Takeda Pharmaceutical Co Ltd (TAK) 2023 Q4 法說會逐字稿

[Interpreted] Thank you very much for joining FY 2022 earnings announcement of Takeda. I will serve as MC, Head of IR. My name is O'Reilly. (Operator Instructions)

[解讀]非常感謝您加入武田的2022財年收益公告。我將擔任 MC，IR 負責人。我的名字是奧萊利。 （操作員說明）

Before starting, I would like to remind everyone that we will be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today. The factors that could cause our actual results to differ materially are discussed in our most recent Form 20-F and in 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 be discussed during this call, definition of our non-IFRS measures and reconciliations risk comparable IFRS measures are included in the appendix to the presentation.

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大不相同。我們最近的 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。另請參閱演示文稿第 2 頁上的重要通知。關於將在本次電話會議期間討論的前瞻性陳述和我們的非 IFRS 財務措施，我們的非 IFRS 措施和調節風險可比 IFRS 措施的定義包含在演示文稿的附錄中。

Now let's move to the presentations. President and CEO, Christophe Weber; and R&D President, Andy Plump; CFO, Costa Saroukos, will provide you with a presentation, then we will have Q&A session. Let's start.

現在讓我們轉到演示文稿。總裁兼首席執行官 Christophe Weber；兼研發總裁 Andy Plump；首席財務官 Costa Saroukos 將為您提供演示，然後我們將進行問答環節。開始吧。

Thank you, Chris. Thank you, everyone, for joining us today. It's a great pleasure to be with you. Fiscal year 2022 has been a very successful year, during which we have been putting our corporate philosophy into action to create long-term business and societal value. Everything we do is guided by our values, brought to life through action based on patient, trust, reputation and business in that order.

謝謝你，克里斯。謝謝大家今天加入我們。很高興和你在一起。 2022 財年是非常成功的一年，在此期間，我們一直將我們的企業理念付諸行動，以創造長期的業務和社會價值。我們所做的一切都以我們的價值觀為指導，通過基於耐心、信任、聲譽和業務的行動來實現。

This is fundamental to our strategy, our identity and our culture. We have been steadily executing towards our vision to discover and deliver life-transforming treatments with a commitment to patients, our people and the planet. A good example is how we have chosen to price our recently approved dengue vaccines QDENGA. We are prioritizing countries with the highest burden of disease and where barriers to access to medicines and vaccines are particularly complex. In line with our cheap pricing strategy, we will adjust QDENGA price according to a country's economic stage and health system maturity to ensure broader access. For example, the private market price for QDENGA in Indonesia will be about 1/3 its European price and far lower than other innovative vaccines in Indonesia.

這是我們戰略、身份和文化的基礎。我們一直在穩步執行我們的願景，即發現並提供改變生命的治療方法，並對患者、我們的人民和地球做出承諾。一個很好的例子是我們如何選擇為我們最近批准的登革熱疫苗 QDENGA 定價。我們正在優先考慮疾病負擔最重以及獲取藥物和疫苗的障礙特別複雜的國家。根據我們的廉價定價策略，我們將根據一個國家的經濟階段和衛生系統成熟度調整 QDENGA 價格，以確保更廣泛的使用。例如，QDENGA在印尼的私人市場價格約為歐洲價格的1/3，遠低於印尼其他創新疫苗。

With regard to our people in priority, our intention is to create an exceptional inclusive people experience wherever we work. For our colleagues who can work virtually as well as in our offices, we emphasize effectiveness, flexibility and inclusion with fit for purpose and regular face-to-face interaction and are leveraging data and insight to inform our approach. We are also committed to delivering a high standard of environmental leadership, and we made important progress toward our greenhouse gas emission goals in fiscal year 2022.

關於我們優先考慮的人員，我們的目的是在我們工作的任何地方創造卓越的包容性人員體驗。對於既能在辦公室工作又能在虛擬環境中工作的同事，我們強調有效性、靈活性和包容性，以符合目的和定期面對面的互動，並利用數據和洞察力為我們的方法提供信息。我們還致力於提供高標準的環境領導力，我們在 2022 財年的溫室氣體排放目標方面取得了重要進展。

As an example of the multiple initiatives we have underway, in March this year, we officially opened our first positive energy manufacturing support building at our site in Singapore. This building actually produced more electricity than it consumes, and it is the first of its kind in the biopharmaceutical industry in Singapore.

作為我們正在進行的多項舉措的一個例子，今年 3 月，我們在新加坡的工廠正式啟用了我們的第一座正能量製造支持大樓。這座建築實際上產生的電力比消耗的電力還多，在新加坡的生物製藥行業中尚屬首創。

In the U.S. Our virtual power purchase agreement with Enel North America is expected to create up to 350,000 megawatt hours of renewable energies credit per year. That accounts for approximately 20% of Takeda's current enterprise, Scope 1 and 2 greenhouse gas emission. We are also doubling down our investment in data, technology and AI with a 10% investment increase in 2022 to improve our productivity across our entire value chain. In these ways, through our core business, Takeda is creating long-term value for patients, shareholders and society, while making a positive impact on our people, communities and the planet.

在美國，我們與 Enel North America 簽訂的虛擬購電協議預計每年可產生高達 350,000 兆瓦時的可再生能源信用額度。這約占武田當前企業範圍 1 和範圍 2 溫室氣體排放量的 20%。我們還將加倍對數據、技術和人工智能的投資，並在 2022 年增加 10% 的投資，以提高我們整個價值鏈的生產力。通過這些方式，通過我們的核心業務，武田正在為患者、股東和社會創造長期價值，同時對我們的人民、社區和地球產生積極影響。

Turning to Slide 5 to our financial performance. I am pleased to say that fiscal year 2022 was an excellent year for Takeda as we delivered our exceeded management guidance for revenue and profit growth. On the top line, we booked revenue of more than JPY 4 trillion for the first time, representing core growth of 3.5% at a constant exchange rate. This performance was driven by our growth in lunch product, which increased 19% at a constant exchange rate and now represents 40% of our total revenue. Core operating profit was nearly JPY 1.2 trillion, representing growth of 9.1% at a constant exchange rate. And core earnings per share was JPY 558 with growth of 13.9% at the constant exchange rate.

轉到幻燈片 5，了解我們的財務業績。我很高興地說，2022 財年對武田來說是出色的一年，因為我們交付了超出預期的收入和利潤增長管理指南。最重要的是，我們的收入首次超過 4 萬億日元，按固定匯率計算核心增長率為 3.5%。這一業績是由我們午餐產品的增長推動的，按固定匯率計算增長了 19%，現在占我們總收入的 40%。核心營業利潤接近 1.2 萬億日元，按固定匯率計算增長 9.1%。每股核心收益為 558 日元，按固定匯率計算增長 13.9%。

I also want to highlight our continued progress in reducing our debt. We have now brought our leverage ratio down to 2.6. This includes the impact of a $3 billion payment we made in Q4 to acquire TAK-279 from Nimbus. Excluding that, we will have reached 2.3x or the low 2s target we set as 1 of our key financial metrics commitment after the Shire acquisition. This achievement enabled us to pivot to a new phase of investing for growth and shareholder returns.

我還想強調我們在減少債務方面的持續進展。我們現在已將槓桿比率降至 2.6。這包括我們在第四季度為從 Nimbus 收購 TAK-279 支付的 30 億美元的影響。除此以外，我們將達到 2.3 倍或我們在收購 Shire 後設定的關鍵財務指標承諾 1 的低 2s 目標。這一成就使我們能夠轉向投資增長和股東回報的新階段。

Moving to the right-hand side of the slide, and our pipeline progress in fiscal year 2022, our dengue vaccine QDENGA received approval in multiple countries, including Indonesia, the European Union, U.K. and Brazil. We have since received additional approvals in Argentina and Thailand and have launched in a number of European and Nordic countries. The U.S. FDA also accepted QDENGA for priority review, and we are looking forward to a potential approval in the U.S. and to expanding access to these vaccines to other regions later this year.

轉到幻燈片的右側，以及我們在 2022 財年的管道進展情況，我們的登革熱疫苗 QDENGA 在多個國家/地區獲得批准，包括印度尼西亞、歐盟、英國和巴西。此後，我們在阿根廷和泰國獲得了額外的批准，並在許多歐洲和北歐國家推出。美國 FDA 也接受了 QDENGA 的優先審查，我們期待在美國獲得潛在批准，並在今年晚些時候將這些疫苗的使用範圍擴大到其他地區。

Also this year, we have positive late-stage clinical trial data readout for TAK-755 and fazirsiran. Based on favorable interim Phase III result, we are on track towards the filing of TAK-755 as a treatment for congenital thrombotic thrombocytopenic purpura, or cTTP, a rare blood clotting disorder with limited therapeutic option. We also announced positive Phase II results for fazirsiran in alpha-1 antitrypsin deficiency associated liver disease. And this year, we have begun dosing patients in the Phase III studies.

同樣在今年，我們獲得了 TAK-755 和 fazirsiran 的積極後期臨床試驗數據。基於有利的中期 III 期結果，我們有望提交 TAK-755 作為先天性血栓性血小板減少性紫癜或 cTTP 的治療藥物，cTTP 是一種治療選擇有限的罕見凝血障礙。我們還宣布了 fazirsiran 在 alpha-1 抗胰蛋白酶缺乏症相關肝病中的 II 期陽性結果。今年，我們已經開始在 III 期研究中對患者進行給藥。

Our Orexin franchise is also advancing. We began a Phase IIb study for TAK-861 in narcolepsy type 1 and type 2 and published positive Phase I data for TAK-925 in the post anesthesia setting. We continue to strengthen our pipeline with external opportunities to complement our innovative internal R&D engine. This included the acquisition of TAK-279 for immune-mediated disease as well as in-licensing agreement for fruquintinib for colorectal cancer and TAK-227 for celiac disease. We are optimistic about this late-stage programs and the potential of this molecules to bring meaningful advancement for patients.

我們的 Orexin 專營權也在推進。我們開始了 TAK-861 在 1 型和 2 型發作性睡病中的 IIb 期研究，並發表了 TAK-925 在麻醉後設置中的陽性 I 期數據。我們繼續通過外部機會加強我們的管道，以補充我們創新的內部研發引擎。這包括收購用於免疫介導疾病的 TAK-279，以及用於結直腸癌的呋喹替尼和用於乳糜瀉的 TAK-227 的許可協議。我們對這個後期項目以及這種分子為患者帶來有意義進步的潛力持樂觀態度。

Looking ahead to fiscal year 2023 on Slide 6. We have been communicating for some time that this coming year will be challenging due to the impact from loss of exclusivity, most significantly VYVANSE in the U.S. and AZILVA in Japan. However, these are temporary headwinds and do not alter the momentum of our growth and launch products nor our excitement in the pipeline to deliver major and long-term growth. As a result of the strong deleveraging progress I highlighted on the previous slide, we are now entering a new phase for the company in terms of capital allocation. I am pleased to announce a planned dividend increase from JPY 180 to JPY 188 per share in fiscal year 2023, underscoring our confidence to grow beyond the near-term challenges in fiscal 2023.

在幻燈片 6 上展望 2023 財年。一段時間以來，我們一直在溝通，由於失去獨家經營權的影響，來年將充滿挑戰，最重要的是美國的 VYVANSE 和日本的 AZILVA。然而，這些都是暫時的逆風，不會改變我們增長和推出產品的勢頭，也不會改變我們對實現重大和長期增長的熱情。由於我在上一張幻燈片中強調了強勁的去槓桿化進展，我們現在正在進入公司在資本配置方面的新階段。我很高興地宣布計劃在 2023 財年將股息從每股 180 日元增加到 188 日元，強調我們有信心在 2023 財年實現增長，克服近期挑戰。

With regard to our guidance for the coming year, for revenue, we expect momentum from our growth and launch product to largely offset the impact of generic insurance. However, we do have an additional headwinds from COVID-19 vaccines expectation. In fiscal year 2022, we actually exceeded our revenue forecast for COVID-19 vaccines in Japan with almost JPY 60 billion in sales. But as a result of softening demand and the government cancellation of their order for Nuvaxovid, we now expect fiscal year 2023 revenue to be minimal. As a result, our management guidance is for core revenue to decline by low single-digit percentage at a constant exchange rate, with COVID-19 vaccines being the main difference from our previously communicated goal of holding revenue flat this year.

關於我們對來年收入的指導，我們預計我們的增長和推出產品的勢頭將在很大程度上抵消普通保險的影響。然而，我們確實對 COVID-19 疫苗的預期有額外的不利因素。在 2022 財年，我們實際上超過了我們對日本 COVID-19 疫苗的收入預測，銷售額接近 600 億日元。但由於需求疲軟以及政府取消了對 Nuvaxovid 的訂單，我們現在預計 2023 財年的收入將微乎其微。因此，我們的管理層指導意見是核心收入按固定匯率下降低個位數百分比，而 COVID-19 疫苗是我們先前傳達的今年保持收入持平的目標的主要區別。

With regard to profits, we do expect an impact from losing the high-margin product generic in 2023, but we are doubling down on OpEx discipline to limit the impact as much as possible. That said, we are not holding back from making the necessary investments to secure future growth, and we'll continue to invest in R&D and data and technology to secure Takeda long-term competitiveness.

關於利潤，我們確實預計 2023 年失去高利潤產品仿製藥會產生影響，但我們正在加倍遵守運營支出紀律，以盡可能限制影響。也就是說，我們不會阻止進行必要的投資以確保未來的增長，我們將繼續投資於研發以及數據和技術以確保武田的長期競爭力。

Although we expect core operating profit to decline in the low 10 percentile, we are still forecasting an absolute amount of more than JPY 1 trillion. Core EPS is expected to be JPY 434.

儘管我們預計核心營業利潤將下降 10 個百分點，但我們仍預測絕對數額將超過 1 萬億日元。核心每股收益預計為 434 日元。

After several years of business transformation, integration and deleveraging, we have built competitive global scale with a strong financial foundation and are confident in our future growth. This enabled us to pivot our capital allocation policy to place less emphasizes on rapid debt paydown and instead allocate more capital towards growth investments and shareholder returns. This includes the adoption of a progressive dividend policy which means that going forward, we intend to increase or maintain our dividend every year, reflecting a new chapter for Takeda with a clear focus on investing for growth and shareholder return.

