Takeda Pharmaceutical Company Limited

Thank you very much for joining us out of your busy schedule today for the earnings call for second quarter fiscal 2023 of Takeda Pharmaceutical Company Limited. I am going to be the moderator today, O'Reilly, the head of IR. Let me explain about a language setting. At the bottom of the Zoom window, there is a language button. If you wish to listen to Japanese, please choose Japanese. And if you wish to listen to English, please choose English. If you just wish to listen to live audio, please turn it off. Before starting, I'd like to remind everyone that we will be discussing forward-looking statements within the meeting, meaning of the Private Securities Legislation 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, 20F, and in our other SEC filings. Please also refer to the important notice on page 2 of the presentation regarding forward-looking statements and our non-IFRS financial measures, which will also be discussed during this call. Definitions of our non-IFRS measures and reconciliations with comparable IFRS financial measures are included in appendix 2 of the presentation. Let's get started with the presentation today. CEO and President, Christophe Weber, and President of R&D, Andy Plump, and Chief Financial Officer, Hasta Sarugas, will be making presentations each. And then we will open the floor for questions. Let's get started. Christophe, over to you.

Thank you, Chris. Thank you, everyone, for joining us today. It's a real pleasure to be with you all. At Takeda, our vision is to discover and deliver life-transforming treatments guided by our commitment to patients, our people, and the planet. This purpose-led approach is at the core of our strategy to deliver long-term value creation for our stakeholders. We are rapidly embracing the use of data, technology, and AI, transforming the company across all functions. We'll provide more details on this remarkable change next year. Our performance in the first half of fiscal year 2023, while facing two setbacks with our pipeline, further demonstrate our progress in executing on our strategy as we look to maximize our portfolio, advance our pipeline, and deliver on our commitments. Turning to slide five, our first semester performance underscores the strength of our core business and our ability to deliver life transforming treatment to patients and communities. Looking at our financial results, revenue for the period was 2.1 trillion yen or 14.1 billion US dollar. Year-over-year growth at a constant exchange rate was 1.4%, driven by momentum in our growth on launch product, which represents 42% of our total revenue and grew at 13% at a constant exchange rate. At actual exchange rate, our top-line growth was plus 6.4%. This top-line growth is despite generics for Vyvanse launching in the US after our patent expiry in August. To date, the impact of Generic's and Vivant's market share has been broadly in line with our expectation. Corporating profit was 588.8 billion yen, or 3.9 billion US dollars, with a decline versus prior year of 9.5%. The year-over-year decline is in line with expectation and reflect the impact of loss of exclusivity for higher margin products, lower coronavirus vaccines demand, as well as our strategic investment in R&D and data and technology to ensure that Takeda long-term competitiveness. Core EPS for the period was 261 yen. On a reported basis, operating profit on EPS were impacted by large non-core items booked in the second quarter, including impairment of intangible assets related to Xquivity and Alofizel. While very unfortunate for patients and material to the company, the two setbacks triggering these impairments don't impact our strategy for delivering a near-term return to growth and long-term sustainable value for shareholders. Costa will go into this item in more detail later in the presentation. Turning to the outlook for the remainder of the fiscal year, we are raising full year revenue on core EPS forecast to reflect updated Forex and tax rate assumptions. We are on track to our management guidance for core growth at a constant exchange rate, and there is no change to our guidance. There is also no change to our full year free cash flow forecast of 400 to 500 billion yen. On a reported basis, we are lowering full year profit forecast due to the impact of the non-core item booked in the second quarter. On slide six, we are advancing our innovative portfolio to reach new patient population, address unmet needs, and provide new treatment options to improve patient outcome and quality of life. Last month, we received FDA approval for the subcutaneous administration of Antivio for maintenance therapy in moderate to severely active ulcerative colitis. This makes Antivio the only FDA-approved biologics in ulcerative colitis that offer patients a choice of two types of administration. We expect Antivio subcutaneous to be available in the U.S. by the end of October, and we are fully committed to the success of its launch. I will come back to Antivio progress and growth outlook on the next slide. The FDA is also evaluating our application for subcutaneous administration of Antivio for the treatment of Crohn's disease, and we expect a decision in the first half of fiscal year 2024. Our dengue vaccine, Scudengia, continues to be recognized as a critical step forward in the fight against dengue fever. Last month, the WHO Strategic Advisory Group of Experts on Immunization recommended its use in high dengue burden and transmission areas for children aged six to 16, where it believes the vaccines will have the greatest public health impact. Other milestones in the first half of the year include approval of Qubitru as our first subcutaneous immunoglobulin product in Japan, delivering on our commitment to reach patients with high unmet needs. And in our oncology portfolio, Acetris received a label extension in Europe for stage 3 patients as a first-line treatment for Hodgkin lymphoma. The approval was based on updated positive overall survival results from the phase 3 echelon 1 study for stage 3 and 4 Hodgkin lymphoma, which demonstrated the first significant improvement in overall survival in two decades in stage 3 and 4 Hodgkin lymphoma. Moving to the right side of the slide to look at progress in our innovative pipeline. In September, we resubmitted tax 721 to the US FDA for the treatment for eosinophilic esophagitis. We expect a decision from the FDA during the first half of calendar year 2024. Also in September, we announced positive top-line results from our phase 2B trial of TAC279 for active psoriatic arthritis. This is a significant milestone in our effort to develop a new treatment option for patients with this debilitating condition. We had a number of filings in Japan in the first half, with frucutinib filed for previously treated metastatic colorectal cancer and TAC755 filed for CTTP. We are pleased to have entered an exclusive licensing agreement with Immunogen to develop and commercialize miavituximab for FR-alpha positive ovarian cancer in Japan. But we also faced some headwinds. In October, we made the voluntary decision to withdraw Excivity in the US based on the outcome of the