Thank you so much for joining us today for Takeda's 2026 Q2 earnings announcement, despite your busy schedule. My name is O'Reilly, Head of IR. I will be serving as the MC today. Thank you for this opportunity. I would like to explain about the language setting first. Please find the language selection button at the bottom of your Zoom window. If you wish to listen to Japanese, please select Japanese. If English, please select English. If you want to listen to the original voice, please turn it off. For those of you who would like to listen to this call in English, please select English in the Zoom language select button.
Before starting, I would like to remind everyone that we will 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 materially are discussed in our most recent Form 20-F and in our other SEC filings.
Please also refer to the important notice on page two of the presentation regarding forward-looking statements and our non-IFRS finance measures, which will also be discussed during this call. Definitions of our non-IFRS measures and reconciliations with the comparable IFRS financial measures are included in the appendix to the presentation. [Non-English content] Now, we would like to start today's presentation. We will hear from President and CEO, Julie Kim, Chief Financial Officer, Milano Furuta, and R&D President, Andy Plump. This will be followed by a Q&A session. Now we will get started. Julie, please go ahead.
Thank you, Chris, and thank you all for joining us today for Takeda's second quarter earnings call for fiscal year 2026. Our goal is to deliver meaningful impact for patients and lasting value for our shareholders. In the first half of this fiscal year, I am proud of what we've accomplished towards achieving that. We'll continue delivering impact and value by leading in our therapeutic areas, building portfolio depth through science, innovation, and speed from discovery to access. Our generational promise to boldly reinvent for a healthier world remains at the heart of everything we do. I want to thank our colleagues, as well as the patients, families, and healthcare professionals who make this progress possible. Starting with slide five, our fiscal 2026 first-half results demonstrate strong execution across our priorities. Let me walk you through the numbers.
In the first half, core revenue was just over JPY 2.4 trillion, a decrease of 1% at constant exchange rate or CER. This reflects the resilience of our core in-line brands and headwinds in our mature and off-patent portfolio that are not yet fully offset by our recent launches. Core operating profit was JPY 710.6 billion, an increase of 0.7% at CER. Core EPS was JPY 308, a decrease of 1.2% at CER. As we outlined in May, core operating profit reflects the investment we're making to support our new launches and our late-stage pipeline. We're largely offsetting those investments with the savings our transformation program is delivering. Overall, our first-half results demonstrate that we are on track against our FY 2026 priorities, and we will continue our disciplined execution to deliver on our revised full-year forecast and management guidance.
The right side of the slide highlights our pipeline and portfolio progress since last earnings. Our first priority in Horizon One is to execute successful new product launches. We are pleased that ORZEYFUL launched in Japan and China this month for the treatment of narcolepsy type one, and we expect to launch in the U.S. in early November following the completion of DEA scheduling. We also launched MIMRYLO in the U.S. in August, a first-in-class new treatment for patients with polycythemia vera. In addition, we secured approval for ELAHERE, which we're commercializing only in Japan for folate receptor alpha-positive platinum-resistant recurrent ovarian cancer. We also made progress with regulatory submissions, reflecting our continued momentum to bring new medicines to patients. The FDA accepted our new drug application for zasocitinib in psoriasis under priority review, and the EMA accepted our marketing authorization application.
We also filed TAK-881, our 20% hyaluronidase-facilitated subcutaneous immunoglobulin program in the U.S. for primary immunodeficiency. Our second priority this year is to advance our late-stage pipeline, where we have made significant progress across other late-stage programs. At the European Society for Medical Oncology Congress last week, we shared positive results from our phase III study of TAK-921 in previously treated advanced gastric cancer. The study met its dual primary endpoints of overall survival and progression-free survival while demonstrating a manageable safety profile. These findings will support our planned regulatory filing in Japan, which we intend to submit during fiscal year 2027. In addition, we've initiated a phase III study of elritercept in myelofibrosis. We also remain committed to supporting our core in-line brands, which continue to deliver value for patients and underpin our performance.
To this end, we presented positive results from the VERDICT Study, adding to the strong body of evidence for ENTYVIO in ulcerative colitis. The study generated compelling evidence that ENTYVIO can achieve deep remission and meaningfully reduce the risk of UC-related complications with sustained benefits over time. Andy will dive deeper into this ENTYVIO study and our pipeline developments later in the call. Lastly, our transformation is progressing well as we continue to strengthen our capabilities and drive efficiencies across the organization. As these initiatives gain traction, the realized savings are funding new launches and late-stage pipeline while protecting core operating profits. Beyond these financial benefits, our transformation is building the agility we need to support Takeda's next phase of growth. Milano will walk through our savings progress later and how we are reinvesting for accelerated growth.
Let me now turn to ORZEYFUL and how excited we are about this new class of medicine. ORZEYFUL is a first-in-class oral orexin receptor 2 agonist for the treatment of narcolepsy type one or NT1. Unlike treatments that focus on individual symptoms, it is designed to address the underlying orexin deficiency. We believe it has the potential to redefine the standard of care by delivering transformative efficacy across a broad range of NT1 symptoms. NT1 diagnosis is a challenge. The diagnosis rate ranges from less than 10% in China to roughly 40% and 50% in Japan and the U.S. respectively. In the U.S., more than half of patients diagnosed with NT1 continue to experience symptoms despite switching treatments or taking multiple medications. In all markets, we will first focus on individuals who have already been diagnosed.
At the time of our last call, ORZEYFUL had just been approved in China, and since then, it has also been approved in the U.S. and Japan, all within about one month. ORZEYFUL launched simultaneously in Japan and China on October 15th, and we're really excited about the potential to fundamentally change how NT1 is managed with great early response from both patients and HCPs. In the U.S., we've been preparing for launch for more than one year, with our medical teams engaging sleep specialists and our specialty pharmacy network and patient support programs now in place. We expect to launch ORZEYFUL through specialty pharmacies as soon as DEA scheduling is complete, which we anticipate by early November. Finally, it makes me extremely proud to share that ORZEYFUL was recently selected as one of Time magazine's Best Inventions of 2026 in the Scientific Innovation category.
