輝瑞 (PFE) 2023 Q1 法說會逐字稿

Good day, everyone, and welcome to Pfizer's First Quarter 2023 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Mr. Chris Stevo, Senior Vice President and Chief Investor Relations Officer. Please go ahead, sir.

大家好，歡迎來到輝瑞 2023 年第一季度收益電話會議。今天的通話正在錄音中。在這個時候，我想把電話轉給高級副總裁兼首席投資者關係官 Chris Stevo 先生。請繼續，先生。

Thank you, Chelsea. Good morning, everyone. Welcome to Pfizer's first quarter earnings call. I'm joined today by Dr. Albert Bourla, our Chairman and CEO; Dave Denton, our CFO; and Dr. Mikael Dolsten, President of Worldwide Research and Development and Medical.

謝謝你，切爾西。大家，早安。歡迎來到輝瑞第一季度財報電話會議。今天，我們的董事長兼首席執行官 Albert Bourla 博士加入了我的行列；我們的首席財務官 Dave Denton；以及全球研發和醫療總裁 Mikael Dolsten 博士。

Joining for the Q&A session, we will also have Angela Hwang, Chief Commercial Officer and President, Global Biopharmaceuticals business; Aamir Malik, our Chief Business Innovation Officer; Dr. William Pao, our Chief Development Officer; and Doug Lankler, our General Counsel.

參加問答環節的還有全球生物製藥業務首席商務官兼總裁 Angela Hwang；我們的首席業務創新官 Aamir Malik；我們的首席開發官 William Pao 博士；和我們的總法律顧問 Doug Lankler。

Before we begin the call, I wanted to remind you of some logistical items. The materials for this call and other earnings-related materials on the Investor Relations section of pfizer.com. Please see our forward-looking statements disclaimer on Slide 3. Additional information regarding these statements and our non-GAAP financial measures is available in our earnings release and our SEC Forms 10-K and 10-Q under Risk Factors and forward-looking information and factors that may affect future results. Forward-looking statements on the call are subject to substantial risks and uncertainties speak only as of the call's original date, and we undertake no obligation to update or revise any of these statements. With that, I'll turn the call over to Albert.

在我們開始通話之前，我想提醒您一些後勤事項。 pfizer.com 投資者關係部分的本次電話會議材料和其他收益相關材料。請參閱我們在幻燈片 3 上的前瞻性聲明免責聲明。有關這些聲明和我們的非 GAAP 財務措施的更多信息可在我們的收益發布和我們的 SEC 表格 10-K 和 10-Q 中的風險因素和前瞻性信息和可能影響未來結果的因素。電話會議的前瞻性陳述受重大風險和不確定性的影響，僅在電話會議的原始日期發表，我們不承擔更新或修改任何這些陳述的義務。有了這個，我會把電話轉給艾伯特。

Thank you, Chris. Hello, everyone, and thank you for joining us today. Q1 was a solid, foundational quarter in what we expect to be an exciting year for Pfizer and patients. Our financial results were as we anticipated. Our non-COVID revenues grew 5% operationally compared with the year-ago quarter, while overall revenues declined 26% operationally primarily due to a previously communicated and expected decline in Comirnaty revenues. Even with Comirnaty's decline, our COVID franchises remained significant contributor to the business with a combined $7.1 billion in revenues during the quarter. This growth was driven primarily by recently acquired products, Nurtec for migraine and Oxbryta for sickle cell disease, our anti-infective Sulperazon, Eliquis, in the non-valvular atrial fibrillation indication in the U.S., and our Vyndaqel family of products for the treatment of transthyretin amyloid cardiomyopathy.

謝謝你，克里斯。大家好，感謝您今天加入我們。第一季度是一個堅實的基礎季度，我們預計這對輝瑞和患者來說將是激動人心的一年。我們的財務結果符合我們的預期。與去年同期相比，我們的非 COVID 收入在運營上增長了 5%，而總體收入在運營上下降了 26%，這主要是由於之前溝通過的 Comirnaty 收入下降和預期下降。即使 Comirnaty 業務下滑，我們的 COVID 特許經營權仍然是該業務的重要貢獻者，本季度的總收入為 71 億美元。這一增長主要是由最近收購的產品推動的，包括治療偏頭痛的 Nurtec 和治療鐮狀細胞病的 Oxbryta，我們在美國用於非瓣膜性心房顫動適應症的抗感染 Sulperazon Eliquis，以及我們用於治療心房顫動的 Vyndaqel 系列產品甲狀腺素運載蛋白澱粉樣變性心肌病。

We also continue to be proud of our patient impact. During the first quarter, more than 250 million patients were treated with our medicines and vaccines. With this solid start to the year, we remain on track to grow our non-COVID revenues by 7-9% operationally in 2023. That's because the majority of our potential near-term product launches as you can see mapped out on this slide, are expected to occur in the second half of the year, following regulatory approvals where not yet secured. As such, we expect our non-COVID revenues to grow at a faster rate in the second half of the year than in the first.

我們也繼續為我們對患者的影響感到自豪。第一季度，超過 2.5 億患者接受了我們的藥物和疫苗治療。憑藉今年的良好開端，我們仍有望在 2023 年將非 COVID 業務收入增長 7-9%。這是因為正如您在這張幻燈片上看到的那樣，我們大多數潛在的近期產品發布，預計將在今年下半年發生，在尚未獲得監管批准之後。因此，我們預計下半年我們的非 COVID 收入將以比上半年更快的速度增長。

Overall, we are in the midst of an 18-month period in which we expect to launch up to 19 potential new products and indications. Over the first four months of the year, we have made excellent progress toward this goal with the approval of Zavzpret, an expanded indication for Cibinqo to include adolescents, and last week's approval of Prevnar 20 for pediatric use all in the U.S. We also have secured regulatory filing acceptances for elranatamab, for Braftovi and Mektovi for non-small cell lung cancer, and for our RSV maternal vaccine candidate, which if approved would be the first vaccine for administration to pregnant individuals to help protect against the complications of RSV disease in infants from birth through six months.

總體而言，我們正處於為期 18 個月的時期，我們預計將推出多達 19 種潛在的新產品和適應症。在今年的前四個月裡，我們在實現這一目標方面取得了巨大進展，Zavzpret 獲得了批准，Cibinqo 的適應症擴大到包括青少年，上週 Prevnar 20 在美國獲得兒科使用的批准。我們還確保了elranatamab、用於非小細胞肺癌的 Braftovi 和 Mektovi 以及我們的 RSV 母體候選疫苗的監管備案接受，如果獲得批准，這將是第一個用於孕婦的疫苗，以幫助預防嬰兒 RSV 疾病的並發症從出生到六個月。

In addition, the U.S. Food & Drug Administration has granted priority review and the European Medicines Agency has accepted our MAA filing for review of Talzenna for use in combination with Xtandi for patients with newly diagnosed metastatic castration-resistant prostate cancer, based on the TALAPRO-2 results.

此外，美國食品和藥物管理局已授予優先審查權，歐洲藥品管理局已接受我們的 MAA 申請，以審查 Talzenna 與 Xtandi 聯合用於新診斷的轉移性去勢抵抗性前列腺癌患者，基於 TALAPRO- 2 個結果。

Regarding our COVID-19 franchise, we continue to expect 2023 to be a transitional year as the virus continues to mutate and to remove from advanced purchases under government contracts to more transitional supply arrangements in the commercial model for both Comirnaty and Paxlovid in the U.S. As previously discussed, in 2023 and 2024, we expect vaccine utilization to decline compared with 2022. Then starting in 2025 and continuing in 2026 and beyond, we expect to see an increase in COVID-19 vaccination rates assuming the successful development and approval of various COVID combination vaccines. Outside the U.S., we expect these general trends to be similar with some variations from country to country.

關於我們的 COVID-19 特許經營權，我們繼續預計 2023 年將是一個過渡年，因為病毒會繼續變異，並從政府合同下的預先採購中移除，以在美國的 Comirnaty 和 Paxlovid 的商業模式中進行更多的過渡性供應安排。之前討論過，在 2023 年和 2024 年，我們預計疫苗使用率將比 2022 年下降。然後從 2025 年開始並持續到 2026 年及以後，假設各種 COVID-19 疫苗的成功開發和批准，我們預計 COVID-19 疫苗接種率將增加聯合疫苗。在美國以外，我們預計這些總體趨勢與國家/地區之間存在一些差異。

Regarding Paxlovid, we continue to expect the government inventory that was built around the world last year to be absorbed by the end of this year. We then expect that in years '24 and beyond, the courses sold and courses used were more closely align. With its robust efficacy, consistent safety profile and potential to help mitigate the burden of COVID-19 on patients and their families, health system and society, Paxlovid is proving to be an important and durable complementary tool to vaccination strategies for the estimated 40% of the global adult population at high risk for progressing to severe disease.