EXCLAIM-2 confirmatory trial and discussion with the FDA. We are discussing next steps with regulators in other countries where EXCIVITY is available as we intend to initiate voluntary withdrawal globally. Patients are our top priority and EXCIVITY remains available to be prescribed in the US while we work with the FDA to formally withdraw within an appropriate timeframe. The withdrawal decision on timeline outside of the US will vary by country. Also in October, we announced that the Phase III ADMIRE-CD2 study of alofizel for the treatment of complex Crohn perianal fistula did not meet its primary endpoint. The study was designed to support a filing in the US, and we are currently evaluating next steps. Importantly, the safety profile was consistent with prior studies, and there were no new safety signals identified. These events highlight the inherent risk in research and development, but as a company focused on delivering life-transforming treatment to patients, we must continue to challenge ourselves at the forefront of innovation. Andy will speak further about our pipeline later in the presentation. Turning now to Antivio growth and outlook on slide seven. In the first half of fiscal year 23, Antivio continued its growth trajectory, increasing market share globally. In the U.S., Antiviu maintains the lead as number one in inflammatory bowel disease overall, as well as in IBD by a naive new start. Volume growth remains strong in the EU, in Europe, at approximately 15%, outperforming the overall IBD advanced therapy market despite pricing headwinds. In the U.S., the IBD market is growing, but diagnosis and advanced therapy initiation remains suppressed compared with the 2016-2019 period, so pre-COVID. Patient data suggests that new diagnosis still haven't recovered to pre-COVID level. Nevertheless, the majority of moderate to severe patients remain untreated or on a conventional therapy. So we continue to see significant opportunities and our commercial organization is working very hard to expand our leadership in this area. Moving to the right side of the slide, a near and long-term growth catalyst. The U.S. approval of the subcutaneous administration for maintenance therapy in ulcerative colitis was a major milestone, making Antivio the only FDA-approved biologic in ulcerative colitis that offered patients a choice of two types of administration. Subcontinuous therapies are estimated to represent approximately 35 to 40% of the total U.S. IBD market. So this is a very significant milestone that will allow us to access this new market segment. We expect Anti-View Pen to be available in the U.S. by the end of October, and we are fully committed to the success of its launch. The FDA is also evaluating our application for subcontinuous administration of Ontario for Crohn's disease. A decision is expected later this fiscal year. We are pursuing new ongoing life cycle management to enhance long-term growth and making significant investment in both ulcerative colitis and Crohn's disease studies to support targets of disease clearance and transmural healing. And we are initiating new studies to support the scientific community to investigate the potential role of combination therapies to break the efficacy sailing with vedolizumab as a backbone. Healthcare professionals and patients are continuing to see the benefit and value that Antiviu offer in IBD, and we remain confident with our peak revenue forecast at $7.5 to $9 billion, with no change to biosimilar entry assumption timing, potentially as late as 2032. On slide eight, Qdenga continues to be recognized as an important development in the fight against dengue fever. We are seeing strong initial demand in private market in endemic countries, as well as strong launches in travel market led by the EU. This makes us optimistic considering that public vaccination program has not started yet. CUNENGA has already launched in dengue endemic countries, Indonesia, Brazil, and Thailand, and recently received approval in Colombia. We expect launch in Argentina in the third quarter of this fiscal year. The vaccine is available in 16 European countries and travel recommendations support its use to help protect travelers to dengue-endemic areas. And we are pursuing private and public partnership with government, institutional businesses, NGOs, and manufacturers to expand access. Last month, the WHO Strategic Advisory Group of Experts on Immunization, or SAGE, recommended its use in high dengue burden and transmission area for children aged six to 16. SAGE assessed that the recommendation in this population would have the greatest public health impact as the vaccines could be administered to children prior to the time in which they are at the greatest likelihood of possible dengue-related hospitalization. The evaluation was based on data from CUDENGA clinical programs with more than 28,000 participants. The recommendation is significant because it will ultimately provide overarching guidance to countries around the world on how and when to implement vaccines into their public vaccination programs and lay the foundation for access to vaccines worldwide, particularly in developing countries. In countries where Qdenga is ultimately approved, it is now up to national authorities to consider the SAGE recommendation and decide how Qdenga should be used locally. Now I'd like to turn to our high level outlook for the near, medium, and long term. Our strategy remain on track as we enter the second half of the fiscal year. Based on our current assumption for fiscal year 23, We expect to return to revenue, profit, and margin growth in the near term, driven largely by the continued expansion of our growth and launch products. We also see significant potential in our late stage pipeline assets. We achieved significant data and regulatory milestone this year and anticipate a number of additional pipeline milestone in the second semesters. Following generic competition for Vyvanse, which is impacting revenue and profit growth in this fiscal year and also in 2024, we will have limited loss of exclusivity exposure until the launch of Antivio biosimilars, which could occur as late as 2032. The momentum from our growth and launch product combined with our continued investment in R&D will drive progress in the medium and long term. Looking ahead, we remain committed to returning to cooperating profit margins in the low to mid 30s, supported by value creation enabled by data and technology, including AI. We will also continue to evaluate asset-specific business development opportunities to further enhance our pipeline and reinforce our growth profile. Finally, our progressive dividend policy of increasing or maintaining the dividend each year will allow us to continue to return value to shareholders. In closing, our strategy remains on track and we are maintaining our management guidance for the full year. We continue to progress our pipeline and manage our on-market portfolio to create long-term value for our stakeholders while we fulfill our purpose of bringing better health for people and a brighter future for the world. I will now pass it on to Andy to talk about our pipeline progress. Thank you.

