Takeda Pharmaceutical Co Ltd (TAK) 2024 Q3 法說會逐字稿

Thank you very much for joining us for Takeda's FY '23 Q3 Earnings Announcement (inaudible) scheduled. I'm the (inaudible) today, I'm already Head of IR.

非常感謝您參加我們預定的武田 23 財年第三季財報公告（聽不清楚）。今天我是（聽不清楚），我已經是 IR 主管了。

First of all, I would like to explain about the language. Please find the language button at the bottom of Zoom window. If you wish to listen in Japanese, please choose Japanese. If in English, please choose English. If you want to listen to the original language, please turn it off.

首先，我想解釋一下語言。請在“縮放”視窗底部找到語言按鈕。如果您想聽日語，請選擇日語。如果是英語，請選擇英語。如果您想聽原版語言，請關閉它。

Before starting, I'd like to remind everyone that we'll be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today. The factors that could cause our actual results to differ materially are discussed in our most recent Form 20-F and our other SEC filings. Please also refer to the important notice on Page 2 of the presentation regarding forward-looking statements and our non-IFRS financial measures, which will also be discussed during this call.

在開始之前，我想提醒大家，我們將討論 1995 年《私人證券訴訟改革法案》含義內的前瞻性陳述。實際結果可能與今天討論的結果有重大差異。我們最新的 20-F 表格和其他 SEC 文件中討論了可能導致我們的實際結果出現重大差異的因素。另請參閱簡報第 2 頁上有關前瞻性陳述和我們的非國際財務報告準則財務措施的重要通知，這些資訊也將在本次電話會議中進行討論。

Definitions of our non-IFRS measures and recommendations. Reconciliations with the comparable IFRS finance measures are included in the appendix to the presentation. Without further ado, we would like to start the presentation today. We have President and CEO, Christophe Weber; R&D President, Andy Plump; and the Chief Financial Officer, Costa Saroukos presenting today, followed by a Q&A session. Now let us begin. [Christophe, please go ahead.]

我們的非國際財務報告準則措施和建議的定義。與可比較的《國際財務報告準則》財務指標的調節表包含在簡報的附錄中。話不多說，我們今天開始演講。我們有總裁兼執行長 Christophe Weber；研發總裁 Andy Plump；財務長 Costa Saroukos 今天進行了發言，隨後進行了問答環節。現在讓我們開始吧。 【克里斯托夫，請繼續。】

Thank you, Chris, and thank you, everyone, for joining our third quarter earnings call for fiscal year '23. Our vision at Takeda is to discover and deliver life-transforming treatments carried by our commitment to patients, our people on the planet. This purpose-led approach is at the core of our strategy for sustained growth and long-term value creation for our stakeholders.

謝謝克里斯，也謝謝大家參加我們 23 財年第三季的財報電話會議。武田的願景是發現並提供改變生命的治療方法，這是我們對病人和地球上人民的承諾。這種以目的為導向的方法是我們為利害關係人持續成長和創造長期價值的策略的核心。

Our performance in the third quarter of fiscal year '23 further demonstrate our progress in executing on that strategy as we look ahead to a return to top line profit and margin growth. Our top line continued to be driven by the strong momentum of our growth on launch product, which now represents 43% of total revenue and which grew at 2.7% year-to-date at constant exchange rate. In Q3 year-to-date, core revenue was JPY 3.2 trillion with flat growth at constant exchange rate compared with the same period in the previous year. And this is despite significant loss of exclusivity impact, primarily from VYVANSE in the U.S. and AZILVA in Japan.

我們在 23 財年第三季的業績進一步證明了我們在執行該策略方面的進展，因為我們期待著恢復頂線利潤和利潤率成長。我們的營收持續受到推出產品強勁成長動能的推動，目前佔總營收的 43%，以固定匯率計算，今年迄今成長了 2.7%。今年第三季迄今，核心營收為 3.2 兆日圓，以固定匯率計算與去年同期相比成長持平。儘管排他性影響力顯著下降（主要來自美國的 VYVANSE 和日本的 AZILVA），情況仍是如此。

On an actual exchange rate basis, revenue grew 4.6%. Core operating profit was JPY 865.6 billion with a decline of 12.7% at constant exchange rate, reflecting the loss of exclusivity on high-margin product as well as our investment in R&D and data and technology to secure long-term competitiveness. At actual exchange rate, our core operating profit declined by 9.3%. Despite this, we remain on track to exceed JPY 1 trillion core operating profit for the full year. On a reported basis, operating profit and EPS were impacted by noncore items, including impairment of intangible assets, which were mostly booked in the second quarter. As you know, we provide full year management guidance for core growth at constant exchange rate, and I am pleased to report that our year-to-date core performance continued to be in line with expectations, keeping us well on track to our management guidance for the year.

以實際匯率計算，營收成長4.6%。核心營業利潤為 8,656 億日元，按固定匯率計算下降 12.7%，反映出高利潤產品獨家經營權的喪失以及我們為確保長期競爭力而對研發、數據和技術進行的投資。以實際匯率計算，我們的核心營業利潤下降了9.3%。儘管如此，我們全年核心營業利潤仍有望突破 1 兆日圓。根據報告，營業利潤和每股盈餘受到非核心項目的影響，包括無形資產減值，這些項目大部分在第二季入帳。如您所知，我們以固定匯率提供核心成長的全年管理指導，我很高興地報告，我們年初至今的核心業績繼續符合預期，使我們能夠順利實現管理指導今年。

On the next slide, we are confident in our R&D strategy, and we continue to advance highly innovative, life-transforming medicines for patients affected by rare or more prevalent disease in our core therapy areas. Our pipeline delivered well in the third quarter with 2 new molecules approval in the United States, FRUZAQLA for previously treated metastatic colorectal cancer and ADZYNMA for an ultra-rare blood clotting disorder called congenital thrombocytopenic purpura, or cTTP.

在下一張投影片中，我們對我們的研發策略充滿信心，我們將繼續在核心治療領域為患有罕見或更普遍疾病的患者推出高度創新、改變生命的藥物。我們的產品線在第三季度表現良好，有2 個新分子在美國獲得批准，FRUZAQLA 用於治療既往治療的轉移性結直腸癌，ADZYNMA 用於治療一種稱為先天性血小板減少性紫斑症（cTTP ）的超罕見凝血疾病。

FRUZAQLA which we acquired through an exclusive license agreement with (inaudible) in March last year, is the first and only targeted therapy approved for metastatic colorectal cancer regardless of biomarker status in more than a decade. In fact, the unmet need is too significant that FRUZAQLA was available within 24 hours following FDA approval with the first prescription received the day after approval. I want to acknowledge here the work of our oncology team in preparing for the launch and giving these patients hope.

去年3 月，我們透過獨家授權協議（聽不清楚）獲得了FRUZAQLA，它是十多年來第一個也是唯一一個被批准用於轉移性結直腸癌的標靶治療藥物，無論生物標記狀態如何。事實上，未滿足的需求非常巨大，以至於 FRUZAQLA 在 FDA 批准後 24 小時內即可上市，並且在批准後的第二天就收到了第一個處方。我想在此感謝我們的腫瘤學團隊在準備啟動並給這些患者帶來希望方面所做的工作。

Regarding ADZYNMA, this is the first and only therapy of its kind for the treatment of cTTP and ultra rare blood clotting disorder. Its approval and launch our significant milestone for this rare disease community, which we are proud to continue focusing on. Since the second quarter since Q2, we have also made strong progress in our existing portfolio with important life cycle management approval for our growth and launch product.

關於 ADZYNMA，這是第一個也是唯一一個用於治療 cTTP 和極其罕見的凝血障礙的療法。它的批准並啟動了我們在這一罕見疾病領域的重要里程碑，我們很自豪能夠繼續關注這一點。自第二季以來，我們在現有產品組合方面也取得了強勁進展，我們的成長和推出產品獲得了重要的生命週期管理批准。

The livtencity is now approved in China for refractory post-transplant CMV. Patients in China now have access to this therapy that can enable sustain an effective treatment against post-transplant cytomegalovirus infection, which could save an organ or a life that might otherwise be lost. In November, the European Union approved takhzyro for pediatric patient with hereditary angioedema.

Livtencity現已在中國獲準用於治療難治性移植後CMV。中國的患者現在可以獲得這種療法，可以持續有效地治療移植後鉅細胞病毒感染，從而挽救可能失去的器官或生命。 11 月，歐盟批准 takhzyro 用於治療患有遺傳性血管性水腫的兒科患者。

It is the first and only long-term proprietary treatment for this rare disease available in the EU for patients under the age of 6. And in January, we had some fantastic progress in our plasma-derived therapy portfolio with 3 approvals for our immunoglobulin portfolio for chronic inflammatory demyelinating polyradiculoneuropathy or CIDP, a rare disorder affecting the peripheral nervous system.

這是歐盟針對6 歲以下患者的這種罕見疾病的第一個也是唯一一個長期專有治療方法。一月份，我們的血漿衍生治療組合取得了一些驚人的進展，我們的免疫球蛋白組合獲得了3 項核准用於慢性發炎性脫髓鞘性多發性神經根神經病變或 CIDP，這是一種影響週邊神經系統的罕見疾病。

HYQVIA, the only facilitated subcutaneous IG was approved by both the U.S. FDA and the European Commission for maintenance treatment of CIDP and Gammagard Liquid was approved by the FDA for the IV treatment of CIDP. We are also expanding our late-stage pipeline through targeted business development. Just a few hours ago, we announced a collaboration and license agreement with Protagonist Therapeutics for the development and commercialization of rusfertide, an investigational therapy in rare hematology. Rusfertide is currently in Phase III development for polycythemia vera, a rare chronic blood disorder. This agreement fits well within our overall business strategy, leveraging our rare disease and hemophilia franchise.

HYQVIA是唯一獲得美國FDA和歐盟委員會批准用於CIDP維持治療的促進皮下注射IG，Gammagard Liquid獲得FDA批准用於CIDP的靜脈注射治療。我們也透過有針對性的業務發展來擴大我們的後期產品線。就在幾個小時前，我們宣布與 Protagonist Therapeutics 就 rusfertide（一種罕見血液學研究療法）的開發和商業化達成合作和許可協議。 Rusfertide 目前正處於治療真性紅血球增多症（一種罕見的慢性血液疾病）的 III 期開發階段。該協議非常適合我們的整體業務策略，充分利用我們的罕見疾病和血友病專營權。

Turning to the next slide, I'd like to provide an update on 2 important products in our growth and launch portfolio, ENTYVIO and Qdenga. ENTYVIO is our #1 product by revenue and it continues to outperform the IBD market with year-to-date revenue growth of 7%, with a slight growth acceleration in Q3. It has maintained its lead in the U.S. as the most prescribed treatment for IBD overall as well as for IBD bio-naive new start. And it is achieving mid-teen percentage patient growth in Europe, driven mostly by our [supineneous] administration. In November, we also launched an ENTYVIO pen in the U.S. for maintenance therapy in moderate to severely active arthritive colitis.

轉向下一張投影片，我想提供有關我們的成長和發布產品組合中 2 個重要產品 ENTYVIO 和 Qdenga 的最新資訊。以營收計算，ENTYVIO 是我們排名第一的產品，其表現持續優於 IBD 市場，年初至今營收成長 7%，第三季成長略有加速。它在美國保持了領先地位，作為 IBD 整體以及 IBD 生物治療新起點最常用的治療方法。在我們的[臨時]政府的推動下，歐洲的患者人數正在實現中位數的成長。 11月，我們也在美國推出了ENTYVIO筆，用於中度至重度活動性關節炎結腸炎的維持治療。

Subcutaneous therapies are estimated to represent approximately 35% to 40% of the total U.S. IBD market. So this (inaudible) a very significant milestone in enabling us to access this segment while providing more flexibility and choice to patients.

據估計，皮下療法約占美國 IBD 市場總量的 35% 至 40%。因此，這是一個非常重要的里程碑（聽不清楚），使我們能夠進入這個細分市場，同時為患者提供更多的靈活性和選擇。

ENTYVIO is now the only branded therapeutics with both IV and subcutaneous maintenance option, and we are seeing a high degree of interest among health care professionals. I'm happy to share some market research data with you. 98% of surveyed health care professional are aware of the ENTYVIO pen and 94% express willingness to prescribe it in the next 6 months. We expect an FDA decision on the entyvio pen in Crohn's disease early in fiscal year '24. Shifting now to Qdenga.