Turning to the next slide, we're also thrilled about the early progress with MIMRYLO, an FDA-approved treatment for erythrocytosis in adults with polycythemia vera. MIMRYLO received FDA approval on August 28th and became commercially available very soon thereafter. This is a first-in-class hepcidin mimetic and is administered once weekly by subcutaneous injection. MIMRYLO provides rapid, stable and durable hematocrit control, the primary goal of PV treatment, and has been shown to reduce the burden of phlebotomy and improve fatigue. The prescribing label allows physicians to use MIMRYLO at any point in the treatment paradigm with no box warning, giving us clear differentiation over other advanced therapies approved in this area. Also, it is the only PV treatment listed as a category one recommendation in the NCCN guidelines for both high and low-risk patients. This medicine addresses a disease affecting approximately 90,000 people in the United States.
We have been educating physicians about the burden of uncontrolled hematocrit and repeated phlebotomy and identifying patients who can benefit from a new treatment option. We are also leveraging our established hematology capability, payer relationships, and patient support resources to support the launch and build momentum. At this early stage, we are focused on raising physician awareness and securing payer coverage so that appropriate patients can access MIMRYLO. Our goal is to build the foundation for both durable adoption and meaningful patient impact. If we go to slide eight, we have talked about ORZEYFUL and MIMRYLO, so let me focus on our third transformative medicine that we expect approval for within this fiscal year, zasocitinib. The FDA has accepted our application under priority review, and the EMA has also accepted our application.
The clinical data for zasocitinib are compelling, including head-to-head phase III results demonstrating superiority versus deucravacitinib in achieving clear skin. These results further strengthen our confidence in zasocitinib's potential to become a leading oral treatment for people with plaque psoriasis, with rapid, durable and consistent skin clearance. Andy will walk you through details of the head-to-head data shortly. Our payer engagement and field team preparations are well underway. We are positioned for potential U.S. launch following the FDA approval decision planned in the fourth quarter of fiscal year 2026. For each of these medicines, we are tailoring our launch approach to the market while applying the same proven fundamentals, engaging with physicians and payers, establishing specialty pharmacy and patient support programs, and preparing our field teams. With ORZEYFUL and MIMRYLO launches already underway, zasocitinib will build on that experience and the experience from across our portfolio.
Today, we are in Horizon One of our two-horizon strategy, and our focus is clear: transform Takeda for growth. We are building the capabilities we need to lead and establish the foundation for accelerated growth. At the halfway point of this fiscal year, I am encouraged by the progress we have made against our priorities. Looking ahead, our focus remains on executing successful launches for medicines that are now reaching patients, advancing our late-stage pipeline with speed and quality, ensuring the resilience of our core in-line brands, and executing transformation to position Takeda for sustainable, profitable growth. Each milestone we achieve builds our path towards Horizon Two, our growth acceleration phase. At our Capital Markets Day later this year, we will share more details on our progress and provide a lens into our longer-term growth strategy. With that, I will hand the call over to Milano.
Thank you, Julie, and hello, everyone. Let me walk you through our FY 2026 first half results and update its full-year outlook. Slide 11 summarizes our H1 results. Overall, I am pleased to say that our financial performance is well on track with our expectations. We have positioned FY 2026 as a year of investment. We are managing headwinds in our mature and off-patent portfolio while advancing our pipeline and launching new products that will be the drivers of future growth. Revenue in H1 was JPY 2.4 trillion, an increase of 8.4% at an actual FX rate or decline of 1% at constant exchange rates or CER. Operating profit was JPY 710.6 billion, up 11.2% at an actual exchange rate and 0.7% at CER. We are seeing the benefits of the transformation program we initiated this year, with savings being reallocated towards investments in new product launches and R&D.
Core EPS was JPY 380, a decline of 1.2% at CER. Meanwhile, reported EPS was JPY 193, with year-on-year growth of 169% at actual FX. This reflects an increase in reported operating profit due to lower amortization and impairment expenses, as well as a very low tax rate in H1 this year, partially due to timing of legal entity restructuring, which will be normalized in H2. Operating cash flow was JPY 431.9 billion, and adjusted free cash flow was JPY 325.7 billion. This was lower than prior year due to reduction of our trade receivables factoring program, as well as a payment to Protagonist Therapeutics related to their decision to opt out of MIMRYLO for commercialization in the U.S. The transformation program started earlier this year, an initiative to strengthen Takeda's competitiveness and accelerate our future growth outlook.
In the six months since we started the program, we have made progress across our transformation initiatives, such as centralizing and streamlining corporate functions such as HR, finance, and communications. Reducing layers, particularly in the commercial organizations, bringing leaders closer to patients and customers, strengthening procurement excellence, and simplifying processes with digital technologies and expanding our global capability centers. Related to the organization design, we have moved with speed to implement changes. As of September 30, approximately 3,000 impacted roles have been communicated. In procurement to date, we have implemented initiatives resulting in approximately JPY 30 billion of annualized savings. This program remains on track to achieve JPY 100 billion of gross savings with JPY 160 billion of restructuring costs in FY 2026, JPY 10 billion less than our original forecast. Over the next few slides, I'll explain more about our year-on-year performance. First, revenue.
New launches, which are products that launched in the past five years, still represent only 4% of total revenue today, but are growing well at 17.3% at CER. We look forward to expanding this category significantly in the coming quarters as we launch and drive uptake of ORZEYFUL, MIMRYLO, and zasocitinib. Core inline brands, which includes large established products such as ENTYVIO, immunoglobulin, and TAKHZYRO, represented 58% of total revenue and grew 0.5% at CER.
The growth of new launches in the core inline brands partially offset headwinds from loss of exclusivity products such as VYVANSE and the mature portfolio such as hemophilia franchise, resulting in overall revenue decline of 1% at CER. On an actual FX basis, the depreciation of the yen had a positive impact of JPY 210 billion, resulting in reported revenue of JPY 2.407 trillion, up 8.4% versus prior year. Slide 14 shows the bridge in the operating profit.