Thank you very much, Christoph, and a big hello to everyone on today's call. If we can go to the next slide, please. We've made solid progress advancing our pipeline this quarter, as you just heard from Christoph. I'll take this opportunity to dive a bit deeper into several of the updates that Christoph just provided. Dr. Pat 279 read out positive phase to be data for the treatment of psoriatic arthritis. Based on these positive data, we will advance tattoo seven nine to a phase three development program for psoriatic arthritis in fiscal year two thousand and twenty four. The full results will be presented at the meeting of the American College of Rheumatology in November as a late breaker abstract. The Subcutaneous Administration of Intivio received a significant approval in the U.S. this quarter for maintenance therapy in adults with ulcerative colitis. This new route of administration provides an additional way for patients to benefit from Intivio at home. Intivio Subcutaneous Administration has also been filed for the treatment of adults with Crohn's disease in the U.S. and is currently under review by the FDA with potential approval in fiscal year 2024. In Japan, antivio subcutaneous administration is now available for both UC and Crohn's disease following successful approvals in fiscal year 2023. As you just heard from Krzysztof, Gdanga received a very important recommendation from the World Health Organization's advisory group endorsing public vaccination programs in countries with high dengue burden in children ages 6 to 16 years. We expect the WHO to update its guidelines shortly based upon these recommendations and look forward to continuing discussions with public health authorities in dengue endemic countries. The resubmission of TAC 721 for eosinophilic esophagitis, or EOE, to the FDA is an essential milestone for this program, as well as for patients. I will describe the process that led to this filing later in the presentation. Momentum this quarter also came from two new additions to our pipeline. We licensed TAC212 from AcuraStem. TAC212 is an intrathecal antisense oligonucleotide targeting PIK5 for the treatment of amyotrophic lateral sclerosis or ALS. We look forward to bringing this near IND ready program to the clinic in the very near future. We also licensed from Immunogen Japan rights to Mervituximab, a promising antibody drug conjugate targeting folate receptor alpha positive ovarian cancer. In addition to these major updates, we also faced a couple of headwinds this past quarter. As Christoph just alluded to, we announced that alofacil did not meet the primary endpoint in the ADMIRE-2 study. The results are disappointing, particularly given the robust benefits previously demonstrated in the ADMIRE-1 phase three study, which served as the basis for approval in Europe and Japan. We continue to believe in the benefits demonstrated by Alofacel in ADMIRE-1, as well as in other trials, such as the positive Japanese pivotal study and the INSPIRE registry, an 800 patient European real world body of evidence. In addition, last quarter we announced that the confirmatory trial for excivity in EGF receptor exon 20 insertion positive non-small cell lung cancer hit futility. We intend to initiate a global voluntary withdrawal of excivity. If you can go to the next slide, please. Depicted here are exciting late stage programs. TAC 279, our highest priority program, has posted the first in a series of phase three protocols for psoriasis on clinicaltrials.gov and is on track to begin enrollment very soon. We believe that TAC 279 is a potential best-in-class oral therapy for psoriasis. As previously mentioned, based on the Phase 2b readout and psoriatic arthritis, we will move forward TAC 279 into a second pivotal Phase 3 development program early in fiscal year 2024. We're also accelerating development of TAC279 in Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, as well as exploring a range of other potential indications. These expansion opportunities are being developed in parallel with psoriasis and psoriatic arthritis. A new addition to the late-stage pipeline is now TAC2721, which was filed in the US for EOE, and I'll talk about that on the next slide. PAK721 is a viscous topical steroid specifically designed to locally treat EOE. You can see on the right side of this slide the significant responses at week 12 on both histology and symptoms, the co-primary endpoints of this pivotal trial. The clinical response in these patients started as early as week four. There's a high unmet medical need in the US for an oral treatment option that can act rapidly and locally in the esophagus. There's only one approved agent for EOE in the US, a systemic biologic that showed significant benefits at 24 weeks. The strong data and remaining unmet need in the US spurred significant grassroots support for TAC 721 from the GI and EOE community. We have been collaborating with these communities to uncover additional benefits. We have now revised our NDA submission package with additional data analyses focused at week 12 and are cautiously optimistic for our filing of 721 for the treatment of EOE. Next slide, please. Here we show our promising mid-stage pipeline. We continue to be energized by recent developments in our orexin franchise. We believe orexin receptor 2 agonists have the potential to be the first agents to address the underlying cause of narcolepsy type 1, offering the potential for functional cures. TAC861 has completed enrollment well ahead of schedule in two phase 2b trials that started in January of 2023. Combined, the narcolepsy type 1 and type 2 phase 2B trials have enrolled approximately 180 patients. TAC861 is a more potent agent that may provide efficacy at a much lower dose than previously tested oral erection agonists. It significantly reduces the potential for adverse effects, including liver toxicity, which tends to be dose-related. The external reviews conducted by the Drug Monitoring Committee confirmed that no liver toxicity signals have been observed. We continue to see nearly all patients who complete the trials enrolling in the long-term extension study, which can extend up to 102 weeks. We remain on track to make a final go-no-go decision to advance TAC861 to phase three in type one narcolepsy and type two narcolepsy in the first half of calendar year 2024. We are also on track to file an IND for our next-generation oral orexin receptor 2 agonist later this fiscal year. Additional oral orexin receptor 2 agonists will allow us to expand into a range of more prevalent disorders with sleep-wake cycle disruptions to fully explore the potential of these agents. Mezogidimab is our fully humanized anti-CD38 monoclonal antibody that has been studied across several rare autoimmune and inflammatory diseases. Mezogidimab depletes plasma cells, resulting in substantial and durable reduction of pathogenic immunoglobulins, leading to potentially meaningful improvements in IgG and IgA-mediated autoimmune diseases. In addition, there is a suggestion that mezagitamab improves the rapidity of the clinical response in immune thrombocytopenic purpura, or ITP, by eliminating CD38-positive immune effector cells, which are directly responsible for platelet destruction. Later this fiscal year, we are looking forward to emerging data in IgA nephropathy and ITP. Go to the next slide, please. Here are select regulatory approvals in Phase III readouts for fiscal year 2023. In addition to updates described previously for subcutaneous intibio and alofascele, Kudanga received approval in Colombia this quarter. This is the fifth endemic country that has approved Kudanga. With the potential approval of PAC 721 later this fiscal year, we now have an opportunity to receive three new molecular entity approvals in the U.S. in fiscal year 2023. This next quarter, we expect to hear a decision in the U.S. about fuquintinib, our selective oral VEGF inhibitor for metastatic colorectal cancer. And we also expect to hear the FDA's response to our submission of PAK755 and ADAMTS13 enzyme replacement therapy for the treatment of congenital thrombotic thrombocytopedic purpura, or CTTP. Approval for this rare pediatric disease would fulfill a major unmet medical need. Thank you very much. And I will now turn it over to Costa.