ENTYVIO 現在是唯一同時具有靜脈注射和皮下維持選項的品牌療法，我們看到醫療保健專業人士對此表現出高度興趣。我很高興與您分享一些市場研究數據。 98% 的受訪醫療保健專業人員了解 ENTYVIO 注射筆，94% 的人表示願意在未來 6 個月內開立該藥。我們預計 FDA 將在 24 財年年初就治療克羅恩病的 entyvio 筆做出決定。現在轉向 Qdenga。

We are very encouraged by how our launch has been progressing globally. To date, we have launched the vaccines in 21 countries, including most recently, Argentina. Qdenga is available in 17 European countries, and travel recommendations support its use to help protect travelers to dengue-endemic areas. There has been a strong initial demand in private market where Qdenga has launched and now we are seeing progress towards inclusion in national immunization program too.

我們對我們的發佈在全球範圍內的進展感到非常鼓舞。迄今為止，我們已在 21 個國家推出了疫苗，其中包括最近在阿根廷。 Qdenga 在 17 個歐洲國家可用，旅行建議支持使用它來幫助保護前往登革熱流行地區的旅客。 Qdenga 推出的私人市場最初需求強勁，現在我們也看到納入國家免疫計劃的進展。

In December '23, Brasil National Commission for the incorporation of Health Technology recommended Qdenga for inclusion in the national (inaudible) program. Subsequently, the Brasilian government has decided to initiate some focused vaccination program in areas with high dengue incidence rates. We are also in productive discussion with government in other endemic countries and we are pushing private and public partnership with government, institutional businesses, NGOs and manufacturer to expand access.

23 年 12 月，巴西國家健康科技委員會建議將 Qdenga 納入國家（聽不清楚）計畫。隨後，巴西政府決定在登革熱高發生地區啟動一些重點疫苗接種計畫。我們也與其他流行國家的政府進行富有成效的討論，並推動與政府、機構企業、非政府組織和製造商建立私人和公共夥伴關係，以擴大獲取機會。

We are committed to our goal of reaching a total manufacturing capacity of $100 million per year to comprehensively address the growing burden of dengue infection. Turning to our high-level outlook for the near, medium and long term. As we have entered the final quarter of this fiscal year, we are confident in our business strategy and are committed to growth and shareholder return.

我們致力於實現每年 1 億美元的總生產能力的目標，以全面應對日益增長的登革熱感染負擔。轉向我們對近期、中期和長期的高層展望。隨著我們進入本財年的最後一個季度，我們對我們的業務策略充滿信心，並致力於成長和股東回報。

Based on our current assumption, we still expect to return to revenue, profit and margin growth in the near term, driven largely by the continued expansion of our growth and launch product. We have achieved significant regulatory milestones since Q2 in the form of new product approval, an important indication expansion for the existing portfolio and we continue to see significant potential in our late-stage pipeline. Generic competition for VYVANSE and azilva continued to impact revenue and profit growth this fiscal year.

根據我們目前的假設，我們仍然預計短期內將恢復收入、利潤和利潤率的成長，這主要是由我們的成長和推出產品的持續擴張所推動的。自第二季度以來，我們以新產品批准的形式實現了重要的監管里程碑，這是現有產品組合的重要適應症擴展，並且我們繼續看到後期管道的巨大潛力。 VYVANSE 和 azilva 的通用競爭持續影響本財年的營收和利潤成長。

However, once that impact has washed out, we'll have limited loss of exclusivity exposure until the launch of entyvio biosimilar, which could occur as late as 2032 in the U.S. Momentum for 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 are committed to returning to core operating profit margin in the low to mid-30s, supported by our growth on launch product, cost control and value creation enabled by data and technology, including AI. We believe AI has the potential to create significant, scalable and sustainable value at Takeda.

然而，一旦這種影響消失，在entyvio 生物相似藥推出之前，我們的獨家經營權損失將有限，這最遲可能於2032 年在美國推出。我們的成長和推出產品的動力，加上我們對研發的持續投資將推動中長期進展。展望未來，我們致力於將核心營業利潤率恢復到 30 多歲左右，這得益於我們推出產品的成長、成本控制以及數據和技術（包括人工智慧）帶來的價值創造。我們相信人工智慧有潛力為武田創造重大、可擴展和可持續的價值。

It will enable us to improve efficiency across our entire value chain, including in R&D, manufacturing, patient engagement and business operation. We believe that data, technology and AI will completely change how we operate as a company, and we are moving at full speed across the value chain to implement digital and AI tools and applications.

它將使我們能夠提高整個價值鏈的效率，包括研發、製造、病患參與和業務營運。我們相信數據、技術和人工智慧將徹底改變我們公司的營運方式，我們正在全價值鏈上全速前進，實施數位和人工智慧工具和應用。

We'll share more detail on this topic in our future presentation. Looking ahead, we'll continue to evaluate asset-specific business development opportunities to further enhance our pipeline and reinforce our growth profile. Our bid strategy has been proving successful with the approval and launch of fruzaqla and the positive progress of TAK279 through this pipeline this fiscal year. This approach to innovation, combined with a robust clinical pipeline of potential best-in-class or first-in-class asset will position Takeda well for the long-term growth.

我們將在未來的演示中分享有關此主題的更多詳細資訊。展望未來，我們將繼續評估特定資產的業務發展機會，以進一步增強我們的管道並增強我們的成長前景。隨著 fruzaqla 的批准和推出，以及 TAK279 在本財年通過該管道的積極進展，我們的投標策略已被證明是成功的。這種創新方法，加上潛在一流或一流資產的強大臨床管線，將為武田的長期成長奠定良好的基礎。

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, we are confident about the path we are on. Our year-to-date performance demonstrate the strong momentum in our growth and launch product, the potential in our pipeline and solid execution against our business strategy.

最後，我們每年增加或維持股利的漸進式股利政策將使我們能夠繼續為股東回報價值。最後，我們對我們所走的道路充滿信心。我們今年迄今為止的業績證明了我們成長和推出產品的強勁勢頭、我們管道的潛力以及我們業務策略的紮實執行。

With the approval and launch of 2 new therapies this quarter in the U.S. and multiple life cycle management approval around the world, we are very much confident that the strength of our commercial execution combined with the potential of our pipeline will help to fuel our long-term growth. And this brings us back to the vision that drives us to discover and deliver life-transforming treatments guided by our commitment to patients, our people on the planet. With that, I will now turn the call over to Andy to update you on our pipeline. Thank you.

隨著本季2 種新療法在美國獲得批准並推出，以及全球多個生命週期管理的批准，我們非常有信心，我們商業執行的實力與我們管道的潛力相結合，將有助於推動我們的長期-期限成長。這讓我們回到了一個願景，推動我們發現並提供改變生命的治療方法，並以我們對患者和地球上的人民的承諾為指導。現在，我將把電話轉給安迪，向您通報我們管道的最新情況。謝謝。

Thank you very much, Christophe, and hello to everyone on today's call, if we can go to the next slide, please. We've had a very successful quarter, delivering some major milestones while continuing to build momentum across our pipeline. Here are a few examples of the significant pipeline achievements from the third quarter.

非常感謝你，Christophe，今天電話會議上的大家好，請轉到下一張投影片。我們度過了一個非常成功的季度，實現了一些重大里程碑，同時繼續在我們的管道中建立動力。以下是第三季取得的重大成果的一些範例。

As Christophe mentioned, Adzynma and Fruzaqla, 2 new molecular entities have received approval in the United States. Adzynma is a recombinant ADAMTS13 protein designed to replace the missing enzyme, which causes patients living with congenital TTP to face serious life-threatening health challenges. This approval is based on Adzynma's favorable efficacy profile, notably a 60% reduction in the incidence of thrombocytopenic events for plasma-based therapies.

正如 Christophe 所提到的，Adzynma 和 Fruzaqla 兩種新分子實體已在美國獲得批准。 Adzynma 是一種重組 ADAMTS13 蛋白，旨在取代缺失的酶，導致先天性 TTP 患者面臨嚴重的危及生命的健康挑戰。此核准是基於 Adzynma 良好的療效，特別是血漿療法可將血小板減少事件的發生率降低 60%。

In fact, Takeda was awarded a priority review voucher for this approval as it addresses a major unmet need in patients with this rare pediatric disease. We are also evaluating adzynma in a Phase IIb study in immune thrombotic thrombocytopenic purpura or ITTP, which is a significantly more prevalent disease.

事實上，武田因此次批准而獲得了優先審查券，因為它解決了患有這種罕見兒科疾病的患者的主要未滿足需求。我們也在一項針對免疫性血栓性血小板減少性紫斑症或 ITTP 的 IIb 期研究中評估 adzynma，這是一種明顯更常見的疾病。

Fruzaqla, an oral VEGF inhibitor was approved in the U.S. for certain patients with previously treated metastatic colorectal cancer. It demonstrated a significant improvement in overall survival with a manageable safety profile and not surprisingly, initial commercial uptake has been quite strong. In addition, we continue to rapidly advance the development of our allosteric TYK2 inhibitor, TAK279, initiating the LATITUDE clinical trial program with 2 Phase III psoriasis trials that are enrolling well.

Fruzaqla 是一種口服 VEGF 抑制劑，在美國獲準用於治療某些先前接受過治療的轉移性大腸直腸癌患者。它證明了整體存活率的顯著改善以及可控的安全性，毫不奇怪，最初的商業應用相當強勁。此外，我們繼續快速推進變構TYK2抑制劑TAK279的開發，啟動了LATITUDE臨床試驗計劃，其中兩項III期乾癬試驗入組情況良好。

Following the presentation of positive and very exciting psoriatic arthritis Phase IIb data at the American College of Rheumatology. We plan to initiate enrollment in the LATITUDE psoriatic arthritis Phase III program in fiscal year 2024. To support the development of TAK279 in inflammatory bowel disease, we aligned with the FDA on the clinical trial design for Phase IIb studies in Crohn's disease and ulcerative colitis utilizing much higher doses than studied in psoriasis or psoriatic arthritis.

美國風濕病學院公佈了積極且非常令人興奮的乾癬性關節炎 IIb 期數據。我們計劃在2024 財政年度啟動LATITUDE 銀屑病關節炎III 期計畫的註冊。為了支持TAK279 在發炎性腸道疾病方面的開發，我們與FDA 就克羅恩病和潰瘍性結腸炎的IIb 期研究的臨床試驗設計達成一致比銀屑病或銀屑病關節炎研究的劑量高得多。

279 is our leading pipeline priority, and we continue to make steady progress as we work to bring this potentially best-in-class treatment to patients. In the third quarter, we also delivered important indication and geographic expansions for our growth and launch products. As Christophe just mentioned, in the U.S., GAMMAGARD LIQUID and HYQVIA received their first approvals for induction and maintenance of CIDP, respectively.

279 是我們的主要管道優先事項，我們將繼續取得穩步進展，努力為患者提供這種可能是一流的治療方法。在第三季度，我們也為我們的成長和推出產品提供了重要的指示和地理擴張。正如Christophe剛才所提到的，在美國，GAMMAGARD LIQUID和HYQVIA分別首次獲得了CIDP誘導和維持的批准。

With these approvals, we can now offer treatment for patients with this rare acquired immune media neuromuscular disorder throughout their journey. HYQVIA was also just approved for CIDP maintenance in the EU. We also continued to expand our pipeline with targeted late-stage deals. A few hours ago, we announced a worldwide license and collaboration agreement with Protagonist Therapeutics for rusfertide. The rusfertide is a first-in-class (inaudible) in a pivotal Phase III trial for the treatment of polycytemiavera, a rare chronic blood disorder that affects as many as 160,000 patients in the United States.