關於 Paxlovid，我們繼續預計去年全球建立的政府庫存將在今年年底前被吸收。然後，我們預計在 24 年及以後，銷售的課程和使用的課程會更緊密地結合在一起。憑藉其強大的功效、一致的安全性和幫助減輕 COVID-19 對患者及其家人、衛生系統和社會的負擔的潛力，Paxlovid 被證明是疫苗接種策略的重要且持久的補充工具，估計有 40% 的人全球成年人口處於發展為嚴重疾病的高風險中。

Now let's take a look at Pfizer's next potential moonshot, the battle against cancer. Oncology remains a core therapeutic area for Pfizer, and we believe the proposed acquisition of Seagen will enhance our position in this important space. Integration planning is already underway and we continue to expect the deal to close in late 2023 or early 2024, subject to the satisfaction of customary closing conditions. By combining Seagen's category-leading antibody-drug conjugate technology with Pfizer's scale, expertise and capabilities, we believe we can accelerate potential breakthroughs in cancer medicines and introduce new solutions to patients around the world. The potential combined commercial infrastructure for Pfizer and Seagen will be 3x the size of that of Seagen alone in the U.S. and 4, 5x larger globally. As a result, we believe acquiring Seagen could contribute more than $10 billion in 2030 risk-adjusted revenue with potential significant growth beyond 2030.

現在讓我們來看看輝瑞的下一個潛在的登月計劃，即與癌症的鬥爭。腫瘤學仍然是輝瑞的核心治療領域，我們相信對 Seagen 的擬議收購將加強我們在這一重要領域的地位。整合計劃已經在進行中，我們繼續預計該交易將在 2023 年底或 2024 年初完成，前提是滿足慣例成交條件。通過將 Seagen 領先的抗體藥物偶聯技術與輝瑞的規模、專業知識和能力相結合，我們相信我們可以加速癌症藥物的潛在突破，並為世界各地的患者推出新的解決方案。輝瑞和 Seagen 的潛在聯合商業基礎設施規模將是 Seagen 在美國的 3 倍，在全球範圍內是 4、5 倍。因此，我們認為收購 Seagen 可以在 2030 年貢獻超過 100 億美元的風險調整後收入，並在 2030 年之後實現顯著增長。

Even with the Seagen deal, given the strength of our balance sheet and cash flows, we continue to have the flexibility to take additional actions to create shareholder value. Dave will provide more details on this during this presentation.

即使與 Seagen 交易，鑑於我們的資產負債表和現金流的實力，我們仍然可以靈活地採取額外行動來創造股東價值。 Dave 將在本次演示中提供更多詳細信息。

One of the key areas of focus for Pfizer in 2023 is continuing to build trust, which is a key asset for every biopharmaceutical company. Since the beginning of the year, we have received 2 accolades that demonstrate we are doing just that. In February, Pfizer was named to the top 10 of Fortune's Most Admired Companies List for the second year in a row. And in March, Ethisphere recognized Pfizer as one of the world's most ethical companies, also for the second year in a row.

輝瑞在 2023 年的重點關注領域之一是繼續建立信任，這是每家生物製藥公司的關鍵資產。自今年年初以來，我們獲得了 2 項榮譽，證明我們正在這樣做。 2 月，輝瑞連續第二年入選《財富》雜誌最受讚賞公司排行榜前 10 名。 3 月，Ethisphere 連續第二年將輝瑞評為世界上最具商業道德的公司之一。

At Pfizer, trust is everything. It gives us our license to operate, allows us to attract the best talent and enables us to deliver breakthroughs that change patients' lives.

在輝瑞，信任就是一切。它為我們提供了經營許可，使我們能夠吸引最優秀的人才，並使我們能夠實現改變患者生活的突破。

With that, I will turn it over to Dave. After Dave, Mikael will provide an update on R&D pipeline. Dave?

有了這個，我會把它交給戴夫。在 Dave 之後，Mikael 將提供研發管道的最新信息。戴夫？

Thank you, Albert, and good morning, everyone. I want to begin with Pfizer's capital allocation strategy before we dive into additional commentary about our quarterly performance and importantly, our outlook for the remainder of 2023. As you know, our strategy includes 3 main pillars: reinvesting in our business, growing and paying dividends and repurchasing our shares. In the first 3 months of 2023, we have invested $2.5 billion in internal R&D and returned $2.3 billion to shareholders via our quarterly dividend. And importantly, allocated approximately $43 billion for the proposed Seagen acquisition. Over the last few years, we have reinvested heavily into our business to drive long-term growth and enhance long-term shareholder value. We have invested in Pfizer's own science while acquiring the best external science to supplement our pipeline.

謝謝你，艾伯特，大家早上好。我想先從輝瑞的資本配置策略開始，然後再深入探討我們的季度業績，重要的是，我們對 2023 年剩餘時間的展望。如您所知，我們的戰略包括 3 個主要支柱：對我們的業務進行再投資、增長和支付股息並回購我們的股份。 2023 年前 3 個月，我們在內部研發方面投入了 25 億美元，並通過季度股息向股東返還了 23 億美元。重要的是，為擬議中的 Seagen 收購分配了大約 430 億美元。在過去幾年中，我們對我們的業務進行了大量再投資，以推動長期增長並提高長期股東價值。我們投資于輝瑞自己的科學，同時獲得最好的外部科學來補充我們的管道。

Since 2022, we have invested approximately $70 billion, including Seagen in business development. In addition, we have continued to grow our dividend. For the past 14 years, we have raised our dividend annually. Since 2010, our quarterly cash dividend grew from $0.16 a share to $0.41 a share in 2023.

自 2022 年以來，我們已投資約 700 億美元，其中包括用於業務發展的 Seagen。此外，我們繼續增加股息。在過去的 14 年裡，我們每年都提高股息。自 2010 年以來，我們的季度現金股息從每股 0.16 美元增加到 2023 年的每股 0.41 美元。

Looking ahead, as we exit this unprecedented period of anticipated launches, we would expect to achieve operating margin improvement over time. As we began to delever our capital structure after the closing of the Seagen transaction, we expect to return to a more balanced capital allocation mix between our 3 pillars. While we will continue to invest in our business, we do expect more balance between that priority and returning value to our shareholders via increased dividends and value-enhancing share repurchases. Our capital allocation strategy is squarely focused on driving shareholder value, while at the same time, remaining committed to a high investment-grade Tier 1 commercial paper rating. Now turning to the quarter.

展望未來，隨著我們結束這個前所未有的預期發布期，我們預計隨著時間的推移將實現營業利潤率的提高。隨著我們在 Seagen 交易結束後開始去槓桿化我們的資本結構，我們預計將在我們的三大支柱之間恢復更平衡的資本配置組合。雖然我們將繼續投資於我們的業務，但我們確實希望通過增加股息和提高價值的股票回購，在這一優先事項和為股東回報價值之間取得更多平衡。我們的資本配置策略專注於推動股東價值，同時繼續致力於高投資級一級商業票據評級。現在轉向季度。

As Albert said, our results were in line with our expectations, albeit slightly better than consensus. As expected, overall revenues declined 26% operationally, primarily driven by the anticipated decline in commodity, which was partially offset by strong Paxlovid sales. I want to point out that our COVID-19 products produced $7.1 billion in revenues in the first quarter alone. Our non-COVID operational revenue growth was solid at 5% year-over-year. Primarily driving this growth was the inclusion of Nurtec ODT and Oxbryta and an increase in Sulperazon revenues in China. Revenues for Eliquis in the U.S. and the Vyndaqel family globally also contributed to this growth.