Thank you, Andy. And hello, everyone. This is Costa Sarucos speaking. Today, I'll walk you through the financial highlights of our fiscal 2023 first half results. Starting with the top line, revenue was 2.1 trillion yen or 14.1 billion US dollars, delivering growth of 1.4% versus prior year at constant exchange rate or 6.4% on an actual basis, including FX upside from the depreciation of the yen. Our top line performance was driven by our growth and launch products, which represents approximately 42% of total revenue and grew 13% at constant exchange rate. Core operating profit was 588.8 billion yen or 3.9 billion US dollars with a core operating profit margin of 28%. Reported operating profit was 119.2 billion yen reflecting the significant impact of non-cash impairment losses and other non-core items that I'll explain in the coming slides. Core EPS was 261 yen and reported EPS was 27 yen, also impacted by several non-core items. While many of these were headwinds to profit, we did book a positive tax gain in H1 as a result of our settlement with Irish revenue over the tax treatment of an acquisition break fee received by Shire in 2014. Moving to cash flow, we continue to see strong cash generation from the business, with operating cash flow of 291.3 billion yen or $1.9 billion for the first half of the year. Free cash flow was minus 71.1 billion yen, reflecting over 250 billion yen of cash out for acquisitions and in licensing so far this fiscal year, including the deals for TAC 279 and Frequitinib. In Q2, we continued to make progress with debt reduction, paying down a billion US dollars bond that matured in September. And we maintain a resilient financial base with 100% of outstanding debt at fixed interest rates with a weighted average rate of approximately 2%. With regards to the outlook for full year fiscal 2023, we have made updates to our foreign exchange rate assumptions and our reported forecast also reflects the impact of the large non-core items we booked in the first half that were not part of the original forecast. Importantly, we continue to track well towards our management guidance for performance at a constant exchange rate. Also, I want to emphasise that we are on track to delivering our full year free cash flow forecast of 400 to 500 billion yen. On slide 18, let me run through the details of our first half financial performance. Starting with our core results on the right of the slide. You can see that revenue was 2.1 trillion yen with growth of 6.4% or 1.4% at a constant exchange rate driven by our growth and launch products. Core operating profit was 588.8 billion yen, a decline of 5.8% on an actual FX basis or 9.5% at constant exchange rate. This reflects the impact of generic competition for high margin products. such as Velcade, Dexilent and Azilver, as well as lower COVID-19 vaccine revenue. There was also a core gross margin impact from the setbacks to Xcivity and Alofisil due to inventory write-off and impairment of manufacturing facilities. Meanwhile, we have continued to make the necessary investment in R&D and data and technology to secure the long-term success of the business. Core net profit and core EPS is impacted by a slightly higher core tax rate compared to last year with core EPS for the first half of 261 yen down 14.4% versus prior year at constant exchange rate. On the left-hand side, you can see our reported results. Reported revenue is the same as core revenue. Reported operating profit was significantly impacted by some large non-core items that we booked in Q2. This included 115.8 billion yen of impairment of intangible assets, mainly related to the phase three study readout of alifisil and our voluntary global withdrawal of excivity. We also booked higher restructuring expenses than the prior year and an additional legal provision resulting in total other operating expenses of 110.2 billion yen. These are reflected in our reported operating profit result of 119.2 billion yen, a year-on-year decline of 53%. Reported net profit and reported EPS declined approximately 75%. Although we did book a 63.5 billion yen tax benefit due to the settlement of a tax dispute with Irish Revenue, our year-on-year net profit comparison was substantially substantially impacted by one-time financial income booked in the first half of last year. As highlighted on the previous slide, free cash flow reflected our cash payments for TAC 279 and for Critanib, but there is no change to our full-year forecast of 400 to 500 billion yen. On slide 19, I would like to highlight the performance of our growth and launch products. which are the key drivers of top-line growth. These products generated 42% of total revenue in the first half, with 13% growth at constant exchange rate. Within our five key business areas, GI grew plus 3% at constant exchange rate, a slowdown versus last year impacted by generic entry of Dexilin in the US in January this year. Our largest product, Intivio, continues to perform well with growth of 6%, but remains a little behind where our expectations had been. As Christophe explained, there continues to be softness in the US IBD market, and we are also being impacted by pricing headwinds in Europe. That said, we maintain the leading market share in the US, both in overall IBD prescriptions and in IBD by naive new patient starts, And with approval last month of the subcutaneous device and ongoing investment in both marketing and lifecycle management, we remain fully confident in the continued growth outlook for the product. In rare diseases, TaxZyro continues its strong momentum with growth of 13%, having successfully launched in over 50 countries and with sustained demand in the US. This has actually led us to raising our full-year forecast for TaxIRO. We also see continued launch success for Liftensity, up 83%, with strong market penetration in the US and rapid geographical expansion within Europe. PDT Immunology continues to deliver outstanding growth of 17%, including 19% growth of immunoglobulin and 11% growth of albumin. Both our IG and albumin products continue to see strong demand. We have continued to expand our plasma donation center network, adding 10 more centers in the first half of the year with the intent to increase by more than 20 new centers by the end of the fiscal year. And we have seen donor compensation on a downward trend since fiscal year 2022. after significant increases during the pandemic. We now modulate compensation in a highly segmented way while achieving the volumes to deliver on our commitments to our patients. Together with initiatives to improve efficiency across the PDT value chain, this has enabled us to improve PDT margins year on year for the first time since the pandemic. Next is oncology. which continues to decline as a result of Velcade generics. However, the timing of loss of exclusivity in May 2022 means that the impact should wash out in the coming quarters. Excluding Velcade, the rest of the portfolio grew 6%, driven by products such as Ellumbrig, Esetris and Eclucig. Excivity remains on this page for now with H1 revenues of 3.5 billion yen or approximately 25 million US dollars. We'll revisit our growth and launch categorization at the end of the fiscal year, taking into consideration the withdrawal of Xcivity, as well as potential new product launches we expect in the second half of the fiscal year. Neuroscience grew at 3% in the first half of the year. We saw strong performance for Vyvanse in the first quarter, But as expected, we have seen several generic launch since the patent expired in August. To date, the generic erosion curve has been generally aligned with our initial estimates. We'll continue to monitor the erosion trend and we'll communicate in future quarters if anything changes our outlook. Finally, the other segment is declining in H1, mainly due to lower revenue from COVID-19 vaccines in Japan. However, this other segment now includes our dengue vaccine, Cudenga, our newest growth and launch product, which is seeing strong initial demand in both endemic and travel markets. Over the next three slides, I'll walk you through some waterfalls to better explain the moving pieces in our first half performance versus prior year. Starting with revenue on slide 20, you can see that versus prior year, our growth and launch products were the main driver of our 1.4% growth at constant exchange rate, more than offsetting the headwinds from loss of exclusivity and lower coronavirus vaccine revenue. On top of this, we had an FX tailwind due to the depreciation of the yen, taking our top line growth on an actual FX basis to 6.4%. Moving to the year-on-year core operating profit bridge on slide 21. Here you can see how loss of exclusivity and coronavirus vaccines are having a larger impact on profit compared to revenue due to their higher margins impacting our product mix. This mix was also impacted by some cost of goods expenses booked in H1 related to excivity inventory write-offs and manufacturing write-offs for alifisil, both of which are treated as core expenses. On the investment side, we continue to allocate resources to R&D to support high potential programs such as TAC 279 and our Ericsson franchise. R&D spend in the first half increased almost 10% on a constant exchange rate basis, but this reflects phasing as expected. And for the full year, we anticipate a mid-single digit increase versus prior year. We also continue to make substantial investment in data and technology, including AI, across the value chain. We believe these investments will have a transformational impact on Takeda's long-term competitiveness, and therefore we continue to allocate capital in these areas as they will play a major role in our return to growth in the near and long term. At the same time, we are applying strict cost discipline to reduce other OPEX versus prior year. I also want to draw your attention to FX, which is less favourable than the FX to revenue. And this is due to much of our expenses being in euros for cost of goods and in US dollars for R&D and other investments. All these factors combined resulted in a first half core operating profit decline of 9.5% on a constant exchange rate basis, or 5.8% decline when factor in the FX. Next is slide 22, which explains the major items impacting our reported operating profit versus previous year. Here, you can see the sizeable increase in impairment of intangible assets, which totaled 115.8 billion yen in the first half, mainly due to the negative phase three study readout of our official and the volatility voluntary global withdrawal of excivity. In addition to that, we had an increase in other operating expenses. This included higher restructuring costs related to exiting AAV gene therapy and consolidating our office footprint. It also includes an additional legal provision booked this year. All these items combined led to the reported operating profit decline of 53.2%. Moving to slide 23 and our outlook for full year fiscal 2023. Based on the first half results, we do not see the need to make any changes for our management guidance at this stage. To date, the generic erosion of Vyvanse and Azulva has been in line with our original expectations and therefore we are keeping our management guidance unchanged. Low single digit percentage decline in revenue low 10 percentage decline in core operating profit and low 20s percentage decline in core EPS or on a constant exchange rate basis. With regards to the reported and core forecast on an actual FX basis, we have updated our FX assumptions resulting in a 140 billion yen increase in our revenue forecast to 3.98 trillion yen. Reported operating profit and reported EPS forecasts have been revised to incorporate the large non-core items that we booked in the first half. On a core basis, our core operating profit forecast is unchanged at 1.015 trillion yen with very small upside from FX being offset by product mix, including the cost of goods impact from excivity and an official that I mentioned earlier. Core EPS is now projected to be 447 yen, an increase from our prior forecast due to a lower assumed core tax rate. Our free cash flow forecast is unchanged at 400 to 500 billion yen, and we remain committed to paying an annual dividend of 188 yen. To close out the presentation on slide 24, I'd like to re-emphasise that total company performance on a core basis is in line with expectations, and we are making steady progress towards our management guidance. There were some large non-core items impacting our reported operating profit in the first half, but these do not derail our strategy. The loss of exclusivity headwinds we face in 2023 are as expected, and we have been preparing for this for many years. We have confidence in our portfolio and pipeline to deliver a return to growth in the near term, and we will continue to allocate capital with discipline as we focus on delivering sustainable growth and competitive shareholder returns. Finally, on slide 25, I would like to highlight our upcoming IR events, including a plasma-derived therapies meeting in early December. I hope that many of you are able to participate for a deeper dive into this important business unit for Takeda. Thank you for your attention, and we can now open up for Q&A.