有了這些批准，我們現在可以為患有這種罕見的獲得性免疫介質神經肌肉疾病的患者提供全程治療。 HYQVIA 也剛獲得歐盟 CIDP 維護批准。我們也繼續透過有針對性的後期交易來擴大我們的管道。幾個小時前，我們宣布與 Protagonist Therapeutics 就 rusfertide 達成全球許可和合作協議。 rusfertide 是一項用於治療多細胞血症的關鍵 III 期試驗中的首創藥物（聽不清楚），多細胞血症是一種罕見的慢性血液疾病，影響著美國多達 160,000 名患者。

The rufertide Phase III trial is expected to complete enrollment soon and will add to our growing late-stage pipeline. If we can get to the next slide, please. Our late-stage pipeline reflects Takeda's commitment to develop life-transforming medicines for rare and more prevalent diseases.

rufertide III 期試驗預計很快就會完成註冊，並將增加我們不斷增長的後期產品線。請讓我們轉到下一張投影片。我們的後期產品線體現了武田致力於開發針對罕見和更常見疾病的改變生命的藥物。

As I mentioned, TAK279 is enrolling patients in 2 Phase III psoriasis trials. Because psoriasis trials have historically lacked representations from patients of color, we are proactively taking steps for the TAK279 LATITUDE psoriasis program to reflect unprecedented patient diversity. TAK279 is a potential best-in-class oral therapy for psoriasis and we'll start a Phase III head-to-head trial against (inaudible) in 2024. Now let me take a step back to remind everyone that Takeda is an industry leader with more than 70 years of experience working in rare diseases and hematology. We remain deeply committed to researching and developing life-transforming medicines many of which will treat patients with rare diseases in our core therapeutic areas of neuroscience, GI and inflammation.

正如我所提到的，TAK279 正在招募患者參加 2 項 III 期乾癬試驗。由於銀屑病試驗歷來缺乏有色人種患者的代表，因此我們正在積極採取措施實施 TAK279 LATITUDE 銀屑病計劃，以反映前所未有的患者多樣性。 TAK279 是一種潛在的同類最佳的牛皮癬口服療法，我們將在 2024 年開始針對（聽不清）的 III 期頭對頭試驗。現在讓我退一步提醒大家，武田是行業領導者在罕見疾病和血液學領域擁有70 多年的工作經驗。我們仍然堅定地致力於研究和開發改變生命的藥物，其中許多藥物將治療神經科學、胃腸道和發炎等核心治療領域的罕見疾病患者。

Moreover, our plasma-derived therapies organization continues to pursue transformational therapies in rare diseases while our oncology team remains focused on cancers with high unmet medical needs across a range of patient populations. Now in keeping with our emphasis on collaboration, we will continue to partner with the health care providers and communities who support these patients while also exploring late-stage business development opportunities like the Protagonist partnership announced just recently, leveraging our deep commercial expertise to bring transformative therapies to patients with rare diseases.

此外，我們的血漿衍生療法組織繼續尋求罕見疾病的轉化療法，而我們的腫瘤學團隊仍然專注於一系列患者群體中醫療需求未被滿足的癌症。現在，為了與我們對合作的重視保持一致，我們將繼續與支持這​​些患者的醫療保健提供者和社區合作，同時探索後期業務發展機會，例如最近宣布的主角合作夥伴關係，利用我們深厚的商業專業知識來帶來變革罕見疾病患者的治療。

And finally, Takeda continuously prioritizes our portfolio to direct resources to our most promising therapies. For example, we have decided to discontinue development of modakafusp alfa. This is a strategic decision based on a number of factors, including the existing data set, the rapidly evolving multiple myeloma treatment landscape and the long development time lines.

最後，武田不斷優先考慮我們的產品組合，將資源引導到我們最有前景的療法上。例如，我們決定停止開發 modakafusp alfa。這是一項基於多種因素的策略決策，包括現有的數據集、快速發展的多發性骨髓瘤治療格局以及漫長的開發時間線。

Takeda remains committed to oncology and will continue to develop therapies across hematologic and solid tumors. Next slide, please. We are rapidly advancing our exciting mid-stage pipeline and anticipate that a number of these programs will progress to Phase III pivotal development in the coming year. Orexin agonists have the potential to be the first agent to address the underlying cause of narcolepsy type 1, offering the potential for functional cures.

武田仍然致力於腫瘤學，並將繼續開發血液腫瘤和實體腫瘤的治療方法。請下一張投影片。我們正在快速推進令人興奮的中期研發項目，並預計其中許多項目將在來年進入第三階段的關鍵開發。食慾素激動劑有可能成為第一個解決 1 型發作性睡病根本原因的藥物，並提供功能性治癒的潛力。

TAK-861, our lead orexin agonist completed enrollment well ahead of schedule in 2 Phase IIb trials that began in January 2023. Combined, the TAK-861 narcolepsy type 1 and type 2 trials have enrolled approximately 180 patients. Nearly all who completed the trial enrolled in the long-term extension study. These Phase II studies in the long-term extension study will help inform the TAK-861 Phase III program. As a reminder, TAK-861 is a more potent agent that may provide efficacy at a much lower dose than our previously tested oral orexin agonist, significantly reducing the potential for adverse effects, including liver toxicity, which tends to be dose-related.

TAK-861 是我們的主要食慾素激動劑，在2023 年1 月開始的2 項IIb 期試驗中提前完成了入組。TAK-861 發作性睡病1 型和2 型試驗合計已入組約180名患者。幾乎所有完成試驗的人都參加了長期擴展研究。長期擴展研究中的這些 II 期研究將有助於為 TAK-861 III 期計劃提供資訊。提醒一下，TAK-861 是一種更有效的藥物，與我們先前測試的口服食慾素激動劑相比，它可以以低得多的劑量發揮功效，從而顯著降低潛在的不良反應，包括肝毒性，而肝毒性往往與劑量相關。

Multiple external reviews by the data safety monitoring committee confirmed that no liver toxicity signals have appeared in TAK-861 Phase II trials. We are on track to make a final go/no-go decision to advance TAK-861 to Phase III in narcolepsy this fiscal year, and we are planning the Phase III program at risk to maintain momentum. Mezagitamab, our fully humanized anti-CD38 monoclonal antibody that is being studied across several rare autoimmune inflammatory diseases.

資料安全監測委員會的多次外部審查證實，TAK-861 II 期試驗中未出現肝毒性訊號。我們預計在本財年做出最終的通過/不通過決定，將 TAK-861 推進到發作性睡病治療的 III 期，並且我們正在計劃面臨風險的 III 期項目以保持勢頭。 Mezagitamab 是我們的全人源化抗 CD38 單株抗體，正在針對幾種罕見的自體免疫發炎疾病進行研究。

It works by depleting plasma cells and plasma blasts resulting in a number of beneficial immunomodulatory effects. We are excited by mezagitamab's mechanism of action, and we look forward to presenting data in ITP and IgA nephropathy at medical conferences later this year. Next slide, please. As you can see, the third quarter was a productive quarter with 2 NME approvals for adzynma and fruzaqla. Important indication expansions for takhzyro, HYQVIA and GAMMAGARD and positive Phase III data for maralixibat in Japan, for which we will seek approval later this year.

它的作用是消耗漿細胞和漿母細胞，產生許多有益的免疫調節作用。我們對 mezagitamab 的作用機制感到興奮，我們期待在今年稍後的醫學會議上展示 ITP 和 IgA 腎病的數據。請下一張投影片。正如您所看到的，第三季度是一個富有成效的季度，adzynma 和 fruzaqla 獲得了 2 項 NME 批准。 takhzyro、HYQVIA 和 GAMMAGARD 的重要適應症擴展以及 maralixibat 在日本的積極 III 期數據，我們將在今年稍後尋求批准。

Takeda has generated considerable pipeline momentum in fiscal year 2023. And as you'll see next, there's much more to come in fiscal year 2024. Next slide, please. In the coming months, we anticipate several meaningful potential approvals and Phase III readouts. These include life cycle expansion opportunities for ENTYVIO subcu for Crohn's disease, potential Iclusig approval for first-line Philadelphia-positive acute lymphoblastic leukemia in the United States, and the potential approval for TAK-721 in the U.S. for eosinophilic esophagitis.

武田在 2023 財年已經產生了相當大的研發勢頭。正如您接下來將看到的，2024 財年還將有更多成果。請看下一張投影片。在接下來的幾個月中，我們預計會有一些有意義的潛在批准和第三階段的結果。其中包括治療克羅恩病的ENTYVIO subcu 的生命週期擴展機會、Iclusig 在美國可能批准用於一線費城陽性急性淋巴細胞白血病的治療，以及TAK-721 在美國可能批准用於治療嗜酸性粒細胞性食道炎的治療。

In addition, there will be 2 Phase III readouts for soticlestat in Dravet syndrome and Lennox-Gastaut Syndrome, 2 rare pediatric epilepsies, which may allow for filing in 2024. As I mentioned earlier, our teams remain laser-focused on developing TAK279 in the first 4 major indications while exploring development in others. Our pipeline is maturing. With 5 new molecular entities in Phase III development, awaiting first approvals. In addition to these 5 global Phase III NME programs, we have prioritized a group of registration-enabling regional development programs outside of the United States.

此外，還將有2 個關於soticlestat 治療Dravet 綜合徵和Lennox-Gastaut 綜合徵（兩種罕見兒童癲癇病）的III 期結果，可能會在2024 年提交申請。正如我之前提到的，我們的團隊仍專注於在該領域開發TAK279。前 4 個主要適應症，同時探索其他適應症的發展。我們的管道正在成熟。 5 個新分子實體處於 III 期開發，等待首次批准。除了這 5 個全球 III 期 NME 項目外，我們還優先考慮了美國以外的一組允許註冊的區域開發項目。

Key data readouts in our exciting -- exciting mid-stage pipeline and targeted business development opportunities will continue to add to our maturing late-stage portfolio. We look forward to important mid-stage milestones in the development of our Orexin franchise like the Phase IIb study readouts of TAK-861, and the Phase I start for our next-generation oral orexin agonist TAP360.

我們令人興奮的中期管道和有針對性的業務發展機會中的關鍵數據讀數將繼續添加到我們日漸成熟的後期投資組合中。我們期待我們的 Orexin 特許經營權發展中的重要中期里程碑，例如 TAK-861 的 IIb 期研究結果，以及我們下一代口服食慾素激動劑 TAP360 的 I 期研究開始。

And as mentioned, mezagitamab's coming ITP and IgA nephropathy data will allow us to make a data-driven go-no-go decision to Phase III. Across our pipeline, we will continue leveraging data, digital and technology to develop programs faster and increase our probability of success. Now for example, we started Phase IIb trials of TAK-861 within 2 weeks of completing Phase Ib by planning at risk.

如前所述，mezagitamab 即將推出的 ITP 和 IgA 腎病數據將使我們能夠做出數據驅動的 III 期試驗決定。在我們的管道中，我們將繼續利用數據、數字和技術來更快地開發專案並增加成功的可能性。例如，我們在完成 Ib 期後兩週內就開始了 TAK-861 的 IIb 期試驗，並進行了風險規劃。

We also leveraged site selection tools trained with our deep site and investigator experience from previous orexin trials. For the TAK-861 Phase IIb studies, we use a proprietary in-house digital tool that provides real-time site performance data to analyze and manage enrollment, allowing us to complete the study 5 months ahead of plan. This tool specifically designed for clinical trial execution also helped us to improve site selection, screen patients and to provide real-time data review, data monitoring and data cleanup.

我們也利用了根據我們先前的食慾素試驗的深厚場地和研究者經驗而訓練的場地選擇工具。對於 TAK-861 IIb 期研究，我們使用專有的內部數位工具，提供即時站點效能數據來分析和管理註冊，使我們能夠比計劃提前 5 個月完成研究。這個專為臨床試驗執行而設計的工具還幫助我們改善地點選擇、篩選患者並提供即時數據審查、數據監控和數據清理。

We will continue utilizing digital tools and proprietary data to help us make critical decisions to advance and deliver our pipeline to patients. Given the strong momentum of our mid- to late-stage pipeline, Takeda plans to host an R&D event in fiscal year 2024 to provide an update on our strategy, present deep dives into our flagship programs and share more about our data, digital and technology efforts. Thank you very much. And now I will turn it over to Costa.

我們將繼續利用數位工具和專有數據來幫助我們做出關鍵決策，以推進並向患者提供我們的產品線。鑑於我們中後期產品線的強勁勢頭，武田計劃在 2024 財年舉辦一次研發活動，以提供我們戰略的最新信息，深入探討我們的旗艦項目，並分享更多有關我們的數據、數字和技術的信息努力。非常感謝。現在我將把它交給科斯塔。

Thank you, Andy, and hello, everyone. This is Costa Saroukos speaking. Today, I'll walk you through the financial highlights of our fiscal 2023 Q3 year-to-date results. Starting with the top line. revenue was JPY 3.2 trillion or USD 22.8 billion, which is flat versus prior year at constant exchange rate or 4.6% on an actual basis, including FX upside from the depreciation of the yen.