正如 Albert 所說，我們的結果符合我們的預期，儘管略好於共識。正如預期的那樣，運營總收入下降了 26%，這主要是由於商品的預期下降，部分被 Paxlovid 的強勁銷售所抵消。我想指出，我們的 COVID-19 產品僅在第一季度就產生了 71 億美元的收入。我們的非 COVID 營業收入同比穩定增長 5%。推動這一增長的主要原因是 Nurtec ODT 和 Oxbryta 的納入以及 Sulperazon 在中國的收入增加。 Eliquis 在美國和 Vyndaqel 家族在全球的收入也為這一增長做出了貢獻。

Now I want to remind you of the seasonality of some of our products. In the first quarter, Nurtec ODT and Oxbryta typically have lower sales quarter-on-quarter due to annual copay reset dynamics with higher sales anticipated in the latter quarters. Most importantly, both products continue to experience strong growth in demand. Sulperazon revenues increased more than $100 million year-over-year due to higher demand in China during the quarter, which we do not expect to be sustained going forward. The demand was due to increased bacterial infection from patients being hospitalized for COVID. To help ensure the success of the expected launches of a large number of new and acquired products and indications, we've increased our investments in SI&A. These investments are squarely focused on Pfizer's 2025 to 2030 growth aspirations.

現在我想提醒您注意我們某些產品的季節性。在第一季度，由於年度共付額重置動態，Nurtec ODT 和 Oxbryta 的季度銷售額通常較低，而後幾個季度的銷售額預計會更高。最重要的是，這兩種產品的需求繼續強勁增長。由於本季度中國的需求增加，Sulperazon 的收入同比增長超過 1 億美元，我們預計這種情況不會持續下去。需求是由於 COVID 住院患者的細菌感染增加。為幫助確保大量新產品和收購產品及適應症的預期發布取得成功，我們增加了對 SI&A 的投資。這些投資直接聚焦于輝瑞 2025 年至 2030 年的增長目標。

Now moving to the bottom line. Reported diluted earnings per share this quarter declined by 29% to $0.97 a share, while adjusted diluted earnings per share of $1.23 declined 20% on an operational basis during the quarter. Once again, this quarter, foreign exchange movements significantly impacted our results, reducing first quarter revenues by $730 million or 3% and adjusted diluted earnings per share by $0.07 or 4% compared to LY.

現在轉到底線。本季度報告的攤薄每股收益下降 29% 至每股 0.97 美元，而調整後的攤薄每股收益為 1.23 美元，在本季度的運營基礎上下降了 20%。本季度，外匯變動再次對我們的業績產生重大影響，與 LY 相比，第一季度收入減少 7.3 億美元或 3%，調整後的攤薄每股收益減少 0.07 美元或 4%。

Now turning to the full year financial outlook for the company. Our full year 2023 guidance remains unchanged. On a total company basis, we continue to expect revenues of $67 billion to $71 billion, reflecting an operational decline of 31% at the midpoint, with 5% operational growth in our non-COVID revenues this quarter, we are on track to achieve our non-COVID revenue guidance of 7% to 9% operational growth for the full year. Given that a large number of launches are expected to incur in the third and fourth quarter of '23, we anticipate our quarterly revenues will not be linear this year and that our non-COVID revenues will grow more quickly in the back half of this year versus the first half of '23.

現在轉向公司的全年財務展望。我們的 2023 年全年指引保持不變。就公司整體而言，我們繼續預計收入為 670 億美元至 710 億美元，反映出中點運營下降 31%，本季度我們的非 COVID 收入增長 5%，我們有望實現我們的目標全年非 COVID 收入指引為 7% 至 9% 的運營增長。鑑於預計 23 年第三和第四季度將進行大量發布，我們預計今年的季度收入將不會呈線性增長，並且我們的非 COVID 收入將在今年下半年增長得更快與 23 年上半年相比。

In terms of our COVID products, Comirnaty and Paxlovid, we expect sales to trend more seasonally this year. Given these dynamics, we expect significantly lower sales contributions from our COVID products in the second quarter versus the first quarter. In fact, given the anticipated timing of approvals for a fall vaccine with strain change, we would expect more substantial vaccine deliveries to start in September, which is late in the U.S. third quarter and the beginning of our international fourth quarter. With respect to Paxlovid, we continue to expect '23 to be a transitional year as we anticipate shifting to a commercial market in the second half of this year. We are reaffirming our adjusted diluted earnings per share guidance range of $3.25 to $3.45 per share. On a full year basis, we expect that foreign exchange will have an unfavorable impact compared with full year 2022 of approximately $0.13 on adjusted diluted earnings per share. We are also reaffirming the remaining components of our full year 2023 guidance which you can find in the appendix of the Q1 '23 earnings presentation.

就我們的 COVID 產品 Comirnaty 和 Paxlovid 而言，我們預計今年的銷售趨勢將更具季節性。鑑於這些動態，我們預計第二季度 COVID 產品的銷售貢獻將大大低於第一季度。事實上，考慮到秋季變毒疫苗的預期批准時間，我們預計將在 9 月開始交付更多疫苗，這是美國第三季度末和我們國際第四季度的開始。關於 Paxlovid，我們繼續預計 23 年將是過渡年，因為我們預計將在今年下半年轉向商業市場。我們重申調整後的稀釋每股收益指導範圍為每股 3.25 美元至 3.45 美元。從全年來看，我們預計與 2022 年全年相比，外匯將對調整後的攤薄每股收益產生約 0.13 美元的不利影響。我們還重申了我們 2023 年全年指導的其餘部分，您可以在 Q1 '23 收益報告的附錄中找到這些部分。

So in closing, this is an exciting period for Pfizer as we continue to invest to drive long-term growth and, importantly, enhance long-term shareholder value.

因此，最後，這對輝瑞來說是一個激動人心的時期，因為我們繼續投資以推動長期增長，重要的是，提高長期股東價值。

With that, now let me turn it over to Mikael.

有了這個，現在讓我把它交給 Mikael。

Thank you, Dave. Today I’ would like to start off with one of the four pillars of our oncology portfolio, which are breast, urogenital, blood cancers and precision medicine.

謝謝你，戴夫。今天，我想從我們腫瘤學產品組合的四大支柱之一開始，即乳腺癌、泌尿生殖系統、血癌和精準醫學。

Within urogenital, prostate cancer is an area in which we have strong momentum. Recent positive study results further strengthen our franchise, building upon the global standard of care set by XTANDI, and underscoring our long-standing commitment to the pursuit of breakthroughs that define new standards of care in prostate cancer.

在泌尿生殖系統中，前列腺癌是我們發展勢頭強勁的領域。最近積極的研究結果進一步加強了我們的特許經營權，建立在 XTANDI 制定的全球護理標準的基礎上，並強調了我們對追求定義前列腺癌護理新標準的突破的長期承諾。

I’ will highlight data from two Phase 3 studies, EMBARK and TALAPRO-2, as well as early, but promising signals from our EZH2 inhibitor, each of which has the potential to reach broader patient populations across the treatment continuum in prostate cancer. Final analysis from TALAPRO-2, evaluating our potential blockbuster PARP inhibitor TALZENNA, in combination with XTANDI were presented at ASCO GU. Results showed significant and clinically meaningful improvement across the all-comers population in radiographic progression-free survival or rPFS, in men with metastatic castration-resistant prostate cancer with or without homologous recombination repair or HRR gene mutation. There was a 37% reduction in risk of disease progression.

我將重點介紹兩項 3 期研究 EMBARK 和 TALAPRO-2 的數據，以及來自我們的 EZH2 抑製劑的早期但有希望的信號，每一項都有可能在前列腺癌的連續治療過程中覆蓋更廣泛的患者群體。 TALAPRO-2 的最終分析評估了我們潛在的重磅炸彈 PARP 抑製劑 TALZENNA 與 XTANDI 的結合，在 ASCO GU 上進行了展示。結果顯示，無論有無同源重組修復或 HRR 基因突變的轉移性去勢抵抗性前列腺癌男性，在放射學無進展生存期或 rPFS 方面，所有參與者均有顯著且具有臨床意義的改善。疾病進展的風險降低了 37%。

Median rPFS in patients treated with TALZENNA and XTANDI was not reached at the time of analysis versus 21.9 months for placebo plus XTANDI. A trend in overall survival favoring TALZENNA plus XTANDI was also observed, though these data are immature. The final OS data will be reported once the predefined number of survival events has been reached. Treatment with TALZENNA and XTANDI resulted in statistically significant improvement in overall response rates, which suggests a potential cooperative effect between the two treatments.

