Takeda Pharmaceutical Company Limited ($4502)

Thank you for joining us for the presentation of our zasocitinib Phase III data and commercial overview. My name is Elizabeth Borgeson. I'm part of the Takeda Investor Relations team. [Operator Instructions] Before starting, I'd like to remind everyone that we'll be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today. The factors that could cause our actual results to differ from are discussed in our most recent Form 20-F and our other SEC filings. Please also refer to the important notice on Page 2 of the presentation regarding forward-looking statements and non-IFRS financial measures, which will also be discussed during the call. Definitions of our non-IFRS measures and reconciliation with comparable IFRS measures are included in the appendix to the presentation. With that, I'll hand it over to Julie Kim, CEO Elect, to start the presentation.

Thanks, Elizabeth, and thanks to everyone joining us as we share Takeda's perspectives on the phenomenal results of the Phase III studies of zasocitinib in psoriasis. I'd like to start by introducing the 2 colleagues who will be presenting today. First, we have Chinwe Ukomadu, Head of Takeda's Gastrointestinal and Inflammation Therapeutic Area unit. Chinwe will review the impressive results of our Phase III clinical trials that were presented to the Dermatology Community a few hours ago in a late-breaking presentation at the American Academy of Dermatology Annual Meeting. Next, I'd like to introduce our second speaker, who is making her first appearance with the Takeda investor community, Rhonda Pacheco. Rhonda joined Takeda last September to assume my former role as President of the U.S. Business Unit and U.S. Country Head. She joined us from Eli Lilly, where she oversaw complex portfolios in a range of leadership roles including the successful launch of the GLP-1 portfolio. I'm happy to have such an accomplished commercial leader join our team as we embark on the next exciting chapter of Takeda's growth. Rhonda will explain why we believe zasocitinib is poised to be a leading oral treatment option for individuals with psoriasis. But before we jump into zasocitinib, I want to provide some context on where we are as a company. Last year, we had 3 outstanding pivotal data readouts for oveporexton, zasocitinib and rusfertide. This is a momentous period for Takeda as we position ourselves for a new chapter of growth. With strong safety and efficacy profiles, all 3 have the potential to transform patient treatment and to be blockbuster brands. The excitement across Takeda is palpable as we are preparing to execute 3 major launches in the next 15 months. Before deep dive on zasocitinib, let me briefly share a few reminders about our other 2 groundbreaking medicines. Starting with oveporexton, an orexin receptor-2 agonist designed to address the underlying orexin deficiency that causes NT1 by restoring orexin signaling. Phase III results presented last year demonstrated oveporexton's potential to achieve outcomes that matter most to individuals with NT1 and with the potential to redefine the standard of care. Oveporexton is the first orexin receptor-2 agonist to have a new drug application accepted by the FDA, and it was granted priority review with an August PDUFA. We are well positioned for a successful launch of oveporexton in the second half of this year. Next is rusfertide, a hepcidin mimetic that demonstrated rapid, consistent and sustained hematocrit control in individuals with polycythemia vera, or PV. Maintaining hematocrit control is the primary treatment goal of PV, yet 4 out of 5 treated patients have uncontrolled hematocrit, putting them at higher risk for cardiovascular and thrombotic events such as heart attack and stroke. The impressive Phase III data presented last year underscores the potential for rusfertide to shift the standard of care for PV patients. Earlier this month, we announced that the FDA accepted our new drug application for rusfertide and granted priority review. We have an August PDUFA date and also expect to launch rusfertide in the second half of this year. Now let's turn our attention to today's focus, zasocitinib. Let me share with you why we are all so excited about zasocitinib, our next-generation, highly selective TYK2 inhibitor and more importantly, what it means for patients. What we hear from individuals with psoriasis is that they want clear skin with a treatment that fits effortlessly into their daily life. Zasocitinib has demonstrated rapid, durable skin clearance in a convenient once-daily pill that does not have any fasting restrictions. Based on this profile, zasocitinib is poised to be a leading oral treatment for psoriasis patients with potential to significantly expand the oral market. With Takeda's proven track record in immunology, we are prepared to execute a successful zasocitinib launch in the first half of 2027. Now I'd like to turn the presentation over to Chinwe to walk us through the data in more detail. Chinwe, over to you.