謝謝你，安迪，大家好。我是科斯塔·薩魯科斯。今天，我將向您介紹我們 2023 財年第三季迄今業績的財務亮點。從頂線開始。營收為 3.2 兆日圓（228 億美元），以固定匯率計算與上年持平，實際成長 4.6%，其中包括日圓貶值帶來的外匯上漲。

We have started to see significant erosion of VYVANSE since generics entered into the U.S. market in August 2023. But offsetting the VYVANSE decline was continued growth of our growth and launch products. These now represent 43% of total revenue and grew 12.7% at constant exchange rate.

自 2023 年 8 月仿製藥進入美國市場以來，我們開始看到 VYVANSE 受到嚴重侵蝕。但我們的成長和推出產品的持續成長抵消了 VYVANSE 的下滑。目前，這些收入佔總收入的 43%，以固定匯率計算成長了 12.7%。

Core operating profit was JPY 865.6 billion or USD 6.1 billion with a core operating profit margin of approximately 27%. Reporting operating profit was JPY 224.1 billion, reflecting the significant impact of noncash impairment losses and other noncore items that were primarily booked in Q2. Core EPS was JPY 412 and reported EPS was JPY 94.

核心營業利潤為 8,656 億日圓（61 億美元），核心營業利益率約 27%。報告營業利潤為 2,241 億日元，反映了主要在第二季入帳的非現金減損損失和其他非核心項目的重大影響。核心每股收益為 412 日元，報告每股收益為 94 日元。

Moving to cash flow. We continue to see strong cash generation from the business with operating cash flow of JPY 437.8 billion or $3.1 billion year-to-date. Free cash flow was JPY 36.3 billion, which reflects almost JPY 300 billion of cash out for acquisitions and in-licensing so far this fiscal year, including the bills for TAK279 and fruzaqla. We maintained a resilient financial base with 100% of outstanding debt at fixed interest rates.

轉向現金流。我們繼續看到該業務產生強勁的現金流，今年迄今的營運現金流為 4,378 億日圓（即 31 億美元）。自由現金流為 363 億日元，反映了本財年迄今為止用於收購和許可的近 3000 億日元現金支出，包括 TAK279 和 fruzaqla 的賬單。我們維持了富有彈性的財務基礎，100% 的未償債務均以固定利率支付。

And I'm pleased to share that our weighted average fixed interest rate has improved from approximately 2% to 1.6%, driven by debt paydown of USD 1.5 billion year-to-date. With regards to the outlook for full year fiscal 2023, we continue to track well towards our management guidance for performance at a constant exchange rate. There is no change to our full year management guidance and no change to our full year P&L forecast.

我很高興地告訴大家，在年初至今 15 億美元債務償還的推動下，我們的加權平均固定利率已從約 2% 提高至 1.6%。關於 2023 財年全年的展望，我們將繼續良好地追蹤我們的管理階層對以固定匯率計算的業績指引。我們的全年管理指引沒有變化，我們的全年損益預測也沒有變化。

However, it's important to note that there is potential upside to revenue and core operating profit if current FX rates continue. Also, I want to emphasize that we are not changing our full year free cash flow forecast of JPY 400 billion to JPY 500 billion with some working capital phasing that has impacted us year-to-date expected to unwind in Q4.

然而，值得注意的是，如果目前的匯率持續下去，收入和核心營業利潤可能會上漲。另外，我想強調的是，我們不會改變全年 4000 億日元至 5000 億日元的自由現金流預測，其中一些營運資本分階段對我們今年迄今的影響預計將在第四季度解除。

On Slide 16, let me run through our Q3 year-to-date financial performance in more detail. Starting with our core results. On the right-hand side, you can see that revenue was JPY 3.2 trillion with growth of 4.6%, all flat at constant exchange rate with our growth and launch products offsetting the significant loss of exclusivity impact. Core operating profit was JPY 865.6 billion, a decline of 9.3% on an actual basis or 12.7% on a constant exchange rate. This reflects the impact of generic competition for high-margin products such as VYVANSE, VELCADE, Dexilant and Azilva as well as lower COVID-19 vaccine revenue. Meanwhile, we have continued to make the necessary investments in R&D and data and technology to secure the long-term success of the business. Core net profit declined by 12.2% at constant exchange rate and core EPS was JPY 412.

在投影片 16 上，讓我更詳細地介紹一下我們今年第三季迄今的財務表現。從我們的核心成果開始。在右側，您可以看到收入為 3.2 兆日元，成長 4.6%，按固定匯率計算全部持平，我們的成長和推出產品抵消了排他性影響的重大損失。核心營業利潤為8,656億日元，實際下降9.3%，以固定匯率計算下降12.7%。這反映了 VYVANSE、VELCADE、Dexilant 和 Azilva 等高利潤產品仿製藥競爭以及 COVID-19 疫苗收入下降的影響。同時，我們繼續在研發、數據和技術方面進行必要的投資，以確保業務的長期成功。以固定匯率計算，核心淨利下降12.2%，核心每股收益為412日圓。

On the left-hand side of the slide, you can see our reported results. Reported revenue is the same as core revenue. Reported operating profit was significantly impacted by large noncore items that we booked in Q2. These are reflected in our reported operating profit results of JPY 224.1 billion or a year-on-year decline of 44.2%. Reported net profit and reported EPS declined approximately 49%, reflecting the decline in reported operating profit. Operating cash flow was JPY 437.8 billion, lower than prior year due to working capital phasing as well as the VYVANSE generic impact. Free cash flow reflected our cash payments for TAK-279 and fruzaqla, but there is no change to our full year forecast of JPY 400 billion to JPY 500 billion.

在投影片的左側，您可以看到我們報告的結果。報告收入與核心收入相同。報告的營業利潤受到我們在第二季度預訂的大型非核心項目的顯著影響。這些反映在我們報告的營業利潤結果中，營業利潤為 2,241 億日元，年減 44.2%。報告淨利潤和報告每股收益下降約 49%，反映出報告營業利潤的下降。由於營運資本分階段以及 VYVANSE 一般影響，營運現金流為 4,378 億日元，低於去年。自由現金流反映了我們對 TAK-279 和 fruzaqla 的現金支付，但我們對全年 4000 億日元至 5000 億日元的預測沒有變化。

On Slide 17, I would like to highlight the performance of our growth and launch products, which are the key drivers of top line performance. These products generated 43% of total revenue Q3 year-to-date with 12.7% growth at constant exchange rate. Within our 5 key business areas, GI grew at 4% at a constant exchange rate, a slowdown versus last year, impacted by generic entry of Dexilant in the U.S. in January 2023.

在投影片 17 上，我想強調我們的成長和推出產品的業績，這是營收業績的關鍵驅動因素。這些產品佔今年第三季總營收的 43%，以固定匯率計算成長 12.7%。在我們的 5 個關鍵業務領域中，受 2023 年 1 月 Dexilant 仿製藥進入美國的影響，GI 按固定匯率計算增長了 4%，較去年有所放緩。

Our largest product, ENTYVIO continues to perform well with growth of 7%, outperforming the overall IBD market, and initial feedback on the ENTYVIO (inaudible) subcutaneous launch has been positive. In rare diseases, Takhzyro continues its strong momentum with growth of 12%, having successfully launched in over 50 countries and with sustained demand in the U.S. Uptake of Livtencity continues to be strong, and I'm also happy to highlight the new launch of Adzynma, the first and only enzyme replacement therapy for cTTP. Although the cTTP indication is a niche commercial opportunity, this new approval is extremely meaningful for patients suffering from this disease. (inaudible) immunology continues to deliver outstanding growth of 16%, including 18% growth of immunoglobulin and 7% growth of albumin. Both our IG and albumin products continue to see strong demand.

我們最大的產品 ENTYVIO 繼續表現良好，成長了 7%，表現優於整個 IBD 市場，並且對 ENTYVIO（聽不清楚）皮下注射的初步回饋是正面的。在罕見疾病領域，Takhzyro 繼續保持強勁勢頭，增長 12%，已在 50 多個國家成功上市，並在美國保持持續需求。Livtencity 的吸收繼續強勁，我也很高興強調新推出的 Adzynma ，第一個也是唯一針對cTTP 的酵素替代療法。儘管cTTP適應症是一個利基商業機會，但這項新的批准對於患有這種疾病的患者來說極其有意義。 （聽不清楚）免疫學繼續實現 16% 的顯著增長，其中免疫球蛋白增長 18%，白蛋白增長 7%。我們的 IG 和白蛋白產品的需求持續強勁。

We have continued to expand our plasma donation center footprint with our global network now exceeding 250 centers. And we have seen donor compensation continue 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 our commitments to our patients.

我們繼續擴大血漿捐贈中心的覆蓋範圍，目前我們的全球網路已超過 250 個中心。我們看到捐款者報酬在疫情期間大幅增加後，自 2022 財年以來持續呈下降趨勢。我們現在以高度細分的方式調整薪酬，同時實現我們對病人的承諾。

Together with initiatives to improve efficiency across the PDT value chain, this has enabled us to improve PDT margins year-on-year in fiscal year '23 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 by the end of this fiscal year. Also, I would like to highlight another new product Fruzaqla, which launched in November 2023 in the U.S. for the treatment of patients with metastatic colorectal cancer. The launch is off to a strong start, having treated the first patient just 24 hours after the approval.

加上提高整個 PDT 價值鏈效率的舉措，這使我們能夠在 23 財年自疫情大流行以來首次同比提高 PDT 利潤率。其次是腫瘤學，由於 Velcade 仿製藥的出現，該領域的銷售額持續下降。然而，2022 年 5 月喪失獨家經營權的時間意味著影響應該會在本財年結束時消失。另外，我想重點介紹另一款新產品 Fruzaqla，該產品於 2023 年 11 月在美國上市，用於治療轉移性大腸直腸癌患者。此次上市有一個良好的開端，在批准後僅 24 小時就治療了第一位患者。

Neuroscience declined minus 6% as a result of VYVANSE generics launching in the U.S. after (inaudible) expiry in August. To date, brand share erosion of VYVANSE has been slightly molder than initially anticipated due to constraints of generic supply. We expect this situation to ease towards the end of this fiscal year, but it does mean we have slightly increased our full year assumption for VYVANSE revenue.

由於 VYVANSE 仿製藥在 8 月（聽不清楚）到期後在美國上市，神經科學下跌了 -6%。迄今為止，由於仿製藥供應的限制，VYVANSE 的品牌份額侵蝕程度比最初預期的要小一些。我們預計這種情況將在本財年末得到緩解，但這確實意味著我們略微提高了對 VYVANSE 全年收入的假設。

Finally, the other segment is declining due to lower revenue from COVID-19 vaccines and generic competition to Azilva in Japan. However, this other segment also includes our dengue vaccine, Qdenga, which is seeing strong initial demand in both endemic and travel markets. Over the next 3 slides, I'll walk you through some waterfalls to better explain the moving pieces in our Q3 year-to-date performance versus prior year.

最後，由於 COVID-19 疫苗的收入下降以及日本 Azilva 的仿製藥競爭，其他細分市場也在下降。然而，這個其他細分市場還包括我們的登革熱疫苗 Qdenga，該疫苗在流行病和旅遊市場的初始需求強勁。在接下來的 3 張幻燈片中，我將引導您瀏覽一些瀑布，以更好地解釋我們今年第三季迄今的業績與去年相比的變化。

Starting with revenue on Slide 18. You can see that versus prior year, our growth in launch products were the main reason we were able to maintain flat growth at constant exchange rates despite JPY 133.3 billion of loss of exclusivity headwinds as well as lower coronavirus vaccine revenue compared to prior year. On top of this, we had an FX tailwind due to the depreciation of the yen, taking our top line growth on an actual basis to 4.6%.

從幻燈片18 上的收入開始。您可以看到，與前一年相比，我們推出的產品的增長是我們能夠在固定匯率下保持平穩增長的主要原因，儘管我們面臨1,333 億日元的獨家經營權損失以及冠狀病毒疫苗銷售下降的不利因素收入與前一年相比。除此之外，由於日圓貶值，我們還獲得了外匯順風，使我們的實際收入成長達到 4.6%。

Moving to the year-on-year core operating profit bridge on Slide 19. Here, you can see how loss of exclusivity and the coronavirus vaccine decline are having a larger impact on profit compared to revenue due to the higher margins. On the investment side, we continue to allocate resources to R&D to support high potential programs such as TAK-279 and our Orexin franchise.