在分析時未達到接受 TALZENNA 和 XTANDI 治療的患者的中位 rPFS ，而安慰劑加 XTANDI 為21.9個月。還觀察到有利於 TALZENNA 加 XTANDI 的總體生存趨勢，儘管這些數據還不成熟。一旦達到預定義的生存事件數，將報告最終的 OS 數據。用 TALZENNA 和 XTANDI 治療導致總體反應率在統計學上顯著提高，這表明兩種治療之間存在潛在的協同作用。

The U.S. FDA has granted priority review for our sNDA for TALZENNA in combo with XTANDI for metastatic castration-resistant prostate cancer with a decision expected in '23. The ongoing TALAPRO-3 study, if successful, may further expand the reach of this potential blockbuster into the HRR-deficient metastatic castration sensitive population. We recently presented data from our Phase III EMBARK study, evaluating XTANDI plus leuprolide in men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence at the American Urological Association's '23 Annual Meeting. The study met its primary endpoint with statistically significant and clinically meaningful improvement in metastasis-free survival with a 58% reduction in risk for radiographic progression or death. Key secondary endpoints were met, including time to PSA progression. These results suggest XTANDI, the only novel hormone therapy approved for 3 disease states of prostate cancer in the U.S., has the potential if approved to expand to patients in the hormone-sensitive or castration-sensitive setting for the first time.

美國 FDA 已批准我們的 TALZENNA sNDA 與 XTANDI 聯合治療轉移性去勢抵抗性前列腺癌的優先審查，預計將在 23 年做出決定。正在進行的 TALAPRO-3 研究如果成功，可能會進一步擴大這種潛在重磅炸彈的應用範圍，使其進入 HRR 缺陷的轉移性去勢敏感人群。我們最近在美國泌尿外科協會的第 23 屆年會上展示了我們的 III 期 EMBARK 研究的數據，該研究評估了 XTANDI 加亮丙瑞林在患有非轉移性激素敏感性前列腺癌且生化復發風險高的男性中的療效。該研究達到了其主要終點，即無轉移生存期有統計學意義和臨床意義的改善，影像學進展或死亡風險降低了 58%。達到了關鍵的次要終點，包括 PSA 進展的時間。這些結果表明，XTANDI 是美國唯一批准用於前列腺癌 3 種疾病狀態的新型激素療法，如果獲得批准，它有可能首次擴展到激素敏感或去勢敏感環境中的患者。

Next, I'd like to share early data from one of our next wave candidate, a potential first-in-class and best-in-class EZH2 inhibitor, which we shorthand as 1497. EZH2 is an epigenetic transcriptional repressor that frequently over-expressed in prostate cancer. We believe that inhibition of EZH2 may provide synergistic effects in combination with XTANDI with a potential to address unmet needs of patients with androgen-sensitive and resistant disease. Here, our data from our ongoing Phase I/II study evaluating 1497 in second-line mCRPC patients with prior abiraterone and/or XTANDI and up to one line of chemo.

接下來，我想分享來自我們下一波候選者之一的早期數據，這是一種潛在的同類首創和同類最佳 EZH2 抑製劑，我們簡稱為 1497。EZH2 是一種表觀遺傳轉錄抑制因子，經常過度-在前列腺癌中表達。我們認為，抑制 EZH2 可能與 XTANDI 聯合產生協同效應，有可能解決雄激素敏感和耐藥疾病患者未滿足的需求。在這裡，我們的數據來自我們正在進行的 I/II 期研究，該研究評估了 1497 名既往接受過阿比特龍和/或 XTANDI 以及最多一線化療的二線 mCRPC 患者。

On the left are updated data from a Phase I dose escalation study shared at ESMO last year. These encouraging results show durable antitumor activity in both XTANDI-naive and experienced patients, with all XTANDI-naive patients having received prior abiraterone. Importantly, this suggests that the addition of our EZH2 inhibitor has the potential to sensitize XTANDI-resistant tumors, which is an increasing clinical unmet need. The early rPFS data also highly encouraging, reaching 8.7 months in XTANDI-experienced and 17.1 months in XTANDI-naive, both of which are notably longer than historical controls. For example, in the control arm of the CARD study, rPFS for XTANDI alone was only 4.8 months in XTANDI-naive patients.

左邊是去年在 ESMO 上分享的 I 期劑量遞增研究的更新數據。這些令人鼓舞的結果表明，在 XTANDI 初治患者和有經驗患者中均具有持久的抗腫瘤活性，所有 XTANDI 初治患者都曾接受過阿比特龍治療。重要的是，這表明添加我們的 EZH2 抑製劑有可能使 XTANDI 耐藥腫瘤敏感，這是一個日益增長的未滿足的臨床需求。早期的 rPFS 數據也非常令人鼓舞，在 XTANDI 經驗中達到 8.7 個月，在 XTANDI-naive 中達到 17.1 個月，兩者都明顯長於歷史對照。例如，在 CARD 研究的對照組中，單獨使用 XTANDI 的 rPFS 在未接受過 XTANDI 治療的患者中僅為 4.8 個月。

And although cross-trial comparison cannot be made these results in combination with emerging objective response rate and PSA50 response are supportive of the contribution of our EZH2 inhibitor candidate in driving these responses. From a safety perspective, the combination was generally well tolerated with mostly Grade 1 and 2 events. The randomized Phase II study in second-line mCRPC is ongoing with data expected early '24.

儘管無法進行交叉試驗比較，但結合新出現的客觀反應率和 PSA50 反應，這些結果支持我們的 EZH2 候選抑製劑在推動這些反應方面的貢獻。從安全的角度來看，該組合通常耐受性良好，主要是 1 級和 2 級事件。二線 mCRPC 的隨機 II 期研究正在進行中，數據預計在 24 年初公佈。

Now we turn to the potential for near-term growth across our respiratory vaccine franchise. Prevnar 20 or our 20-valent pneumococcal conjugate vaccine is now approved for children aged 6 weeks through 17 years. We are confident in our ability to maintain leadership in the pneumococcal vaccine space with Prevnar 20, which offers the broadest serotype coverage of any pediatric pneumococcal conjugate vaccine helping to protect against the 20 serotypes in the vaccine. We have strong momentum with our RSV vaccine candidate, having received a positive VRBPAC committee vote, supporting potential approval to help combat RSV in older adults and PDUFA dates for our older adults and maternal indications in quick succession in the coming months. And just last month, New England Journal of Medicine published results from the 2 positive Phase III studies.

現在我們轉向我們呼吸道疫苗特許經營權的近期增長潛力。 Prevnar 20 或我們的 20 價肺炎球菌結合疫苗現已獲准用於 6 周至 17 歲的兒童。我們有信心憑藉 Prevnar 20 保持在肺炎球菌疫苗領域的領先地位，它提供了任何兒科肺炎球菌結合疫苗中最廣泛的血清型覆蓋範圍，有助於預防疫苗中的 20 种血清型。我們的 RSV 候選疫苗勢頭強勁，已獲得 VRBPAC 委員會的積極投票，支持可能批准幫助對抗老年人的 RSV 和我們老年人的 PDUFA 日期以及未來幾個月快速連續的孕產婦適應症。就在上個月，新英格蘭醫學雜誌發表了 2 項陽性 III 期研究的結果。

Emerging data from the middle of the second RSV season in the Northern Hemisphere in the Phase III older adult study support meaningful durable vaccine efficacy. We will share the data once completed. In the coming months, we plan to start the Phase III study of the RSV vaccine candidate in 18- to 60-year-olds at high-risk for RSV and in immunocompromised adults 18 and over and a Phase I study in 2 to 18 year old at high risk.

III 期老年研究中北半球第二個 RSV 季節中期的新數據支持有意義的持久疫苗效力。我們將在完成後共享數據。在接下來的幾個月裡，我們計劃在 18 至 60 歲的 RSV 高危人群和 18 歲及以上的免疫功能低下的成年人中開展 RSV 候選疫苗的 III 期研究，並在 2 至 18 歲的人群中開展 I 期研究高危老人。

With the potential to expand broadly the reach of our vaccine candidate, both to those age 18 to 60 with high-risk condition as well as to pediatrics and adolescents.

有可能廣泛擴大我們候選疫苗的覆蓋範圍，包括 18 至 60 歲的高危人群以及兒科和青少年。

Our RSV-flu coadministration study met its primary endpoint, demonstrating non-inferiority for all four flu strains and the RSV A and B strains. This suggest the RSV vaccine candidate, if approved, could be co-administered with flu vaccination and add an important component of seasonal protection against respiratory pathogens.