Thank you, Julie, and welcome, everyone. My name is Chinwe Ukomadu. I'm the therapeutic area head for GI and Inflammation at Takeda. And it is my great pleasure to share with you the exciting data that we presented today at the annual meeting of the American Academy of Dermatology. We're going to talk about zasocitinib and its role in the treatment of moderate-to-severe plaque psoriasis. Zasocitinib is an investigational, next-generation oral inhibitor of TYK2. Zasocitinib is extremely selective for TYK2, displaying more than 1 million fold greater binding selectivity for TYK2 when compared to similar kinases, JAK1, 2 and 3. In addition, it inhibits the kinase exquisitely, maintaining inhibition over 24 hours at drug levels that prevent signaling through an immune disease-driving pathway as shown to the right of this slide. We previously shared with you our Phase IIb data using zasocitinib in patients with moderate-to-severe plaque psoriasis. And we had told you that the drug was well tolerated and efficacious. As a result, we designed 2 Phase III studies, next slide, referred to as LATITUDE-PsO-3001 and 3002. For the remainder of this presentation, I will refer to these studies simply as 3001 and 3002. These were randomized, multicenter, double-blind, placebo and active comparator-controlled Phase III studies. The subjects in these studies were adults with moderate-to-severe plaque psoriasis. There were 2 co-primary endpoints. The first, the static Physician Global Assessment, sPGA and, in this case, sPGA of scores 0/1. The second, PASI, PASI 75 in this case. There were a number of secondary endpoints, which were either evaluated at week 16 against placebo or at week 16 and 24 against the active comparator apremilast. Now a word on the studies themselves. Study 3001 randomized around 690 patients in a 3:1:1 ratio to receive zasocitinib 30 milligrams by mouth once daily, apremilast 30 milligrams by mouth twice daily and placebo. Study 3002 randomized over 1,100 patients to receive zasocitinib 30 milligrams by mouth once daily, apremilast 30 milligrams by mouth twice daily and placebo in a 2:1:1 ratio. In addition, in Study 3002, patients who attained a PASI of 75 at week 40, underwent a randomized withdrawal. Patients could continue on zasocitinib or went on placebo in a 2:1 ratio until week 60. For this presentation, I will concentrate on events from the start of the study until week 24 for both studies. In addition, for Study 3002, I will also highlight events during the randomized withdrawal portion of the study. Next slide, please. The baseline demographics and the disease characteristics for the study were generally balanced across the treatment parts. A number of things were highlighted. One, at the very bottom of this chart shows you the data on the percentage of bio-experienced patients. Roughly 1/3 of the patients in both studies were bio-experienced. The second point to make is that there was a trend towards: one, higher BMI; two, longer duration of disease; and three, more severe psoriasis for patients in the 3002 study. Next slide, please. Now the results. The study met both its primary endpoints and all 44 ranked secondary endpoints. There are 4 data highlights that I would like to convey to you from the slide that is being shown right now and I will do this sequentially. First, the primary endpoint, sPGA 0/1. This was evaluated against placebo at week 16, and as you can see, in Study 3001, 71% of the patients and in Study 3002, 69% of the patients achieved this endpoint. This compares to 11% and 13% of placebo respectively in these studies. To the right, are graphs for the second co-primary endpoint, PASI 75, also evaluated against placebo at week 16. And we showed that 76% of the patients on zasocitinib in 3001 and 71% on zasocitinib in 3002 achieved this endpoint compared to only around 12% in both studies. The third point to make is the comparison between zasocitinib and apremilast. Across both studies and both endpoints, zasocitinib was vastly superior to apremilast, displaying across the board between weeks 16 and 24, a twofold difference in efficacy in both studies and both endpoints. And lastly, I want to point to you -- point out to you the events that become obvious by week 4. As shown here already, you can appreciate that there is numerical advantage of achieving these endpoints in patients who received zasocitinib versus those who were on placebo. And this is shown better in the next slide, please. Here, we are showing you the data from week 0 to week 4 in these studies, and you can see that across the board, we have nominal statistical significance of zasocitinib over placebo as early as 4 weeks of treatment. Next slide, please. We then asked how, what would happen when we use a higher and harder-to-obtain endpoint in these studies. We are showing you the data for PASI 90 for both Study 3001 and Study 3002. By 24 weeks, up to 69% of our patients have attained PASI 90 in this study versus around 20% with apremilast. The picture on the right shows 1 such patient, who entered the study with 25% body surface area covered with psoriatic plaques. And you can see that by week 16, this has largely resolved and what you have left are areas of pigmentation that are visible on the picture. Next slide. But patients really want clear skin. And so we ask how do patients fare with regards to clear skin in our studies? To the left, we are measuring clear skin using sPGA 0 and you can see that for both Study 3001 and 3002, we have