Overall, growth was 0.7% at CER, with OpEx savings from our transformation program helping to fund increased investments behind our growth priorities, including the launch preparation for ORZEYFUL, MIMRYLO, and zasocitinib, and the continued progression of our R&D pipeline. FX was also positive for operating profit, pushing the growth to 11.2% at an actual exchange rate. Next, reported operating profit on slide 15. The main items driving the 60.4% improvement versus prior year were lower amortization costs due to the conclusion of VYVANSE amortization in January 2026 and lower impairments of intangible assets compared to prior year, mainly due to a charge in FY 2025 related to discontinuation of our cell therapy efforts. Moving now to our updated outlook for full year FY 2026. Starting with management guidance for CER growth, we maintain our revenue guidance of low single-digit percent decline.
We have made some adjustments on a product-by-product basis, which you can confirm in our supplemental materials. This includes reducing our forecast for albumin to reflect ongoing market dynamics, while on the other hand, increasing VYVANSE and TRINTELLIX. We maintain our outlook for immunoglobulin with expectation of a growth rebound in the second half, and we will continue to monitor competitive and pricing dynamics. We are raising our management guidance for core operating profit and Core EPS to reflect transaction FX benefits. Outside of FX, the underlying business continues to perform very much in line with our initial expectations for the year. The bottom half of the slide shows our forecast on an absolute basis. We are raising our revenue forecast by JPY 60 billion and the core operating profit forecast by JPY 30 billion, also mainly due to a change in FX rate assumptions.
The final slide in my section shows a bridge from our original core operating profit forecast of JPY 1.16 trillion to the revised forecast of JPY 1.19 trillion. As explained on the previous slide, the main reason for the increase is FX. There is some movement by line item in our forecast as a savings target originally in the as-budget has been reallocated to opportunities we identified in R&D and cost of goods. Overall, the key message here is that our first half results are on track. We are tightly managing costs across the P&L whilst still making the necessary investments to drive future growth. Thank you for your attention. I will now hand over to Andy for pipeline highlights.
Thank you, Milano. And hello to everyone joining us on the call. Today, I would like to focus on three areas: emerging data for our flagship brand, ENTYVIO, that could change clinical practice, pipeline progress with an emphasis on our launch products, and exciting new data for TAK-921. Together, these updates demonstrate progress against our Horizon One priorities, strengthening the resilience of our core in-line brands, delivering successful launches, and advancing our pipeline. Treat-to-target strategies have improved outcomes across many chronic diseases by moving beyond symptom control towards deeper objective measures of disease control. VERDICT is the first and only prospective treat-to-target trial in both moderate and severe ulcerative colitis patients, evaluating whether treating to more stringent composite endpoints with gut-focused ENTYVIO can improve long-term outcomes. Patients received standard ENTYVIO induction and every eight week maintenance with steroid tapering.
Physicians had the option to escalate treatment to every four weeks as needed to hit targets. The results demonstrate that treating to more stringent endpoints with ENTYVIO reduced the risk of UC-related complications by approximately 70%, with this benefit extending up to 80 weeks after target achievement. ENTYVIO has been on the market for over 12 years with over two million patient-years of therapy and a strong safety profile. It was thus not surprising that the safety was similar across the groups, even with the potential for more frequent dosing. VERDICT also provides compelling evidence that deep remission is achievable with ENTYVIO. More than half of the patients, 52.1% assigned to group three, achieved the stringent disease clearance target. These findings reinforce an important shift in our ambition for UC, moving beyond symptom control towards disease clearance.
By treating earlier and to more stringent targets with ENTYVIO, we have the potential to reduce future complications and change the trajectory of this progressive disease. These data were very well-received at the United European Gastroenterology Week, or UEG, and provide important new evidence supporting the role of ENTYVIO in a treat-to-target approach. Let me now turn to our rapidly maturing pipeline that we believe can drive Takeda's next phase of growth. As Julie mentioned, we believe these three medicines will change the trajectory of Takeda's growth and importantly, make a meaningful difference for patients. ORZEYFUL is one of the most exciting stories in medical science today. The journey began with Emmanuel Mignot and Masashi Yanagisawa, whose identification of orexin deficiency as the root cause of narcolepsy earned them the 2026 Albert Lasker Basic Medical Research Award.
This summer, ORZEYFUL's phase III data were published in The New England Journal of Medicine, the third time orexin biology has been highlighted there. More recently, as Julie shared, Time magazine named ORZEYFUL one of the Best Inventions of 2026. Narcolepsy type one is a lifelong disorder caused by the loss of orexin signaling, leading to disabling daytime and nighttime symptoms. We have presented groundbreaking phase III results and continue to generate additional data across the broad disease spectrum, which includes daytime symptoms like excessive daytime sleepiness and cataplexy, as well as nighttime symptoms, cognitive symptoms, functional improvements, and quality of life. ORZEYFUL does more than manage symptoms. It addresses the underlying orexin deficiency in NT1. As a single, well-tolerated oral therapy, it could restore how a majority of NT1 patients feel and function. ORZEYFUL is now available in Japan and China.
We anticipate a DEA scheduling decision in the coming days with the U.S. launch to begin immediately thereafter. MIMRYLO, our first-in-class hepcidin mimetic, represents a fundamentally different approach to managing polycythemia vera, or PV. Rather than relying on repeated phlebotomy to remove excess red blood cells, MIMRYLO mimics the physiologic action of hepcidin, restricting iron availability for erythropoiesis and thereby controlling excessive red blood cell production. In clinical trials, MIMRYLO was able to provide rapid, stable, and durable hematocrit control, reduce phlebotomy requirements, and improve fatigue. Following its late August approval, MIMRYLO was rapidly incorporated into the NCCN guidelines in September as the only category one option for both low and high-risk PV. Category one is reserved for medicine supported by high-level phase III evidence and uniform expert consensus. Encouraging early physician and patient feedback further reinforce the potential for MIMRYLO to change how PV is managed.