轉到幻燈片 19 上的同比核心營業利潤橋樑。在這裡，您可以看到由於利潤率較高，與收入相比，獨家經營權的喪失和冠狀病毒疫苗的下降對利潤的影響更大。在投資方面，我們繼續向研發分配資源，以支持 TAK-279 和我們的 Orexin 特許經營權等高潛力項目。

R&D spend increased 7.3% year-to-date on a constant exchange rate basis, but this does reflect some phasing. And we still aim to land the full year with a mid-single-digit increase. We also continue to make substantial investments 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 play an important role in our return to growth, and therefore, we continue to allocate capital in these areas. All these factors combined resulted in our first half core operating profit decline of 12.7% on a constant exchange rate basis or 9.3% decline when factoring in the benefit of FX.

以固定匯率計算，研發支出今年迄今成長了 7.3%，但這確實反映了一些階段性的變化。我們的目標仍然是全年實現中個位數成長。我們也持續對數據和技術進行大量投資，包括整個價值鏈的人工智慧。我們相信這些投資將對武田的長期競爭力產生變革性影響，並在我們恢復成長方面發揮重要作用，因此，我們繼續在這些領域配置資本。所有這些因素綜合起來，導致我們上半年的核心營業利潤以固定匯率計算下降了 12.7%，如果考慮到外匯收益，則下降了 9.3%。

I would also highlight that although the depreciation of the yen had a significant impact, upside impact on our revenue, the benefit to profit is less pronounced. This is because of our substantial overseas expenses. And in fact, the depreciation of the yen versus the euro is actually negative to profits due to our higher proportion of cost of goods in euro.

我還要強調的是，儘管日圓貶值對我們的收入產生了重大影響，產生了上行影響，但對利潤的好處卻不太明顯。這是因為我們大量的海外開支。事實上，由於我們以歐元計價的商品成本比例較高，日圓兌歐元貶值實際上對利潤產生負面影響。

Next is Slide 20, which explains the major items impacting our reported operating profit versus prior year. In addition to the decline in core operating profit, we had a sizable increase in impairment of intangible assets, which year-to-date totaled JPY 119.3 billion. Most of this was already booked in Q2 when we recognized impairments related to the negative Phase III study readout of Alofisel and the voluntary global withdrawal of Exkivity. In addition, we have higher restructuring costs this year related to exiting AAV gene therapy and consolidating our office footprint. All these items combined led to the reported operating profit decline of minus 44.2%.

接下來是投影片 20，它解釋了影響我們報告的營業利潤與前一年相比的主要項目。除了核心營業利潤下降外，我們的無形資產減損也大幅增加，年初至今總計達 1,193 億日圓。其中大部分已在第二季度預訂，當時我們認識到與 Alofisel 的負面 III 期研究結果和 Exkivity 的全球自願撤回相關的減值。此外，今年我們因退出 AAV 基因治療和鞏固我們的辦公室足跡而面臨更高的重組成本。所有這些項目加起來導致報告的營業利潤下降-44.2%。

Moving to Slide 21 and our outlook for full year fiscal 2023. Based on our year-to-date performance, we do not see the need to make any changes to our management guidance at this time. We still anticipate low single-digit percentage decline in revenue, low 10s percentage decline in core operating profit and low 20s percentage decline in core EPS, all on a constant exchange rate basis.

轉向幻燈片 21 和我們對 2023 財年全年的展望。根據我們今年迄今的業績，我們認為目前沒有必要對我們的管理指導進行任何改變。我們仍然預期收入將出現個位數百分比下降，核心營業利潤將下降 10 個百分點，核心每股收益下降將下降 20 個百分點，所有這些都是在固定匯率的基礎上進行的。

We are also keeping our reported and core forecast on an actual FX basis unchanged. There is some potential upside to revenue and core operating profit if current FX rates continue, and we've included a currency sensitivity chart on Slide A19 in the appendix for your reference. Our free cash flow forecast is unchanged at JPY 400 billion to JPY 500 billion with some of the working capital phasing I mentioned earlier, expected to unwind in Q4, and we remain committed to paying the fiscal year '23 dividend of JPY 188.

我們也保持基於實際匯率的報告和核心預測不變。如果目前的匯率持續下去，收入和核心營業利潤可能會出現一些上漲，我們在附錄中的投影片 A19 上提供了貨幣敏感度圖表，供您參考。我們的自由現金流預測保持在4000 億日元至5000 億日元不變，其中我之前提到的部分營運資金預計將在第四季度解除，並且我們仍然致力於支付23 財年188 日元的股息。

On Slide 22, we show our updated debt maturity ladder. By the end of December, we had prepaid all of the USD 1.5 billion of bonds maturing this fiscal year, which brought our weighted average interest rate down to 1.6%.

在投影片 22 上，我們展示了更新後的債務到期階梯。截至12月底，我們已經預付了本財政年度到期的全部15億美元債券，加權平均利率降至1.6%。

As a reminder, 100% of our debt is at fixed rates with an average maturity of approximately 8 years. I would also highlight that our repayment obligations in fiscal year '24 and fiscal year '25 are minimal which means we have flexibility in how we allocate cash over the next couple of years, including potentially prepaying some of the fiscal year '26 maturities.

提醒一下，我們 100% 的債務都是固定利率，平均期限約為 8 年。我還要強調的是，我們在24 財年和25 財年的還款義務很小，這意味著我們在未來幾年如何分配現金方面具有靈活性，包括可能預付26 財年的部分到期款項。

To close out on the presentation on Slide 23, I'd like to reemphasize that we are well on track towards our full year management guidance. We have been preparing for the loss of exclusivity headwinds we faced in fiscal year 2023 for many years. We have confidence in our portfolio and pipeline to deliver our 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. I'd like to now hand it back to Christophe. Thank you.

為了結束投影片 23 的演示，我想再次強調，我們正在順利實現全年管理指導。多年來，我們一直在為 2023 財年面臨的失去獨家經營權的不利因素做好準備。我們對我們的投資組合和管道在短期內實現成長回報充滿信心，我們將繼續嚴格分配資本，專注於實現可持續成長和有競爭力的股東回報。我現在想把它還給克里斯托夫。謝謝。

Thank you, Costa. As you might have seen earlier today, we announced that after 20 years working abroad, Costa has decided to return home to Australia to be closer to his family. He will step down as the Chief Financial Officer on April 1 and remain with the company as a Board Director until June 28, 2024. Milano Furuta who is currently President of Takeda Japan Pharma Business Unit will succeed Costa as CFO, effective April 1, 2024. Costa joined Takeda in 2015 as the CFO of the [U-Can] business unit, and he was appointed global CFO in April 2018 at the time of Takeda proposed acquisition of Shire.

謝謝你，科斯塔。正如您今天早些時候可能已經看到的那樣，我們宣布，在國外工作 20 年後，科斯塔決定返回澳大利亞，以便與家人更親近。他將於4 月1 日辭去首席財務官職務，並繼續擔任公司董事，直至2024 年6 月28 日。現任武田日本製藥業務部總裁的Milano Furuta 將接替Costa 擔任首席財務官，自2024 年4 月1 日起生效Costa於2015年加入武田，擔任[U-Can]業務部門的首席財務官，並於2018年4月武田擬收購Shire時被任命為全球首席財務官。

Since then, he has been instrumental in Takeda's transformation into a global biopharmaceutical company and is handing over an exceptional finance organization. Costa has been a trusted colleague to me, the (inaudible) and the Board, and I wish him all the best as he returns to his home country. I'm very pleased that Milano Furuta will succeed Costa as Global CFO, to continue to drive our strategy forward and deliver growth and shareholder return. Milano is a long-time Takeda colleague with a deep understanding of Takeda's business and culture.

從那時起，他在武田向全球生物製藥公司轉型的過程中發揮了重要作用，並移交了一個卓越的財務組織。科斯塔一直是我、（聽不清楚）和董事會值得信賴的同事，我祝他在返回祖國後一切順利。我很高興 Milano Furuta 將接替 Costa 擔任全球財務官，並繼續推動我們的策略向前發展，實現成長和股東回報。 Milano 是武田的長期同事，對武田的業務和文化有著深刻的了解。

He has held a number of leadership role at Takeda around the world. Prior to joining Takeda in 2010, Milano worked as an equity research analyst at an investment management firm in the United States. He began his career in 2019 in banking and private equity investment in Japan, where he was involved with several type of financial transactions, including leverage buyout and debt restructuring.

他曾在武田全球各地擔任過多個領導職務。在 2010 年加入武田之前，Milano 曾在美國一家投資管理公司擔任股票研究分析師。他於 2019 年在日本的銀行和私募股權投資領域開始了自己的職業生涯，參與了多種類型的金融交易，包括槓桿收購和債務重組。

Prior to becoming President of the Japan Pharma Business Unit, Milano served for 2 years as Corporate Strategy Officer and Chief of Staff. He has been a member of the Takeda executive team for the last 5 years. I would like to invite Costa and Milano to say a few words. Costa, would you like to go first.

在成為日本製藥業務部總裁之前，Milano 曾擔任兩年企業策略長和幕僚長。過去 5 年他一直是武田管理團隊的成員。我想請科斯塔和米蘭說幾句話。科斯塔，你想先走嗎？

Thank you, Christophe, for the kind words. It's been an incredible journey and a true privilege to work at Takeda for the best part of a decade, in particular, the past 6 years as the Global CFO. It's been a point of pride to come to work every day at a company with a deeply rooted values-based culture and with colleagues who really put patients at the center of everything we do. I'm immensely proud of what we've accomplished through a period of unprecedented transformation and growth for Takeda.

謝謝克里斯托夫的客氣話。這是一段令人難以置信的旅程，在武田工作了十年的大部分時間，特別是在過去擔任全球財務長的六年裡，我感到非常榮幸。每天來到一家有著根深蒂固的價值觀文化的公司工作，並與真正將患者置於一切工作中心的同事一起工作，是一件令人自豪的事情。我對武田在前所未有的轉型和成長時期所取得的成就感到非常自豪。

But as Christophe said, after 20 years working abroad, I'm ready to move back to Australia to be closer to my family. Until the end of March, my focus will be on delivering our management guidance for fiscal year 2023 and ensuring we are set up for success in fiscal year 2024. I will also be working closely with Milano on the transition. I would truly like to thank you all for your support and friendship, and I wish Takeda and you all the best. I'll pass it now over to Milano for a few words. Thank you all.

但正如 Christophe 所說，在國外工作 20 年後，我準備搬回澳大利亞，離家人更近一些。在 3 月底之前，我的重點將是提供 2023 財年的管理指導，並確保我們為 2024 財年的成功做好準備。我還將與 Milano 就過渡事宜密切合作。我衷心感謝大家的支持和友誼，並祝福武田和你們一切順利。我現在將其轉交給米蘭幾句話。謝謝你們。

Thank you, Christophe, and thank you, Costa. Hi, everyone. My name is Milano. And I have -- I have been -- first of all, I would like to congratulate (inaudible) for all the great achievement he has been delivered in the past 6 years. And I'm really (inaudible) to be the part of the financial organization and in the future, leading the finance organization. And then looking forward to meeting you -- many of you after April. And I have been -- as Christophe said, I have been as a member of the Takeda executive team members for the past 5 years, and I'm fully aligned with Takeda's strategy, especially for the investment, for the growth and the shareholder returns.

謝謝你，克里斯托夫，謝謝你，科斯塔。大家好。我的名字是米蘭。我──我一直──首先，我要祝賀（聽不清楚）他在過去六年中所取得的所有偉大成就。我真的（聽不清楚）是金融組織的一部分，並在未來領導金融組織。然後期待與你們見面——你們中的許多人在四月之後。正如 Christophe 所說，過去 5 年我一直是武田高階主管團隊的一員，我完全贊同武田的策略，特別是投資、成長和股東回報。

But after April 1, I'm very much looking forward to meeting you all and then listen and discover the new chapter. Thank you.

但 4 月 1 日之後，我非常期待與大家見面，然後聆聽並發現新的篇章。謝謝。

[Interpreted] Now we would like to entertain questions from the participants. Christophe and Costa, Milano will be answering. In addition, U.S. President, Julie Kim will be participating. (Operator Instructions). First question from Citigroup.

[解讀]現在我們回答與會嘉賓的提問。米蘭的克里斯托夫和科斯塔將予以答覆。此外，美國總統朱莉·金也將參加。 （操作員說明）。花旗集團的第一個問題。

This is Yamaguchi from Citi. I'll have to make briefly 2 questions. The first question is regarding Entyvio. Is it true that the Entyvio sales in the dollar term is growing a bit compared to Q-on-Q. But at the same time, (inaudible) still sort of high single-digit growth. So can you give us some current situation, how the new patient situation is? And also you talk about SG, but can you give us some penetration ratio basically -- sorry, if you have so first one is regarding Entyvio.