我們的 RSV-flu 聯合給藥研究達到了主要終點，證明了所有四種流感毒株以及 RSV A 和 B 毒株的非劣效性。這表明 RSV 候選疫苗如果獲得批准，可以與流感疫苗聯合接種，並增加針對呼吸道病原體的季節性保護的重要組成部分。

Finally, the FDA recently updated the EUA for our Omicron BA.4/5 bivalent COVID-19 vaccine to enable those at high risk of severe COVID-19 illness, including the elderly and immunocompromised to partner with the health care providers to be proactive in helping them to protect themselves against COVID-19. We anticipate another update from FDA in June that will provide guidance on COVID-19 vaccine strains and vaccination timing for the 2023 fall and winter season. Beyond vaccines, antivirals are an important component of our strategy in respiratory viruses. Here, we share data for the first time from our second gen oral COVID-19 antiviral candidate, a potent and selective SARS-CoV-2 Mpro inhibitor that is currently in Phase I. We designed this candidate to achieve clinical exposure that would have similar antiviral activity to PAXLOVID, but without the need for ritonavir boosting and with the potential for reduced drug interactions.

最後，FDA 最近更新了我們的 Omicron BA.4/5 雙價 COVID-19 疫苗的 EUA，以使那些處於嚴重 COVID-19 疾病高風險中的人，包括老年人和免疫功能低下的人能夠與醫療保健提供者合作，積極主動地幫助他們保護自己免受 COVID-19 的侵害。我們預計 FDA 將在 6 月發布另一次更新，為 2023 年秋冬季節提供有關 COVID-19 疫苗株和疫苗接種時間的指導。除了疫苗，抗病毒藥物是我們應對呼吸道病毒的戰略的重要組成部分。在這裡，我們首次分享了我們的第二代口服 COVID-19 抗病毒候選藥物的數據，這是一種強效和選擇性的 SARS-CoV-2 Mpro 抑製劑，目前處於 I 期。我們設計該候選藥物是為了實現與臨床暴露相似的對 PAXLOVID 的抗病毒活性，但不需要利托那韋加強，並有可能減少藥物相互作用。

Early results from Phase I dose escalation are encouraging with no dose-limiting safety tolerability findings. Dosing achieve concentration manyfold over in vitro EC90 and is, therefore, expected to have similar antiviral activity to PAXLOVID. On the right of preliminary results from our Phase I pharmacokinetic study of midazolam drug interaction, which is a well-known standard for indicating CYP3A4-mediated drug-drug interaction.

I 期劑量遞增的早期結果令人鼓舞，沒有發現劑量限制安全耐受性。給藥後濃度達到體外 EC90 的許多倍，因此，預期具有與 PAXLOVID 相似的抗病毒活性。右邊是我們關於咪達唑侖藥物相互作用的 I 期藥代動力學研究的初步結果，這是指示 CYP3A4 介導的藥物相互作用的眾所周知的標準。

These data show there is a lack of such drug-drug interactions, suggesting there may be no related restrictions of co-dosing with drugs metabolized by CYP enzymes.

這些數據表明缺乏這種藥物間相互作用，表明與 CYP 酶代謝的藥物共同給藥可能沒有相關限制。

Based on these encouraging data, we are planning to advance to Phase II dose-ranging study in the first half of this year.

基於這些令人鼓舞的數據，我們計劃在今年上半年推進 II 期劑量範圍研究。

In addition to the assets I spoke about today, we continue to make progress on the pipeline with more than 25 milestones recently achieved or anticipated through the first half of '24. As examples, in inflammation and immunology, the FDA has approved our sNDA for CIBINQO, enabling a label expansion for adolescents with moderate-to-severe dermatitis. In internal medicine, ZAVZPRET, the migraine nasal spray has received FDA approval expanding our migraine portfolio. Recently, the FDA Advisory Committee voted in support of PAXLOVID's favorable benefit-risk profile with a soon PDUFA date in May.

除了我今天談到的資產外，我們繼續在管道上取得進展，最近實現或預計到 24 年上半年實現了超過 25 個里程碑。例如，在炎症和免疫學方面，FDA 已批准我們用於 CIBINQO 的 sNDA，從而為患有中度至重度皮炎的青少年擴大標籤範圍。在內科領域，偏頭痛鼻腔噴霧劑 ZAVZPRET 已獲得 FDA 批准，擴大了我們的偏頭痛產品組合。最近，FDA 諮詢委員會投票支持 PAXLOVID 有利的收益-風險概況，PDUFA 日期很快將在 5 月公佈。

In closing, we are very excited about the potentially transformative catalyst expressed across the entire pipeline as we work with continued urgency to bring breakthroughs to patients. Thank you.

最後，我們對整個管道中表達的潛在變革催化劑感到非常興奮，因為我們繼續緊迫地工作，為患者帶來突破。謝謝。

Let me turn it over to Chris to start Q&A.

讓我把它交給克里斯開始問答。

Thank you, Mikael. All right. Chelsea, please queue up us for Q&A. We have at least 30 minutes for Q&A.

謝謝你，米凱爾。好的。 Chelsea，請讓我們排隊接受問答。我們至少有 30 分鐘的問答時間。

(Operator Instructions) And our first question will come from Umer Raffat with Evercore ISI.

（操作員說明）我們的第一個問題將來自 Evercore ISI 的 Umer Rafat。

I have 2 here, if I may. First, your expectations on the cisplatin eligible in the EV-302 trial especially because it's so significant to the acquisition you're going down the track on? And then secondly, based on my...

如果可以的話，我這裡有 2 個。首先，您對 EV-302 試驗中符合條件的順鉑的期望，尤其是因為它對您正在進行的收購如此重要？其次，基於我的...

Umer, can you repeat the question, I'm not sure, we understood it.

Umer，你能重複這個問題嗎，我不確定，我們理解它。

Sure. On the Seagen trial on PADCEV, EV-302, I know there's been a huge emphasis on cohort K, which is a cisplatin ineligible. My question is, this ongoing trial also has cisplatin-eligible, which is 2/3 of the target population. What's your expectation there? Because it was -- I felt like it was not a coincidence, Seagen never showed any data disclosure from the eligibles Part A. And secondly, for the guidance for the full year, I noticed there's perhaps $1 billion-or-so worth of contribution from new launches. And I'm just trying to make sense of that in light of the fact that these are going to be launches sort of in the fall of this year? I realize it's important like RC (inaudible), but is it reasonable to expect $1 billion-or-so, so early into the launch from those?

當然。在關於 PADCEV、EV-302 的 Seagen 試驗中，我知道人們非常重視隊列 K，這是不符合順鉑資格的。我的問題是，這項正在進行的試驗也符合順鉑的條件，佔目標人群的 2/3。你在那裡有什麼期望？因為它 - 我覺得這不是巧合，Seagen 從未展示過符合條件的 A 部分的任何數據披露。其次，對於全年的指導，我注意到可能有 10 億美元左右的貢獻從新發布。鑑於這些將在今年秋天推出的事實，我只是想弄清楚這一點？我意識到它像 RC（聽不清）一樣重要，但是期望 10 億美元左右是合理的嗎？

Yes. Thank you very much. Angela, why don't you take the second question about the guidance, about $1 billion estimate sales in the last quarter.

是的。非常感謝。安吉拉，你為什麼不回答關於指導的第二個問題，上個季度的銷售額估計約為 10 億美元。

Sure. So from a launch perspective, I think the 2 big ones to look out for this year are Prevnar 20 peds and RSV adult. And as you know, it goes through the typical ACIP process or recommendation and then launches can really only happen or commercialization of the publication of MMWR. So if you consider all of that, that puts us into fourth quarter, which is when Prevnar 20 peds as well as when RSV older adult will actually be commercialized and revenue being generated. And so yes, we are anticipating that there's going to be a big bolus of revenue because, first of all, if you think about Prevnar 20 peds, that is going to be a conversion from Prevnar 13 peds and Prevnar 13 today has a significant market share, right, in pediatric pneumococcal is 80% market share.