high rates of clear skin. By week 24 up to 49% of our patients have attained clear skin as measured this week. You can also appreciate that at this point, there is already around a sixfold difference in the efficacy regarding clear skin between zasocitinib and apremilast. To the right of this slide is clear skin as measured by PASI 100. We showed that up to 42% of our patients attained this endpoint and that's close to a tenfold difference in efficacy between zasocitinib and apremilast. In all the comps that I've shown you, there's another factor that's really obvious, which is that between week 16 and week 24, the efficacy continued to improve. Lastly, on this slide, you also see 1 thing that's really obvious, that by 8 weeks, that's clearly superiority of zasocitinib with regards to clear skin when compared to both the active comparator and to placebo. Next slide. This shows a picture of such patients who attained clear skin. This patient had 62% of their body surface covered with psoriatic plaques and by week 16, there was no evidence of the disease plaques on the patient's body. How about how patients feel? Next slide. We used a commonly used tool in dermatology to evaluate what the impact of the disease is on a patient's quality of life. This is called the Dermatology Life Quality Index. In this case, the question is, does zasocitinib treatment improve patients' quality of life? DLQIs of 0/1 imply that psoriasis is not affecting the patient's quality of life. And you see 2 things that I would mention in the graph that are in front of you. The first is that by week 24, up to 60% of the patients are reporting DLQIs of 0/1, which says that psoriasis is not affecting their quality of life. The second is that this is manifest as early as week 4 during the treatment. Next slide, please. The drug was very well tolerated, and we saw no new safety signals from what we had previously reported in our Phase IIb study. Most of the treatment-emergent adverse events were mild or moderate in nature. We saw no trends towards laboratory abnormalities, such as blood counts, liver enzymes or lipids. The most frequent treatment-emergent adverse events were related to infections of the respiratory tract -- or respiratory tract infections or nasopharyngitis. We did see some acne, but a very low rate of only around 6%, and most patients continued through the study with no treatment or with just mild topical treatment to a large extent. There was a death in the study, and this is not unusual in large studies of psoriasis, where most patients are often elderly and have comorbidities and this was the case with this patient who died during the study, unfortunately, and investigator reported that the death was not related to the drug that he had received. Next slide. Now I'd like to call your attention back to what I told you earlier about the randomized withdrawal part of the study. Just to refresh your memory, I told you that patients who had attained PASI 75 by week 40, were either randomized to continue receiving zasocitinib or transitioned to placebo in a 2:1 ratio. Next slide. We have some exciting and remarkable data here. We show that patients maintained response they had up until week 60. SPGA 0/1, PASI 75 and PASI 90 of greater than 90% from the response they had before. The second thing is that for those who transitioned to placebo, the pace of loss of response was very slow. And even 20 weeks afterwards across the board, across these 3 end points, more than 50% of all the patients continued to maintain the response that they had before. This suggests that in a real-world setting, where people might miss a dose or 2 because of travel or life events, the fear of losing the response is -- might be diminished. Next slide, please. So where are we with the ambition we had for zasocitinib at the time we in-licensed this asset? Well, I've just shared with you the data for the Phase III readout of psoriasis, we will have more psoriasis data this coming fiscal year as we read out our head-to-head against deucravacitinib. We've begun our study in pediatrics and we are well on our way to finish in the Phase III study for psoriatic arthritis. We have 4 additional indications. Crohn's disease and ulcerative colitis, which we anticipate study readouts for the Phase II studies in FY 2026, and vitiligo and hidradenitits suppurativa, which we anticipate -- which have started, and we will give you more information in the near future. Next slide, please. So what have I told you? I have told you that this is a drug that delivers rapid and durable skin clearance as a convenience one-daily pill. The data that I've shared with you point to this across the board as follows: 49% -- up to 49% of patients achieved clear skin as measured by sPGA 0 by week 24. The response is rapid. We've shown you data that you can see this as early as week 4, either with PASI 75 or sPGA 0/1. The response is durable. Patients can maintain this response up to 60 weeks out, and we've shown you that the treatment comes with an improved quality of life for those patients who have to disrupt the disease. The drug was well tolerated, with a safety profile that's consistent with what we've shown you previously and we saw no labs such as cholesterol or lipid increases that are worrisome in the study so far. Next slide. Now it is my great opportunity to turn the presentation over to my colleague, Rhonda Pacheco, who will then tell us how we can get this amazing drug to our patients who are waiting for it.