我是花旗銀行的山口。我必須簡短地提出兩個問題。第一個問題是關於 Entyvio 的。與上一季相比，以美元計算的 Entyvio 銷售額確實有所增長嗎？但同時，（聽不清楚）仍保持較高的個位數成長。那麼可以為我們介紹一下目前的情況嗎？新的患者狀況如何？您還談到了 SG，但是您能給我們一些基本的滲透率嗎？抱歉，如果您有的話，第一個是關於 Entyvio 的。

The second one is the direction (inaudible) timing. You talk about this discovery meaning by the end of March. I thought it looks a little bit expedited, but I thought it was April to June. So is it fair to say that you are going to decide by March, then how are you going to share some data with us after this decision? And if this decision will be public announced because it's going to be interesting -- the data. And that's the second question. So timing and why it is expedited I think -- if it is expedited, and there's 2 questions.

第二個是方向（聽不清楚）時機。您將在三月底談論這項發現的意義。我覺得看起來有點快，但我以為是四月到六月。那麼可以公平地說，你們將在三月做出決定，那麼在做出決定後你們將如何與我們分享一些數據呢？如果這個決定會被公開宣布，因為它會很有趣——數據。這是第二個問題。因此，我認為時間安排以及為什麼要加急——如果加急，就會有兩個問題。

Great. Thank you, Yamaguchi-san. So the first question on ENTYVIO in terms of the market evolution and uptake of the ENTYVIO pen. I'd like to ask Julie to comment on that. And then the second question on Orexin timing and the communications around that. I'd like to ask Andy to comment on that one.

偉大的。謝謝你，山口先生。關於ENTYVIO 的第一個問題是市場演變和ENTYVIO 筆的採用情況。我想請朱莉對此發表評論。然後是關於食慾素時間安排和圍繞該問題的溝通的第二個問題。我想請安迪對此發表評論。

Thank you, Yamaguchi-san for the question. In regards to ENTYVIO, let me talk a little bit about overall our position as well as subcu. So from an overall perspective and in terms of new patient starts, as Christophe mentioned, we still remain the market leader in terms of IBD bio-naive new patient starts.

謝謝山口先生的提問。關於ENTYVIO，讓我談談我們的整體立場以及subcu。因此，從整體角度來看，正如 Christophe 所提到的，就新患者啟動情況而言，我們仍然是 IBD 生物新患者啟動的市場領導者。

And particularly in UC, I'm pleased to share that our share grew by 1.1% in UC over the last 12 months and that's the significant growth within that indication. So when you look at the start of Entyvio pen in the U.S., please remember that new patients have to be have an induction period on IV first.

特別是在 UC 領域，我很高興地告訴大家，在過去 12 個月裡，我們在 UC 領域的份額增加了 1.1%，這是該指標中的顯著增長。因此，當您看到 Entyvio 注射筆在美國上市時，請記住，新患者必須先經歷靜脈注射誘導期。

So at this point, it's very early to say what the patient uptake has been on ENTYVIO pen. But as Christophe mentioned, we're very -- we're very pleased with the information to date in terms of the awareness of pen amongst our HCPs, our target HCPs, and I'm also happy to share that we've recently signed an agreement with one of the big 3 national PBMs as well as signing agreements with 5 regional plans as well. So very pleased with the direction of progress, and we hope to share more detailed information on patient uptake with the pen at a future call.

因此，目前判斷患者對 ENTYVIO 注射筆的使用還為時過早。但正如 Christophe 所提到的，我們對迄今為止在我們的 HCP、我們的目標 HCP 中筆意識方面的信息非常滿意，我也很高興分享我們最近簽署的協議與三大國家PBM 之一簽署協議，並與5 個地區計劃簽署協議。對進展方向非常滿意，我們希望在未來的電話會議上分享有關患者使用筆的更多詳細資訊。

Yamaguchi san, it's Andy. So good evening. You're correct that the orexin program has accelerated. So you remember, we started the 2 Phase IIb studies for TAK-861 in type 1 narcolepsy and type 2 narcolepsy in January of last year on the heels of finishing our Phase I program in just December. So we had accelerated the start of that study. Our expectation was that, that study would take about 18 months to fully enroll and complete and we ended up completing it in under 12 months.

山口先生，我是安迪。晚安.你說得對，食慾素程序已經加速了。所以你還記得，去年 1 月完成 I 期計畫後，我們在去年 1 月開始了 TAK-861 治療 1 型發作性睡病和 2 型發作性睡病的 2 項 IIb 期研究。所以我們加快了這項研究的啟動。我們的預期是，研究需要大約 18 個月的時間才能完全註冊並完成，而我們最終在 12 個月內完成了它。

So that study, both studies, the type 1 and type 2 narcolepsy studies have completed enrollment, and we're waiting to see data. And correct, we'll be making a decision this fiscal year before March to move forward with the Phase III program. We're planning the Phase III program at risk because of our enthusiasm. The excitement -- the ability to roll the study quickly stems from probably a number of different factors. One is the excitement that patients and investigators have over this mechanism. The second is our experience now in narcolepsy. And the third, as I mentioned, are our new tools that we're leveraging to accelerate our clinical trial. So we're very excited to move that forward. In terms of when and how data will be presented, we're still working through that internally.

因此，這項研究、1 型和 2 型發作性睡病研究均已完成入組，我們正在等待查看數據。正確的是，我們將在本財年三月前做出決定，以推進第三階段計畫。由於我們的熱情，我們正冒著風險規劃第三階段專案。令人興奮的是，能夠快速進行研究可能源自於許多不同的因素。一是患者和研究人員對這種機制感到興奮。第二個是我們現在在發作性睡病的經驗。正如我所提到的，第三個是我們用來加速臨床試驗的新工具。因此，我們非常高興能夠推動這項進程。至於何時以及如何呈現數據，我們仍在內部解決這個問題。

So the next question will be from Seiji Wakao from JPMorgan. Wakao-san. Please go ahead.

下一個問題將由摩根大通的 Seiji Wakao 提出。若尾桑。請繼續。

I have 2 questions. First, about safety profile, 861. So I understand that there has been no (inaudible) or vision progress with 861. On the other hand, you have committed our conference -- our conference that 861 need to be checked for (inaudible) risk. I'd like to understand more on this point. Should we be cautious about the (inaudible) risk of 861, or is it not of a big issue? This is a first. And second is the gross margin on the 3 months of the third quarter. Third quarter gross margin seems to be declined compared to second quarter. Could you please explain this? And is this (inaudible)? And how should we consider the gross margin in the fourth quarter? This is second question.

我有 2 個問題。首先，關於安全概況，861。所以我知道861 沒有（聽不清）或願景方面的進展。另一方面，你已經在我們的會議上承諾了——我們的會議需要檢查861 的（聽不清）風險。我想在這一點上了解更多。我們是否應該對 861 的（聽不清楚）風險保持謹慎，或者這不是一個大問題？這是第一次。其次是第三季三個月的毛利率。第三季的毛利率比第二季似乎有所下降。您能解釋一下嗎？這是（聽不清楚）嗎？那我們該如何看待第四季的毛利率呢？這是第二個問題。

Great. Thank you, Wakao san. So the first question on TAK-861, safety on the hepatotoxicity, the visual side effects but also specifically on CV risk. I'd like to ask Andy to comment on that. And then the second question on gross margin. In Q3, the reasons for the gross margin decline and also the outlook for Q4. I'd like to ask Costa to comment on that.

偉大的。謝謝你，若尾桑。所以關於 TAK-861 的第一個問題是，肝毒性、視覺副作用以及心血管風險的安全性。我想請安迪對此發表評論。然後是關於毛利率的第二個問題。第三季毛利率下降的原因以及第四季的展望。我想請科斯塔對此發表評論。

Thanks, Chris. Thanks, Wakao-san. So in order to fully understand the safety profile of TAK-861, we need to look at the full data set. What I can say is that based on the blinded data, we don't see any evidence of visual disturbances. Based on the blinded data and the data safety monitoring board looking at unblinded data, we don't see any evidence of liver toxicity.

謝謝，克里斯。謝謝若尾桑。因此，為了充分了解 TAK-861 的安全性，我們需要查看完整的資料集。我能說的是，根據盲法數據，我們沒有看到任何視覺障礙的證據。根據盲法數據和數據安全監測委員會查看的非盲法數據，我們沒有看到任何肝毒性的證據。

And in terms of cardiovascular risk, it's something that we have a deep understanding of, and at this point, don't have concerns that that's going to be a significant issue for this program.

就心血管風險而言，我們對此有深入的了解，目前並不擔心這將成為該計劃的一個重要問題。

Thank you, Wakao-san for your question. Typically, we prefer to look at year-to-date because of fluctuations and phasing on a quarter-by-quarter basis. So year-to-date, the gross profit margin has declined from a reported basis by 2.1%. It's on target to our internal forecast -- is predominantly driven by the loss of exclusivity headwinds. We have a higher loss of exclusivity margins for products like VYVANSE, Velcade, Azilva, and less revenue for COVID vaccines.

謝謝若尾同學的提問。通常，我們更願意關注年初至今的情況，因為每個季度都會出現波動和階段性變化。因此，今年迄今為止，毛利率較報告基礎下降了 2.1%。它符合我們的內部預測目標——主要是由排他性喪失的不利因素推動的。我們的 VYVANSE、Velcade、Azilva 等產品的獨家利潤損失更大，而新冠疫苗的收入則更少。

The growth in launch products, although they're growing quite considerably at 12.7%. They're still not at the level to offset the loss of exclusivity headwinds. But overall, the 2.1% decline versus prior year is on track to our internal forecast and externally. Thank you.

發布產品的成長，儘管成長相當可觀，達到 12.7%。它們仍然沒有達到抵消排他性損失的逆風的水平。但總體而言，與前一年相比下降 2.1% 符合我們的內部和外部預測。謝謝。

Okay. The next question, we'd like to take from Mike Nedelcovych from Cowen.

好的。下一個問題是來自考恩 (Cowen) 的 Mike Nedelcovych。

I have 2. The first is broadly on the oncology segment. You've had some wins and some setbacks in this area. But I think it's fair to say that this segment lacks what could be considered a flagship product or pipeline candidate. Would you disagree with that statement? And what oncology asset do you think deserves more attention than it perhaps receives.

我有兩個。第一個主要是關於腫瘤學領域。您在這方面取得了一些勝利，也經歷了一些挫折。但我認為可以公平地說，這個細分市場缺乏可以被視為旗艦產品或候選產品的產品。您不同意這種說法嗎？您認為哪些腫瘤學資產值得更多關注？

And then my second question is on Qdenga. You've made impressive progress so far. How should we think about the path from here to potential USD 2 billion in peak sales. Will growth come in big boluses as government contracts are signed? Or will it be more linear and gradual.

我的第二個問題是關於 Qdenga 的。到目前為止，您已經取得了令人印象深刻的進步。我們應該如何思考從現在到潛在 20 億美元銷售額高峰的路徑。隨著政府合約的簽署，經濟成長會大幅成長嗎？或會更加線性和漸進。

Great. Thank you, Mike. So the question on Qdenga, I'd like to ask Christophe to take that one. And on the oncology, the portfolio and the pipeline, perhaps Christophe can comment on that, and then Andy can follow up with some pipeline comments.

偉大的。謝謝你，麥克。關於 Qdenga 的問題，我想請 Christophe 回答這個問題。關於腫瘤學、投資組合和管道，也許克里斯托夫可以對此發表評論，然後安迪可以跟進一些管道評論。

Thank you, Michael. I think, it's a combination actually because of the private markets. So when you introduce the vaccines in the private market, that's -- that's a bit more linear. So it's -- we can modelize or takeoff. But the big volume is more a national immunization program. And that's more nonlinear, if you like, because certainly, if a country like Brazil, for example, want to introduce a very vast immunization program, obviously, you have, you will have a sort of a big jump when that happens. So that's why it's not obviously quite difficult to actually forecast long term this type of vaccines.