當然。因此，從發布的角度來看，我認為今年值得關注的兩大產品是 Prevnar 20 peds 和 RSV adult。如您所知，它經過典型的 ACIP 流程或建議，然後發布真的只能發生或 MMWR 的出版物商業化。因此，如果你考慮所有這些，那麼我們將進入第四季度，也就是 Prevnar 20 peds 以及 RSV 老年人實際商業化並產生收入的時候。所以是的，我們預計會有大量收入，因為首先，如果你考慮 Prevnar 20 peds，那將是 Prevnar 13 peds 的轉換，而 Prevnar 13 今天有一個重要的市場份額，對，在兒科肺炎球菌中是 80% 的市場份額。

So we're going to be converting those accounts, the physicians, the inventory, all of that from 13 over to 20. And so if you look at, I guess, a good analogue for that would be our Prevnar 20 adult launch, which was the conversion of the Prevnar 13 adult launch. And there, it went really well. Today, we have, what, over 95% market share. And then, of course, the second one is the RSV adult. And there, it plugs into an already established commercial infrastructure that we've built around COVID, around the Prevnar franchise, the adult franchise. It comes at a great time during the fall in the winter when vaccinations for respiratory vaccines actually increases. So there's a lot of reasons to believe why that fourth quarter is going to be a really big quarter for both Prevnar peds as well as RSV adult.

因此，我們將把這些賬戶、醫生、庫存，所有這些從 13 個以上轉換為 20 個。所以，如果你看一下，我想，一個很好的類比是我們的 Prevnar 20 成人發布，它是 Prevnar 13 成人發射的轉換。在那裡，一切都很順利。今天，我們擁有超過 95% 的市場份額。然後，當然，第二個是 RSV 成人。在那裡，它插入了我們圍繞 COVID 建立的已經建立的商業基礎設施，圍繞 Prevnar 特許經營權，成人特許經營權。它正值秋季和冬季的好時機，此時呼吸道疫苗的接種量實際上有所增加。因此，有很多理由相信為什麼第四季度對於 Prevnar peds 和 RSV adult 來說都是一個非常重要的季度。

Thank you, Angela. On the question about the Seagen asset, although it should be very careful because we can't comment on that. But maybe you can make William quick comments generally speaking.

謝謝你，安吉拉。關於 Seagen 資產的問題，雖然它應該非常小心，因為我們不能對此發表評論。但也許你可以讓 William 在一般情況下快速發表評論。

Yes, sure. I would say we're just very excited about the recent approval in the first-line ineligible population, which Seagen just got, which is about 8,000 to 9,000 patients in the U.S. And we're excited to see additional data coming in the first-line cisplatin eligible EV-302 study, which, as you know, is Padcev plus pembro versus platinum gemcitabine. We can't comment any further at Seagen study. And it's that positive that would increase the eligible population by another 10,000 to 12,000.

是的，當然。我想說我們對最近在一線不合格人群中的批准感到非常興奮， Seagen 剛剛獲得，在美國大約有 8,000 到 9,000 名患者。我們很高興看到更多的數據首先出現 -順鉑符合條件的 EV-302 研究，如您所知，是 Padcev 加 pembro 對比鉑吉西他濱。我們無法在 Seagen 研究中進一步發表評論。正因為如此，符合條件的人口將再增加 10,000 至 12,000 人。

Doubling the population that excites us. But of course, we can't comment on Seagen's progress.

使我們興奮的人口增加一倍。但當然，我們不能評論 Seagen 的進展。

Our next question will come from Evan Seigerman with BMO Capital Markets.

我們的下一個問題將來自 BMO Capital Markets 的 Evan Seigerman。

This is [Keith] on for Evan. Maybe just shifting to M&A execution. Thinking about your recent acquisitions with Nurtec and Oxbryta. You've done a great job describing the plans to add value, drive commercial and clinical synergies. We're seeing the outcomes on our end. Could you comment on how this is going from year-end? And then could you talk about specifics for operationalizing the same for Seagen integration, and how this would differ from recent examples, that would be great.

我是 [Keith] 替 Evan 發言。也許只是轉向併購執行。考慮您最近對 Nurtec 和 Oxbryta 的收購。你在描述增加價值、推動商業和臨床協同效應的計劃方面做得很好。我們正在看到結果。你能評論一下從年底開始的情況嗎？然後你能談談為 Seagen 集成實施相同操作的具體細節，以及這與最近的例子有何不同，那會很棒。

Again, Angela, back to you.

再次，安吉拉，回到你身邊。

Sure. So we are incredibly proud of the work that we've done with -- on Nurtec since the acquisition. As you know, in July of 2022, we had already begun a co-promote with Biohaven to ensure that we were co-promoting the product early. And I think that has really paid off. If you really look at what has happened from a just leading indicators as well as actuals. Today, Nurtec is the leading product in the oral CGRP class with over 47.5% market share. It is also the leading product when it comes to new-to-brand prescription share at a high of 46%. It also has the highest number of prescribers at over 110,000 prescribers and 80% of new CGRP prescribers choose Nurtec.

當然。因此，我們為自收購以來在 Nurtec 上所做的工作感到無比自豪。如您所知，在 2022 年 7 月，我們已經開始與 Biohaven 共同推廣，以確保我們儘早共同推廣該產品。我認為這確實得到了回報。如果你真的從領先指標和實際情況來看發生了什麼。如今，Nurtec 是口服 CGRP 類別中的領先產品，市場份額超過 47.5%。在新品牌處方份額方面，它也是領先產品，高達 46%。它還擁有最多的處方者，超過 110,000 名處方者，80% 的新 CGRP 處方者選擇了 Nurtec。

So I think we've demonstrated in the time that we've had it, that we are able to drive performance and drive excellent education and awareness of the product. And we're seeing consistent great metrics as it pertains to Nurtec. And of course, the opportunity is huge, right? Because we have zavegepant launching later this year. We also know that as a whole, there are over 1 billion migraine sufferers and only 18% of them are using CGRPs today. So we have a great opportunity to expand the class of CGRPs, but specifically Nurtec.

所以我認為我們已經證明了我們已經擁有它，我們能夠提高性能並推動優秀的教育和產品意識。我們看到了與 Nurtec 相關的一致的出色指標。當然，機會是巨大的，對吧？因為我們將在今年晚些時候推出 zavegepant。我們還知道，總體而言，有超過 10 億偏頭痛患者，其中只有 18% 目前在使用 CGRP。因此，我們有一個很好的機會來擴展 CGRP 的類別，特別是 Nurtec。

Thank you, Angela. Next question, please.

謝謝你，安吉拉。請下一個問題。

Our next question will come from Mohit Bansal with Wells Fargo.

我們的下一個問題將來自 Wells Fargo 的 Mohit Bansal。

If I may ask 2 questions here. So on [European] negotiation, just because there was some news this week. Just how much can you comment on that? And the real question there is that, I know you when you provided guidance in the beginning of the year, you anticipated some of that. But so far as the negotiation see any risk to the guidance as the negotiations get finalized in that? And the other question I have is more about the -- your demand chart for PAXLOVID in vaccinations board. It seems like you are assuming both PAXLOVID and vaccination utilization going up into 2024 plus timeframe. Would it be both demand -- demands going up, or do you think it will be either or as vaccinations come down, probably the demand for PAXLOVID would go up. How should we think about that?

如果我可以在這裡問 2 個問題。所以關於[歐洲]談判，只是因為本周有一些消息。你對此有多少評論？真正的問題是，當你在今年年初提供指導時，我知道你，你預料到了其中的一些。但就談判而言，隨著談判最終確定，指導是否存在任何風險？我的另一個問題更多是關於——您在疫苗接種委員會中對 PAXLOVID 的需求圖表。您似乎假設 PAXLOVID 和疫苗接種利用率都會上升到 2024 年以上的時間範圍。無論是需求——需求上升，還是您認為兩者都會是，或者隨著疫苗接種率下降，對 PAXLOVID 的需求可能會上升。我們應該如何考慮？

Maybe I can answer those questions. So on the Seagen negotiations, they are still ongoing. So we can't comment on that. Yes, we have included part of -- included our estimation of how these negotiations will end up in our guidance. And still, we are not closing. So I can't make any comments on that. It wouldn't be appropriate as the discussions are still ongoing. As regards to the demand for PAXLOVID or for vaccines. As we had said, we expect that the demand for vaccines will go down. We gave estimations that will go down to approximately 24% of people in the U.S. and relevant numbers, different country by country as underlying demand for boosters. And things -- I think our progress towards that goal, we will have to see as most of this will happen in the last after summer when it is the traditional period that through is also vaccinations are happening. Demand for PAXLOVID right now is following very, very accurately the infection rates. So when we monitor it on a weekly basis. And really, it is going when we have almost equal percentage of infections is equal percentage of the case for PAXLOVID. And so we expect that will continue going like that. Because we have less compliance with the vaccination recommendations across the world as people are tired with COVID, and we expect that fewer people, as I said, this year will get a vaccine compared to last year. And so this means that the immune protection of the operation will go down. As a result, we expect that we have more infections and that will drive more use of PAXLOVID. But of course, that's what our geological models are telling us, we'll have to see what eventually will happen in real life.