Thank you so much. Let's first start with the market and the unmet needs within the market. Of the 1 million moderate-to-severe patients treated today, only 50% are on advanced therapy. Why is that? Patients stay on ineffective conventional therapies longer than they should because they want to avoid biologics, maybe because of injections, safety concerns and the impact on their daily lives. Also, there hasn't been a highly efficacious and safe oral treatment available, but as we know, that's changing, resulting in a growth opportunity with orals being the fastest-growing segment, projected to triple from 100,000 patients to 300,000 patients in the next decade, driven by patient preference for next-generation orals like zaso who help patients achieve clear skin in a convenient once-daily pill. Next slide. When we speak to patients and healthcare professionals, patients are seeking an oral medicine that, does it work? Does it work fast and last? And is it safe? We also hear a lot about convenience. Can it fit into my daily life, orals over injectables, once daily versus twice daily and no worries about food or timing of when to take it. We are excited about zaso and the data because it aligns to what patients are asking for. Does it work? And does it work fast and last? Yes. Zaso delivered clear to almost clear skin in 70% patients by week 16. It delivered rapid clearance at week 4, and we heard from patients, they feel better, giving them the confidence that it's working, demonstrated by strong durability with 90% of patients maintaining response at week 60. Is it safe on top of efficacy? The data showed no new safety signals. And lastly, does it fit into patients' daily lives, getting to that convenience piece? Yes, again, zaso comes in a once-daily pill that can be taken any time because it has no fasting restrictions. With this data and excitement also comes preparation for a successful launch, which we won't take for granted with no stone unturned because we want to get zaso into the hands of patients that need it. The team is extremely focused on launch readiness, and I want to highlight a few things. Entering a highly competitive market, we know that. We're familiar to that. it's familiar to us as we have done it before with ENTYVIO in IBD, very successfully, and we will build on that experience. Because of ENTYVIO, we have experience with payer dynamics and know how critical access is for zaso's success. That's why we are engaged with payers and will continue to do so. External engagement with thought leaders, patient advocacy groups and other stakeholders is also important for us. We will listen carefully to their needs and continue to educate the community about the TYK2 mechanism and its safety profile. Lastly, we understand strong investment is needed to maximize commercialization of zaso, starts with strong data, which you saw today, and we have the right team and investment to realize zaso's market potential. Bottom line, we believe zaso is positioned to transform and expand the oral advanced therapy market. In PsO market, in the psoriasis space, next-gen orals like zaso will drive significant growth of the oral class. We believe zaso is poised to lead among the oral options as the number of patients treated will triple in the next decade. Beyond psoriasis, we are also seeking a PsA indication, with data expected next year. PsA indication will further support our psoriasis business, providing an oral solution across psoriatic disease. This combined opportunity could bring revenues of $3 billion to $6 billion globally. We also have several other Phase II programs across derm and GI. In dermatology, we started 2 studies this past year in vitiligo and HS. In GI, we expect Phase II data in both UC and Crohn's disease in this coming year. In closing, we're excited that zaso is poised to be leading the oral treatment for patients with psoriasis, significantly expanding the oral market. Data today reinforces that zaso brings rapid and durable skin clearance and importantly, with no new safety signals. Zaso meets patients' needs by providing a convenient once-daily pill without fasting restrictions. As we know, zaso is a next-generation, highly selective oral TYK2 inhibitor developed to advance psoriasis therapy. Along with zaso, U.S. filing is on track for this year with global filings to follow. And with that, the end of the presentation.