謝謝你，麥可。我認為，這實際上是由於私人市場的緣故。因此，當你在私人市場推出疫苗時，那就更加線性了。所以我們可以建模或起飛。但大卷更多的是國家免疫計劃。如果你願意的話，這更非線性，因為當然，如果像巴西這樣的國家想要引入一個非常龐大的免疫計劃，顯然，你已經做到了，當這種情況發生時，你將會有一個巨大的跳躍。因此，這就是為什麼實際預測此類疫苗的長期發展顯然並不困難。

Now the [1.6 billion to 2 billion] peak is really correlated to -- now to our ability to reach the [100 million dose] per annum production capability. We are not there yet, but we are very, very actively looking at expanding our own manufacturing capacity in our site in Singen in Germany, we have a current CMO, and we are in discussion with other potential partner to go to this 100 million dose as quickly as possible.

現在，[16 億至 20 億] 高峰確實與我們達到每年 [1 億劑] 生產能力的能力相關。我們還沒有做到這一點，但我們正在非常非常積極地考慮擴大我們在德國辛根工廠的生產能力，我們目前有一位首席營銷官，我們正在與其他潛在合作夥伴討論這一 1 億劑疫苗盡快。

As you know, the data has been even stronger than what we expected. The approval, the label also. And so frankly, today, the demand is greater than the supply of these vaccines. So we are very actively looking at expanding our manufacturing capacity. On the oncology, we had some wins. We had some setbacks. We want to be a leader in oncology. We are not there yet. So we are very much active on that. They are actually in our pipeline, there are less -- they are less advanced some other assets like 861 and 279 in Phase III, they're not there yet. But we have a couple of asset in our pipeline, which are very promising, perhaps Andy can say a few words about these assets.

如您所知，數據比我們預期的還要強勁。核准，標籤也。坦白說，今天這些疫苗的需求大於供應。因此，我們非常積極地尋求擴大我們的製造能力。在腫瘤學方面，我們取得了一些勝利。我們遇到了一些挫折。我們希望成為腫瘤學領域的領導者。我們還沒到那一步。所以我們對此非常積極。它們實際上已經在我們的管道中，數量較少——它們不如第三階段的 861 和 279 等其他資產先進，它們還沒有出現。但我們有一些資產正在醞釀中，非常有前途，也許安迪可以談談這些資產。

Yes. Thanks, Christophe. Thanks, Mike. And I'll mention that having worked in R&D for 25 years, in some ways, the most exciting therapeutic area. But also the most challenging that I've been involved in has been oncology. And we know that if we look at the investment in oncology in the venture world, if we look at the amount of NIH and academic research that's focused on oncology, there isn't an area where we spend more and where we understand more. And there also isn't an area where we face as many challenges.

是的。謝謝，克里斯托夫。謝謝，麥克。我要提到的是，我在研發領域工作了 25 年，從某種程度上來說，這是最令人興奮的治療領域。但我參與過的最具挑戰性的領域也是腫瘤學。我們知道，如果我們看看創投界對腫瘤學的投資，如果我們看看美國國立衛生研究院(NIH) 和專注於腫瘤學的學術研究的數量，就會發現沒有一個領域是我們花費更多、了解更多的領域。我們還沒有哪個領域面臨這麼多的挑戰。

The failure rates in oncology continued to be amongst the highest in the industry. So I don't think it's just us. I think this is the field. On the flip side, the opportunity to change patients' lives and the revenue potential is just immense. And so we're really committed to oncology. We're really excited about our pipeline. We still haven't had that breakthrough out.

腫瘤學的失敗率仍然是業界最高的。所以我認為不只是我們。我想這就是領域。另一方面，改變患者生活的機會和收入潛力是巨大的。因此，我們真正致力於腫瘤學。我們對我們的管道感到非常興奮。我們還沒有取得突破。

That -- but I think, as you know, it can happen very quickly. We have a handful of programs in mid-stage development right now. Subasumstat is the lead. We have 2 STING agonist. We have 2 T-cell engagers that came in through a company that we bought a few years ago that we had to help to create -- called Maverick Therapeutics.

但我認為，正如你所知，這可能會很快發生。我們現在有一些專案處於中期開發階段。 Subasumstat 是領先者。我們有 2 個 STING 激動劑。我們有 2 名 T 細胞參與者，他們是透過我們幾年前收購的一家公司進來的，這家公司是我們幫助創建的——Maverick Therapeutics。

And then we have a number of programs in early development, and we have our cell therapy engine. So we feel that we're making the right investments in oncology. And the key now is to leverage the excellence that we're building in development and just bring these programs to decisions. I'll mention that just Monday, we actually brought in a new oncology R&D, had [PK Moro], who's a real deep (inaudible), highly experienced across oncology and multiple modalities. So we're really looking forward to PK taking the reins and carrying our oncology efforts forward, Mike. Thank you.

然後我們有許多處於早期開發階段的項目，我們有我們的細胞治療引擎。因此，我們認為我們在腫瘤學方面的投資是正確的。現在的關鍵是利用我們在開發方面所取得的卓越成果，並將這些計劃付諸決策。我要提到的是，就在周一，我們實際上引入了一項新的腫瘤學研發，[PK Moro]，他在腫瘤學和多種模式方面非常深入（聽不清楚）、經驗豐富。因此，我們真的很期待 PK 掌管並推動我們的腫瘤學工作向前發展，麥克。謝謝。

Great. Thank you, Mike. Okay. So the next question, we're going to take from Shinichiro Muraoka from Morgan Stanley. Muraoka-san, please go ahead and ask your question.

偉大的。謝謝你，麥克。好的。下一個問題將由摩根士丹利的 Shinichiro Muraoka 提出。村岡先生，請繼續提問。

[Interpreted] This is Muraoka, Morgan Stanley. My first question is to Christophe. Next fiscal year and how do we look at this. Well, FX is positive right now. VYVANSE is not declining as fast and based on the situation, how do we look at the next year. Three months ago, you said next fiscal year was going to be tough. But 3 months have passed since then. Have you changed your mind about what would happen in the next fiscal year or not. That's my first question.

[解說]我是摩根士丹利的村岡。我的第一個問題是問克里斯托夫的。下一個財年以及我們如何看待這個問題。嗯，外匯現在是正面的。 VYVANSE 的下滑速度沒有那麼快，根據目前的情況，我們如何看待明年。三個月前，您曾說過下一個財年將會很艱難。但距離那時已經過去3個月了。您是否改變了對下一個財政年度會發生什麼的想法？這是我的第一個問題。

And my second question is about 279 pipeline. UC and CD high dose Phase IIb is going to start. And I want to know the pathway until filing or approval. After Phase IIb, Phase III will be conducted first, and then for UC and CD, you'll have separately? Or is there a pathway that would accelerate this process? Those are my questions.

我的第二個問題是關於279管道的。 UC 和 CD 高劑量 IIb 期即將開始。我想知道提交或批准之前的途徑。 IIb期之後，先進行III期，然後UC和CD，你們會分別進行嗎？或是有什麼途徑可以加速這個過程？這些都是我的問題。

The first question to Christophe on thoughts for next fiscal year, fiscal year 2024. Q2, you said it would be a tight year. Has anything changed over the past 3 months since your previous comments on FY 2024 outlook. And then the second question on TAK-279 on the path to submission in ulcerative colitis and Crohn's disease. Will we need to do a Phase III study in both those indications after the Phase IIb. So what is the path to submission in those indications? I'd like to ask Andy to take that question.

向 Christophe 提出的第一個問題是關於下一財年（即 2024 財年）的想法。第二季度，您說這將是緊張的一年。自從您之前對 2024 財年展望發表評論以來，過去 3 個月有什麼變化嗎？然後是關於 TAK-279 的第二個問題，關於潰瘍性結腸炎和克隆氏症的提交之路。在 IIb 期之後，我們是否需要對這兩個適應症進行 III 期研究？那麼這些適應症的提交途徑是什麼呢？我想請安迪回答這個問題。

Thank you, Chris. Thank you, Muraoka-san. Obviously, we'll give a precise guidance on next year on fiscal year '24 in May. But what we described earlier remain valid. It will be a tight year. It will be -- we can describe it as flattish year, flattish perhaps slightly positive or slightly negative. We need to see how VYVANSE is evolving still in the next 3 months. But it will be a flattish year, certainly in both revenue and core operating profit margin.

謝謝你，克里斯。謝謝你，村岡同學。顯然，我們將在 5 月的 24 財年給出明年的準確指導。但我們之前描述的仍然有效。這將是緊張的一年。這將是——我們可以將其描述為平淡的一年，平淡也許略有積極或略有消極。我們需要看看 VYVANSE 在未來 3 個月內將如何發展。但這將是平淡的一年，尤其是在收入和核心營業利潤率方面。

Because the way to see it is that the first semester will still be a declining semester because of the generic introduction of VYVANSE in August '23. So you see it will impact the first semester. On the other hand, the second semester, it will be on a like-for-like if you like. So there will be much less generic impact and headwinds in the second semester. That's why overall the year will be flattish, but we'll provide precise guidance in May. Thank you.

因為從表面上看，由於 23 年 8 月 VYVANSE 的通用引入，第一學期仍將是一個下降的學期。所以你看這會影響第一學期。另一方面，如果你願意的話，第二學期將會是類似的。因此，第二學期的一般影響和阻力將會少得多。這就是為什麼今年整體表現將持平，但我們將在 5 月提供精確的指導。謝謝。

And Muraoka-san, maybe I can dial up and walk you just briefly through the strategy for TAK-279. So first and foremost is to push forward in this continuum of psoriasis and psoriatic arthritis, where we have strong proof of concept. Our hope is that the psoriasis Phase III program, which is enrolling quite well, we can accelerate, bring that to market in the 25% to 27% range. Shortly thereafter, we'll start -- we're starting our Phase III studies in psoriatic arthritis, the Latitude program, shortly after approval in psoriasis, we're looking forward to approval in psoriatic arthritis.

Muraoka-san，也許我可以撥通電話並簡要介紹 TAK-279 的策略。因此，首先也是最重要的是推動銀屑病和銀屑病關節炎的連續發展，我們在這方面有強有力的概念證明。我們希望銀屑病 III 期計畫的入組情況相當好，我們可以加快步伐，將其推向市場，使其覆蓋率達到 25% 至 27%。此後不久，我們將開始——我們將開始銀屑病關節炎的 III 期研究，即 Latitude 項目，在銀屑病批准後不久，我們期待著銀屑病關節炎的批准。

And as we've discussed, this is a continuum of disease, and we strongly believe that TAK-279 will be a best-in-class. This year, we'll start a head-to-head in psoriasis against [ducavacitinib] to demonstrate that experimentally. So we're very excited about pushing that psoriasis psoriatic arthritis spectrum forward as rapidly as possible.

正如我們所討論的，這是一種疾病的連續體，我們堅信 TAK-279 將是同類最佳藥物。今年，我們將在銀屑病領域與 [ducavacitinib] 展開一場正面交鋒，以實驗證明這一點。因此，我們非常高興能夠盡快推動銀屑病和銀屑病關節炎譜系的發展。

For IBD, it may be getting a little bit ahead of ourselves to start to predict approval time lines. I think the first -- the first inflection for us is really demonstrating that a TYK2 inhibitor can be effective in Crohn's disease and ulcerative colitis. We believe strongly, based on the genetic data that exists based on the role that TYK2 plays in cytokine signaling based on robust animal model data, we really believe that with a higher dose, we can be efficacious. But it's incumbent on us to demonstrate that in clinical trials.

對於 IBD 來說，開始預測批准時間表可能有點超前了。我認為第一個——對我們來說第一個變化確實證明了 TYK2 抑制劑可以有效治療克羅恩病和潰瘍性結腸炎。我們堅信，基於 TYK2 在細胞激素訊號傳導中所發揮的作用（基於可靠的動物模型數據）所存在的遺傳數據，我們確實相信，使用更高的劑量，我們可以有效。但我們有責任在臨床試驗中證明這一點。

So first and foremost is getting the Phase IIb studies off the ground. The Crohn's study should start in the next couple of months. UC study shortly thereafter. And then if those studies are successful, we -- that's our plan. The acceleration path, unfortunately, IBD is somewhat of a long development track. The acceleration path is through excellence in clinical trial execution. And that's something, as I mentioned with 861, we feel we're really getting a handle on with the model that we have in place and with the digital and technology tools that we're starting to implement in our development programs. If everything goes well, I think we'll be looking at approvals in IBD by the end of this decade.