也許我可以回答這些問題。因此，關於 Seagen 的談判，他們仍在進行中。所以我們不能對此發表評論。是的，我們已經包括了一部分 - 包括我們對這些談判將如何結束的估計在我們的指導中。而且，我們還沒有關閉。所以我不能對此發表任何評論。這不合適，因為討論仍在進行中。關於對 PAXLOVID 或疫苗的需求。正如我們所說，我們預計對疫苗的需求將會下降。我們估計將下降到美國約 24% 的人和相關數字，不同國家/地區對助推器的潛在需求不同。事情——我認為我們在實現這一目標方面取得的進展，我們將不得不看到，因為其中大部分將發生在夏季過後的最後一個時期，當時是傳統時期，疫苗接種也在進行。現在對 PAXLOVID 的需求非常非常準確地跟隨感染率。因此，當我們每週對其進行監控時。實際上，當我們的感染百分比與 PAXLOVID 病例的百分比幾乎相等時，它就會發生。因此，我們希望這種情況會繼續下去。因為人們對 COVID 感到厭倦，我們對世界各地的疫苗接種建議的遵守程度較低，而且我們預計，正如我所說，與去年相比，今年接種疫苗的人數會減少。因此，這意味著手術的免疫保護將下降。因此，我們預計我們會有更多的感染，這將推動 PAXLOVID 的更多使用。但當然，這就是我們的地質模型告訴我們的，我們必須看看現實生活中最終會發生什麼。

Next, we have Robyn Karnauskas with Truist Securities.

接下來，我們有來自 Truist Securities 的 Robyn Karnauskas。

Just 2 big picture ones. Just first on for your vaccine franchise, we think about the competitive landscape, a couple of things. What do you think is going to be the most important differentiation for you versus the competition that will drive the most uptake as people have different options. And have you developed any new LNP technology that might reduce the biggest pushback with the vaccines as people feel stick still when they get them for some of your products. And then lastly...

只有2張大圖。就您的疫苗特許經營權而言，我們首先考慮了競爭格局，還有幾件事。您認為對您來說最重要的區別是什麼，因為人們有不同的選擇，這將推動最多的競爭。你有沒有開發出任何新的 LNP 技術來減少疫苗的最大阻力，因為人們在為你的某些產品購買疫苗時會感到停滯不前。然後最後...

We couldn't hear, which product you spoke about?

我們聽不到，您說的是哪種產品？

Oh, I was just talking about the (inaudible) vaccine franchise for RSV and flu and COVID, thinking big picture, how you are differentiated? And what do you think is going to be key because you're all competing to make -- to determine who's going to be the winner. And the second question is, there's big proposal out of Europe for new legislation for drugs. And since you're launching all the new products in Europe. I just want to get your thoughts on whether or not you think that legislation may hold? Or what kind of impact that might have?

哦，我只是在談論 RSV、流感和 COVID 的（聽不清）疫苗專營權，從大局著眼，你們如何區分？你認為什麼是關鍵，因為你們都在競爭——以確定誰將成為贏家。第二個問題是，歐洲提出了新的藥品立法提案。而且由於您要在歐洲推出所有新產品。我只是想了解一下您是否認為該立法可能成立？或者會產生什麼樣的影響？

And maybe I can give you a very general answer, and then if Angela wants to chime in, please. On the COVID, we are the winners right now, all right? We have the big markets there. And we plan to maintain that. So I think we are there. When it comes to RSV, we are the only ones that we have both or we have positive data on both on adults and on maternal, and which have already approved for the adults and then we are expecting approval for the maternal so that the strength of our data with efficacy and safety profile that we think is differentiated, will provide us with what we hope also to be the winners in that one. And the flu on mRNA technology still the jury is out.

也許我可以給你一個非常籠統的答案，然後如果安吉拉想插話，請。在 COVID 上，我們現在是贏家，好嗎？我們那裡有大市場。我們計劃保持這一點。所以我認為我們在那裡。說到 RSV，我們是唯一同時擁有這兩種病毒的公司，或者我們擁有關於成人和母體的積極數據，並且已經批准用於成人，然後我們期待母體獲得批准，這樣力量我們的數據具有我們認為與眾不同的功效和安全性，將為我們提供我們希望也成為該領域的贏家的東西。對 mRNA 技術的影響尚無定論。

We are very optimistic with a little target of the data that we are having from our flu vaccine, and we will wait to see, of course, how that will continue. And then, of course, the winners will be also those that they will be able to build from delay of all of that. So the fact that we have all 3 of them, or we have a good chance to have all 3 of them if the studies are successful and if the products are approved, of course, also provides a good differentiation. In addition to all of that, I think the trust to the Pfizer brand name, which has been very, very strong, I think, also plays a key differentiator.

我們對我們從流感疫苗中獲得的數據有一個小目標非常樂觀，當然，我們將拭目以待，這將如何繼續。然後，當然，贏家也將是那些他們能夠從所有這些延遲中建立起來的人。因此，如果研究成功並且產品獲得批准，我們擁有所有 3 個，或者我們有很好的機會擁有所有 3 個，當然，這也提供了很好的差異化。除了所有這些，我認為對輝瑞品牌的信任，我認為，它一直非常非常強大，也是一個關鍵的差異化因素。

Now as regards to the EU legislation that we have just seen in the recent days, we are noticing the positive things of EU trying to be more competitive in attracting reserves and creating a regulatory framework for more rapid approvals. Clearly, we are also concerned at the same time with provisions that would like to reduce exclusivity of data and other provisions. So we hope that there will be an open dialogue with the EU so that we can create a framework that really will enhance innovation. Angela, anything that you want to add to all of that?

現在，關於我們最近幾天剛剛看到的歐盟立法，我們注意到歐盟試圖在吸引儲備和建立監管框架以加快審批方面更具競爭力的積極方面。顯然，我們同時還關注那些希望降低數據排他性的條款和其他條款。因此，我們希望與歐盟進行公開對話，以便我們能夠創建一個真正能促進創新的框架。安吉拉，你想補充什麼嗎？

Maybe just to add to your question specifically about the adult portfolio, I really do believe that this plays into our sweet spot. You know through the last several years, both from the Prevnar franchise and for vaccination, vaccinating adults through our work in COVID, we've learned that the clinical profile is one thing that you really need reliable supply, you need a commercial infrastructure. You need a great ability to educate, raise awareness and drive people to vaccination. And I think on all of those counts, Pfizer is a winner. And so we look forward to having a growing and a very robust respiratory portfolio that really leverages off of this incredible commercial machinery.

也許只是為了增加你關於成人作品集的問題，我真的相信這會成為我們的最佳選擇。你知道，在過去的幾年裡，無論是從 Prevnar 特許經營權還是疫苗接種，通過我們在 COVID 方面的工作為成年人接種疫苗，我們了解到臨床資料是你真正需要可靠供應的一件事，你需要商業基礎設施。您需要具備強大的教育能力、提高認識和推動人們接種疫苗的能力。我認為在所有這些方面，輝瑞都是贏家。因此，我們期待擁有不斷增長且非常強大的呼吸產品組合，真正利用這種令人難以置信的商業機器。

Next, we have Louise Chen with Cantor.

接下來，我們請來 Louise Chen 和 Cantor。

So I want to ask you about margin improvement. You talked about that in your opening remarks. I'm curious when we might start to see that? And does that include the Seagen acquisition in your comments. And second question I have for you is, what are some of the key steps that you've taken already to transition Comirnaty and PAXLOVID in the commercial market? And when will you know how the Seagen will shape up?

所以我想問你關於提高利潤率的問題。你在開場白中談到了這一點。我很好奇我們什麼時候可以開始看到它？這是否包括您評論中的 Seagen 收購。我要問你的第二個問題是，你已經採取了哪些關鍵步驟來將 Comirnaty 和 PAXLOVID 轉移到商業市場？你什麼時候才能知道 Seagen 會怎樣？

Thank you very much, Louise. Dave, you want to take the margin improvements and then Angela, the Comirnaty and PAXLOVID.