經過幾年的業務轉型、整合和去槓桿，我們已經建立了具有競爭力的全球規模和強大的財務基礎，並對我們未來的增長充滿信心。這使我們能夠調整我們的資本分配政策，減少對快速償還債務的重視，而是將更多資本分配給增長投資和股東回報。這包括採用漸進式股息政策，這意味著在未來，我們打算每年增加或維持股息，反映武田的新篇章，明確關注投資增長和股東回報。

Moving to the right of the slide, our upcoming pipeline milestones also support our confidence in the future. First, we are expecting some significant life cycle management expansion this fiscal year as we now anticipate regulatory decisions in the U.S. for Entyvio subcutaneous formulation for ulcerative colitis and for HYQVIA and GAMMAGARD LIQUID for CIDP. We also expect the readout for ALOFISEL Phase III ADMIRE study, which we believe will support the U.S. filing of this highly innovative cell therapy for complex perianal fistula. And as I mentioned, we also anticipate further approval decision for QDENGA, including in the U.S. as well as an approval decision in the U.S. for TAK-755 for cTTP.

在幻燈片的右側，我們即將到來的管道里程碑也支持我們對未來的信心。首先，我們預計本財年將有一些重大的生命週期管理擴展，因為我們現在預計美國將對 Entyvio 皮下製劑治療潰瘍性結腸炎以及 HYQVIA 和 GAMMAGARD LIQUID 治療 CIDP 做出監管決定。我們還期待 ALOFISEL III 期 ADMIRE 研究的讀數，我們相信這將支持美國提交這種針對複雜肛周瘻管的高度創新細胞療法。正如我所提到的，我們還預計將對 QDENGA 做出進一步的批准決定，包括在美國，以及在美國對用於 cTTP 的 TAK-755 做出批准決定。

Lastly, we expect to obtain Phase IIb results for TAK-279 in psoriatic arthritis and initiate a pivotal Phase III program in psoriasis. Andy will share additional information on these programs later in the presentation.

最後，我們希望獲得 TAK-279 在銀屑病關節炎中的 IIb 期結果，並啟動銀屑病的關鍵 III 期計劃。 Andy 將在稍後的演示中分享有關這些程序的更多信息。

Turning to Slide 7 on our high-level outlook for the near, medium and long term. Based on our current assumption for fiscal 2023, we expect to return to revenue, profit and margin growth in the near term, driven by continued expansion of our growth and launch product such as ENTYVIO, TAKHZYRO, LIVTENCITY and our plasma-derived therapies. We will also start to see meaningful contribution from QDENGA.

轉到幻燈片 7，了解我們對近期、中期和長期的高層展望。根據我們目前對 2023 財年的假設，我們預計在我們的增長和推出產品（如 ENTYVIO、TAKHZYRO、LIVTENCITY 和我們的血漿衍生療法）的持續擴張的推動下，收入、利潤和利潤率將在短期內恢復增長。我們也將開始看到 QDENGA 做出有意義的貢獻。

We are also excited about our late-stage pipeline and anticipate significant milestone in '23 and onwards, as I have already touched upon. Following the temporary generic headwinds we faced this year, we have no significant loss of exclusivity exposure until the launch of Entyvio biosimilars, which could be as late as 2032, and therefore, the momentum from our growth and launch products, coupled with new launches from the pipeline will continue to drive growth into the medium term. Beyond that, we expect our investment in R&D to continue to pay off in the medium and long term with progress in our clinical pipeline.

正如我已經提到的，我們也對我們的後期管道感到興奮，並預計 23 年及以後的重要里程碑。繼我們今年面臨的暫時性仿製藥逆風之後，直到 Entyvio 生物仿製藥上市（可能最遲到 2032 年）之前，我們並沒有顯著喪失獨占權，因此，我們的增長和上市產品的勢頭，加上來自該管道將繼續推動中期增長。除此之外，我們預計我們在研發方面的投資將隨著臨床管道的進展在中長期內繼續獲得回報。

As we look to the future, we remain committed to returning to a core operating profit margin in the low to mid-30s, supported by productivity improvements driven by data, digital and technology. We will also continue to evaluate asset-specific business development opportunities to further enhance the pipeline and reinforce our growth profile.

展望未來，在數據、數字和技術推動的生產力提高的支持下，我們仍然致力於在 30 年代中期恢復到核心營業利潤率。我們還將繼續評估特定資產的業務發展機會，以進一步加強管道並鞏固我們的增長前景。

Finally, as I mentioned, our updated capital allocation policy include our progressive dividend policy of increasing or maintaining our dividend each year.

最後，正如我提到的，我們更新的資本配置政策包括我們每年增加或維持股息的漸進式股息政策。

In closing, fiscal year 2022 was a year of growth and strategy execution. We continue to deliver on our long-term commitment, progress our pipeline and return value to our stakeholders while leading up to our values and bringing life-transforming treatments to patients.

最後，2022 財年是增長和戰略執行的一年。我們將繼續履行我們的長期承諾，推進我們的管道並為我們的利益相關者回報價值，同時引領我們的價值觀並為患者帶來改變生活的治療。

With that, I will turn the call over to Andy to update you on our pipeline. Thank you.

有了這個，我會把電話轉給安迪，讓你了解我們的管道。謝謝。

Thank you, very much, Christophe, and hello to everyone on today's call. If we can go to the next slide, please, Slide 9. We continue to build forward momentum with our innovative pipeline this past year. I'm very excited to share our progress and highlight major milestones achieved in fiscal year 2022 as well as highlight expected major events in the coming year 2023. As Christophe mentioned, we had multiple pipeline successes this past year. We received several approvals for QDENGA in endemic markets.

非常感謝 Christophe，今天的電話會議大家好。如果我們可以轉到下一張幻燈片，請轉到第 9 張幻燈片。在過去的一年裡，我們繼續通過我們的創新管道建立前進的勢頭。我很高興能分享我們的進展，強調 2022 財年取得的主要里程碑，以及 2023 年預計發生的重大事件。正如 Christophe 提到的，我們在過去的一年中取得了多項成功。 QDENGA 在流行市場獲得多項批准。

We also had approval in Europe and a positive CHMP opinion that could support the approval in 8 additional dengue endemic countries participating in the first-ever EU medicines for all procedure. The WHO estimates around 4 billion people are at risk of dengue infection globally with an estimated 400 million infections, 500,000 hospitalizations and 25,000 deaths each year and most of these deaths occurring in children. In our 4.5-year TIDES clinical outcomes trial, QDENGA demonstrated an 84% reduction in hospitalizations. As we work to provide broad access to endemic regions around the world, we now have the potential to significantly reduce the hospitalizations and deaths caused by dengue infection in the decades to come.

我們還在歐洲獲得了批准，CHMP 的積極意見可以支持另外 8 個登革熱流行國家的批准，這些國家參與了有史以來第一個用於所有程序的歐盟藥物。世界衛生組織估計，全球約有 40 億人面臨感染登革熱的風險，每年估計有 4 億人感染、50 萬人住院和 25,000 人死亡，其中大部分死亡發生在兒童身上。在我們為期 4.5 年的 TIDES 臨床結果試驗中，QDENGA 證明住院率降低了 84%。隨著我們努力為世界各地的流行地區提供廣泛的途徑，我們現在有可能在未來幾十年內顯著減少因登革熱感染導致的住院和死亡。

We also had a number of positive study readouts to further advance our pipeline this year. And as Christophe mentioned, these include a Phase III readout for TAK-755, a Phase II readout for fazirsiran and proof-of-concept data for our Orexin franchise. These positive studies support important program stage ups. We are on track to file TAK-755 for the treatment of congenital TTP in the U.S. with submissions in other regions to follow.

我們也有一些積極的研究讀出，以進一步推進我們今年的管道。正如 Christophe 提到的，這些包括 TAK-755 的 III 期讀數、fazirsiran 的 II 期讀數和我們 Orexin 特許經營的概念驗證數據。這些積極的研究支持重要的項目階段。我們正按計劃在美國提交 TAK-755 用於治療先天性 TTP，隨後將提交其他地區的申請。

We initiated a Phase III pivotal trial for fazirsiran. Fazirsiran is an innovative and very promising RNA interference therapy that may stop the buildup of harmful protein aggregates in the liver, which can cause inflammation, fibrosis and ultimately liver failure. Fazirsiran has the potential to reduce the inflammation and fibrosis and prevent liver failure in patients with alpha-1 antitrypsin deficiency.

我們啟動了 fazirsiran 的 III 期關鍵試驗。 Fazirsiran 是一種創新且非常有前途的 RNA 干擾療法，可以阻止有害蛋白質聚集體在肝臟中的積累，這種聚集體會導致炎症、纖維化並最終導致肝功能衰竭。 Fazirsiran 有可能減少炎症和纖維化，並預防 alpha-1 抗胰蛋白酶缺乏症患者的肝功能衰竭。

We also advanced TAK-861 into Phase IIb dose-ranging studies for patients with both narcolepsy type 1 and narcolepsy type 2.

我們還將 TAK-861 推進到針對 1 型發作性睡病和 2 型發作性睡病患者的 IIb 期劑量範圍研究。

While this has been a strong year for pipeline growth, it has not been without its headwinds. Based on feedback from regulatory agencies, we decided not to pursue approval for LIVTENCITY in first-line CMV infections. We continue to believe there was a net positive benefit shown against the standard of care in the frontline trial. But after discussions with regulatory agencies have decided to make the trial results available to transplant physicians via publications but not pursue a label supplement. LIVTENCITY remains the only approved therapy for refractory CMV infection and has made meaningful impact to the lives of patients in the post-transplant setting. In the coming year, we see significant opportunities to further expand our growth and launch products. The potential approval of Entyvio subcu in the U.S. for ulcerative colitis and potential approvals for HYQVIA and GAMMAGARD LIQUID in the U.S. for CIDP. Both represent expansion opportunities for 2 of our largest franchises.

儘管今年是管道增長強勁的一年，但也並非沒有阻力。根據監管機構的反饋，我們決定不尋求批准 LIVTENCITY 用於一線 CMV 感染。我們仍然相信，與一線試驗中的護理標準相比，顯示出淨積極收益。但在與監管機構討論後，決定通過出版物向移植醫生提供試驗結果，但不尋求標籤補充。 LIVTENCITY 仍然是唯一獲批的治療難治性 CMV 感染的療法，並且對移植後患者的生活產生了有意義的影響。在來年，我們看到了進一步擴大增長和推出產品的重要機會。美國可能批准 Entyvio subcu 治療潰瘍性結腸炎，以及美國可能批准 HYQVIA 和 GAMMAGARD LIQUID 治療 CIDP。兩者都代表了我們最大的兩個特許經營權的擴張機會。

In fiscal year 2022, we also made significant investments to enhance our long-term growth prospects with a number of pipeline-enhancing deals. These include TAK-279, which I will highlight in more detail later in the presentation; fruquintinib, a highly selective oral potent inhibitor of VEGF receptor 1, 2 and 3 with very strong overall survival data in previously treated metastatic colorectal cancer.

在 2022 財年，我們還進行了大量投資，通過一系列管道增強交易來增強我們的長期增長前景。其中包括 TAK-279，我將在稍後的演示中更詳細地強調它； fruquintinib，一種高度選擇性的口服強效 VEGF 受體 1、2 和 3 抑製劑，在既往治療過的轉移性結直腸癌中具有非常強的總生存期數據。

This program has already been filed in the United States, and TAK-227, a potential first-in-class oral celiac disease therapy with strong data in the human gluten challenge study that was recently published in the New England Journal of Medicine. Next slide, please.

該項目和 TAK-227 已在美國提交申請，TAK-227 是一種潛在的一流口腔乳糜瀉療法，在最近發表在《新英格蘭醫學雜誌》上的人類麩質挑戰研究中具有強大的數據。請換下一張幻燈片。

Through our disciplined prioritization process, we also made a number of strategic and data-driven decisions to prioritize investments in our most promising programs which further propelled the progression of our pipeline. As a result, we achieved 41 clinical stage ups and 8 approvals from the 4 major regulatory agencies around the world. We also continue to evolve our strategic focus.

通過我們嚴格的優先排序流程，我們還做出了一些戰略和數據驅動的決策，以優先投資於我們最有前途的項目，這進一步推動了我們管道的進展。因此，我們獲得了全球 4 大監管機構的 41 個臨床階段升級和 8 個批准。我們還繼續發展我們的戰略重點。

As an example of our disciplined decision-making, we discontinued R&D efforts in adeno-associated virus or AAV gene therapy. This decision will allow us to focus even more deeply in areas of cell and gene therapy, we believe we can offer transformative therapies to patients and become industry leaders. These include our innovative allogeneic NK and gamma delta cell therapy platforms as well as next-generation delivery mechanisms for gene therapy. Next, Slide 11, please.

作為我們嚴格決策的一個例子，我們停止了腺相關病毒或 AAV 基因療法的研發工作。這一決定將使我們能夠更深入地關注細胞和基因治療領域，我們相信我們可以為患者提供變革性療法並成為行業領導者。其中包括我們創新的同種異體 NK 和 γ δ 細胞治療平台以及用於基因治療的下一代傳遞機制。接下來，請看幻燈片 11。

Depicted here are our late-stage development programs. TAK-755 had strong interim results from our Phase III trial in congenital TTP, a rare disease caused by a deficiency of the protease ADAMTS13. TAK-755, our recombinant ADAMTS13 designed to replace this missing enzyme, showed a 60% reduction in the incidence of thrombocytopenic events versus the standard of care. TAK-755 was also better tolerated. Treatment-related adverse events were 9% for TAK-755 and 48% for the standard of care. We are on track for our first filing in the U.S.

這裡描述的是我們的後期開發計劃。 TAK-755 在先天性 TTP（一種由蛋白酶 ADAMTS13 缺陷引起的罕見疾病）的 III 期試驗中取得了很好的中期結果。 TAK-755 是我們的重組 ADAMTS13，旨在替代這種缺失的酶，與標準治療相比，血小板減少事件的發生率降低了 60%。 TAK-755 的耐受性也更好。 TAK-755 的治療相關不良事件為 9%，標準治療為 48%。我們正在按計劃在美國提交第一份申請

As previously mentioned, we have an exciting late-stage addition to our pipeline in TAK-279, a highly selective oral allosteric TYK2 inhibitor. We'll be starting a pivotal development program in psoriasis in fiscal year 2023. Additionally, we will have a Phase IIb readout for psoriatic arthritis this fall and are preparing at risk to start a pivotal development program for these patients in early fiscal year 2024.