Zasocitinib is our next-generation, highly selective oral TYK2 inhibitor, which has demonstrated rapid and durable skin clearance in a convenient once-daily pill. We have filed for approval in the U.S. and Europe. We also had new data presented at EADV that makes the profile even more compelling. The phase III LATITUDE Atlas trial directly compares zasocitinib with deucravacitinib using PASI 100 as the primary endpoint. The key takeaway is straightforward. At week 16, 36.5% of patients treated with zasocitinib have achieved complete skin clearance. This is the highest rate of skin clearance demonstrated by an oral therapy in psoriasis. For patients, complete clearance is the desired outcome. We also saw improvement in itch in zasocitinib beginning as early as week two. Importantly, the safety profile was consistent with prior trials. Taken altogether, these results reinforce our confidence in zasocitinib as a potentially important oral treatment for people living with psoriasis.
We are looking forward to updating you on our regulatory progress in the U.S. and Europe. Later this fiscal year, we plan to share additional zasocitinib data, including robust 52-week durability data from our 3003 study. We continue to execute across our broad late-stage portfolio with many important phase II and phase III readouts ahead. Today, I will focus on two programs that generate frequent questions, zasocitinib in ulcerative colitis and Crohn's disease, and TAK-360 in narcolepsy type two and idiopathic hypersomnia. While we had initially planned to disclose the zasocitinib UC and Crohn's results together, we have decided to share a directional summary of the UC data today. Our expectations had been somewhat more measured in UC, given the mechanistic rationale, which we believe may be even stronger in Crohn's disease. Against that backdrop, we found the UC results encouraging.
In brief, we have completed our zasocitinib phase II ulcerative colitis study and are pleased with the clinical remission rate observed at week 12. We saw a strong separation from placebo and a nominally significant p value at one of the two doses tested. Overall clinical remission results are on par with other investigational oral products in phase II UC studies. Safety across all dose arms remained consistent with our experience in previous trials. While we have not observed a dose-dependent efficacy effect, this is not unusual in dose ranging IBD studies, and we are actively evaluating potential factors that may have contributed to the dose response profile. Importantly, the full dose-ranging Crohn's disease study will provide additional data. We expect the phase II-B Crohn's readout around the end of fiscal year 2026. We are planning for success, and our team is working on phase III scenarios in both indications.
Ultimately, our path forward will be based on the totality of evidence across the program. Next, the orexin franchise continues to advance well with ORZEYFUL approved in the United States, Japan, and China for narcolepsy type one. NT1 is the only orexin-deficient disease. In other, more heterogeneous patient populations, we are working hard to untangle the biology and determine the right orexin profile for each central disorder of hypersomnolence and for the other potential indications. TAK-360 is being studied in orexin-normal populations like NT2 and idiopathic hypersomnia, where we aim to address key symptoms and expect to have results in Q4 of fiscal year 2026. Now let me turn to oncology. Oncology continues to execute across its broad portfolio with the approval of MIMRYLO in the U.S. Elritercept has started phase III trials in myelofibrosis and in first-line myelodysplastic syndrome and is enrolling well.
TAK-921 had potentially practice-changing data in advanced gastric cancer, which we will review shortly. In PDT, we have completed a U.S. regulatory filing for TAK-881, our 20% next generation facilitated subcutaneous IG for primary immune deficiency, and are on track to complete filings in multiple indications in Europe and Japan later this fiscal year. Let me close our pipeline review with the latest data for TAK-921. TAK-921 is our investigational Claudin 18.2 targeted antibody drug conjugate with an Fc-silenced backbone delivering a potent exatecan topoisomerase I inhibitor payload to tumors. Last week at ESMO, we presented groundbreaking phase III data for TAK-921 in advanced gastric cancer versus chemotherapy. The patients enrolled were refractory to at least three lines of therapy, with 30% of patients on their fourth or fifth line, representing an area of true unmet need.
In this very sick patient population, TAK-921 delivered an exceptional improvement in objective response rate, statistically significant progression-free survival that hit at the first interim analysis, and statistically significant and clinically meaningful overall survival with a hazard ratio of 0.57. The CDE also remained differentiated with limited severe gastrointestinal toxicities, including nausea and vomiting. Grade three or higher treatment-related adverse events, dose reductions, and delays were less frequent than in the chemotherapy arm. We believe TAK-921's Fc-silenced design provides a competitive advantage in gastrointestinal tolerability relative to other Claudin 18.2 targeted therapies. This profile may make it more suitable for combination with current and future standards of care in first-line gastric and pancreatic cancer. We plan on filing for approval in Japan for previously treated advanced gastric cancer in fiscal year 2027.
Proof of concept studies are ongoing globally for first-line gastric and pancreatic cancer, with readouts expected over the next 18 months. Let me conclude by repeating that this is the best pipeline Takeda has had in the modern era. I have never been more confident in the science, the team behind it, or our ability to improve our patients' lives and build a healthier world for generations. We look forward to sharing our continued progress with you. Thank you. With that, I'll now turn it back to Julie for closing remarks. Julie?
Thank you, Andy. As you've heard today, we are making steady progress across all four of our Horizon One priorities. We are building new growth drivers through the ongoing and upcoming launches of three new medicines: ORZEYFUL, MIMRYLO, and zasocitinib. Our late-stage pipeline continues to move through key inflection points, including positive overall survival and progression-free survival data for TAK-921 and the start of a phase III study for elritercept.
Our core inline brands, such as ENTYVIO, continue to be resilient and perform broadly in line with our expectations. Our transformation is delivering. It is unlocking new capabilities and generating savings that we are reinvesting in our launches and pipeline. Taken together, this progress gives us confidence in our trajectory. Each milestone strengthens the foundation for Horizon Two and brings us closer to sustainable, profitable growth and greater impact for patients. With that, I'll turn the call over to Chris for questions.
[Non-English content] Now we would like to start receiving questions. We have Julie, Furuta, and Andy, and also Rhonda Pacheco, President, U.S. Business Unit, Teresa Bitetti, President, Oncology Business Unit, and Ramy Riad, President, Plasma-Derived Therapies Business Unit as well. If you wish to ask a question, please use the raise the hand button on your Zoom screen. If you are participating on the Japanese channel, please speak in Japanese. If you are on the English channel, please speak in English. If you are listening to the original language only, you can use either of the two languages. Please keep the number of questions to a maximum of two, and please ask all the questions at once. Thank you. The floor is now open. [Non-English content] First question, Yamaguchi-san from Citi. Please unmute your microphone and ask your question. Yes, we can hear you.