因此，首要任務是啟動 IIb 期研究。克羅恩病的研究應該在接下來的幾個月內開始。不久後就進入UC學習。然後，如果這些研究成功，這就是我們的計劃。不幸的是，IBD 的加速路徑有點漫長。加速路徑是透過卓越的臨床試驗執行。正如我在 861 中提到的，我們覺得我們確實已經掌握了現有的模型以及我們開始在開發計劃中實施的數位和技術工具。如果一切順利，我認為我們將在本十年末考慮 IBD 的批准。

So next question, moving on. I'd like to call on Hiroyuki Matsubara from Nomura. Matsubara san, please unmute and ask your question.

那麼下一個問題，繼續。我想請野村證券的松原博之 (Hiroyuki Matsubara) 發言。松原先生，請取消靜音並提問。

[Interpreted] first question about (inaudible), and switch back is developing nucleic acid and the efficacy seems better than (inaudible), what do you think of this? And the next-generation Orexin and the potential of the next generation and what's the difference between the next-generation compound and 861.

[解讀]第一個問題關於（聽不清楚），轉回來正在開發核酸，效果似乎比（聽不清楚）更好，您對此有何看法？還有下一代Orexin和下一代的潛力以及下一代化合物和861有什麼區別。

(inaudible) how we're seeing the competitive landscape evolving, including both switchback from orladeyo, but also next line of therapies coming through. I'd like to ask Julie perhaps to comment on that. And then the next question on the next-generation Orexin agonist, how are we positioning that vis-a-vis TAK-861, I'd like Andy to comment on that.

（聽不清楚）我們如何看待競爭格局的演變，包括從奧拉德約的折返，以及即將推出的下一系列療法。我想請朱莉對此發表評論。然後關於下一代 Orexin 激動劑的下一個問題是，我們如何定位 TAK-861，我希望 Andy 對此發表評論。

Matsubara-san, for the question. In regards to takhzyro, when you look at the patient switching from takhzyro. We have seen patients switch back to takhzyro. Again, takhzyro has very strong efficacy and safety data proven over multiple years. And so that has been the reason why patients switch back to takhzyro from Orladeyo, the convenience of the oral does not trump the stronger efficacy that takhzyro presents.

松原先生，請教這個問題。關於 takhzyro，當你看到病人從 takhzyro 切換過來。我們已經看到患者重新使用 takhzyro。同樣，takhzyro 擁有經過多年證明的非常強的功效和安全性數據。這就是病人從 Orladeyo 轉回 takhzyro 的原因，口服的便利性並不能勝過 takhzyro 所呈現的更強功效。

In regards to new entrants, you were mentioning, in particular, garadacimab. What we've seen from the data that's been shared thus far, it does seem to have efficacy that is similar to takhzyro. But again, we believe that with takhzyro's strong position in the marketplace. We have market share leadership, particularly in the prophylaxis segment of HAE. That -- that long performance in terms of efficacy and safety is a benefit for takhzyro.

關於新進者，您特別提到了加拉達西單抗。從迄今為止共享的數據來看，它似乎確實具有與 takhzyro 類似的功效。但我們再次相信 takhzyro 在市場上的強大地位。我們擁有市佔率領先地位，特別是在 HAE 預防領域。在功效和安全性方面的長期表現對 takhzyro 來說是一個好處。

And Matsubaro-san, on the next-generation Orexin, oral Orexin agonist, TAK-360, which is going to have its IND filed in the next several weeks. It's an entirely novel structure relative to TAK-861 in novel properties, potency, PK, et cetera. How we position that to a large extent will depend on the data sets that we'll see in the near future on TAK-861. But there are lots of possibilities. And it's something that we hope that we'll be able to share during an extended discussion at an R&D event that we're planning for later in 2024.

Matsubaro-san 正在研發下一代 Orexin（口服 Orexin 激動劑 TAK-360），該藥物將在未來幾週內提交 IND 申請。相對於 TAK-861，它在特性、效力、PK 等方面都是全新的結構。我們如何定位在很大程度上取決於我們在不久的將來將在 TAK-861 上看到的資料集。但還有很多可能性。我們希望能夠在計劃於 2024 年稍後舉行的研發活動的擴展討論中分享這一點。

Okay. Let's move on to the next question. I'd like to call upon (inaudible) from Jefferies. It looks like the hand has been lowered. So I'd like to move on to the next question from Macquarie. So if Frande from Macquarie is still on the line. Please go ahead and unmute and ask your question. Hello, is that you, Tony?

好的。讓我們繼續下一個問題。我想請杰弗里斯（聽不清楚）。看起來手已經垂了下來。我想繼續回答麥格理的下一個問題。如果麥格理的弗朗德還在電話裡的話。請繼續取消靜音並提出您的問題。你好，是你嗎，東尼？

This is Tony Ren from Macquarie.

我是麥格理的托尼·任。

Hi, yes, Tony. Yes, we can hear you.

嗨，是的，托尼。是的，我們能聽到你的聲音。

Okay. Perfect. Okay, sorry. So a couple of questions. So first of all, about the licensing of Protagonist Therapeutics, rusfertide. Just want to get a sense from you about your expectation of this asset. When do you think it's going to launch? What's the peak sales estimate. So that sound like rusfertide.

好的。完美的。哦抱歉。有幾個問題。首先，關於Protagonist Therapeutics rusfertide的許可。只是想了解您對此資產的期望。您認為它將什麼時候推出？預計最高銷售量是多少？所以這聽起來像 rusfertide。

The other one is that I want to go back to -- I want to go back to ENTYVIO again. So basically, I always think about ENTYVIO as the market size in terms of the size of the pie which is determined by the number of colonoscopy procedures being performed. I want to see how that's trending after COVID. And then the other one is that I did notice, I think on Slide #27, there was a bit of a market share decline compared to the second quarter slides. So I just want to get some clarity on that.

另一個是我想回到——我想再次回到ENTYVIO。所以基本上，我總是將 ENTYVIO 視為市場規模，即蛋糕的大小，而蛋糕的大小取決於正在進行的結腸鏡檢查程序的數量。我想看看新冠疫情之後的趨勢如何。另一個是我確實注意到，我認為在幻燈片#27 上，與第二季的幻燈片相比，市場份額略有下降。所以我只是想澄清一下這一點。

Okay. Julie, would you like to take both of those questions perhaps.

好的。朱莉，也許你想回答這兩個問題。

Sure. Thanks, Tony, for the questions. In terms of rusfertide, we've not provided peak market share data yet. We will do that in the future. In terms of when we expect launch, as Andy mentioned, currently, the product is in Phase III clinical trials. We do understand that the trial is enrolling quite well.

當然。謝謝托尼提出的問題。就rusfertide而言，我們尚未提供峰值市場份額數據。我們將來也會這樣做。至於預計上市時間，正如Andy所提到的，目前該產品正處於III期臨床試驗階段。我們確實了解到該試驗的招募情況相當不錯。

So it will still be a few years before we see launch. But again, we will provide more details later on in terms of rusfertide. For the questions in regards to ENTYVIO, as I mentioned earlier, in terms of first-line treatment where ENTYVIO is strong. We still maintain our market share leadership position where we have seen some market share loss is in second line and further. This is where the new competitive entrants have come in, and that's typically where they come in second line and beyond. And so you are correct in that overall, it has led to a slight market share decline, but we remain quite strong in first line.

因此，我們還需要幾年時間才能看到發布。但同樣，我們稍後將提供有關 rusfertide 的更多詳細資訊。關於ENTYVIO的問題，正如我前面提到的，在一線治療方面，ENTYVIO是強項。我們仍然保持市場份額的領先地位，但我們看到一些市場份額的損失是在二線甚至更遠的地方。這是新的競爭者進入的地方，通常也是他們進入二線及以上的地方。因此，總體而言，您是正確的，這導致了市場份額略有下降，但我們在一線仍然相當強大。

Thank you, Tony. And I think, [Yamagita-san] from Jefferies is back. Yamagita-san or if that's Steve Barker perhaps, if you would like to unmute and ask a question, please.

謝謝你，托尼。我想，來自 Jefferies 的 [Yamagita-san] 回來了。 Yamagita-san 或如果那是 Steve Barker，如果您想取消靜音並提問，請。

It's Steve Barker from Jefferies. My first question is related to Qdenga. I'm looking at the geographic split of the sales to date. And it looks like it's about 70% weighted towards emerging markets. I was wondering if you expected that to continue or whether the weight of emerging markets would be higher in the future. And then also potential $2 billion peak sales related to a 100 million doses, should we assume that you're aiming for an average sales price of about $20 per dose?

我是傑富瑞 (Jefferies) 的史蒂夫巴克 (Steve Barker)。我的第一個問題與 Qdenga 有關。我正在研究迄今為止銷售的地理分佈。看起來新興市場的比重約為 70%。我想知道您是否預計這種情況會持續下去，或者新興市場的權重未來是否會更高。然後，與 1 億劑相關的潛在峰值銷售額為 20 億美元，我們是否應該假設您的目標是每劑約 20 美元的平均銷售價格？

And then my second question is related to margins. you are aiming to get your core OPM back up -- well, back up to low to mid-30s ultimately. I was hoping you could help us understand the path to that high level of profitability in terms of improvements for cost ratios and GPM. Where is the improvement likely to come from?

我的第二個問題與利潤有關。你的目標是讓你的核心 OPM 恢復——好吧，最終恢復到 30 左右。我希望您能幫助我們了解在改善成本比率和毛利率方面實現高獲利水準的途徑。改進可能來自哪裡？

Great. Thank you, Steve, for those questions. So a question on Qdenga and the revenue split and also average cost of dose and then also the return to low to mid-30s. I'd like to ask Christophe to comment on both of those questions.

偉大的。謝謝你，史蒂夫，提出這些問題。因此，關於 Qdenga 和收入分配以及平均劑量成本以及回歸到 30 多歲左右的問題。我想請 Christophe 對這兩個問題發表評論。

Thank you, Steve. I think the -- on Qdenga, as we progress, most of the revenue will come from emerging countries. So in fact, it will come from endemic countries and the countries which are initiating on national immunization program. Right now, we are more in the private market and the travel market. And so I think the large volume type of demand will come later from on the mid countries.

謝謝你，史蒂夫。我認為，在 Qdenga 上，隨著我們的進步，大部分收入將來自新興國家。所以實際上，它將來自流行國家和正在啟動國家免疫計劃的國家。目前，我們更涉足私人市場和旅遊市場。因此，我認為中等國家稍後將出現大量需求。

And I think obviously, you can do the ratio between the [100 million dose] and the [2 billion.] So yes, I mean, on average, we will be around that type of price per dose. I mean, today, in the private market in Indonesia, we launched at USD 26 per dose in Indonesia.

我認為顯然，你可以計算 [1 億劑] 和 [20 億劑] 之間的比率。所以是的，我的意思是，平均而言，我們將圍繞每劑的這種價格。我的意思是，今天，在印尼的私人市場上，我們以每劑 26 美元的價格推出。

And typically, the national immunization program to allow lower price when we contract with government. So -- and that's what our intent, our intent was to make these vaccines, to create access and to -- this is a very innovative vaccines. But we want these vaccines to be bringing -- to be brought into immunization program rapidly. And so that's our strategy. Regarding return to low to mid-30s corporating profit margin, we'll give more detail in May about the path to get there, it will to be a combination of revenue return to growth.

通常，當我們與政府簽訂合約時，國家免疫計劃會允許較低的價格。所以——這就是我們的意圖，我們的意圖是製造這些疫苗，創造機會並獲得——這是一種非常創新的疫苗。但我們希望這些疫苗能迅速納入免疫計畫。這就是我們的策略。關於公司利潤率恢復到 30 多歲左右的水平，我們將在 5 月提供更多關於實現這一目標的路徑的細節，這將是收入恢復成長的結合。

And our growth of launch product gross margin is high because they're highly innovative medicine. So that will help. It will be about leveraging technology, AI and gain productivity and it will be also cost control. So it will be a combination of all 3. But in May, we will be more indication about how and how quickly we'll go back to low to mid-30s.

我們推出的產品毛利率成長很高，因為它們是高度創新的藥物。所以這會有幫助。這將涉及利用技術、人工智慧並提高生產力，同時也涉及成本控制。所以這將是所有這三個因素的結合。但在 5 月份，我們將更多地表明我們將如何以及以多快的速度回到 30 多歲的低點。

[Interpreted] Since time is up, we would like to close the Q&A session at this point. Again, thank you for joining us despite your busy schedule, and thank you for your continued support.

[解讀] 由於時間已到，我們的問答環節到此結束。再次感謝您在百忙之中參加我們的活動，並感謝您一直以來的支持。