[Operator Instructions] The first question, the first question comes from Shinichiro Muraoka of Morgan Stanley. Muraoka-san, please go ahead.

[Interpreted] I am Muraoka from Morgan Stanley. Congratulations on excellent results. I'd like to ask you a question in Japanese. And I would like to ask a question comparing different clinical trials compared to other companies' clinical trials. What is your assessment of these trials? Zaso showed excellent results. But if we look at these 2 trials, there are some variances, but other companies' trials, they show in some cases, some differences. In some other cases, not. So could you comment on the differences that you saw in these 2 trials? And second question is that as an oral treatment option, you are going to be #2 in the market. Then in order for you to become a leading oral option, which particular points you'd like to appeal going forward?

Thank you for the questions, Muraoka-san. For the first one in regard to the differences between zaso and other options that are available. I will ask Chinwe to address that. But let me start by saying, in general, it is challenging to make cross-trial comparisons, but Chinwe can provide some of his perspectives on how we view zaso in particular. For your second question, in terms of being second to launch, behind ico. I think that's what you were referring to. I will ask Rhonda to give her view on how we think we will differentiate ourselves vis-a-vis the rest of the oral treatment options in psoriasis. So Chinwe, first to you.

Yes. Thank you for the question. We obviously do not comment usually on other people's trial since we were not involved in running them. But I can tell you how excited we are about the data we have and why we view the data from both of our trials as being completely consistent with what we expected. So in this study, as we've mentioned, the drug is rapid. It starts to have an effect quite early in the treatment period as early as 4 weeks. The response is durable. We show that 70% of our patients achieved clear or manually clear skin by week 16. We show that responses in both studies continue to deepen even after you go past week 16. We are reaching clear skin rates of 49% when we evaluate clear skin by sPGA 0 and 42% when we use PASI 100. Now between the 2 trials, obviously, subtle differences in numbers. This is not unexpected in trials that are of this size and actually is typical of other trials run elsewhere. And the reasons could be anything from regional variations, could be as a result of the instruments that are used and their complexities and the way they're used in different parts of the world. What is remarkable, if you look across the totality of the data, is the pattern and the trend of the data looks pretty similar across the board. So we are ecstatic. We think this data is as good as we would want it. And even on the safety side, we saw nothing new that would be of concern to us. So overall, it's a solid data package as we would have expected despite the small differences in the 2 trials.

Building on the excitement of the data, zaso's profile excites us because of how fast it works. We see a rapid response at week 4, exactly the kind of quick relief patients are looking for because they want to feel better early knowing the drug is working. And that early response just keeps getting better. We see that rapid response continue to mature to week 16 and remains durable out to week 60. All of this comes in a simple once-daily pill with no fasting restrictions. Convenience in this space matters. Unlike competition, zaso does not require an empty stomach or timing around meals, eliminating a real-world barrier that can affect adherence and potentially a food effect that could impact the competitor's efficacy. Competition expands this category and grows the overall oral market, it doesn't shrink it. Keep in mind that today, over 100,000 patients per year are treated with an oral advanced therapy with less favorable profile than zaso, presenting a great opportunity to convert many of these patients. We expect the number of patients treated with an oral therapy to triple over the next decade and as you saw from our profile, it shows that we have real confidence because we provide rapid, durable and convenience with no fasting restrictions.

Our next question comes from Hidemaru Yamaguchi of Citi. Yamaguchi-san, please go ahead.

Can you hear me?

Yes, we can.