Until 7.15 PM Japan time, we would like to entertain your question. Christophe Costa and Andy will answer. Additionally, Ramona Seguera, President of Global Portfolio Division, Julie Kim, President of US Business Unit, and Furuta Murano, president of Japan Pharma Business Unit. If you want to ask a question, please use the raise hand button on the Zoom. If you are in Japanese language, please ask in Japanese language. If you are on English, please ask in English. If you are live original channel, then you can ask in either language. We would like to limit the number of questions up to two. Please mention your questions up front, two questions all together. Thank you. First question from SITI, Yamaguchi-san, please go ahead.

Yes, great, thank you. Thank you. So this is Yamaguchi from SITI. I have two questions. The first question is regarding a margin for the Q2. I understand there are lots of exclusivities happening, but the currency is positive, the PDT is doing good, but R&D goes up. So margin of the Q2 is around 25%, which sounds a bit low compared to Q1. So do you think this is still lower than your expectation as far as Q2 is concerned? Why not? So that's the first question. A second question, you mentioned about the PDT margin is getting better first time after COVID. What do you think, what do you mean by the PDT margin? Is it operating margin you're talking about or Q1 or Q2 or first half compared to last year? Can you elaborate what is doing better on your PDT margin, which will be a crucial factor for next fiscal year? Thank you.

Okay. Thank you, Yamaguchi-san. So a question on the margins and also on PDT margins specifically. So I'd like to ask Costa to respond to those questions.