如前所述，我們在 TAK-279（一種高選擇性口服變構 TYK2 抑製劑）的管線中有一個令人興奮的後期補充。我們將在 2023 財年啟動銀屑病的關鍵開發計劃。此外，我們將在今年秋天對銀屑病關節炎進行 IIb 期讀數，並準備在 2024 年初為這些患者啟動關鍵開發計劃。

In parallel, we will be accelerating the development of TAK-279 Crohn's disease, ulcerative colitis and systemic lupus erythematosus as well as exploring a broad range of additional indications. So next, Slide 12, please.

與此同時，我們將加快 TAK-279 克羅恩病、潰瘍性結腸炎和系統性紅斑狼瘡的開發，並探索廣泛的其他適應症。接下來，請看幻燈片 12。

Now I'd like to remind you why we are so excited about TAK-279. Firstly, TAK-279 is over 1.4 million-fold selective for TYK2 versus the JAK family receptors, important for a best-in-class TYK2 inhibitor given the known safety concerns associated with the JAK inhibitors. Secondly, as presented at the American Academy of Dermatology in March, TAK-279 has very strong Phase IIb clinical data in moderate-to-severe plaque psoriasis. 33% of patients taking a 30-milligram pill achieved clear skin or PASI 100 with a once daily administration.

現在我想提醒您為什麼我們對 TAK-279 如此興奮。首先，TAK-279 對 TYK2 的選擇性是 JAK 家族受體的 140 萬倍以上，考慮到與 JAK 抑製劑相關的已知安全問題，這對於一流的 TYK2 抑製劑很重要。其次，正如 3 月份在美國皮膚病學會發表的那樣，TAK-279 在中度至重度斑塊狀銀屑病方面具有非常強大的 IIb 期臨床數據。服用 30 毫克藥丸的患者中，有 33% 的患者在每天服用一次的情況下獲得了光潔的皮膚或 PASI 100。

In addition to the strong efficacy profile, adverse events were generally low. The most common adverse events were COVID-19 and acne, and importantly, acne and its related forms resolve while patients continued treatment in all but 1 study participants by week 12.

除了強大的療效外，不良事件普遍較低。最常見的不良事件是 COVID-19 和痤瘡，重要的是，到第 12 週，除 1 名研究參與者外，所有患者繼續接受治療，痤瘡及其相關形式都會消退。

We are looking forward to advancing TAK-279 into 2 Phase III trials in psoriasis and conducting a head-to-head trial against deucravacitinib based on these promising data. The figure at the bottom of this slide shows a high-level time line of our anticipated clinical milestones over the next 2 years. Next, Slide 13, please.

我們期待將 TAK-279 推進 2 項銀屑病 III 期試驗，並根據這些有希望的數據開展針對 deucravacitinib 的頭對頭試驗。這張幻燈片底部的圖顯示了我們預期的未來 2 年臨床里程碑的高級時間表。接下來，請看幻燈片 13。

I'd like to now focus on our promising mid-stage pipeline. We are quite energized by recent developments in our Orexin franchise. Earlier this year, we advanced TAK-861, our oral Orexin program into Phase IIb. Thanks to our knowledge of the narcolepsy space, experience with orexin agonists and close site engagement, we were able to start Phase IIb studies in both narcolepsy type 1 and narcolepsy type 2 within days of establishing proof-of-concept.

我現在想專注於我們有前途的中期管道。我們對 Orexin 特許經營權的最新發展感到非常興奮。今年早些時候，我們將口服 Orexin 項目 TAK-861 推進到 IIb 期。由於我們對發作性睡病領域的了解、使用食慾素激動劑的經驗和密切的現場參與，我們能夠在建立概念驗證後的幾天內開始對 1 型發作性睡病和 2 型發作性睡病進行 IIb 期研究。

We recently started enrollment in our long-term extension study that will provide valuable insights on both long-term safety as well as efficacy. In addition, we recently presented data for TAK-925, our intravenous orexin agonist at the International Anesthesia Research Society. There is significant unmet need in post-anesthesia recovery due to respiratory depression caused by anesthetics, leading to complications and admission to the intensive care unit.

我們最近開始參加我們的長期擴展研究，該研究將提供有關長期安全性和有效性的寶貴見解。此外，我們最近在國際麻醉研究協會展示了我們的靜脈注射食慾素激動劑 TAK-925 的數據。由於麻醉劑引起的呼吸抑制，導致並發症和進入重症監護病房，麻醉後恢復存在顯著未滿足的需求。

In our study, healthy volunteers recovering from opioid-induced respiratory depression had significant benefits following TAK-925 administration. In this trial, we saw the potential of TAK-925 to reverse respiratory depression while maintaining analgesic effect. Thus, having the potential to reduce complications.

在我們的研究中，從阿片類藥物引起的呼吸抑制中恢復的健康志願者在服用 TAK-925 後具有顯著益處。在該試驗中，我們看到了 TAK-925 在保持鎮痛作用的同時逆轉呼吸抑制的潛力。因此，有可能減少並發症。

TAK-925 is now recruiting in a large Phase II study to explore potential postoperative benefits in patients with obstructive sleep apnea and others at high risk for respiratory complications. We are evaluating accelerated pass-through approval in a variety of surgical settings.

TAK-925 現在正在招募大型 II 期研究，以探索阻塞性睡眠呼吸暫停患者和其他呼吸系統並發症高風險患者的潛在術後益處。我們正在評估各種手術環境中的加速通過批准。

Next, TAK-227 is a potential first-in-class therapy designed to prevent the immune response to gluten in celiac disease and is now the most advanced program in our celiac disease portfolio. These are the first of many new molecular entities that will emerge from our rich and transformative early to mid-stage pipeline, which we are confident will add to our growing late-stage portfolio. Next slide 14, please, my last slide.

其次，TAK-227是一種潛在的一流療法，旨在預防乳糜瀉中對麩質的免疫反應，現在是我們乳糜瀉產品組合中最先進的項目。這些是我們豐富且具有變革性的早期到中期管道中出現的許多新分子實體中的第一個，我們有信心將其添加到我們不斷增長的後期產品組合中。下一張幻燈片 14，我的最後一張幻燈片。

2022 was a strong year for our pipeline. In addition to the progress already mentioned, we had significant life cycle advances for our marketed growth and launch products. Based on the progress in 2022, in the coming year, we have the potential approval of ENTYVIO subcutaneous in the United States for ulcerative colitis, the potential approval of HYQVIA as a maintenance therapy for CIDP in the U.S. and Europe, potentially a large growth driver for plasma-derived therapy and ALOFISEL, our mesenchymal stem cell therapy will have a Phase III readout. If positive, we plan to submit a BLA in the U.S. for complex perianal fistulas this year. We expect these data to support the concept of cell-mediated closure, which could drive significant growth for ALOFISEL.

2022 年對我們的管道來說是強勁的一年。除了已經提到的進展之外，我們在銷售增長和推出產品方面取得了顯著的生命週期進步。根據 2022 年的進展，明年我們有可能在美國批准 ENTYVIO 皮下注射治療潰瘍性結腸炎，在美國和歐洲可能批准 HYQVIA 作為 CIDP 的維持療法，這可能是一個巨大的增長動力對於血漿衍生療法和 ALOFISEL，我們的間充質乾細胞療法將有一個 III 期讀數。如果結果呈陽性，我們計劃今年在美國提交複雜肛周瘻管的 BLA。我們預計這些數據將支持細胞介導閉合的概念，這可能會推動 ALOFISEL 的顯著增長。

Overall, we are pleased with how we progress the pipeline in fiscal year 2022 and excited about the strong momentum and meaningful advances we can make in 2023.

總的來說，我們對我們在 2022 財年如何推進管道感到滿意，並對我們在 2023 年可以取得的強勁勢頭和有意義的進展感到興奮。

Thank you, and I will now turn it over to Costa.

謝謝，我現在將它交給 Costa。

Thank you, Andy, and hello, everyone. This is Costa Saroukos speaking. Today, I'll walk you through the financial highlights of our fiscal 2022 full year results and our outlook for 2023. Starting with fiscal 2022 results. I'm pleased to say that it was an excellent year for the company as we delivered or exceeded management guidance and booked a record JPY 4 trillion in revenue and core operating profit of almost JPY 1.2 trillion. Starting from the top line, core revenue for the full year was JPY 4.03 trillion or approximately USD 30.3 billion. Despite the entry of VELCADE generics in May 2022, we delivered solid revenue growth, up 3.5% versus prior year at constant exchange rate, driven by our growth and launch products. These products now represent 40% of total revenue and grew at 19% on a constant exchange rate.

謝謝你，安迪，大家好。我是 Costa Saroukos。今天，我將向您介紹我們 2022 財年全年業績和 2023 年展望的財務亮點。從 2022 財年業績開始。我很高興地說，這對公司來說是出色的一年，因為我們交付或超過了管理指導，並創下了創紀錄的 4 萬億日元收入和近 1.2 萬億日元的核心運營利潤。從頂線開始，全年核心收入為 4.03 萬億日元，約合 303 億美元。儘管 VELCADE 仿製藥於 2022 年 5 月上市，但在我們的增長和推出產品的推動下，我們實現了穩健的收入增長，按固定匯率計算比上年增長 3.5%。這些產品現在佔總收入的 40%，按固定匯率計算增長了 19%。

Reported revenue growth was 12.8% with business momentum and FX upside more than offsetting the impact of a JPY 133 billion gain from the sale of the Japan Diabetes business that was booked in Q1 of the prior year. Core operating profit grew at 9.1% at a constant exchange rate to JPY 1.19 trillion, breaking the JPY 1 trillion threshold for the first time in Takeda's long history. And our core operating profit margin was 29.5%, an increase of 1.6 percentage points on a year-over-year basis. This year-on-year margin improvement is an indicator of our financial discipline and our ability to control costs. In fact, at constant exchange rate, our SG&A spend was lower than last year.

報告的收入增長為 12.8%，業務勢頭和外匯上漲足以抵消去年第一季度入賬的出售日本糖尿病業務帶來的 1330 億日元收益的影響。按固定匯率計算，核心營業利潤增長 9.1%，達到 1.19 萬億日元，在武田公司悠久的歷史上首次突破 1 萬億日元的門檻。我們的核心營業利潤率為 29.5%，同比增長 1.6 個百分點。這種同比利潤率的提高是我們財務紀律和控製成本能力的一個指標。事實上，按固定匯率計算，我們的 SG&A 支出低於去年。

Reported operating profit grew at 6.4% versus prior year, overcoming the high hurdle set by the gain on the diabetes portfolio in the prior year. Free cash flow for fiscal 2022 was JPY 446.2 billion. But excluding the $3 billion upfront payment we made in Q4 for the acquisition of TAK-279 from Nimbus, it would have been JPY 837.3 billion or USD 6.3 billion. As a reminder, the total upfront consideration for TAK-279 was $4 billion, and the remaining $1 billion will be paid in the first half of fiscal 2023.

報告的營業利潤比上一年增長了 6.4%，克服了上一年糖尿病產品組合收益設置的高障礙。 2022 財年的自由現金流為 4462 億日元。但不包括我們在第四季度為從 Nimbus 收購 TAK-279 支付的 30 億美元預付款，則為 8373 億日元或 63 億美元。提醒一下，TAK-279的總前期對價為40億美元，剩餘的10億美元將在2023財年上半年支付。

We finished March with net debt to adjusted EBITDA of 2.6x. If we exclude the Nimbus upfront payment from the calculation, it would have been 2.3x, meaning we would have achieved the low 2s deleveraging 1 year ahead of our target. This closes the chapter on the last major financial target from the Shire integration. Going forward, we'll continue to focus on financial discipline and maintaining solid investment-grade credit ratings, but we are no longer in a phase of rapid deleveraging.

我們在 3 月份結束時的淨債務為調整後 EBITDA 的 2.6 倍。如果我們從計算中排除 Nimbus 預付款，它會是 2.3 倍，這意味著我們會比我們的目標提前 1 年實現低 2s 的去槓桿化。關於夏爾整合的最後一個主要財務目標的章節到此結束。展望未來，我們將繼續關注財務紀律並維持穩健的投資級信用評級，但我們不再處於快速去槓桿化階段。

After a record year for core earnings in fiscal 2022, we faced significant loss of exclusivity headwinds in 2023, making it a challenging year. Momentum of our growth and launch products is expected to largely offset the revenue impact of losses of exclusivity, predominantly from VYVANSE in the U.S. and AZILVA in Japan. However, year-over-year revenue and profit growth will also be impacted by lower expectations for coronavirus vaccines in Japan.

在 2022 財年核心收益創紀錄之後，我們在 2023 年面臨排他性損失的重大逆風，這使它成為充滿挑戰的一年。我們的增長和推出產品的勢頭預計將在很大程度上抵消排他性損失對收入的影響，主要來自美國的 VYVANSE 和日本的 AZILVA 。然而，收入和利潤同比增長也將受到日本冠狀病毒疫苗預期下降的影響。

In fiscal 2022, we booked almost JPY 60 billion in revenue for Nuvaxovid and Spikevax. But we expect the contribution in fiscal 2023 to be minimal. On the OpEx line, we will stay disciplined to limit the margin impact from generic entry of VYVANSE and AZILVA which are high-margin products. That said, we will not compromise on making the necessary investments in R&D and data and digital to secure long-term competitiveness.

在 2022 財年，我們為 Nuvaxovid 和 Spikevax 預訂了近 600 億日元的收入。但我們預計 2023 財年的貢獻將微乎其微。在 OpEx 線上，我們將保持紀律，以限制高利潤產品 VYVANSE 和 AZILVA 的仿製藥進入對利潤率的影響。也就是說，我們不會在研發、數據和數字方面進行必要的投資以確保長期競爭力方面做出妥協。

Lastly but importantly, we are updating our capital allocation policy to reflect the achievement of our deleveraging target with the planned dividend increase, our first in 15 years to underscore our confidence in the mid- to long-term growth outlook of the company.