I have 2 questions. This is Yamaguchi from Citi. The first question is that I didn't have a chance to listen to AAD call itself [indiscernible]. Can you give us some, I don't know, feedback or atmosphere or whatever it is of a live sort of impression you had at the meeting of AAD if some of the members did attend the meeting. That's the first one. The second one, you gave me a $3 billion to $6 billion sort of assumption at the moment, together with the market to grow from 1 million to 1.3 million patients. And calculating back to the numbers, it looks like you're talking about 10% to 20% market share of this new market? Is it the right assumption or not really? Can you give us some rough guidance, what kind of market share you're assuming from this assumption? That's the second question.

So thank you for the questions, Yamaguchi-san and [Foreign Language], I'm also in Tokyo. So unfortunately, I'm not with the team at AAD, but both Chinwe and Rhonda were there. So I will ask them to provide commentary on the atmosphere and the reception that we had for zasocitinib. And then in regard to your second question about our commercial assumptions, I will ask Rhonda to address that question. So Chinwe, do you want to start?

Yes. We're excited, and I think everybody is excited at what the data for this drug showed. The presentations at AAD are very short. They are 12 minutes long. But what's remarkable is the number of people who've come up to us since the meeting to tell us how exciting the data is and how they feel this could be something very impactful for patients. We've had the opportunity to meet with our investigators and our advisory boards who are equally excited about the data that we have presented here. So overall, I think the entire Takeda team feels that this was a really great day for us to share with the world the potential of this asset that we brought into the company around 3 years ago.

Great. I'll go through the market question. Getting back to maybe high level, how we're viewing the market is supposed to expand significantly, driven by, as I talked about, this unmet need that we're hearing from patients and healthcare providers. And today, we see many patients on suboptimal treatments and a high unmet need for efficacious oral options. 10% of the moderate-to-severe market are on orals which is roughly that 100,000 patients with 50% of those patients stopping therapy within 6 months due to limited efficacy. Clearly, there's the unmet need that exists. In addition, as we talked about, over the next decade, oral penetration is expected to roughly double with 3x the amount of patients treated on an oral. Growth comes primarily from patients stuck on that conventional therapy cycle that they're in today and some will come from patients on injectable biologics that are waiting for better oral therapy option like zaso. Again, with our data, we can finally give patients a rapid, durable and convenient oral option, and we believe that zaso can lead the way in this class.

And let me just end by saying, as I said, I am not at the meeting with the team, but I have seen pictures and heard from many of our team members who are there today. Takeda has a significant presence at AAD. And you would not know that we were a new company to this space, if you were there yourself, Yamaguchi-san. So we'll send you some photos. .

Our next question comes from Hiroyuki Matsubara of Nomura Securities.

Can you hear me?

Yes, we can.

I'm Matsubara from Nomura. I have the 3 questions. My first question is efficacy. In the subgroup of the patients who had prior exposure to biotic medicines, so what are the PASI and sPGA result if you have? And the second question about the treatment process shown on Slide 18. Okay. Could you explain the reason behind the loss of efficacy in 5% of patient at PASI 75 and 90% at PASI 90. Also, how long can patients typically remain on zasocitinib? And second -- sorry, third question concerns the side effects. So serious side effect occur in the 3% of patients. So what are the main causes and is the event manageable? And also compared to the other competitor drugs, the side effect is slightly higher than others. So what do you think about the side effect? That's all for me.

Okay. Thank you for the questions, Matsubara-san. So all 3 are really addressed to Chinwe in terms of the data from our clinical trial. So I'm going to hand it over to Chinwe to answer them one by one. So actually I'm forgetting the first one. So Chinwe, hopefully, you wrote it down.

Biologics, okay.

Yes. biologics patient results.

And then the second one is...

Treatment persistence.

Why it's not 100%.

Yes.

Okay. And then the third is side effects, you said. Yes. But I didn't quite get.

Yes. What is the main reason for the patient or the 3% of serious side effect and also compared to the other competitor drugs, the side effect is -- onset rate is slightly higher than others. So what do you think about this side effect?