Great. Thank you, Yamaguchi-san. Thank you for your question. You specifically asked for Q2 itself. So let me just walk you through the changes to the margin question for Q2. So Q2 core gross margin had declined for the quarter, mainly because of two reasons. One, as you highlighted already, the product mix. So we saw loss of exclusivity of high margin products such as Dexilent, Velcator, Zilver, coupled with lower COVID vaccine revenue versus last Q2 fiscal year 2022. In addition to that, we saw cost of goods impact of alofisal and excivity write-offs due to the setbacks that we had. So that put pressure on our margin for quarter two, our gross profit margin. On a core operating profit margin, on top of the product mix, COVID vaccine and COGS impact, we had R&D phasing. So we had a ramp up of R&D expenses, but this is phasing and it's aligned to our forecasts. And in addition to that, we did see some wind down costs due to exclusivity. But nevertheless, on a year-to-date basis, we're tracking aligned to our plan, which is 28% cooperating profit. As a total full year perspective, we're targeting 1,015 billion yen. Again, second year in a row that we exceed 1 trillion yen for Takeda on a cooperating profit and year to date on a run rate where we're very much on track to delivering that all year target. So thank you very much on that question. On the PDT margin, what's improving? It's gross profit margins improving as well as cooperating profit is improving. So we're seeing the gross profit margin improving mainly because of product mix within the portfolio. But on the cooperating profit margin, we're seeing significant improvements overall driven by a really efficient end-to-end process, whether it's leveraging data digital technology throughout the PDT value chain or manufacturing capacity. So overall, we're very pleased with the performance, not only on the top line growth for PDT, but also on its profitability. And this is something that we expect to continue for many years to come.

Thank you. Sorry, one quick update on PDT. Talk about first half or Q2, Q1?

This is year-to-date, so I'm looking at... Oh, year-to-date, first half. Yeah, year-to-date, first six months.

Okay, thank you. Thank you.

Next question. Muraoka-san from Morgan Stanley. Please ask your question.

Hello.

Hello, this is Muraoka from Morgan Stanley. I hope you can hear me. Yes, we can hear you. Thank you. So recovery to growth from next fiscal year. I think this message was repeated several times today. And this year, violence was maybe a little bit too good.

So for the next fiscal year, I cannot imagine you returning to profit growth in the next fiscal year, but you sound very confident that you can return to growth in terms of profit.

Is that the correct understanding?

OK, thank you, Muraoka-san. So a question about our return to growth. So I'd like to ask Christoph to answer this one.

Thank you, Muraoka-san. The return to growth will happen in 2024 or 2025. That's why we are seeing in the near term 2024 or 2025. We might be able to return to growth in 2024, but in any case, it will be very, very tight. It's very clear in 2025, but in 2024... It will depend on how the 23 happen fully with the vitamins, especially generic erosion. So far, it's happening as planned, but things can fluctuate quite a bit. So in the near term, we are very clear that we will return to growth. Will it happen in 24, 25? We'll have to see. If it happens in 24, it's possible, but it will be very tight.

I forgot to mention my second question.

Is it okay to ask it now? Yes, of course. Sorry, thank you. Slide 14. So this is the pipeline and proof of concept readout for FY24. I can see four items listed here. And in the sequence of time, which one will be read out first, which one is second, so on and so forth.

On this slide, the 2024 readouts, any more color on the timing within FY24 of these four important readouts?

Chris, it's Andy. Maracasan, thank you. So the first readouts that will come from these data will be in our RECSIN program for TAC861 for both type 1 narcolepsy and type 2 narcolepsy. And those will have final data for both studies in early 2024. We've actually completed enrollment of both of those phase 2b studies. It's an eight-week primary endpoint for the study with the transition to an open label extension. I'll say that we're already planning for phase three at risk. We're planning for successful data from those studies based on everything that we know. So those would be the first that will come. We also expect to see data later this fiscal year for mezogidemab in ITP and then early in fiscal year 2024 for IgA nephropathy. And then the remaining readouts will come later in the year.

Thank you.

Moving on to the next question. Next is Mr. Wakau from JP Morgan. Please go ahead. I'm Wakau from JP Morgan. I have two questions about Intibio. The first one, Intibio next fiscal year's forecast. With regard to this fiscal year, the revenue plan was revised downward. But looking at the situation, next fiscal year, are we supposed to be more cautious? Or from next fiscal year, SC contribution will be there and you will be on the recovery trend. Is that how we look at it? And that's the first question. And secondly, I would like to be informed of the most recent performance of NTVO. You explained a lot, but what about the competitive landscape? You didn't mention any competitors. So there is intense competition and they are doing marketing proactively. So has there been any change in the competitive landscape?

Thank you. So some questions on Intivio, specifically the outlook for next year, expectations for subcutaneous, and then some more detail on what we're seeing on the ground, including competition. So I'd like to ask Christoph to say a couple of comments at the beginning and then maybe hand over to Julie to give more detail, particularly on the US market.

Okay, thank you. I think obviously we'll give next year guidance in May next year, but I think there are very two important parameters that are important to consider. One is that the launch of the SubQ will certainly be leveraged overall. So we expect a very significant positive impact on the overall brand. I mentioned earlier that around 35 to 40% of the US market is a SubQ formulation market. So it will allow us to compete in this segment that we didn't have access to in the past. So that's one. And two, it will be very interesting to see how the overall market is evolving. We believe that new patient treatment initiation is still quite low. The market growth in volume has been quite lower than what we expected. We know that we are not at the pre-COVID level in terms of new treatment initiations. It will be very interesting to see if things will remain like that or we will see a rebound. So overall, I would suspect that we will see an increased growth. I will let Julie mention the competition. Obviously, there is a lot of competition. We can zoom on the US. But before that, I would like to mention that Antivio is also growing very well outside of the US, in Europe, in China, in Japan.

julie perhaps you can comment on the competition yes thanks christoph and thank you for the question in terms of the competition in the u.s as you've rightly pointed out there is increased competition through new entrants and even yesterday there was an announcement of a new entrant from celtrion so we continue to see multiple different mechanisms of actions entering into the IBD space, but Antivio continues to be the only gut-selective MOA, and it continues to be the market share leader in terms of overall bionic share as well as overall IBD market share. So this is an area where we will continue to emphasize the benefits of Antivio in the IBD space, and with the launch of the subcutaneous formulation, AntivioPen, we're quite confident in our ability to continue to support Antivio growth in the U.S. despite new entrants coming in.