最後但重要的是，我們正在更新我們的資本配置政策，以反映我們去槓桿化目標的實現以及計劃中的股息增加，這是我們 15 年來首次強調我們對公司中長期增長前景的信心。

Slide 17 shows our results versus full year guidance for fiscal 2022. We're delighted with our performance as we delivered growth at a constant exchange rate at or above management guidance for revenue and profits. For core revenue, we achieved strong top line growth of 3.5%, and at the high end of our guidance for low single-digit growth, driven by our growth and launch products, which more than offset the impact of VELCADE generics from May 2022. Core operating profit grew at 9.1%, also at the high end of our guidance range for high single-digit growth. This strong performance was driven by the expansion of high-margin products, coupled with our OpEx discipline to deliver operating leverage.

幻燈片 17 顯示了我們的結果與 2022 財年的全年指導。我們對我們的表現感到滿意，因為我們以恆定匯率實現了增長，達到或超過收入和利潤的管理指導。對於核心收入，在我們的增長和推出產品的推動下，我們實現了 3.5% 的強勁收入增長，並且處於我們低個位數增長指導的高端，這大大抵消了 VELCADE 仿製藥從 2022 年 5 月開始的影響。核心營業利潤增長 9.1%，也處於我們高個位數增長指導範圍的高端。這種強勁的表現得益於高利潤產品的擴張，以及我們提供運營槓桿的運營支出紀律。

For core EPS, I'm pleased to say we exceed the guidance of high single-digit growth, growing at 13.9% at constant exchange rate, reflecting strong business performance and a more favorable core tax rate due to recognition of previously unrecognized tax losses.

對於核心每股收益，我很高興地說我們超過了高個位數增長的指導，按固定匯率計算增長了 13.9%，反映出強勁的業務表現和更優惠的核心稅率，這是由於確認了以前未確認的稅收損失。

Finally, on free cash flow, the Nimbus deal was not factored into our estimates when we gave a forecast of JPY 650 billion to JPY 750 billion at Q2 earnings, which itself was an upgrade from the initial guidance of JPY 600 billion to JPY 700 billion given in May last year. Including the Nimbus payment we made in Q4, free cash flow for fiscal 2022 was JPY 446.2 billion. However, excluding Nimbus, it would have been JPY 837.3 billion, well exceeding our forecast.

最後，在自由現金流方面，當我們預測第二季度收益為 6500 億至 7500 億日元時，Nimbus 交易並未計入我們的估計，這本身就是從 6000 億日元的初始指導升級至 7000 億日元去年5月給的。包括我們在第四季度支付的 Nimbus 款項，2022 財年的自由現金流為 4462 億日元。但是，如果不包括 Nimbus，則為 8,373 億日元，遠超我們的預期。

Slide 18 goes into more detail on the full year 2022 performance versus prior year. As already highlighted, we delivered excellent results this year, driven by business momentum demonstrated in our constant exchange rate growth in the far right column of the slide. If we look at the actual numbers, we also saw a significant tailwind from FX due to the depreciation of the yen, resulting in double-digit reported and core revenue growth and reported in core EPS growth of over 30%.

幻燈片 18 更詳細地介紹了與上一年相比的 2022 年全年業績。正如已經強調的那樣，我們今年取得了出色的成績，這得益於我們在幻燈片最右欄中匯率持續增長所體現的業務勢頭。如果我們看一下實際數字，我們還看到由於日元貶值，外匯帶來了巨大的推動力，導致報告和核心收入實現兩位數增長，核心每股收益增長超過 30%。

I'd like to highlight again our core operating profit of almost JPY 1.2 trillion, the highest amount in Takeda history with a 1.6 percentage point year-on-year margin improvement to 29.5%. Core EPS for the year was JPY 558.

我想再次強調我們的核心營業利潤接近 1.2 萬億日元，是武田歷史上最高的利潤率，同比增長 1.6 個百分點至 29.5%。全年核心每股收益為 558 日元。

Let me go into more detail on the full year revenue performance versus prior year on Slide 19. On the left is a waterfall chart for reported revenue which grew at 12.8% year-on-year with business momentum and FX favorability more than offsetting the impact of JPY 150 billion in one-off revenue we booked last year related to asset transfers, including the Japan Diabetes portfolio and JPY 150 billion of loss of exclusivity impact most significantly from VELCADE in the U.S. Core revenue on the right-hand side adjust the 2021 baseline to exclude the one-off revenue book from asset transfers last year.

讓我在幻燈片 19 上更詳細地介紹全年收入表現與上一年的對比情況。左邊是報告收入的瀑布圖，同比增長 12.8%，業務勢頭和外匯有利程度抵消了影響我們去年登記的與資產轉讓相關的 1500 億日元一次性收入中，包括日本糖尿病投資組合和 1500 億日元的獨占權損失對美國 VELCADE 的影響最為顯著。右側的核心收入調整 2021 年從去年的資產轉讓中排除一次性收入賬簿的基線。

You can see that our business momentum driven by the growth and launch products delivered 3.5% growth at constant exchange rate, with the additional tailwind of FX raising total core revenue growth to 17.7%.

您可以看到，我們的業務增長和推出產品推動的業務勢頭以固定匯率計算實現了 3.5% 的增長，外彙的額外推動使核心總收入增長達到 17.7%。

On Slide 20, you can see the key driver of top line growth is our portfolio of growth and launch products, which generated approximately JPY 1.6 trillion or 40% of total revenue, with 19% growth at constant exchange rate. Incrementally, these products added JPY 435.8 billion or USD 3.3 billion of revenue compared to last year. This is the portfolio driving total company growth this year despite the VELCADE loss of exclusivity. And we expect that continued momentum of these products will allow us to largely offset the impact of loss of exclusivities, including VYVANSE in 2023.

在幻燈片 20 上，您可以看到收入增長的主要驅動力是我們的增長和推出產品組合，這些產品產生了約 1.6 萬億日元或總收入的 40%，按固定匯率計算增長了 19%。與去年相比，這些產品的收入增加了 4358 億日元或 33 億美元。儘管 VELCADE 失去了獨家經營權，但這是今年推動公司整體增長的投資組合。我們預計這些產品的持續發展勢頭將使我們能夠在很大程度上抵消失去獨占權的影響，包括 2023 年的 VYVANSE。

Within our 5 key business areas, GI, our largest area by revenue, grew at 9% on a constant exchange rate basis. This was spearheaded by ENTYVIO, which grew at 15% and is now the #1 prescribed biologic for IBD in the U.S. We will see significant growth potential for ENTYVIO towards its peak sales estimate of $7.5 billion to $9 billion and achieved an important milestone with the recent resubmission of the subcutaneous formulation in the U.S.

在我們的 5 個關鍵業務領域中，GI 是我們收入最大的領域，按固定匯率計算增長了 9%。這是由 ENTYVIO 帶頭的，它以 15% 的速度增長，現在是美國排名第一的 IBD 處方生物製劑。我們將看到 ENTYVIO 的巨大增長潛力，達到其 75 億至 90 億美元的最高銷售額估計，並實現了一個重要的里程碑最近在美國重新提交了皮下製劑

In rare diseases, we see continued demand and geographic expansion for TAKHZYRO, including recent listings on the NRDL in China to deliver growth of 25%. We have also delivered a very successful launch of LIVTENCITY with 98% of transplant centers in the U.S. having now initiated therapy on at least 1 patient and real-world physician utilization demonstrating longer duration of treatment than we had initially anticipated.

在罕見病領域，我們看到 TAKHZYRO 的持續需求和地域擴張，包括最近在中國 NRDL 上的上市實現了 25% 的增長。我們還非常成功地推出了 LIVTENCITY，美國 98% 的移植中心現已開始對至少 1 名患者進行治療，現實世界中的醫生使用表明治療持續時間比我們最初預期的要長。

PDT Immunology continues to be very strong with 15% growth, including 16% growth of immunoglobulin and 19% growth of albumin, reflecting strong demand. We have continued to expand our plasma donation center network, adding 29 centers in the fiscal year to date, bringing our total global footprint now to 233 centers.

PDT 免疫學繼續保持強勁增長 15%，其中免疫球蛋白增長 16%，白蛋白增長 19%，反映出強勁的需求。我們繼續擴大我們的血漿捐贈中心網絡，本財年迄今增加了 29 個中心，使我們目前的全球足跡總數達到 233 個中心。

I'm very pleased to announce that we have now achieved our target of over 65% increase in plasma supply and manufacturing capacity versus the 2018 baseline, 1 year ahead of plan. This is despite the COVID-19 pandemic, during which we consistently outperform the industry and met all our planned commitments to patients. A fantastic achievement by the team and a testament to how successfully we are managing our end-to-end PDT business.

我很高興地宣布，我們現在已經實現了血漿供應和製造能力比 2018 年基線增加 65% 以上的目標，比計劃提前一年。儘管發生了 COVID-19 大流行，但在此期間我們的表現始終優於行業，並履行了我們對患者的所有計劃承諾。團隊取得的一項了不起的成就，證明了我們管理端到端 PDT 業務的成功程度。

We are continuing to make investments in data, digital and technology-led transformation and capacity expansion across the value chain including plans to increase our donation center network by another 20-plus centers in fiscal 2023 and investments across the manufacturing network, including the recently announced facility we plan to build in Japan. We intend to give an update on our future capacity increase goals at a PDT-focused investment later in the fiscal year.

我們將繼續投資於數據、數字和技術主導的轉型以及整個價值鏈的產能擴張，包括計劃在 2023 財年將我們的捐贈中心網絡增加另外 20 多個中心，以及整個製造網絡的投資，包括最近宣布的我們計劃在日本建造的設施。我們打算在本財年晚些時候以 PDT 為重點的投資中更新我們未來的產能增加目標。

Next is Oncology, which is declining year-on-year as expected, given that VELCADE generics entered the U.S. market from May 2022. Excluding VELCADE, the rest of the portfolio grew 5%, driven by ALUNBRIG, EXKIVITY, Adcetris and Iclusig.

其次是腫瘤學，鑑於 VELCADE 仿製藥從 2022 年 5 月開始進入美國市場，該藥物如預期的那樣同比下降。在 ALUNBRIG、EXKIVITY、Adcetris 和 Iclusig 的推動下，除 VELCADE 外，其餘產品組合增長了 5%。

Finally, Neuroscience continues to perform very well with growth of 12%, driven by VYVANSE and Trintellix. As we have previously communicated, we expect generic versions of VYVANSE to launch in the U.S. in August of 2023, which means that we do not expect the neuroscience -- sorry, we do expect the Neuroscience business to decline in the coming year.

最後，在 VYVANSE 和 Trintellix 的推動下，神經科學繼續表現出色，增長了 12%。正如我們之前所傳達的那樣，我們預計 VYVANSE 的通用版本將於 2023 年 8 月在美國推出，這意味著我們預計神經科學領域不會出現——抱歉，我們確實預計神經科學業務在來年會下降。

Finally, the Other segment is declining mainly due to some regional loss of exclusivities in Japan. This other segment now includes our newly launched vaccine QDENGA for the prevention of dengue disease, which we are also classifying as our newest growth and launch product. We've already had a number of important approvals, including Brazil, Indonesia, Thailand and EU, and we look forward to ramping up our vaccine rollout in 2023.

最後，其他部分正在下降，這主要是由於在日本失去了一些區域獨占權。這另一個部分現在包括我們新推出的用於預防登革熱的疫苗 QDENGA，我們也將其歸類為我們最新的增長和推出產品。我們已經獲得了一些重要的批准，包括巴西、印度尼西亞、泰國和歐盟，我們期待在 2023 年加大疫苗的推廣力度。

The other segment also includes our COVID-19 vaccines in Japan. These generate almost JPY 60 billion in revenue in fiscal 2022. But as we look ahead to fiscal 2023, we expect them to decline based on lower market demand and the Japanese government's canceled purchase order for Nuvaxovid. As a result, we expect to see minimal revenue contribution from the COVID-19 vaccines in 2023, and therefore, they will no longer be classified as growth and launch products going forward.

另一部分還包括我們在日本的 COVID-19 疫苗。這些在 2022 財年產生了近 600 億日元的收入。但展望 2023 財年，我們預計它們會因市場需求下降和日本政府取消對 Nuvaxovid 的採購訂單而下降。因此，我們預計 2023 年 COVID-19 疫苗的收入貢獻微乎其微，因此，它們將不再被歸類為增長和推出的產品。

Moving down to the P&L. On Slide 21, we show the key drivers of reported and core operating profit performance for fiscal 2022. Reported operating profit was JPY 490.5 billion, growing at 6.4% versus prior year with business momentum and FX benefits more than overcoming the impact of the sale of the Japan diabetes portfolio, which generated or contributed JPY 131.4 billion to reported operating profit in fiscal 2021.

向下移動到損益表。在幻燈片 21 上，我們展示了 2022 財年報告和核心營業利潤業績的主要驅動因素。報告的營業利潤為 4905 億日元，比上年增長 6.4%，業務勢頭和外匯收益超過了出售日本糖尿病產品組合在 2021 財年報告的營業利潤中產生或貢獻了 1314 億日元。

On the right side of the slide, you can see the core operating profit was almost JPY 1.2 trillion with our growth and launch products coupled with OpEx discipline, driving a very strong performance of 9.1% growth at constant exchange rate. FX was an additional benefit, resulting in actual core operating profit growth of 24.4%.

在幻燈片的右側，您可以看到核心營業利潤接近 1.2 萬億日元，我們的增長和推出的產品加上 OpEx 紀律，以固定匯率推動了 9.1% 的非常強勁的增長。外匯是一個額外的好處，導致實際核心營業利潤增長 24.4%。

Slide 22 shows our net debt balance compared to the end of March 2022 and demonstrates the continuation of our steady deleveraging progress from 2.8 down to 2.6x. Again, this number reflects the $3 billion upfront payment that we made to Nimbus in quarter 4 for TAK-279. Excluding this payment, we would be at 2.3x which is comfortably in the low 2s, a target we had set to hit by fiscal 2023 as part of the Shire integration.