Okay. I will start with the efficacy, the bio experience. So we obviously have a lot of data that we are working through. But what I can tell you is that having looked through various subgroups, including the bio-experienced group, we do not see any differences in efficacy between that group and the other groups. We would love to present that data at a future date. Two, this was about why not 100%? My view here is that because data is being reanalyzed over time that it would be probably difficult to maintain 100% efficacy in a rerandomization at week 40. What is remarkable actually is that most of those patients stay at the same rate, which says that this was not a random occurrence at week 40. And then lastly, regarding adverse events, almost all the events were mild to moderate, and the higher rates were mostly due to upper respiratory tract infections and acne. In fact, I think with comparison to the active comparator apremilast, if you remove the upper respiratory tract infections, there was pretty close to a balance in the number of adverse events. So the SAE rates are low. Most of them are related to infections and the rate of discontinuations across all 3 arms whether it is zasocitinib, whether it is apremilast or placebo were similar. So we didn't -- we don't think there is anything unusual in the adverse event rates that we obtained in this study.

Our next question comes from Seiji Wakao of JPMorgan.

This is Wakao from JPMorgan. Congratulations for your great data. So I have 2 questions. First about onset. Onset -- regarding onset, the results appear favorable based on the Study 3002 both trials. We understand that zaso's onset being broadly the same as icotrokinra. How do you assess zaso's onset relatable to icotrokinra? Do you see it as superior or essentially the same? Second question about marketing. So could you share your strategy for zaso? What do you see are the key success factors for the launch of zaso? In particular, how do you plan to offset the roughly 1-year delay in launch versus icotrokinra? I understand the clear difference from icotrokinra is no food drug interaction. So I'd like to know so no food drug interaction, how is it meaningful advantage? And could you share your thoughts on the target patient population? Who do you see as the primary target for zaso, biologics naive or patient? That's it from me.

So thank you for the questions, Wakao-san. In terms of the first one, I will ask Chinwe to address that. And in terms of the second one with the positioning, et cetera, and the time difference for zaso versus ico, I will ask Rhonda to address that one. So the rapidity of onset, Chinwe, over to you.

Yes. Thank you very much. It's a good question. Can't really comment on any comparison with ico, as I noted earlier. But I can tell you why the rapidity here is extremely exciting to us. What patients have told us is they want a drug that will work quickly and work durably. So with response to quickly, we have seen effects as early as week 4. And we have additional data in what I've just shown you to actually also back that up. So I showed you the data on the effect of zasocitinib on quality of life. And you also start to see that impact as early as week 4. What that says to us is that with regards to our drug, we are seeing effects in patients who are taking this medicine that suggest that skin is improving and improving rapidly. Since we have not done a head-to-head against anybody else outside of apremilast so far, we cannot comment on other people's claim on rapidity, but our own data does show that we have something that works quickly and helps patients start to feel better in a short period of time.

Great. I'm excited to share 3 things when I -- when we think about our go-to-market strategy, one is the positioning. Zaso is poised to be a leading oral option and the Phase III data that you saw gives us that confidence. The product positioning is critical, and that's why our focus is disciplined execution and clearly demonstrating zaso's strong clinical profile. As you saw today, we demonstrated rapid and durable skin clearance in a convenient once-daily pill, which is really good news for zaso's positioning. Second is access, working with payers to see our value proposition with the goal of speed and quality when it comes to access. We expect steady early adoption, followed by acceleration as confidence and access bills and growth should accelerate that acceleration growth over the next 8 to 12 months after launch. Lastly is awareness to activation. This is a competitive market, and we know that. And like any major launch, it's going to take time to build that base of patients but again, we're focused on executing, which is critical. That starts with our medical teams today around the TYK2 class and safety, and we'll continue as we continue to build our field force and get really smart with key channels like direct-to-consumer to, again, not only awareness but to activate patients to come into offices and ask for zaso. Your second question I'll get to is around the market. Growth for zaso will come primarily from patients stuck on conventional therapy, that cycling that happens with psoriasis patients. And some will also come from patients on injectables right now, injectable biologics that are waiting for a better oral therapy option like zaso. Again, we're extremely excited because zaso provides that rapid, durable and convenient option for patients.