Thank you.

Next question from Jeffrey.

You can go ahead.

Yes, Steve Barker here. Thanks very much for taking my question. I have two questions for Andy related to your narcolepsy candidate, TAC861. Specifically, I wanted to ask about the phase one results that were presented at World Sleep this week. Firstly, could you discuss the doses that were tested in phase one in the context of the phase two program? And secondly, Are you concerned that TAC861 might be at a commercial disadvantage if it needs to be dosed twice per day? The context of the second question is, of course, the data presented on the Alkermes orexin agonist, which looks like it can be developed as a once-per-day therapy. Thank you.

Well, hi, Stephen. I'll take the first question, and then I'll ask Ramona to chime in if she can on the commercial positioning of a once versus a twice daily dosing. So the phase 1B data that we presented at the sleep conference just this week was really very small numbers, really proof of concept. The doses that we've used in our phase 2B studies are significantly lower than what you saw this week. And then lastly, I'll say that we haven't decided on our dosing regimen yet for our phase three program. That's something that we'll decide after we see our full phase 2B data. And I think that we have to be cautious when we look at any data set, ours or competitors, from small phase 1B studies in terms of understanding what administration schedules will look like. Ramona? Yeah.

Yeah, Andy, I can, I can chime in on the efficacy and, and, you know, we had a very large team at the sleep conference this week and are very excited about the orexin franchise that we have at Takeda for 861. We still believe it's going to be the first in class and the best in class to treat narcolepsy. And as we do research with physicians and patients really around the world as you know, most importantly in the U S as well it, it, there is such a high need for better treatment options to really help people live a more functional life with narcolepsy. And so it's always going to be a trade-off with the dosing and the actual functionality that we can get. And so we are very confident that whatever profile we go for with dosing will be to really maximize functionality in these patients. And as Andy said, it's early days to say now exactly how we're going to plan to do that. but we're very confident in our target product profile for 861.

Thanks. Just one quick follow-up regarding the safety. So you were testing very large doses in this phase one versus what you are testing in phase two, and the safety profile looks very good. Does that improve your confidence about the safety of this asset?

Stephen, the more experience we have, the stronger we feel about the safety profile of 861. And I'll just reiterate something I said during the presentation, which is that we've now enrolled 180 patients approximately in between the two Phase IIb studies. We've obviously been very cautious around all safety parameters, especially liver function tests. And we have an independent data safety monitoring board that's been tracking And we haven't seen any signals consistent with liver toxicity. And it's very consistent with the margins that we have and the doses that we're using. So we feel quite good about the overall safety and tolerability profile at this point. Thank you.

Thank you. Thank you.

Daiwa Securities, Hachiguchi-san, please ask your question. Yes, this is Hachiguchi. Thank you.

TAC-279 Phase II daughter in psoriatic arthritis.

ACR presentation. I actually read the abstract of this presentation. And the SOTIC-2 data, compared to that data, I believe that the efficacy is actually about the same. And the AEs, adverse events, about the same in low dose. And in higher dose, TAC-279 has a higher incidence of AEs, it seems. I understand that it's a different population. And I want to understand how to interpret the data from this study. And for TAC279, how do you assess the competitiveness of this compound? That's my question.

Thank you, Hachiguchi-san, for the question. So a question on the TAC279 psoriatic arthritis phase 2 abstract that was recently published. Andy, your thoughts on that?

Sure. Thanks, Chris. And thanks, Haseguchi-san. So not to steal the thunder from the presentation that's coming up in just a few weeks, let me just make a few high-level comments. The first is that it's very important to look at the study differences between our study and previous previous studies in psoriatic arthritis, and in particular the timing of the endpoint. So we're looking at a 12-week time point, and most other studies look at a 16-week endpoint. It's also important to look at the differences in the underlying patient population, and we'll discuss some of those differences at the presentation next month. And then the third point I'll make is that the psoriatic arthritis is often misunderstood in terms of its disease presentation. It's actually in a continuum with psoriasis. So most patients with psoriatic arthritis have skin lesions, plaque, and most patients with psoriasis actually end up developing some joint problems. And so the two diseases are highly related. And so when we're looking at endpoints in psoriatic arthritis, we're looking at both joint endpoints and skin endpoints. What we've learned through multiple mechanisms that inhibit these cytokines, IL-12, IL-23, interferon, is that the dose response characteristics on the joint endpoints tend to be fairly flat. That's something that we consistently see across therapies. What we're expecting to see significant differentiation from our competitors is, again, going to be on the skin endpoints. So you'll see more of those data and we'll provide some additional details around those data during the presentation.

Thank you very much. Thank you very much for the question.

Okay, so next we'd like to take a question from Cowan, Mike Nidalcovich. Please unmute and ask your question.

Thank you for the question. My question is on Intivio. It's a bit surprising to hear that COVID is still measurably affecting IBD diagnoses and treatment rates. And I imagine it's difficult to tease that impact out from other factors. So I'm curious, are you seeing that diagnosis and treatment in other therapeutic categories are showing a lingering effect of the pandemic? And if not, what do you think is different about IBD? And what is your best guess at what we might see in normalization? And then on the subcutaneous launch, I know it's very early, but I'm curious if you see any early indicators that the subcutaneous product will push Intivio toward the higher end of management's peak sales guidance, or do you think that headwinds such as the competition you described and the lingering effects of COVID might cause you to lean more cautiously?

Thanks, Mike. Julie, would you like to answer that question or those questions?