幻燈片 22 顯示了我們與 2022 年 3 月底相比的淨債務餘額，並表明我們繼續穩步去槓桿化，從 2.8 倍降至 2.6 倍。同樣，這個數字反映了我們在第 4 季度為 TAK-279 向 Nimbus 支付的 30 億美元預付款。排除這筆付款，我們將達到 2.3 倍，處於 2s 的低位，這是我們作為 Shire 整合的一部分設定的到 2023 財年實現的目標。

With this target achieved, we can close out the final chapter of the integration and look ahead to a new phase of capital allocation. Although we continue to make progress with debt repayments in fiscal 2022, paying over JPY 280 billion, the amount of debt on our balance sheet in Japanese yen terms increased over the period due to the depreciation of the yen versus the dollar and the euro, and this movement is captured within the other bar in the chart. However, as a reminder, the depreciation of the yen also benefited EBITDA, which means the impact of FX on our leverage ratio is minimal. Also, we have structured the currency denomination of our debt to mirror our cash flow, which ensures that over time, we'll be able to pay down debt with minimal impact from FX movements.

隨著這一目標的實現，我們可以結束整合的最後一章，並展望新的資本配置階段。儘管我們在 2022 財年的債務償還方面繼續取得進展，支付了超過 2800 億日元，但由於日元兌美元和歐元貶值，我們資產負債表上以日元計算的債務金額在此期間有所增加，並且該運動在圖表的另一個條形圖中被捕獲。然而，提醒一下，日元貶值也有利於 EBITDA，這意味著外匯對我們槓桿率的影響微乎其微。此外，我們構建了債務的貨幣計價以反映我們的現金流，這確保隨著時間的推移，我們將能夠在外匯變動的影響最小的情況下償還債務。

On Slide 23, you can see our debt maturity ladder as of March 2023. We paid off a significant amount of debt again this fiscal year, including a total of $1.2 billion of higher interest USD-denominated bonds and EUR 750 million of floating rate bonds. We also did some recent refinancing of 2022 and 2023 Japanese yen-denominated loans with new maturities in fiscal years 2028 and 2030. As a result, we are able to maintain a very comfortable debt maturity profile over the coming years. And importantly, our debt remains at 100% fixed rate with a weighted average interest of approximately 2%.

在幻燈片 23 上，您可以看到我們截至 2023 年 3 月的債務到期階梯。我們在本財年再次償還了大量債務，包括總計 12 億美元的高息美元計價債券和 7.5 億歐元的浮動利率債券.我們最近還對 2028 年和 2030 財年到期的 2022 年和 2023 年日元計價貸款進行了一些再融資。因此，我們能夠在未來幾年保持非常舒適的債務到期狀況。重要的是，我們的債務保持 100% 的固定利率，加權平均利率約為 2%。

Next, moving to Slide 24 and our outlook for fiscal 2023. As we've communicated for some time, fiscal year 2023 will be a challenging year due to loss of exclusivity impacts including VYVANSE in the U.S. and AZILVA in Japan. In fact, the total revenue impact from generic entry is expected to be approximately JPY 330 billion this coming year.

接下來，轉到幻燈片 24 和我們對 2023 財年的展望。正如我們已經溝通了一段時間，由於失去包括美國 VYVANSE 和日本 AZILVA 在內的獨家經營權影響，2023 財年將是充滿挑戰的一年。事實上，明年仿製藥進入的總收入影響預計約為 3300 億日元。

While we expect our growth and launch products to offset much of this impact on revenue, we also faced the additional headwind from lower expectations from COVID-19 vaccine revenues. Starting with core revenue, we are forecasting JPY 3.84 trillion or a decline of 4.7%. In addition to the loss of exclusivity and coronavirus impact, this also reflects a slight headwind from FX. Excluding that, on a constant exchange rate basis, our management guidance is for a low single-digit percent revenue decline.

雖然我們預計我們的增長和推出的產品將抵消大部分對收入的影響，但我們還面臨著 COVID-19 疫苗收入預期較低的額外阻力。從核心收入開始，我們預測為 3.84 萬億日元或下降 4.7%。除了排他性和冠狀病毒影響的喪失外，這還反映了外彙的輕微逆風。排除這一點，在固定匯率的基礎上，我們的管理層指導是收入下降百分比較低。

Core operating profit is being impacted by product mix due to higher-margin products facing generic entry, but we are striving to minimize the impact through OpEx discipline. We still forecast to land above JPY 1 trillion core operating profit in fiscal 2023, with a year-on-year decline in the low 10s percentile on a constant exchange rate basis.

由於利潤較高的產品面臨仿製藥進入，核心營業利潤正受到產品組合的影響，但我們正在努力通過 OpEx 紀律將影響降至最低。我們仍然預測 2023 財年的核心營業利潤將超過 1 萬億日元，按固定匯率計算，同比下降 10% 的低百分位數。

Core EPS is projected to be JPY 434 with a year-on-year decline in the low 20s percentile reflecting a more normalized tax rate versus the benefit we had in fiscal year 2022. We expect reported EPS to decline by 56%, reflecting some onetime items on top of the headwinds impacting our core numbers, including an expectation for higher restructuring costs and lower financial income.

核心每股收益預計為 434 日元，同比下降 20 個百分點的低位，反映出與我們在 2022 財年獲得的收益相比更加正常化的稅率。我們預計報告的每股收益將下降 56%，反映了一些曾經影響我們核心數據的不利因素之上的項目，包括對更高重組成本和更低財務收入的預期。

Moving to free cash flow, where we expect to generate between JPY 400 billion to JPY 500 billion next year. Please note that this forecast reflects JPY 180 billion of CapEx related to the remaining USD 1 billion upfront payment for TAK-279, the Nimbus acquisition, and the $400 million we paid to Hutchmed in April for fruquintinib. Adjusting for those deals, you can calculate that free cash flow would be in the JPY 600 billion to JPY 700 billion range, which is the same as our initial forecast for fiscal year 2022.

轉向自由現金流，我們預計明年將產生 4000 億至 5000 億日元。請注意，該預測反映了 1800 億日元的資本支出，與剩餘的 10 億美元 TAK-279 預付款、Nimbus 收購以及我們在 4 月份支付給 Hutchmed 的 fruquintinib 的 4 億美元相關。調整這些交易後，您可以計算出自由現金流將在 6000 億至 7000 億日元之間，這與我們對 2022 財年的初步預測相同。

We believe this guidance demonstrates our ability to weather the storm through the loss of exclusivity headwind in the coming year. Importantly, we are confident in our ability to return to growth in the near term and to continue to grow the business into the future. Underscoring this confidence and supported by our robust cash flow outlook is our decision to adopt a progressive dividend policy with an increase from JPY 180 to JPY 188 in our fiscal 2023 forecast.

我們相信，這一指引表明我們有能力在來年失去獨家經營權的逆風中度過難關。重要的是，我們對在短期內恢復增長並在未來繼續發展業務的能力充滿信心。在我們穩健的現金流前景的支持下，我們決定採用漸進式股息政策，將 2023 財年的預測從 180 日元上調至 188 日元，這凸顯了這種信心。

On the next couple of slides, let me go into a little more detail on the pushes and pulls of fiscal year 2023 forecast. Starting with revenue on Slide 25. You can see that the growth and launch products are expected to offset a significant portion of the JPY 330 billion loss of exclusivity impact. However, we are now expecting the additional headwind of COVID-19 vaccine revenue declining year-on-year. In fiscal year 2022, we recognized revenue of JPY 58.9 billion from our COVID vaccine program in Japan, higher than our forecast of JPY 50 billion. However, revenue is expected to decline in fiscal '23 based on outlook for lower demand and the Japanese government cancelation of the Novavax supply contract in February of 2023. Previously, we have been expecting coronavirus vaccine revenues to grow in fiscal 2023, which would have enabled us to maintain total revenue broadly flat on a constant exchange rate basis.

在接下來的幾張幻燈片中，讓我更詳細地介紹 2023 財年預測的推動和拉動。從幻燈片 25 的收入開始。您可以看到，增長和推出的產品預計將抵消 3300 億日元的排他性損失影響的很大一部分。然而，我們現在預計 COVID-19 疫苗收入同比下降的額外逆風。在 2022 財年，我們從日本的 COVID 疫苗項目中確認了 589 億日元的收入，高於我們預測的 500 億日元。然而，基於需求下降的前景和日本政府在 2023 年 2 月取消 Novavax 供應合同，預計 23 財年的收入將下降。此前，我們一直預計冠狀病毒疫苗收入將在 2023 財年增長，這本來可以使我們能夠在固定匯率的基礎上保持總收入大致持平。

However, this change in vaccine expectation is the main reason why we are now projecting low single-digit decline at constant exchange rate. On an actual currency basis, we also expect FX to be a headwind in 2023, resulting in a total revenue decline of minus 4.7% year-on-year.

然而，疫苗預期的這種變化是我們現在預測以固定匯率計算的低個位數下降的主要原因。在實際貨幣基礎上，我們還預計 2023 年外匯將成為逆風，導致總收入同比下降 -4.7%。

Slide 26 shows the factors impacting our core operating profit forecast. We have bucketed the loss of exclusivity and coronavirus impact together here. And in total, these do represent higher-margin products, which is why the impact on profit growth is more substantial than the impact on revenue. I did want to highlight on this slide that we are continuing to make the necessary investments in R&D and data and digital to support the long-term growth of the company, but that we are being very disciplined in our approach to OpEx. As you can see from the chart, while we plan to increase R&D investment by 4%, we expect non-R&D OpEx to be flat year-on-year on a constant exchange rate basis despite the inflationary challenges that we face. FX is also a headwind to our forecast but in spite of that, we are still projecting to deliver core operating profit of more than JPY 1 trillion in fiscal year 2023.

幻燈片 26 顯示了影響我們核心營業利潤預測的因素。我們在這裡將排他性的喪失和冠狀病毒的影響放在一起。總的來說，這些確實代表了更高利潤的產品，這就是為什麼對利潤增長的影響比對收入的影響更大。我確實想在這張幻燈片上強調，我們將繼續在研發、數據和數字方面進行必要的投資，以支持公司的長期發展，但我們在運營支出方面非常自律。正如您從圖表中看到的那樣，雖然我們計劃將研發投資增加 4%，但我們預計非研發運營支出在固定匯率基礎上同比持平，儘管我們面臨通脹挑戰。外匯也是我們預測的不利因素，但儘管如此，我們仍預計 2023 財年的核心營業利潤將超過 1 萬億日元。

Moving on to Slide 27. I want to speak to the updates we are making to our capital allocation policy. You will recall that previously, our policy consisted of 3 pillars: investing for growth, deleveraging rapidly and shareholder returns. As we have shown today, we would have reached low 2s net debt to adjusted EBITDA in March 2023 if we exclude the upfront payment to Nimbus for TAK-279. We are really proud of this deleveraging achievement as it reflects on the excellent work we have been doing day-to-day to grow revenues while maintaining strong OpEx discipline and continuing to invest in our future growth. We have made great progress in creating a strong financial foundation and precisely because of that progress, we are now able to enter into a new phase.

轉到幻燈片 27。我想談談我們對資本配置政策所做的更新。你會記得以前，我們的政策包括三大支柱：投資增長、快速去槓桿和股東回報。正如我們今天所展示的那樣，如果我們排除為 TAK-279 向 Nimbus 支付的預付款，我們將在 2023 年 3 月達到調整後 EBITDA 的低 2s 淨債務。我們為這一去槓桿化的成就感到非常自豪，因為它反映了我們為增加收入所做的出色工作，同時保持嚴格的運營支出紀律並繼續投資於我們的未來增長。我們在建立強大的財務基礎方面取得了長足進步，正是由於這一進步，我們現在能夠進入一個新階段。

While focusing on maintaining our solid investment-grade credit ratings, we no longer include deleveraging rapidly as a core pillar of our capital allocation policy, meaning we can pivot more towards investing in growth and shareholder returns. Investing for growth will continue to consist of strategic investments in internal and external opportunities to enhance the pipeline with the recent numbers and Hutchmed deals as a good example. We will also continue to invest in maximizing the potential of our marketed portfolio while maintaining our focus on expanding our plasma drive therapies business to reinforce our leading position and maximize our growth potential.

在專注於維持我們穩健的投資級信用評級的同時，我們不再將快速去槓桿化作為我們資本配置政策的核心支柱，這意味著我們可以更多地轉向投資於增長和股東回報。增長投資將繼續包括對內部和外部機會的戰略投資，以最近的數字和 Hutchmed 交易作為一個很好的例子來加強渠道。我們還將繼續投資以最大限度地發揮我們已上市產品組合的潛力，同時繼續專注於擴大等離子驅動療法業務，以鞏固我們的領先地位並最大限度地發揮我們的增長潛力。

With regards to shareholder returns, we are adopting a progressive dividend policy, which means our intention will be to increase or maintain the dividend each year going forward. The incremental amount may fluctuate each year depending on our cash flow outlook. And for fiscal 2023, we are raising the dividend to JPY 188 per share from JPY 180 per share. Share buybacks when appropriate, also remain an option for reinforcing shareholder returns, although we do not anticipate implementing a buyback in the immediate future.

關於股東回報，我們正在採用漸進式股息政策，這意味著我們打算在未來每年增加或維持股息。根據我們的現金流量前景，增量金額每年可能會波動。對於 2023 財年，我們將股息從每股 180 日元提高到每股 188 日元。在適當的時候回購股票，也仍然是加強股東回報的一種選擇，儘管我們預計不會在不久的將來實施回購。

To close out today's presentation, I'd like to revisit the slide Christophe showed you, outlining our long-term commitment to growth and shareholder returns. While fiscal year 2023 will be a challenging year, the headwinds we face are temporary, and we expect to return to sales, profit and margin growth in the near term. Our growth and launch products continued to deliver strong momentum, representing 40% of our portfolio and growing at 19% at constant exchange rate in fiscal year 2022, and we expect these products to further expand over the coming years, including our newest launch, QDENGA.

為了結束今天的演講，我想重溫一下 Christophe 向您展示的幻燈片，其中概述了我們對增長和股東回報的長期承諾。雖然 2023 財年將是充滿挑戰的一年，但我們面臨的阻力是暫時的，我們預計在短期內將恢復銷售、利潤和利潤增長。我們的增長和推出產品繼續保持強勁勢頭，占我們產品組合的 40%，並在 2022 財年以固定匯率計算增長 19%，我們預計這些產品將在未來幾年進一步擴大，包括我們最新推出的 QDENGA .