Okay. Could you comment on the no food drug interaction. How is it important for penetration for zaso?

Yes. Unlike the competition, zaso does not require an empty stomach or timing around meals. It's simple. Talking even to HC -- healthcare professionals today, it's just 1 less thing to worry about when prescribing a psoriasis medication, we will have to see how it plays out in the real world. But if we have a convenient option that once daily and has none of those fasting restrictions..

And I would just say, Wakao-san, when you think about your own life and having to measure time when taking medicine, I know for me, that would be a barrier for me taking a medicine just given how busy schedules are and how they can change. So we do think that this -- in a market where individuals value convenience that this will be a differentiator.

Our next question comes from Tony Ren at Macquarie. Tony-san, please go ahead.

Congratulations on the very strong results. I wanted to ask you a couple of questions. First of all, about your -- the responses we see in the control arm on Slide #10. We can see that on both the PASI 75 and the sPGA measures, patients on placebo and apremilast performed extremely well, much better than the -- what we see in the FDA label for apremilast as well as the [indiscernible], I think presented at the same conference, can you think of any reason why the control arms did so well? That's my first question. The second one is that in the apremilast FDA label, we -- the FDA required a dose titration, right, of going over 5 days. Did you do the dose titration for apremilast? Do you think it might have affected the DLQI? And lastly, have you seen any rhabdomyolysis in your study?

Okay. Thank you for those questions, Tony. I'm going to hand those all over to Chinwe. The first was, I believe, the placebo effect, particularly in our PASI 75 score, I think, is what you were focused on. And second was, in general, the performance of apremilast and did we do the dose titration that's required on the label for apremilast. So Chinwe, if you could address those, please?

Yes. So for the very first question on the placebo rate. So these placebo rates to my knowledge are similar to what has been seen in other studies usually around 9% to 12%, which is right where we fall. Two, we have no cases of rhabdomyolysis that we've seen in this study, and yes, we did do the dose titration in the study.

Our next question comes from Hiroshi Wada at SMBC Nikko Securities. Wada-san, please go ahead.

[Interpreted] This is Wada, SMBC Nikko Securities. Can you hear me?

Yes, we can hear you.

[Interpreted] Yes, I have some questions. First of all, about the overall market. which segment of the market is going to grow? And what is the positioning? So this is the overall market question. And with injectables, for example, I think there are long-acting injectables. In other words, the administration can be only once every 3 months, for example. But as the overall products continue to grow, which part of the market -- segment of the market, will it take? Are you going to take the patients who are not on these long-acting injectables or you will also go for patients who are not on injectables? So how do you think the oral market will grow?

Okay. Thank you for those questions, Wada-san. And I will ask Rhonda to share with you again our thinking behind where the patients will come from for zasocitinib and why we think the oral segment will continue to grow. So Rhonda, over to you.

Sure. So if you look at today, the advanced therapy market is about 50% and 10% of that is orals. And we see the oral market growing in the next decade from 10% to 22%, which again is that 100,000 patients to 300,000 patients. So not only it's growing the advanced therapy market, but also the oral piece of that advanced therapy market. And your question about where we find our growth from is, again, primarily from patients that are stuck on that 50% today of conventional therapies but continue to cycle and try things. And so that is where zaso is positioned. And again, we'll compete to move patients from conventional to orals also is there are patients that are on injectable biologics today and will be in the future, but they don't have something to come to when it comes to an oral, and they prefer an oral therapy, but nothing has been efficacious today. And we believe that there is some growth with patients that are on biologics that will come over to zaso but most of it is our focus, is really getting patients to get off those conventional therapies into a very effective medicine like zaso quickly.

[Interpreted] Next question, ico in oral. My question is a head-to-head study against icotrokinra. Do you have a plan to do that?

So Wada-san, I can tell you, we currently do not have plans to do a head-to-head study with ico.

With that, we will conclude our call today. Thank you, Julie. Thank you, Rhonda. Thank you, Chinwe and thank you to all other participants. Have a great rest of the weekend. [Portions of this transcript that are marked [Interpreted] were spoken by an interpreter present on the live call.]