection in the U.S. and Europe and is largely undiagnosed, is 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, particularly in the U.S. where the treatment diagnosis and treatment rates are particularly a bit low. I think, also Martin Gilligan, who's our Chief Commercial Officer, to make a comment.

Yes. What we find is that the patients who are diagnosed treated are those that present with symptoms. And it's an onset of symptoms within probably a couple of months if they actually reach a position. 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 million in annual sales, something like that. What market share does it have in H. pylori? And of that $800 million sales, roughly, how much would you tease out that are actually in H. pylori currently?

Yes. We don't have visibility to that data by indication, but conversations with the Japanese team would expect to be around 10% market share of their revenue.

Your next question in queue comes from Gary Nachman from BMO Capital.

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? In terms of commercializing, would you be focusing on one over the other? And would you have also remind us on how many sales reps would you need to actually commercialize both of the products?

So maybe, Azmi, if you take the first question?

Yes. So I was saying for the dual and triple therapy, it looks like the clari-resistant intent-to-treat population were pretty similar. It was 65.8% for triple therapy and 69.6% for the dual therapy. 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 clari-resistant strains of H. pylori, do you have it now?

Yes. So we...

Yes, I can address it. Sorry, on the first -- I can address it just quickly, Terrie. And then on the commercial implication of the data, I'll leave that to you. So there're not really good resistance rate 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 on the region. Europe has even wider range. And we -- I 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 that to Terrie and Martin.

Yes. So we intend to take both the dual therapy as well as the triple therapy forward. And we believe that with the data as it's read out, we've fully 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 dual therapy or using the [indiscernible] load or triple therapy. That's not [indiscernible].

Yes. One of the things that we -- as Terrie just said, that we hear from physicians is that they like the flexibility of having the choice and with the dual therapy potentially using one less antibiotic. You -- also part of your question was the sales force sizing. We're taking that work on right now. I mean our ingoing 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 physicians represent 70% of the scripts. So as we go through a sizing exercise, we're looking somewhere in the 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 we're moving forward with our commercial planning, and we'll start to dig down even deeper in the numbers.

I just wanted to clarify as well, just a comment that I made earlier. The market share for vonoprazan in Japan in the H. pylori segment of the market is more than 85% market share. And the revenue in Japan of that $800 million, about 10% of that is from the H. pylori indication. Just wanted to clarify that.

Your next question comes from Yatin Suneja from Guggenheim Partners.

Congrats on good results. Just 2 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 vono? Whether it's a triple regimen or a dual regimen given that lanso is also driving similar eradication rate?

I can't speak that clinically. So you can just ask me and I'll speak. So when you look -- in that population, which are sensitive, if I heard you right, sensitive to the antibiotics. So they're nothing compared by the resistance. Clearly vonoprazan triple therapy shines 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 prespecified, that's prespecified, that's exploratory and we show superiority in the triple vonoprazan versus triple lansoprazole. 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. And hopefully, we'll be able to get the label as well.

Yes. I think 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 -- they can start prescribing this product. And without knowing whether a patient's clari resistant or not, they're starting with the therapy that's most effective and superior than the standard of care from the beginning. So it's going to be very important differentiation for us in the marketplace.

Got it. Got it. That's very helpful. I think another question on the 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 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 vonoprazan, we showed them the Japanese [indiscernible] 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 I say [indiscernible], it's going to be very compelling. And, Martin, if you wanted to add anything?

Yes. I would just add in, earlier on in the call, Azmi gave, what our expectations were of the study. And the difference is not only did we hit them, but in some cases, we actually exceeded them. And as Terrie 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 patient -- 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, vonoprazan will certainly shine through now that we have actual data to share.

So Yatin, just to highlight on this. This is Azmi. We aim to show 10% separation in the overall population. And we've shown -- with the triple, we've shown 12% and 15% -- over 12% and over 15%, respectively, in the mITT and per-protocol. And we knew 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 which then showed 30%, and we knew that's a very healthy and even more than acceptable separation, we showed 33% -- over 33% and 38% in the mITT, per-protocol, respectively. So as Martin said, we exceeded, actually, those -- the estimates that we moved into the design win.

Your next question comes from Paul Choi from Goldman Sachs.

My congratulations as well on the data. My first question is with regard to -- as we think about the -- 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 have -- you 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 or 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 that antibiotic resistance for the primary endpoint?

Yes. So let me [indiscernible] on call here. Can you?

Yes, sure. Can hear me. I'm happy to answer that. So I think, if you look, to be clear, the non-inferiority test, including the resistant patients, the reason that the agency questioned that we do that is for a non-inferiority test, they wanted to do an apples-to-apples comparison and time frame with the lansoprazole therapy when there wasn't resistance. So that's really the purpose why this primary analysis was in this particular subset of patients. But really, the agency is going to be interested in the whole dataset. 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 now 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 1 factor or 1 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, [indiscernible], but you're not showing that in the all-comers. But we show it in the all-comers and we show it in the non-resistant population. So that consistency in the data is seldom seen in trial. So I think that will help the discussion with the FDA because it has public health implication for better utilization of therapy for patients the way treatments are delivered to them, ignoring the -- or not identifying the resistance of H. pylori.

So I think importantly, that superiority data will -- the expectation is that will be in our label for both dual and triple therapy. So from a differentiation perspective, it's very compelling.

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 dual 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 contract with. So at launch, we'll have the availability of either the Takeda supply or the alternative. So we're in a really good position.

Your next question comes from Joseph Stringer from Needham.

Congrats on the data. I guess a similar question in terms of where this fits into the treatment paradigm, obviously, based on the data today. How -- do you think this initially sort of as a first option post first-line treatment? How soon do you think this either dual or triple vonoprazan could be used as a first-line option, maybe some additional thoughts on that? And more than the hurdles and dynamics to sort of move it the 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 dual 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 the [indiscernible] information. So when you take a look at the data that Azmi 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.

Your next question comes from [ Prakhar Agarwal ] from [indiscernible].

Congratulations on the data. My first question, the QIDP designation for vonoprazan 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 time lines for potential partnerships ex-U.S.?

Sure. So I'll give you [indiscernible] on the QIDP. So we have QIDP status that's been 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. So 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 Azmi 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 will ensure that we really understand the size of the opportunity based upon these data before we make a decision.

Yes, on the filing -- Prakhar, this is Azmi. So we are -- as I mentioned, pursuing the FDA filing. Now we have discussed with the EMEA, the design of the program and all the 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 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 preference to certain elements applied and potential label and so on. So that's a call we'll make later. But from an operational perspective and data perspective, everything is suitable for European filing.

Thanks, Azmi. Thanks, Prakhar, for these questions. So I think we just have a couple of minutes remaining here. Operator, if there are any last questions, we'll take them. Otherwise, we can wrap up the call.

There are no further questions in queue. Please continue.

Okay, right.

Thank you so much for joining us today. Thank you for listening in. And please see our website, and we'll have the complete slides available there. And if you would like to contact for additional questions, we're happy to have those calls and catch with you. Thank you very much.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Presenters, please stay.