On top of that, we expect further launches from our late-stage pipeline, such as fruquintinib, TAK-755 and soticlestat in the near term and TAK-279 and fazirsiran later in the decade. Once VYVANSE and AZILVA are behind us, we anticipate limited loss of exclusivity exposure until Entyvio biosimilar launch potentially as late as 2032.

最重要的是，我們預計我們的後期管道將進一步推出，例如短期內的 fruquintinib、TAK-755 和 soticlestat，以及十年後的 TAK-279 和 fazirsiran。一旦 VYVANSE 和 AZILVA 落後於我們，我們預計在 Entyvio 生物仿製藥可能最晚於 2032 年推出之前，排他性曝光的損失有限。

And by then, we plan to further build out our pipeline and portfolio through internal R&D efforts as well as asset-specific business development, enabling us to secure a long-term growth into the next decade.

到那時，我們計劃通過內部研發工作以及特定資產的業務發展進一步擴大我們的管道和產品組合，使我們能夠確保在下一個十年的長期增長。

Meanwhile, we will remain focused on cost discipline with data and digital playing a huge role in how we optimize our cost base and increase productivity supporting our return to low to mid-30s core operating profit margins. We're extremely confident in the near term as underscored by our dividend increase this year and look forward to delivering growth and shareholder returns over the near, medium and long term. Thank you, and now we'll open it up for some Q&A.

與此同時，我們將繼續專注於成本紀律，數據和數字在我們如何優化成本基礎和提高生產力方面發揮著巨大作用，支持我們恢復到 30 年代中期的核心營業利潤率。正如我們今年股息增加所強調的那樣，我們對近期非常有信心，並期待在近期、中期和長期內實現增長和股東回報。謝謝，現在我們將打開它進行一些問答。

[Interpreted] I would like to take questions from the participants. In this Q&A session, we have Christophe, Andy, Costa and Ramona Sequeira, Global Portfolio Division President; Julie Kim, U.S. Business Unit President; Milano Furuta, Japan Pharma Business Unit President; Giles Platford, PDT Business Unit President; and Teresa Bitetti, Global Oncology Business Unit President, are also on the panel. (Operator Instructions) So the first question is Yamaguchi-san, Citigroup.

[翻譯]我想回答與會者的問題。在這個問答環節，我們有 Christophe、Andy、Costa 和全球投資組合部總裁 Ramona Sequeira；美國業務部總裁 Julie Kim； Milano Furuta，日本製藥事業部總裁； PDT 業務部總裁 Giles Platford；全球腫瘤學業務部總裁 Teresa Bitetti 也參加了小組討論。 （操作員說明）第一個問題是花旗集團的山口先生。

This is Yamaguchi from Citi. I would (inaudible) two questions first of all. First question is just a meeting of March '24 but -- because March '24 is now very clear. Investors are interested in March '25 where the VYVANSE (inaudible) is getting much smaller, but still there is. So do you see March '25 -- sales going to grow, I understand that. But operating profit is going to come back to growth as well. That's what you see? That's the first question. The second question is that Nimbus products, those finding questions. Even though, it is a great data so far, but do you see there is a need to add one more higher dose like a 45-milligram per day to boost up the efficacy because there is a good balance of efficacy and side effect? That's the second question.

我是花旗銀行的山口。首先，我會（聽不清）兩個問題。第一個問題只是 3 月 24 日的會議，但是——因為 3 月 24 日現在非常明確。投資者對 25 年 3 月 VYVANSE（聽不清）變得更小但仍然存在感興趣。所以你看到 25 年 3 月了嗎——銷售額會增長，我明白這一點。但營業利潤也將恢復增長。那是你看到的？這是第一個問題。第二個問題是 Nimbus 產品，那些發現問題的人。儘管到目前為止，這是一個很好的數據，但您是否認為有必要增加一個更高的劑量，例如每天 45 毫克，以提高療效，因為療效和副作用之間存在良好的平衡？這是第二個問題。

Thank you, Yamaguchi-san. I think -- so for the first question on the growth outlook for year ending March 2025, I'd like Christophe to answer that. And your question on TAK-279, whether we would do any further dose finding, I'd like to ask Andy to comment on that.

謝謝你，山口桑。我認為 - 所以對於第一個關於截至 2025 年 3 月的年度增長前景的問題，我希望 Christophe 回答這個問題。還有你關於 TAK-279 的問題，我們是否會做任何進一步的劑量發現，我想請安迪對此發表評論。

Thank you, Yamaguchi-san. It's Christophe. So we -- if you look, our growth is very much impacted by VYVANSE, especially because it's such a big product. We have modelized a very significant decline of VYVANSE starting in August 2023. There will still be an impact on fiscal year '24, but much less than '23. But that's a big parameter, if you like, that we'll have to monitor moving forward. So we expect to return to growth with a near term because we are not 100% sure about the VYVANSE decline. If it is as we have forecasted, we will rebounce in '24, but if -- for example, the decline of VYVANSE is less in '23, more in '24, it could have an impact on our return to growth. But for sure, once the VYVANSE is washed out, if you like, our growth and launch product are there as we continue to grow. We have much less exposure to generic until the introduction of biosimilars of ENTYVIO. So we'll return to growth in revenue and profit and our margin will start re-expanding, if you like, towards low to mid-30s as it is our goal.

謝謝你，山口桑。是克里斯托夫。所以我們 - 如果你看，我們的增長受到 VYVANSE 的很大影響，特別是因為它是一個如此大的產品。我們已經模擬了從 2023 年 8 月開始的 VYVANSE 非常顯著的下降。對 24 財年的影響仍將存在，但遠小於 23 財年。但這是一個很大的參數，如果你願意的話，我們將不得不監控前進。因此，我們預計短期內會恢復增長，因為我們不能 100% 確定 VYVANSE 的下降。如果像我們預測的那樣，我們將在 24 年反彈，但如果——例如，VYVANSE 的下降在 23 年減少，在 24 年下降更多，這可能會對我們恢復增長產生影響。但可以肯定的是，一旦 VYVANSE 被淘汰，如果你願意，我們的增長和發布產品就會隨著我們的繼續增長而存在。在 ENTYVIO 的生物仿製藥推出之前，我們對仿製藥的接觸要少得多。因此，我們將恢復收入和利潤的增長，我們的利潤率將開始重新擴大，如果你願意的話，向 30 多歲的中低水平擴張，因為這是我們的目標。

So it's really up to the VYVANSE sales decline speed, which could be quicker or slower, that's going to have a legendary impact for next fiscal, which is still unknown. That's what you say?

所以這真的取決於 VYVANSE 的銷售下降速度，它可能更快或更慢，這將對下一個財政年度產生傳奇般的影響，這仍然是未知的。那是你說的？

Yes. Look at our forecast and this is our best assessment at the moment but we'll have to monitor that because it's -- VYVANSE is also a controlled substance. So it is more complicated than usual. And that could have a big swing on our 2023 actually numbers but -- as well as '24. But at the moment, that's our best assessment. If you have more specific questions on VYVANSE, Julie is here, she can answer as well.

是的。看看我們的預測，這是我們目前最好的評估，但我們必須對其進行監控，因為它—— VYVANSE 也是一種受控物質。所以它比平時更複雜。這可能會對我們的 2023 年實際數字以及 24 年產生很大影響。但目前，這是我們最好的評估。如果你有更具體的關於VYVANSE的問題，Julie在這裡，她也可以回答。

Yamaguchi-san, it's Andy. So on your question with respect to TAK-279 and dose ranging, a couple of comments. The first is that we feel very confident in the dose range that we have and the 30-milligram dose, and we're not intending to do additional dose ranging at this point in psoriasis. We feel that with the 30-milligram dose, we have a best-in-class molecule with the best-in-class dose. We do think in other indications based on the genetics of TYK2 biology and based on some of the preclinical studies, we think that there's a potential that we may need higher exposures and activity in some diseases, for example, IBD.

山口先生，我是安迪。所以關於你關於 TAK-279 和劑量範圍的問題，有幾點評論。首先是我們對現有的劑量範圍和 30 毫克的劑量非常有信心，我們不打算在銀屑病的這一點上進行額外的劑量範圍。我們認為，憑藉 30 毫克的劑量，我們擁有一流的分子和一流的劑量。基於 TYK2 生物學的遺傳學和一些臨床前研究，我們確實認為在其他適應症中，我們認為在某些疾病（例如 IBD）中我們可能需要更高的暴露和活性。

So we'll be doing -- we'll be considering additional dose ranging in other diseases. The biology is quite complex with TYK2, as you know, they're -- we're talking about the inhibition of multiple pathways, multiple inflammatory pathways, many of which are actually quite difficult to measure in humans. And so, we feel with the 30-milligram dose we have outstanding 24-hour coverage to support a best-in-class profile in psoriasis.

所以我們會做——我們會考慮在其他疾病中增加劑量範圍。 TYK2 的生物學非常複雜，正如你所知，它們是——我們正在談論抑制多種途徑，多種炎症途徑，其中許多實際上很難在人類身上測量。因此，我們認為 30 毫克的劑量具有出色的 24 小時覆蓋率，可以支持牛皮癬的同類最佳概況。

Great. Thank you, Yamaguchi-san. Okay, we would like to take the next question. So for the next question, I would like to call on Tony Ren from Macquarie.

偉大的。謝謝你，山口桑。好的，我們想回答下一個問題。因此，對於下一個問題，我想請麥格理的 Tony Ren 發言。

Sure. Yes. Thank you for the opportunity to pose this question. And congratulations on a set of very strong results and achieving your deleveraging target, I think, slightly ahead of schedule. So a couple of questions from me. So the first 1 is also on the TYK2 TAK-279 program. So I just wanted to get some understanding on how many trials you guys are looking to run? I think looking at slide -- I think it's slide -- just give me 1 second, going back to the slide here. I think if I look at Slide 12, it looks like you guys are proposing 2 trials plus a head-to-head trial against an opponent likely deucravacitinib. So I just want to understand your thinking on that and perhaps a little bit also on the dose. You guys circled the 30-milligram dose on the Slide 12. So is that the dose you guys are thinking about taking into your Phase III studies? And also, will -- this is probably more of a business question, not a clinical development question. Will you guys put TAK-279 under the GI business unit? So that's on TAK-279.

當然。是的。感謝您有機會提出這個問題。祝賀您取得了一系列非常強勁的成果，並提前實現了您的去槓桿化目標。我有幾個問題。所以第一個1也在TYK2 TAK-279程序上。所以我只是想了解一下你們希望進行多少次試驗？我想看看幻燈片——我想這是幻燈片——給我 1 秒鐘，回到這裡的幻燈片。我想如果我看一下幻燈片 12，你們似乎提議進行 2 項試驗，再加上針對對手可能是 deucravacitinib 的頭對頭試驗。所以我只想了解您對此的想法，也許還有一點關於劑量的想法。你們在幻燈片 12 上圈出了 30 毫克的劑量。你們正在考慮的 III 期研究劑量是多少？而且，這可能更像是一個商業問題，而不是臨床開發問題。你們會把 TAK-279 歸入 GI 業務部門嗎？所以這是在 TAK-279 上。

And also about your ENTYVIO subcu submission that you guys are handing to the U.S. FDA in April. I recall this application was rejected by the U.S. FDA related to the injection device back in 2019. So I just want to understand how important do you think this will be possibly delaying biosimilar competition?

還有關於你們在 4 月份提交給美國 FDA 的 ENTYVIO subcu 提交。我記得這個申請在 2019 年被美國 FDA 拒絕了與註射裝置有關的申請。所以我只想了解你認為這對延遲生物仿製藥競爭有多重要？

Great. Thank you, Tony. So I think the first question on the study plans, about TAK-279, if Andy could kindly comment on that. And then on the subcutaneous for ENTYVIO, I don't know if -- perhaps Andy, but then maybe also Julie might want to add some comments on that from the U.S. business perspective as well.

偉大的。謝謝你，托尼。所以我認為關於研究計劃的第一個問題是關於 TAK-279，請安迪對此發表評論。然後關於 ENTYVIO 的皮下注射，我不知道是否——也許安迪，但也許朱莉也可能想從美國商業角度對此發表一些評論。

Great. Thanks, Chris, and thanks, Tony. So TAK-279 is hands down, our most heavily resourced program at this point. And we have a project team that -- underneath it has a group that's focusing in dermatology, in inflammatory disorders and then in exploring additional range of additional disorders. In terms of the number of studies, it will be quite significant. So firstly, we'll be running a half dozen Phase I studies this year to support the overall program and registration across multiple indications. So those -- I know that's not what you're asking, but those are critical as we move forward to filing to understand activity in special populations, to understand drug-drug interactions, et cetera, all part of a regulatory package.

偉大的。謝謝，克里斯，謝謝，托尼。所以 TAK-279 無疑是我們目前資源最豐富的項目。我們有一個項目團隊——在它下面有一個小組，專注於皮膚病學、炎症性疾病，然後探索更多的其他疾病。就研究的數量而言，這將是相當重要的。因此，首先，我們今年將進行六項 I 期研究，以支持跨多個適應症的整體計劃和註冊。所以那些 - 我知道這不是你要問的，但這些是至關重要的，因為我們向前推進以了解特殊人群的活動，了解藥物 - 藥物相互作用等，所有這些都是監管計劃的一部分。

For psoriasis, we'll start 2 Phase III studies this year. We'll start a head-to-head study around deucravacitinib next year minimally. And then for psoriatic arthritis, as I mentioned, we're planning at risk for favorable Phase IIb data, so we're planning for Phase III study to start early next year. We're also going to be starting Phase IIb studies in Crohn's disease and ulcerative colitis and lupus. And our aspirational goal is to have those studies started in this fiscal year or early next year.

對於銀屑病，我們今年將啟動 2 項 III 期研究。我們將在明年最低限度地開始圍繞 deucravacitinib 的頭對頭研究。然後對於銀屑病關節炎，正如我提到的，我們正計劃面臨有利的 IIb 期數據的風險，因此我們計劃在明年初開始 III 期研究。我們還將開始克羅恩病、潰瘍性結腸炎和狼瘡的 IIb 期研究。我們的理想目標是在本財年或明年初開始這些研究。

So it's a very substantive program. And by the end of this year, actually, our hope is that we have an ongoing Phase III program, multiple ongoing Phase IIb programs, [Phase I] studies to support registration and then an exploratory package to look beyond those 5 core indications. I think Julie, I'll hand -- should I hand it over to you to talk a bit about the business construct for 279 and ENTYVIO?