Thank you. Thank you very much for taking my question. I have two questions. The first question is regarding MIMRYLO. The product looks pretty good, but you hinted that it takes some time to get the reimbursement treatment. Can you give me some early launch sort of impressions, number-wise or some other key success factor-wise? That is the first question. The second question is that thank you very much for sharing the UC, the top-line data of [inaudible]. The information you gave me is still confusing to me, especially those dependency issues. And I understand, if has happened on [inaudible] in the past. But can you clarify out of two dosage which has the good data which [inaudible] didn't. What do you need to understand further to decide whether you can go to the phase III or not because [inaudible] Thank you
Thank you Yamaguchi-san for your questions. So the first question on MIMRYLO launch uptake and reimbursement. President of Oncology Teresa Bitetti can answer that question, and your second question on the UC topline announcement and what we would need to see for a phase III decision. Andy Plump can comment on that one, please.
Good morning all, this is Teresa. Thank you so much for that question. We're very excited around how the launch is going, I'll remind you that MIMRYLO was the first time in over 10 years that we'd have had a new mechanism in this marketplace, which fully addresses the gold standard of treatment for PV. Which is keeping that inadequate level consistently, durably and rapidly below the 45% range. And as we move into this market, we know 78% of the patients remain above at various points in time, the 45% mark. And if you're above the 45% mark you were four times higher risk of death or cardiovascular event.
So we have found the reception. It is early days in the launch. We were approved at the end of August. The reception from the HCP market and from patients has been very excited, very positive. Execution of the launch is going very well. It is early days, so we do not have quantitative measures to share, but I can tell you from what I am hearing on the ground that there is enthusiasm across the board, and things are proceeding exactly as we planned, with a real focus on education, awareness, as well as ensuring access. Thank you for the question.
Yamaguchi-san, this is Andy, and thank you very much for the question. We were, of course, expecting questions on the UC zaso disclosure. You may recall that we had originally disclosed that we would share data together for UC and Crohn's. We decided to pivot, and there are a couple of reasons behind the pivot. One is that there's going to be about a six to seven month delay between the UC data and the Crohn's disease data. That's a bit longer than what we had hoped for. The second is that the UC data were actually more encouraging in many ways than what we had expected. As we've discussed previously, we're quite excited about the broad profile of zasocitinib, and we think that this is truly a best-in-class TYK2 inhibitor.
The mechanism in ulcerative colitis has carried a little bit of baggage historically because there's been two failed trials in UC, and mechanistically, the rationale points to, we think, a greater likelihood of success in Crohn's disease. We put all that together. Our initial plan was to disclose the two datasets as one. When we saw the UC dataset, we were quite pleased with the efficacy at the middle dose and as I mentioned in the presentation, directionally, the efficacy is on par with what's been seen with other oral agents in ulcerative colitis. Importantly, at both doses, the safety profile was very consistent with the safety profile that we've seen at the 30 mg dose in psoriasis. The study is a complex study, though, because we don't see a dose response.
We see a robust efficacy at the 50 mg dose with a strong nominal P value, but we're not seeing that with the 75 mg dose. As I mentioned, it's not uncommon in IBD to see, especially in smaller phase II-B studies, a lack of a dose response. We're working hard to understand this mechanistically, and in the end, we'll look forward to seeing the Crohn's data and putting those two datasets together to make a decision on whether and how we move forward with phase III.
Just a little bit of update. You're happy with the 50 mg, but the 50mg and 75mg didn't show. Is it fair to say you can go ahead with the 50 mg, or you need more dose dependency analysis even further?
Well, I think that the data as stands suggests that we have a path forward in IBD. Before we make that decision and before we decide what phase III will look like, we really want to look at the Crohn's disease data and put the two datasets together. I will say, and many of you may have seen this from the United European Gastroenterology Week, there is a huge push towards combination therapies, particularly with parenterally administered agents. But I think that is going to happen more and more with oral agents. We think, given the nature of zasocitinib and the early data that we have seen in UC, we will wait for Crohn's disease. We think that not only could this be effective as a monotherapy, but this could be a cornerstone of combination therapies potentially in the future.
Okay. Thank you.
[Non-English content] Thank you. Next. Morgan Stanley, Muraoka-san. Please unmute and ask your question.
Thank you very much. Muraoka from Morgan Stanley. My first question is about that UC topic and in your presentation deck, clinical remission rate compared to other investigational oral drugs, it was comparable. That 30% and 20% at the doses over 400 mg and at 200 mg, respectively. That number was not obtained, but you saw the dose dependency. Is that right understanding? My next question is about NT2. I think the way that you disclose the data, did you say January through March it will be press release first, and then it will be presented at the medical scientific convention? Is it what you are planning? These are two questions.
I will pick up your questions. So the first, if we could provide any more insight onto the comment around the zasocitinib UC data being on par with other orals in this space. Then the second question on TAK-360. We commented data expected in January to March 2027. What will be the plan in terms of disclosing the top line, whether a press release and/or a congress presentation? Andy Plump to take both of those questions, please.
Thank you, Muraoka-san. So again, on the zasocitinib UC phase II data, we see a strong nominal P value at the 50 mg dose. We see a robust effect size on our primary endpoint clinical remission. We see consistent effects on our secondary endpoints, including objective endoscopic endpoints. And directionally, these are on par with what's been seen with other oral agents. At this point, we don't have additional details to share. When we get the Crohn's disease data, which we anticipate at the end of this fiscal year, we'll have a chance to evaluate those data together and share them as a complete data set. With regards to TAK-360, two ongoing studies in IH and in type two narcolepsy. As we've discussed previously, the design of these studies is adaptive.
It allows us within the study to rapidly shift from different doses and different dosing administration strategies, which we think is critical to understanding how you thread the needle with dosing in these populations, given the potential for efficacy and for some of the tolerability issues. The data from those studies will be presented later in the fiscal year. We will have the data from those studies later in the fiscal year. How and where exactly we share those data will depend on what those data look like and strategically how we'd like to disclose. We don't have a precise plan at this point.