Yes, sure. Thanks, Mike, for the questions. In terms of the comments around the suppression of diagnosis, what we're looking at is in terms of claims data, there are a number of different claims databases that you can see in the U.S. to give you an indication. And when we look at, for example, Crohn's disease in particular across two different claims databases in the U.S., there's a roughly One shows 8% to 10% decline in diagnosis in Crohn's disease in particular, and the other shows closer to 20% decline in diagnosis in the last 12 months that we have in terms of the claims data. So that's why we're saying that the diagnosis rates are still being impacted post-COVID. Now you asked about other areas. So we did take a look at a number of other areas. And while I don't have the specific numbers off the top of my head, we did see similar suppression, although not at the high level of Crohn's disease, but we did see similar suppression and diagnosis in a few other areas as well. So not quite sure why, you know, there are some theories out there in terms of the suppression of inflammation overall because of COVID. but it's something that we are keeping a close eye on and continuing to monitor. We're focusing on what we can focus on in terms of supporting the need for treatments based on the mechanism of action of antivio and our continued demonstration of safety in the IBD space. And so the subcutaneous pen is another opportunity for us to demonstrate the value of Antivio in IBD, and we're very excited about that. I think I covered all of them, Chris, but if I missed something, please.

I think there's a question on peak sales. Maybe, Christoph, if you'd like to jump in on the peak sales and how SubQ impacts the potential.

Thank you, Mike, for the question. Well, when we look at Antivio positioning and its market share that Antivio has, especially for bio-naive patients, combined with the launch of the Antivio Pen, Combined with the growth of Antiviu actually also outside of the US, we are very much confident about our peak estimate of between 7.5 and 9 billion US dollars. Actually, if you do the math, compared to our current situation, our current revenue in 2023, a peak of 7.5 to 9, that's equivalent to a CAGR between 4 and 6. for the product. So we feel it's completely achievable, considering the strength of the Antivio profile, as well as the launch of the pen. Thank you.

Thank you.

Thank you, Mike. Okay, next question, we'd like to call upon Miki Sogi from Bernstein. Please unmute and ask your question.

Thank you. I also have a question regarding the Entivio. So I understand that, you know, you are expecting the sub-Q to be a new growth driver for this product. But I also like to understand, you know, source of business for the subcutaneous, you know, the formulation. I imagine that, you know, the majority of source of business is coming from existing Entivio patients, right? And potentially more of the additional growth will come from new patients. Is that the right understanding? And also when you say 30 to 40% of the IBD patients will be on SC. So is this something additional or just replacing the current market?

Thank you. So a question about the source of business for NTVO subcutaneous. Perhaps I'd like to ask Ramona to comment on experience that we've seen in markets where we've already launched the subcutaneous device. In Europe, of course, one example. And then if Julia has anything to add after that, please jump in. Ramona?

Yes, absolutely. Hi, this is Ramona here. So As we look at launching the sub-Q in the U.S. and take the learnings from what we've seen when we've launched the sub-Q in a number of markets in Europe now and are launching in other parts of the world, including Japan, there's two things that happen. One is we are able to go to new customers. So if you think about the U.S., we've got as well as Europe and other markets. We've got customers that are heavy infusion prescribers, but we've got other customers that aren't as linked to infusion clinics and tend to prescribe much more sub-Q. Our focus has been more on the infusion providers to this stage in Intibio's life cycle. As we bring the sub queue out, it gives us new customers, new providers to go to, and that allows us to access new patients. So that's where we've seen a lift around the world as we brought the sub queue out in accessing these new providers and new patients that are new to the franchise. On the other side, we also have some cannibalization of existing patients. So they're Now we become the only product really that has both sub-Q and IV options, a really excellent pen, along with all the other benefits of Antivio, gut selective, long-term safety and efficacy data, and really an ideal first choice when conventional therapies fail. And so we do see some patients now that would be on the IV switching to the sub-Q. That ends up being net neutral to us, but it just gives more options for patients now. who want to stay in the Antibio family and stay on Antibio and have different options for taking it. Thank you.

Thank you.

Okay, thank you very much. Okay, since we are getting close to the end of the call, the next question will be our final question. So I'd like to call upon Ueda-san from Goldman Sachs. Ueda-san, onegaishimasu.

Yes, this is Ueda, Goldman Sachs.

Thank you for this opportunity. I would like to ask two questions about the business development. First of all, on page 19, you are showing this information about oncology, excivity, negative progress, and Alumbric, strong competition, and growth and launch products are struggling in this background. Do you feel that you need to do something additional to counter this situation? That's my first question. And the second question is, in relation to that, you talked about strengthening the pipeline. So currently, what kind of franchise or what kind of phase, development phase, are you considering for potential in-licensing? Please share with us your current thoughts.

Thank you, Ueda-san, for that question. So a question around our business development plans. First of all, in oncology to supplement the portfolio, and then looking at the pipeline, which phases, which therapeutic areas. I'd like to ask Christoph to comment on this.

Thank you for the question. So first, I would say that we are not looking, I would just reconfirm to everyone that we are not looking at large M&A for scale purpose. We are very competitive in all the key countries where we operate. So we don't have a scale or a competitive issue in that regard. So it's all about portfolio pipeline, so targeted BD. On oncology, if we can bring new assets like Fruzacla, Frucutinib that were just in license, that would be terrific. So we are looking at this type of deals to complement our portfolio. We have a very attractive pipeline, but it's more mid-stage. So many of these products in our pipeline will be launched toward the end of the decade. So if we can bring more assets to enrich our portfolio, we'll do. We follow, in fact, roughly the same approach across the therapy area. Obviously, we are a leader in the GI space, so if we can bring other assets, we'll do. We shouldn't forget that we have a very strong position in rare disease, in LSD disease. So we are looking at that. In plasma-derived therapies, there is not much to do. So it's really about making our portfolio and pipeline more competitive. So I think we are quite agnostic on the phase, but we are very focused on the therapy, on the disease area, because we want to leverage... where we are strong and where we have a very strong corporate knowledge about the disease. So that's what is guiding us for our business development strategy.

Thank you very much.

That's all from me. Thank you very much.

We would like to conclude today's webinar.

Thank you very much for your presence despite your busy schedule today. We would like to ask for your continued support going forward.