所以這是一個非常實質性的計劃。實際上，到今年年底，我們希望我們有一個正在進行的 III 期項目，多個正在進行的 IIb 期項目，[I 期] 研究以支持註冊，然後是一個探索性的包，以超越這 5 個核心適應症。我想 Julie，我會交——我應該把它交給你來談談 279 和 ENTYVIO 的業務結構嗎？

The dose of 30 milligrams?

30毫克的劑量？

I'm sorry, I'm sorry. So our intent is to move forward with the 30-milligram dose. Of course, it's going to require discussions with regulatory agencies before we have a final decision on dose. Sorry about that, Tony.

對不起，對不起。所以我們的目的是推進 30 毫克的劑量。當然，在我們對劑量做出最終決定之前，需要與監管機構進行討論。對不起，托尼。

Yes. And in terms of the way that we're looking at TAK-279 from a commercial perspective, I'll share a few comments with you. First, when you look at our launch of LIVTENCITY. LIVTENCITY wasn't a new therapeutic area for us, and we were able to build a commercial team and launch that product successfully. And so we're confident in our ability to build the commercial capabilities to support TAK-279 when it is ready to launch in psoriasis. In addition, we're also very excited about the opportunity for TAK-279 to expand our presence in IBD beyond ENTYVIO.

是的。就我們從商業角度看待 TAK-279 的方式而言，我將與您分享一些評論。首先，當您查看我們推出的 LIVTENCITY 時。 LIVTENCITY 對我們來說不是一個新的治療領域，我們能夠建立一個商業團隊並成功推出該產品。因此，當 TAK-279 準備好在銀屑病中推出時，我們對我們建立商業能力以支持 TAK-279 的能力充滿信心。此外，我們也很高興 TAK-279 有機會在 ENTYVIO 之外擴大我們在 IBD 的業務。

And about the 2019 FDA rejection, was that related to the medical device used for injection? And would it be -- would this be critical in delaying biosimilar competition until 2032?

關於 2019 年 FDA 的拒絕，是否與用於注射的醫療器械有關？這對將生物仿製藥競爭推遲到 2032 年是否至關重要？

Yes. So this will not have an impact in terms of delaying biosimilar competition, but in terms of the FDA response in 2019, yes, it was related to the device, and there was no concern about the product itself, and we're very much looking forward to being able to launch ENTYVIO subcu in the U.S. later this year. It's been doing quite well in other geographies, and Ramona can speak to that if needed.

是的。所以這不會在延遲生物類似藥競爭方面產生影響，但就 2019 年 FDA 的反應而言，是的，它與設備有關，並且沒有對產品本身的擔憂，我們非常期待期待今年晚些時候能夠在美國推出 ENTYVIO subcu。它在其他地區的表現一直很好，如果需要，Ramona 可以就此發表意見。

Okay. Great. Actually, I also have a question on fruquintinib, but I'm happy to go back to the queue if there are a lot of people waiting.

好的。偉大的。其實，我也有一個關於呋喹替尼的問題，但如果有很多人在等，我很樂意回到隊列中。

Thanks, Tony. Maybe we'll move on to another question for now. We'll come back to you later if necessary. Thanks, Tony.

謝謝，托尼。也許我們現在可以繼續討論另一個問題。如有必要，我們稍後會回复您。謝謝，托尼。

Okay. I'd like to take the next question then from JPMorgan, Wakao-san.

好的。接下來我想從 JPMorgan Wakao-san 那裡回答下一個問題。

[Interpreted] This is Wakao from JPMorgan. I have 2 questions. So the first is after 2024, the forecast for the R&D in the 2024, you don't have much large budget for the R&D. According to the explanation, then TAK-279 is also going to run for the R&D. So then there will be a net growth for the R&D even after 2024. So then the [OpEx,] then the 30% or to the mid will be the amount of the budget you are considering for the R&D and also the balance of the OP margins?

[解讀] 我是摩根大通的 Wakao。我有兩個問題。所以首先是 2024 年之後，對 2024 年研發的預測，你沒有太多的研發預算。據解釋，屆時TAK-279也將參加研發。因此，即使在 2024 年之後，研發也會出現淨增長。那麼 [OpEx，] 那麼 30% 或中間將是您正在考慮的研發預算金額以及 OP 的餘額邊距？

And also, second is regarding the increase of the -- increase of share and the diverging and the increased stock share. And then you indicated this would be good. But in what occasion are you going to increase the share -- cost of the share? And also if the profit will increase, then are you going to increase the stock price or -- next term or the next -- there's not that major -- the return of the expense, so the -- according to [concern] from this -- the [current stations,] so from the next year on, are you also going to increase the stock price?

而且，其次是關於份額的增加以及股票份額的分散和增加。然後你表示這會很好。但是在什麼情況下你會增加份額——份額的成本？而且如果利潤會增加，那麼你會增加股價，還是 - 下一個或下一個 - 沒有那麼大 - 費用的回報，所以 - 根據[關注] ——【當前站】那麼從明年開始，你們是不是也打算提高股價？

Thank you, Wakao-san for your questions. So the first question was on the outlook for R&D expenses from fiscal '24 and beyond. And then what impact that could have on our margin targets? And then the second question on the criteria for a dividend increase. So maybe, I'd like Costa to take these questions and then perhaps, Andy, if you have anything to add, you could jump in later.

謝謝 Wakao-san 的提問。因此，第一個問題是關於 24 財年及以後的研發費用前景。那麼這會對我們的利潤率目標產生什麼影響？然後是關於增加股息標準的第二個問題。所以也許，我希望科斯塔回答這些問題，然後安迪，如果你有什麼要補充的，你可以稍後再插話。

Sorry, Chris, can you repeat that? You are breaking up? Can you repeat those questions again?

抱歉，克里斯，你能重複一遍嗎？你要分手？你能再重複一遍那些問題嗎？

Yes, certainly. So the first question was on the outlook for R&D expenses from fiscal year '24 onwards. Obviously, we have with TAK-279 coming into the pipeline, is that going to need a significant step-up in R&D spend from fiscal 2024? And if so, what impact does that have on our target to return to the low to mid-30s. And then the second question was on the dividend increase. What would be the criteria if the dividend increases in the future? Is it linked to profit growth, cash flow, outlook? What are the criteria?

是的，當然了。因此，第一個問題是關於從 24 財年開始的研發費用前景。顯然，隨著 TAK-279 的推出，是否需要從 2024 財年開始大幅增加研發支出？如果是這樣，這對我們回到 30 年代中期的目標有什麼影響。然後第二個問題是關於股息增加。如果未來增加股息，標準是什麼？它與利潤增長、現金流、前景有關嗎？標準是什麼？

Great. So Wakao-san, thank you very much for your question. When we communicate the getting back to returning to our low to mid-30s in the near to medium term, that factors in the incremental investment in R&D, and it also follows the moving pipeline as it progresses as well. So in our assumptions, in our financials, it does include that.

偉大的。 Wakao-san，非常感謝您的提問。當我們傳達在中短期內回到 30 多歲的低到中期時，這會影響研發的增量投資，並且隨著它的進展，它也會跟隨移動的管道。因此，在我們的假設中，在我們的財務中，它確實包括了這一點。

And what we're seeing is very much laser-focused on the other operating expenses, in particular, SG&A. So we're really doubling down on our focus on finding productivity gains there. So in fact, what you saw in fiscal year '22, we did increase R&D, but SG&A was actually declining at a constant exchange rate. We're leveraging data, digital, technology throughout the value chain. We're seeing improvements in manufacturing, in sales and marketing and back-office G&A. So we'll continue down that path. And we'll, again, align to our capital allocation policy, we're investing for growth and part of that is definitely investing in R&D as the pipeline declares itself.

我們看到的是非常專注於其他運營費用，特別是 SG&A。因此，我們真的加倍關注在那裡尋找生產力的提高。所以事實上，你在 22 財年看到的，我們確實增加了研發，但 SG&A 實際上以固定匯率下降。我們在整個價值鏈中利用數據、數字和技術。我們看到了製造、銷售和營銷以及後台 G&A 方面的改進。所以我們將繼續沿著這條路走下去。我們將再次與我們的資本分配政策保持一致，我們正在為增長而投資，其中一部分肯定是投資於研發，正如管道宣稱的那樣。

But at the same time in fiscal year '23, we're doubling down on our focus on R&D, factoring in 279, 861 and other TAK-999 yet the R&D cost is increasing at 4% at a constant exchange rate. So Andy is also managing the budget based on prioritization as well. So that's really something that we'll continue to keep an eye on. With regards to dividend, we're very much excited about the dividend policy on the capital allocation policy. One reason, as I highlighted, we've been able to really deleverage faster than what we expected. So we did get down to low 2x, excluding the TAK-279 Nimbus deal.

但與此同時，在 23 財年，我們加倍關注研發，將 279、861 和其他 TAK-999 考慮在內，但研發成本以固定匯率增長 4%。因此，Andy 也根據優先級來管理預算。所以這真的是我們將繼續關注的事情。關於股息，我們對資本配置政策的股息政策感到非常興奮。正如我所強調的，原因之一是我們能夠真正以比預期更快的速度去槓桿化。所以我們確實降到了低 2 倍，不包括 TAK-279 Nimbus 交易。

Off the back of that, that closes the Shire financial criteria that we had to address. And it really switches the focus, and we pivot more towards investing for growth and shareholder returns. And this dividend policy, which we've added is a progressive dividend policy where we increase or maintain each year. And the determinating factor would be what is determining whether we increase the dividend, there will be some financial metrics that we look at, for example, free cash flow ratio to the dividend and also dividend payout ratios, et cetera. So we will look at all these ratios and make those decisions at the executive team at the Board each year and communicate that accordingly. Thank you very much.

除此之外，這關閉了我們必須解決的 Shire 財務標準。它確實改變了重點，我們更多地轉向投資增長和股東回報。我們添加的這種股息政策是我們每年增加或維持的累進股息政策。決定因素是決定我們是否增加股息的因素，我們會考慮一些財務指標，例如，自由現金流與股息的比率以及股息支付比率等。因此，我們將研究所有這些比率，每年在董事會的執行團隊中做出這些決定，並相應地進行溝通。非常感謝。

[Interpreted] Well, we would like to move on to the next question. Next is BofA Securities, Mamegano-san. Mamegano, can you hear me?

[解釋] 那麼，我們想繼續下一個問題。接下來是美銀證券，Mamegano-san。豆野，你能聽到我說話嗎？

[Interpreted] yes, I can. I have 2 questions. One is on PDT. Concerning PDT business, the supply and the manufacturing capacity expansion over 60%, you achieved it with a 1-year acceleration. That's a great achievement. And in your pipeline, TAK-771 and 881 are also ongoing. And these assets whether or not they would just further accelerate the expansion of the PDT business? That's my first question.

[解釋] 是的，我可以。我有兩個問題。一個是在 PDT 上。關於PDT業務，供應和產能擴張超過60%，你們以1年的加速實現了。這是一個偉大的成就。在您的管道中，TAK-771 和 881 也在進行中。而這些資產是否會進一步加速PDT業務的擴張？這是我的第一個問題。

Second question is about TAK-755. In cTTP, you had a positive result. And currently, I think you are preparing or fighting in the U.S. various iTTP seems to be a little delayed. If so, what is the reason behind?

第二個問題是關於TAK-755。在 cTTP 中，你得到了一個積極的結果。目前，我認為您正在美國準備或戰鬥。各種iTTP似乎有點延遲。如果有，背後的原因是什麼？

Thank you for the question. So the first question on plasma-derived therapies, achieving 65% capacity a year ahead of plan. So what were the drivers for that? And then also referring to some of the programs we have in development. So for example, TAK-881 in the pipeline and what the potential impact of these could be in the future? I'd like to ask Giles to answer that question. And then the second question was on TAK-755. We've talked about our submission on track in cTTP, but has there been a delay with the iTTP program? And if you can provide any comments on that, I'd like to ask Andy to comment on that one.

感謝你的提問。所以第一個問題是關於血漿衍生療法，提前一年實現 65% 的產能。那麼，驅動因素是什麼？然後還提到了我們正在開發的一些程序。因此，例如，正在籌備中的 TAK-881 及其未來的潛在影響是什麼？我想請 Giles 回答這個問題。然後第二個問題是關於 TAK-755 的。我們已經討論過我們在 cTTP 中的提交是否正常，但 iTTP 程序是否有延遲？如果你能就此提出任何意見，我想請 Andy 對此發表意見。

Yes. Thank you very much for the question. This is Giles. We're very happy to announce that we have achieved the commitment that we made in 2019 to expand our capacity between 18 to 23 by more than 65%. We have achieved that 1 year early, thanks to continued and consistent investment in capacity expansion both in our plasma sourcing network and across our network of manufacturing sites around the world, combined with improvements in efficiency and productivity, and we are confident that the investments that are ongoing to expand our capacity and further improve efficiency will support the growth both of our on-market portfolio, our near-term launches like HYQVIA in CIDP, which is expected to be approved and launched in the U.S. and Europe in fiscal '23 as well as the launch of our pipeline, including TAK-881, the high concentration facilitated SCIG, which will start Phase III study in fiscal '23. Thank you.

是的。非常感謝你的提問。這是吉爾斯。我們很高興地宣布，我們已經實現了我們在 2019 年做出的承諾，將 18 至 23 人的產能擴大 65% 以上。我們提前 1 年實現了這一目標，這要歸功於我們在血漿採購網絡和全球製造基地網絡中對產能擴張的持續和持續投資，以及效率和生產力的提高，我們相信這些投資正在繼續擴大我們的產能並進一步提高效率，這將支持我們在市場上的產品組合的增長，我們近期推出的產品，如 CIDP 中的 HYQVIA，預計將於 23 財年在美國和歐洲獲得批准並推出以及我們管道的啟動，包括 TAK-881，高度集中促進 SCIG，它將在 23 財年開始 III 期研究。謝謝。

And then Mamegano-san, it's Andy, Andy Plump. Just on your question with respect to 755. So we're on track for submission in cTTP. The results have been quite extraordinary against the standard of care, both in terms of efficacy and safety, on track to submit in the U.S. and then plans to expand globally.