Thank you, Muraoka-san, for your questions. Up next, I'd like to call on Stephen Barker from Jefferies. Steve, please unmute and ask your question.
Yes. Thanks. Steve Barker from Jefferies. Two questions again about zasocitinib in UC and MIMRYLO. So, regarding zasocitinib in UC, can you clarify if it was the high dose or the low dose which showed indications of efficacy? And then, regarding MIMRYLO, can you give us some indication of what the percentage of covered lives is right now and how long, what's the path to broader coverage, please?
Thanks, Steve. Again, question on zaso UC for Andy on the dosing clarification, and then MIMRYLO on reimbursement to Teresa again, please. Thank you.
Hi, Stephen. We saw the robust effect with the strong nominal P value at the 50 mg dose. We did not see that effect at the 75 mg dose.
As a follow-up, considering that the high dose did not reach significance, is there any reason to think that the low dose result is meaningful rather than just by chance?
Well, of course, that is always a concern when you see a study with a lack of a dose responsiveness. There are a few pieces that make us feel that this is a robust result. The first is the magnitude of the results, and again, we are not going to share numbers, but we have said that directionally it is on par with what has been seen with other agents. This is a well-powered phase II-B study with approximately 210 patients enrolled over the three arms.
The second is we see consistency of data across both the clinical endpoints and the objective endoscopic endpoints. Then third, we have some mechanistic rationale that we are building that might explain why a TYK2 inhibition at higher doses may actually, one may lose some of the anti-inflammatory and gain some pro-inflammatory effects at higher doses. We are going to try to put all of that together.
But of course, in the end, the Crohn's disease study will be, we think, definitive in terms of understanding the robustness of the UC data and what that path forward will look like.
Understood. Thank you.
This is Teresa. Thank you for the question around MIMRYLO. I will remind you, it is still early days, so the data is coming in. What I can tell you is that given the fact that this is the first time in 10 years that we really have an agent that is consistently addressing the gold standard of treatment, which is maintain hematocrit below 45%. We have also seen that reflected in the fact that we have NCCN category one for both low risk and high risk. So that bodes very well as we move forward in our access discussions. As you would typically see, we expect Medicare to come on first, followed more by the commercial.
But what I can tell you right now is that we see scripts that are going through the system with prior auth, and we are feeling very good about the early conversations that we are having with payers who are clearly recognizing the value that we are bringing to patients with this medicine. And of course, that is reflected in the NCCN category one listing. So thank you for the question.
Just to follow up, can you comment on the mix between low risk thrombotic patients and those that the high risk patients already on therapy?
Your high risk patients are defined by patients that are 65 years and older or have had one thrombotic event. I would say that given that it tends to be a larger population, probably skew a little bit more towards the high risk. But I would say rather evenly distributed.
Understood. Thank you.
[Non-English content] Thank you. Next question, Nomura Securities, Matsubara-san, please unmute your microphone and ask your question.
This is Matsubara-san. Can you hear me?
Yes.
My first question is about zasocitinib in UC. Dose dependency is still being analyzed in detail. How does it compare against ENTYVIO? In terms of safety, is there any problem, for example, for ORZEYFUL? Diagnosis rate and the treatment rate improvement. How is it working? Sales started in Japan and China. Do you have any feedback through the education of the physicians in the U.S.? How is the initial action?
The first on zasocitinib in UC, any further commentary you can give on efficacy, for example, compared to ENTYVIO or anything in the safety profile worth noting. Andy can comment on that one. The second question on pre-launch activities for ORZEYFUL in the U.S., any initial feedback from HCPs, et cetera? Any detail as we prepare to get the launch underway shortly in the U.S. Rhonda Pacheco to answer that one, please.
Matsubara-san, thank you very much. The efficacy at the 50 mg dose looks robust and directionally on par with what we have seen in UC for other oral agents. Unlike in areas like psoriasis, the parenteral agents are typically on par as well. I would say directionally, and we will have a chance early next year to share these data with you on par with what has been seen with other agents. I think we were particularly pleased to see that at both the 50 mg and the 75 mg dose, the safety profile for zasocitinib was very consistent with what we had seen previously in our psoriasis and psoriatic arthritis studies at the 30 mg dose.
Sorry, I'll jump in here. This is Rhonda. Thank you for the question. I'll start with launch preparation in the U.S. We are ready. We are ready across the field to access and patient support. We have all commercial and medical teams in the field, and we're focused on three things. First is education. We're building that awareness of the NT1 true burden and the role of orexin in NT1 for patients and HCPs, making significant investments in supporting disease awareness and education. We initiated the non-branded disease awareness campaign in the U.S., and we have reached thousands of HCPs across individual meetings, congress participation, and supported educational programs. The feedback has been overwhelmingly positive, and they are ready and excited for ORZEYFUL launch. The second topic that we're focusing on is access and patient support. Our payers have been engaged pre-approval to support broad formulary coverage.
Our specialty pharmacy distribution is ready, and our patient support program is prepared and committed to helping patients gain access to medication at launch. This is an area where we bring real experience because of our rare disease portfolio. Lastly is diagnosis, which we know is important for this launch, improving the accurate and early diagnosis of NT1. We have been leveraging data, digital, and technology that aim to accelerate accurate diagnosis and improve the patient journey. For example, we're pursuing digital and fluid biomarker tools to support diagnosing the NT1 from other sleep wake disorders.
Lastly, partnerships like with EnsoData on developing and validating AI-based PSG algorithms to improve the detection and diagnosis of NT1 during routine sleep lab studies. Lastly, in bottom line, we are ready. We're building that awareness to activation, which means making sure HCPs and patients are aware of ORZEYFUL through all competitive channels, and we're meeting our customers where they are through direct-to-consumer initiatives. Thank you for the question.
Matsubara-san, this is Julie. Let me just add a quick comment about Japan and China. As I shared during the presentation, we launched in both countries on October 15th. It's only been two weeks, but we're very pleased with the initial response. In terms of targeting, we are also in both Japan and China, targeting patients who have already been diagnosed and are on treatment first, and then we'll have to work on the diagnosis.
Thank you, Matsubara-san, for the question. Okay, moving on to the next question in the line. I would like to call on Mike Nedelcovych from TD Cowen. Mike, please unmute and ask your question.
Hi. Thanks so much for the questions. I have some clarifying questions on zasocitinib in Crohn's, and then a question on TAK-360. In Crohn's, can you remind us why there is greater confidence for zasocitinib relative to ulcerative colitis? Depending on those phase II data, is it possible you would pursue pivotal trials for zasocitinib only in Crohn's and not in ulcerative colitis? Then just to clarify, what is the reason for the delay that emerged between the two phase II readouts? Those are my zasocitinib questions.
Then on TAK-360, management had previously articulated some good reasons why marketing two different products for NT1 and NT2 made commercial sense. Of course, you have now initiated a phase II trial of TAK-360 in both NT1 and NT2. My question is, why did you change course on that front? It seems to me one possibility is that the company wants to put its best foot forward in all indications and likes what it sees so far from TAK-360. Could that have been part of the reasoning? Thank you.
Thank you, Mike. The questions on zaso, and CD rationale, and then on TAK-360 NT1 and NT2 studies. Andy, if you could answer those ones, please.
Sure. Thank you very much, Mike. Firstly, why mechanistically do we believe that there's a greater likelihood for benefits in Crohn's for a TYK2 inhibitor such as zasocitinib in UC? There are two lines of evidence. The first is that agents that signal through TYK2, when you look at medicines that block those agents, they tend to have stronger effects in Crohn's than in UC. Secondly, when we look at the human genetics which has been a guide post for us these years, patients that have heterozygous loss of function in their TYK2 gene are protected from Crohn's but not from ulcerative colitis. Patients have to have homozygous deficiencies in TYK2 to be protected for ulcerative colitis. So those would be the two reasons we think Crohn's has a stronger rationale. Then the second you ask about the timing of the two trials.
There are really two reasons that create the separation. The first, and most importantly, is the Crohn's study is a larger study. The UC study has three dose arms and the Crohn's study has four dose arms. The second reason is that right now, Crohn's is an incredibly competitive space to enroll trials in. To be very frank, we've been working with a disadvantage given the experience of investigators with prior TYK2 inhibitors. As we've said all along, zasocitinib is truly a best-in-class molecule, and we think that now the UC data confirm that, and we'll really look forward to seeing the Crohn's disease data. We think, Mike, that having some positive halo behind a TYK2 inhibitor and IBD will help us to really accelerate that Crohn's trial as well. For TAK-360, I wouldn't look too deeply into our decision to run an NT1 study.
It's a relatively small proof of concept study. As you know, we've talked about this many times. We are incredibly enthusiastic about ORZEYFUL and the ORZEYFUL profile. Truly believe that it's not just a first-in-class, but it's a best-in-class agent. We're running the phase II study for TAK-360 in NT1 really just to keep our options open.
Thanks so much.
Thank you, Mike. Moving to the next question, I would like to call upon Tony Ren from Macquarie, please. Tony, please unmute and ask your question.
Hi. Tony Ren from Macquarie. Can you guys hear me?
Yes, Tony, we hear you.
Yeah. Okay, perfect. Yeah, thank you for taking my questions. My first question is on your Claudin 18.2 data presented at ESMO, and then I will also ask about ORZEYFUL's launch pricing and the strategy. So first, Claudin 18.2. So at ESMO, AstraZeneca presented some data with their competing Claudin 18.2 at the presidential symposium. I think it is probably fair to say that it is generally considered practice-changing based on the feedback that I have gathered at the conference. It appears to be slightly ahead of you guys in regulatory timeline. They are in the second-line plus setting with that Claudin 18.2 cutoff of 25%. How do you expect to differentiate? Would you say that in a disease setting where the medium overall survival is about 10-11 months, safety alone may not be a good enough selling point? That is my first question.
The second one is that you launched ORZEYFUL in both Japan and China. Could you comment on the launch pricing? We recently saw several large European pharmaceutical companies saying that they will carefully consider their ex-U.S. launches because of MFN. You guys are obviously thinking about this quite differently. Could you explain that as well? Thank you.
Okay. Thank you, Tony, for your questions. The first on our recently announced data for TAK-921 and how we may differentiate versus other Claudin 18.2 ADCs. Andy can take that question. Then the second question on ORZEYFUL pricing ex-U.S. in the markets where we've already launched, Julie can take that question.
Thank you, [inaudible]. I will also ask if Teresa may want to add to the 921 discussion. Tony, thank you very much. We are incredibly excited by the data that we presented for 921 at ESMO, and we think that it has, when you look at all the endpoints, OS, highly significant effects in PFS and overall response rate as well as safety and tolerability. We think that this is a best-in-class profile. Remember that this is an extremely refractory third-line plus population. In fact, 30% of the patients enrolled in this study were fourth-line or fifth-line. This is really a very high unmet medical need, very sick patient population. To see overall survival rates of over 10 months median is really just extraordinary.
Remember that this is an Asian study that was enrolled in China and Japan and will be filed and eventually launched in those two countries. We do not have the intent of bringing the program into highly refractory settings in U.S. and Europe. Our goal is to rapidly move towards a first-line study, and we are evaluating a number of different combinations with established standards of care, chemotherapy regimens, as well as now KRAS agents. We think that this data sets us up extremely well to be highly competitive in the first-line setting.
Yeah. Andy, if I could just add on to that. Tony, thanks for the question. We are actually feeling very confident, because when you look at our data, indeed, the safety was something outstanding and very reflective of the mechanism that we have with Fc-silenced linker, as well as the fact that we have a Topo1 payload, which is very strong, very low on the GI tox. So we do stand out there. But the efficacy, when you look at what we delivered in what was a very sick patient population, we are feeling very confident in terms of our ability to compete on both efficacy and safety, and we are looking forward to moving at speed to get TAK-921 into frontline studies. So thank you for that question.