然後是 Mamegano-san，是 Andy，Andy Plump。關於您關於 755 的問題。所以我們正按計劃在 cTTP 中提交。就療效和安全性而言，與護理標準相比，結果非常出色，有望在美國提交，然後計劃在全球範圍內擴展。

For [iTTP,] the original proof-of-concept study that we have done was on top of standard of care, which is quite burdensome, the plasma exchange. It was actually difficult to demonstrate significant differences of the combined therapy. And actually, we're in the process now of starting a second proof-of-concept study with a very different approach that's intended to fundamentally change the standard of care where TAK-755 will go up against the standard of care plasma exchange. Plasma exchange is quite burdensome, high volumes, poorly tolerated variable efficacy. And so TAK-755, very low injection volume, very well tolerated. So we're quite excited to get that study up and running this year and see the results.

對於 [iTTP，] 我們所做的最初概念驗證研究是在標準護理之上進行的，這非常繁瑣，即血漿置換。實際上很難證明聯合治療的顯著差異。實際上，我們現在正在開始第二項概念驗證研究，採用一種非常不同的方法，旨在從根本上改變 TAK-755 將與血漿交換護理標準相悖的護理標準。血漿置換相當繁瑣，體積大，耐受性差，療效可變。所以 TAK-755，非常低的注射量，非常好的耐受性。因此，我們很高興今年能夠啟動並運行該研究並看到結果。

[Interpreted] Thank you. Next question from Morgan Stanley, Muraoka-san.

[翻譯] 謝謝。 Muraoka-san 摩根士丹利的下一個問題。

[Interpreted] From Morgan Stanley. My name is Muraoka. Do you hear me?

[解讀] 來自摩根士丹利。我的名字是村岡。你聽到了嗎？

Yes.

是的。

[Interpreted] AAV gene therapy development was discontinued. So let me clarify, gene therapy, cell therapies will continue, but specifically AAV development is discontinued. That's my understanding. Is that right? And why AAV only is discontinued? Can you explain the background, please? That's my first question. Second question, PDT, Japan plant to be constructed. To have a plant in Japan, what's the advantage? That's my question. Is that a cost, regulations or any other factors? In Japan to have a plant and what advantage -- I don't know much in pharma or other industries. So can you explain that, please?

[解釋] AAV 基因治療開發已停止。所以讓我澄清一下，基因療法、細胞療法將繼續，但特別是 AAV 的開發已經停止。這是我的理解。是對的嗎？為什麼只停產 AAV？你能解釋一下背景嗎？這是我的第一個問題。第二個問題，PDT，日本工廠要建設。在日本建廠有什麼優勢？那是我的問題。這是成本、法規還是任何其他因素？在日本建廠有什麼優勢——我對製藥或其他行業了解不多。那麼你能解釋一下嗎？

Thank you, Muraoka-san. So the first question was on the announcement to discontinue research in AAV gene therapy. So the question is, will we continue to research other gene therapies and cell therapy? And if it's only AAV that we're discontinuing, what is the reason for that? I'd like to ask Andy to comment on that question. And then the second question on our recently announced new plasma-derived therapies facility -- manufacturing facility in Japan. What are the advantages of building that facility in Japan? Is it from a cost basis or a regulatory basis? I'd like to ask Giles to comment on that.

謝謝你，村岡先生。所以第一個問題是關於停止 AAV 基因治療研究的公告。那麼問題來了，我們還會繼續研究其他的基因療法和細胞療法嗎？如果我們只是停止使用 AAV，原因是什麼？我想請 Andy 對這個問題發表評論。然後是關於我們最近宣布的新血漿衍生療法設施——日本製造設施的第二個問題。在日本建設該設施有哪些優勢？是基於成本還是基於監管？我想請 Giles 對此發表評論。

Thanks, Chris, and thanks, Muraoka-san. So firstly, you're correct. We made the focused decision to discontinue AAV gene therapy, but we're still very much engaged in cell therapy, in particular, in our plasma -- in our human-derived NK and gamma delta platforms, and we have earlier efforts in nonviral gene therapy. So the question, why did we decide to discontinue the AAV platform, so 2 comments. The first is we're always looking at the -- at our portfolio and making prioritization decisions to ensure that we're investing in the programs that are most likely to emerge and deliver transforming medicines to patients and drive growth for Takeda.

謝謝，Chris，也謝謝 Muraoka-san。所以首先，你是對的。我們做出了停止 AAV 基因治療的重點決定，但我們仍然非常專注於細胞治療，特別是在我們的血漿中——在我們的人源 NK 和伽馬三角洲平台上，我們在非病毒基因方面有較早的努力治療。所以問題是，為什麼我們決定停止 AAV 平台，所以有 2 條評論。首先，我們一直在審視我們的投資組合併做出優先級決策，以確保我們投資於最有可能出現的項目，並為患者提供轉化藥物並推動武田的增長。

AAV gene therapy has 2 main challenges. The first is that there are a substantial number of individuals in the population that have neutralizing antibodies to AAV and can never be administered in AAV gene therapy. That's probably somewhere in between 30% and 50% of the population. And then secondly, there's a limited [repertoire] of tissues that you can target AAV to.

AAV 基因治療有兩個主要挑戰。首先是人群中有相當數量的個體具有 AAV 中和抗體，並且永遠無法在 AAV 基因治療中進行管理。這可能在人口的 30% 到 50% 之間。其次，你可以將 AAV 靶向的組織 [庫] 有限。

We actually had made great progress in our platform. But as we started to move forward as we started to recognize some of the cost structures, which are -- which have grown considerably over the years as we started to experience some of the challenges in the external landscape, the regulatory and payer bars that will -- started to change to what they were when we started this program 4 or 5 years ago. We came to the conclusion that while there's still opportunity, our resources are better invested in other platforms.

我們實際上在我們的平台上取得了很大的進步。但隨著我們開始向前邁進，我們開始認識到一些成本結構，這些成本結構在過去幾年中大幅增長，因為我們開始經歷外部環境中的一些挑戰，監管和付款人酒吧將-- 開始改變到我們 4 或 5 年前開始這個項目時的樣子。我們得出的結論是，雖然仍有機會，但我們的資源最好投資於其他平台。

And with regards to the question on the investment in the end-to-end manufacturing facility in Japan, plasma-derived therapies remain a high unmet need area in Japan, while demand is growing, timely diagnosis and treatment rates with immunoglobulins are currently much lower than other parts of the world. So regulatory efforts are underway to elevate the standard of care in Japan and introduce more of our global plasma-derived therapies portfolio into Japan through the next decade to improve patient access.

而關於日本端到端製造設施的投資問題，血漿衍生療法在日本仍然是一個高度未滿足的需求領域，雖然需求在增長，但免疫球蛋白的及時診斷和治療率目前要低得多比世界其他地區。因此，監管部門正在努力提高日本的護理標準，並在未來十年內將更多我們的全球血漿衍生療法產品組合引入日本，以改善患者的可及性。

This will be our first global plasma facility in Japan, our biggest ever manufacturing investment in the country and the largest facility of its kind in the country, reflecting our commitment to our long and proud heritage and to Japanese patients. Investment in a state-of-the-art facility with global processes and capabilities have fully leveraged the latest automation and digitalization technologies, will enable us to better serve the growing market in Japan sustainably, in line with local requirements, to secure local supply as well as to add incremental capacity to our global network.

這將是我們在日本的第一個全球血漿設施，是我們在該國有史以來最大的製造投資，也是該國同類設施中最大的，體現了我們對我們悠久而引以為豪的傳統以及對日本患者的承諾。對具有全球流程和能力的最先進設施的投資充分利用了最新的自動化和數字化技術，將使我們能夠根據當地要求更好地可持續地服務於日本不斷增長的市場，以確保當地供應以及為我們的全球網絡增加增量容量。

So we'll be the only leading company to have both local and global plasma products in Japan. And the only local fractionator to have a global footprint, bringing greater supply resilience domestically and overseas. I would also say that investment in existing Takeda manufacturing location, where we have multiple operations like Japan enables us to find cost savings, synergies and efficiencies by leveraging adjacent infrastructure, services and relationships.

因此，我們將成為唯一一家在日本同時擁有本地和全球血漿產品的領先公司。並且是唯一一家擁有全球足蹟的本地分餾廠，為國內外帶來更大的供應彈性。我還要說的是，對現有武田製造基地的投資，我們在日本擁有多個業務，使我們能夠通過利用相鄰的基礎設施、服務和關係來節省成本、協同效應和效率。

Thank you very much for the question. Okay. For the next question, we would like to take from TD Cowen, Michael Nedelcovych.

非常感謝你的提問。好的。對於下一個問題，我們想听取 TD Cowen 和 Michael Nedelcovych 的意見。

There's been a recent proliferation of oral agents in development for immunology indications, including IBD and dermatology. This would seem to be a near midterm risk to drugs in your portfolio like vedolizumab, especially the subcutaneous formulation, but of course, also an opportunity if those markets do shift more toward oral agents from biologics given your own development efforts in that space. So I'm curious how you think about the competitive landscape across these therapeutic areas over the next, say, 5 years? And where you see Takeda's participation being most important?

最近針對免疫學適應症（包括 IBD 和皮膚病學）開發的口服藥物激增。這似乎是您投資組合中的藥物（如維多珠單抗）的近中期風險，尤其是皮下製劑，但當然，如果這些市場確實更多地從生物製劑轉向口服藥物，那麼考慮到您在該領域的開發努力，這也是一個機會。所以我很好奇您如何看待未來（比如 5 年）這些治療領域的競爭格局？您認為武田的參與在哪些方面最為重要？

Thank you, Michael, for that question. Perhaps I'd call on Ramona to answer this question.

邁克爾，謝謝你提出這個問題。也許我會請 Ramona 來回答這個問題。

Yes, absolutely. It's Ramona here, Michael. Thanks for the question. And that is something that we're keeping a close eye on really across our therapy areas. But of course, as you mentioned, in IBD and our autoimmune areas in general. So that was 1 of the drivers behind our acquisition of TAK-279. But I would say, we have a very, very high bar for efficacy and safety in this space. So if we believe something is oral and can come in and really transform the treatment paradigm, that is where we want to focus. And we believe we have that with TAK-279.

是的，一點沒錯。我是雷蒙娜，邁克爾。謝謝你的問題。這是我們在整個治療領域都在密切關注的事情。但是，當然，正如你提到的，在 IBD 和我們一般的自身免疫領域。所以這是我們收購 TAK-279 背後的驅動因素之一。但我要說的是，我們在這個領域的有效性和安全性方面有非常非常高的標準。因此，如果我們相信某些東西是口頭的並且可以進來並真正改變治療範式，那就是我們要關注的地方。我們相信我們擁有 TAK-279。

It's a product that can come in and actually transform the treatment paradigm in psoriasis and the other areas, for instance, IBD, where we'll be investigating it. However, if we feel something is going to come in as an oral and just provide more convenience but not really transformative in the treatment paradigm, we are not going to invest and focus there.

這是一種可以進入並實際改變牛皮癬和其他領域（例如 IBD）的治療模式的產品，我們將在這些領域進行研究。然而，如果我們覺得某些東西會以口頭形式出現，只是提供更多的便利，但在治療範式上並沒有真正的變革，我們就不會在那裡投資和關注。

So we're looking at assets across the board, and we're keeping a close eye on things, including the 1 in development for IBD, as you mentioned, oral vedo. But really, we'd like to see a little bit more data before we determine if that's really going to meet the bar that we have set for efficacy and for transforming the treatment paradigm. Thank you.

所以我們正在全面關注資產，我們正在密切關注事物，包括 IBD 開發中的第一個，正如你提到的，oral vedo。但實際上，在我們確定這是否真的會達到我們為療效和轉變治療模式設定的標準之前，我們希望看到更多的數據。謝謝。

Thank you very much. Okay. I think we probably have time for 1 final question. So I would like to call on Miki Sogi from Bernstein.

非常感謝。好的。我想我們可能有時間回答最後一個問題。所以我想拜會 Bernstein 的 Miki Sogi。

I have a couple of questions regarding TAK-279. So on the Page 19, you disclosed a high-level plan for development program. And can I -- first of all, my first question is this -- the head-to-head study, this is superiority study or noninferiority study against deucravacitinib. And also the duration of study for this head-to-head appear to be a much longer than the other of the Phase III studies that you are planning. Is this because of the longer [time] duration or because of the size of the -- sample size that require longer enrollments?

我有幾個關於 TAK-279 的問題。所以在第 19 頁，你披露了一個高層次的發展計劃。我可以 - 首先，我的第一個問題是 - 頭對頭研究，這是針對 deucravacitinib 的優勢研究或非劣效性研究。而且這種頭對頭的研究持續時間似乎比您計劃的其他 III 期研究要長得多。這是因為 [時間] 持續時間更長，還是因為需要更長時間註冊的樣本量大？

Andy, would you like to comment on that?

安迪，你想對此發表評論嗎？

Yes. Sure. Sure, Miki, thank you for the question. So we haven't finalized the design of the head-to-head study yet, but it's our intent to run the head-to-head study because we believe that TAK-279 is a superior molecule that we can demonstrate that in a clinical study.

是的。當然。當然，Miki，謝謝你的提問。所以我們還沒有完成頭對頭研究的設計，但我們打算進行頭對頭研究，因為我們相信 TAK-279 是一種優秀的分子，我們可以在臨床試驗中證明這一點學習。

And then secondly, please don't look at the size of the graphic to -- as an indication of the study time line. Those are just kind of general indicators as to approximate start times for the various studies.

其次，請不要將圖形的大小視為研究時間表的指示。這些只是各種研究的大致開始時間的一般指標。

Okay. Thank you for your question. So with that, I'd like to bring today's conference call to a close. Thank you very much, everybody, for participating today. And if you have any follow-up questions, please reach out to the Investor Relations team. Thank you very much, and have a good evening or good day.

好的。謝謝你的問題。因此，我想結束今天的電話會議。非常感謝大家今天的參與。如果您有任何後續問題，請聯繫投資者關係團隊。非常感謝，祝您度過一個美好的夜晚或美好的一天。

[Portions of this transcript that are marked [Interpreted] were spoken by an interpreter present on the live call.]

[此記錄中標記為 [已翻譯] 的部分由現場通話中的口譯員說出。]