And Tony, I will take your question about pricing for ORZEYFUL in both Japan and China. For China, let me clarify that for NRDL reimbursement, there is only one opportunity per year to submit for NRDL reimbursement, and we received approval for ORZEYFUL after that date. So right now we are selling via the private market, and so we do not have the NRDL listing yet. So we will be submitting that next summer, and then we should have an NRDL listing, hopefully in January of 2028. For Japan, we have received pricing in Japan, as you may be aware, and the equivalent in U.S. dollars is roughly about $100,000 on an annualized basis.
Very good. Thank you very much.
[Non-English content] Thank you. Next question from Wakao-san, JP Morgan. Please unmute your microphone. Ask the question. Thank you.
Thank you for taking my question. This is Wakao from JP Morgan. First about zaso IBD in our Capital Markets Day. I understand you will show our true colors in December at Capital Markets Day. Is there a phase III development strategy for zaso in IBD has not yet been finalized until the Capital Markets Day. How will you reflect that opportunity and its uncertainty in the outlook? Also giving the encouraging signal at 15 mg UC, is it fair to say that we should not be overly pessimistic about the lack of dose response? Second, about the PDT performance. Could you provide some more color on the second quarter performance and second half outlook for ENTYVIO and PDT? ENTYVIO delivered strong results in second quarter.
What were the key driver of this performance, and do you expect this possible momentum to continue into the second half, giving you confidence in achieving your revised full-year guidance? In PDT world, second quarter was weak. What were the main reason for the weakness? What is your outlook for the second half, and how confident are you in achieving your full-year guidance? That is it. Thank you.
Thank you, Wakao-san. The first question around whether we will have any further updates on zasocitinib in IBD by Capital Markets Day in December. Again, a question around how we should think about the lack of dose response. Andy, call on you again for that question. Next, a couple of product-specific questions on Q2 performance and rest of the year outlook. First one, ENTYVIO. Perhaps Rhonda can take that one, to talk a little bit about the U.S. performance. Then on our IBD portfolio, Ramy can comment on that one, please.
Great. Thank you very much, Wakao-san. If you could see me, I have a big smile because we knew that there would be a lot of questions on the UC zasocitinib data. Maybe if I may, let me dial up for a second and just paint the picture for zasocitinib. This is a best-in-class TYK2. It is a once-daily, conveniently administered oral agent. We have just filed for psoriasis with really, truly best-in-class data. We have just completed a head-to-head study against deucravacitinib that shows the strongest PASI 100 data in psoriasis that any agent has ever seen. We are incredibly excited to get this launched in psoriasis. Next year, we will have phase III data in psoriatic arthritis. Our phase II-B results that we presented last year are very compelling. We have four phase II studies. The UC is the first to read out.
We'll have Crohn's reading out at the end of the fiscal year, and then next year we'll see data from HS and very excitingly, vitiligo, and both of those studies are enrolling extremely well. We are very enthusiastic about the potential for zasocitinib. Drilling down on UC and what we'll present at Capital Markets Day. We will not share the UC data at Capital Markets Day. As I mentioned, our intent would be to share the UC and Crohn's disease data sets together, and we'll see those data towards the end of this fiscal year. We're sharing the data today because we were encouraged, to be frank, by the data. It's a complex data set. Anytime you have a lack of dose response and a stronger effect in a middle dose versus a higher dose, it creates some complexity.
But given the robustness of those data directionally in line with what other agents have seen, other oral agents and even many parenterally administered agents, and the robustness of the nominal p value, we felt it was important to get those data out there. We think that this will change the mindset around TYK2 and IBD. In the end, we'll look forward to seeing the Crohn's disease data to see what that overall data set will look like.
Thank you for the ENTYVIO question. A couple of points on ENTYVIO performance. ENTYVIO is performing in line with our expectations, and we remain on track against the plan we laid out for 2026. That is driven by sustained demand growth and a favorable comparison to a softer Q4 FY 2025. ENTYVIO is in its 13th year on the market and continues to deliver sustained growth. As you see in Q2, global growth was 2.7% at constant exchange rates. The brand is growing with the market in first line, which is where our strategy is, supported by our continued uptake of the pen formulation across different regions. Specifically in the U.S., again, in line with our expectations, with overall demand continuing to grow. In summary, and to conclude, we remain confident in our ENTYVIO's guidance for 2026. Thank you for your question.
Thank you for the PDT question. I will start with IG first, for Q2 IG. Overall, we have a very solid underlying demand that continued to grow by mid single- digits. For the H1 results, it's in line with our expectation. SCIG continued to grow by double-digit growth, 17% growth, supported by our broad differentiated portfolio. For IV, we declined versus the last year first half as a result of the phasing as well as market and price dynamics. H2, we expect the SCIG, the subcutaneous IG, to sustain its strong growth. IVIG growth, we expect it to accelerate, driven by the momentum of the large contracts and in the U.S. specifically. At this time, we are continuing to monitor the market because we are in supply-demand dynamic change emerging. However, we are also balancing our short-term growth of profitability and margin expansion with the revenue growth.
For albumin, to continue the PDT portfolio. Albumin for PDT continue to be very important product for our portfolio. For the first half of the year, it's impacted by phasing in U.S. specifically and stronger than expected cost containment measures in China. China remains our largest market for albumin and underlying demand remains very positive and strong. We expect China to return to growth in the near term as cost containment policies settle and demand rebounds. At the same time, we are diversifying the growth by building sustainable markets, ex-China, securing tenders outside China, where we started to already deliver in and is contributing to our performance side. Thank you.
Thank you.
Thanks, Ramy, and thank you everyone for your questions. Apologies, we ran a few minutes over, but hopefully, you've seen that we've made notable progress in the first half of the fiscal year, and our focus now is on continued disciplined execution, bringing these medicines to patients, supporting access, and driving adoption. At the same time, our transformation is strengthening the capabilities and agility we need to lead in every therapeutic area where we operate and sustain long-term growth. We look forward to connecting today's progress with our longer-term ambition at our Capital Markets Day on December 11, where we will share more details on our growth strategy and how we will build sustainable leadership in our core therapeutic areas. Thank you, and have a good rest of your day or evening.