非常感謝你，路易絲。 Dave，你想提高利潤率，然後是 Angela、Comirnaty 和 PAXLOVID。

Yes. Thank you for your question. It is our expectation that as we integrate Seagen in either late '23 or '24. Early '24, we will begin to see margin improvement, and that will happen as we continue to improve our performance from a top line perspective. At the same time, we're going to be very efficient and really work to minimize our SI&A investments going forward. So I think you should start to see that post the integration and the closing of the Seagen transaction.

是的。謝謝你的問題。我們期望在 23 世紀末或 24 世紀末整合 Seagen。 24 年初，我們將開始看到利潤率有所提高，這將隨著我們從頂線的角度繼續提高我們的業績而發生。與此同時，我們將非常高效地努力減少我們未來的 SI&A 投資。所以我認為你應該開始看到 Seagen 交易的整合和結束。

Thank you, David. And Angela, how are we preparing to transition commercial commitment?

謝謝你，大衛。安吉拉，我們如何準備過渡商業承諾？

So Louise, as you know, both of these products, both Comirnaty and PAXLOVID are products are very familiar to us. They fit very well in the existing portfolio of products that we have. So the ability for us to move from an EUA into a full launch or into, it is business as usual for us, right? So the typical things that we would always do, which is awareness building with physicians and with patients that has begun and is well underway. The things that you would do as a regard your discussions with payers to demonstrate value and to create your value argument for reimbursement and access, that has begun.

所以路易絲，正如你所知，這兩種產品，Comirnaty 和 PAXLOVID 都是我們非常熟悉的產品。它們非常適合我們現有的產品組合。因此，我們從 EUA 進入全面發布或進入的能力，對我們來說一切照舊，對吧？因此，我們會一直做的典型事情是與醫生和患者建立意識，這已經開始並且正在進行中。你會做的事情是關於你與付款人的討論，以證明價值並為報銷和訪問創造你的價值論據，這已經開始了。

We have done a tremendous amount of work as it pertains to retailers and making sure that we have our distribution and our supply chain well oiled and the ability to be able to supply and to vaccinate to administer these products at both -- at a physical side like a retailer or even in the case of PAXLOVID getting telehealth and sort of remote health capability set up. So all of these capabilities in many of them, in fact, have been underway throughout the entire time of the pandemic. So I think we're in a very, very good position to seamlessly transition into commercialization.

我們已經做了大量與零售商有關的工作，並確保我們的分銷和供應鏈運轉良好，並且能夠在實體方面供應和接種疫苗以管理這些產品就像零售商，甚至在 PAXLOVID 的情況下，也可以建立遠程醫療和某種遠程醫療功能。因此，實際上，在整個大流行期間，其中許多公司的所有這些能力都在發揮作用。所以我認為我們處於非常非常好的位置，可以無縫過渡到商業化。

Our next question will come from Akash Tewari with Jefferies.

我們的下一個問題將來自 Jefferies 的 Akash Tewari。

Can you talk about your next-gen CDK4 program? You'll have first-in-human data at ASCO. Why does your team believe just hitting CDK4 allows you to improve on IBRANCE's efficacy. And are there any plans to combine that drug with the Arvinas SERD, given the DDI that's been shown up with IBRANCE. And then on your next-gen PAXLOVID program, can you confirm that it can achieve multiple fold over the EC90 when adjusted for plasma protein binding? And is that -- for time lines on that product, is the earliest possible commercial entry 2026? Or is there a path for expedited approval?

您能談談您的下一代 CDK4 程序嗎？您將在 ASCO 獲得首次人體數據。為什麼您的團隊認為只需擊中 CDK4 就可以提高 IBRANCE 的功效。考慮到 IBRANCE 顯示的 DDI，是否有任何計劃將該藥物與 Arvinas SERD 結合使用。然後在您的下一代 PAXLOVID 程序中，您能否確認在針對血漿蛋白結合進行調整後，它可以實現 EC90 的多倍？那是——對於該產品的時間表，最早可能的商業進入是 2026 年嗎？或者有沒有加快審批的途徑？

Thank you very much. Mikael, I think both questions can go to you.

非常感謝。 Mikael，我想這兩個問題都可以問你。

Thank you. We are very excited about the next-gen CDK4 inhibitor. It's looking really good in 2 aspects. You can dose and get activity after patients paying CDK4/6 because it deals with higher inhibition of this mechanism. And you have a better tolerability with no -- with much less neutropenia, less risk for infections. We expect midyear to report out, and we have an aspirational target to start Phase III late this year, possibly early. At the same time, as you asked, we are now running combination studies CDK4 with KAT6. Another inhibitor that has a nice single agent activity and seem to combine well. We have a second combination with CDK2. And we think this would allow us next year to pick 1 or 2 combinations to advance up the lines with more potent treatment what's available today. Similarly, we're looking at combination with 471, as you alluded to, in order to benefit from the Arvinas collaboration. Next Gen PAXLOVID, yes, as I alluded to in my introductory remarks, we have many fold above EC90. And as you know, for PAXLOVID, what's unique with that drug that the manifold exposure above EC90 as this fall led to no detectable meaningful emergence of mutations, which is always what you fear in antiviral single-agent therapy, and this has been unique for PAXLOVID versus other agents that have been used so far, whether antibodies or antivirals, and this is exactly the profile for the next-gen, but without DDIs that allow us to improve and also to move into other supplementary segments. We're planning soon to start a Phase II and pending data possibly move quickly to Phase III. And of course, we would like to see that agent introduced as soon as possible. I think we can hope to move swiftly pending event rates of COVID that will happen in the fall and further on that influence enrollment. So I think you said '26, and I would certainly hope we'll be ahead of that.

謝謝。我們對下一代 CDK4 抑製劑感到非常興奮。它在兩個方面看起來非常好。您可以在患者支付 CDK4/6 後給藥並獲得活性，因為它處理了對該機制的更高抑制。而且你有更好的耐受性 - 中性粒細胞減少症更少，感染風險更低。我們預計年中將報告出來，我們有一個雄心勃勃的目標，即在今年晚些時候（可能提前）開始第三階段。同時，正如您所要求的，我們現在正在進行 CDK4 與 KAT6 的聯合研究。另一種抑製劑具有良好的單藥活性並且似乎可以很好地結合使用。我們有與 CDK2 的第二種組合。我們認為這將使我們明年能夠選擇 1 種或 2 種組合，以使用當今可用的更有效的治療方法來提升產品線。同樣，正如您提到的那樣，我們正在考慮與 471 的結合，以便從 Arvinas 的合作中受益。下一代 PAXLOVID，是的，正如我在介紹性發言中提到的那樣，我們在 EC90 以上有很多倍。正如你所知，對於 PAXLOVID，該藥物的獨特之處在於，今年秋天超過 EC90 的多方面暴露導致沒有可檢測到的有意義的突變出現，這一直是你在抗病毒單藥治療中所擔心的，這是獨一無二的PAXLOVID 與迄今為止使用的其他藥物相比，無論是抗體還是抗病毒藥物，這正是下一代的概況，但沒有 DDI，這使我們能夠改進並進入其他補充領域。我們計劃很快開始第二階段，待定數據可能會迅速轉移到第三階段。當然，我們希望看到該代理盡快推出。我認為我們可以希望迅速改變將在秋季發生的 COVID 未決事件率，並進一步影響入學率。所以我想你說的是 26 年，我當然希望我們能領先於此。

Next, we have Terence Flynn with Morgan Stanley.

接下來，我們有來自摩根士丹利的 Terence Flynn。

Maybe 2 for me because I'm not sure you'll be able to answer one of them. I guess any -- would love your latest thoughts on your seasonal flu mRNA vaccine just in light of some of the Moderna data on the B-antigen side. Just how should we think about your profile there? And then there's been some focus on this ADCETRIS versus OPDIVO first-line Hodgkin's lymphoma data that's going to be presented at ASCO. Just wondering if you can offer your high-level perspective on how you see that frontline landscape evolving?

對我來說可能是 2 個，因為我不確定您是否能夠回答其中一個問題。我想任何人都會喜歡你根據 B 抗原方面的一些 Moderna 數據對季節性流感 mRNA 疫苗的最新想法。我們應該如何看待你在那裡的個人資料？然後有一些關注將在 ASCO 上展示的 ADCETRIS 與 OPDIVO 一線霍奇金淋巴瘤數據。只是想知道您是否可以就您如何看待前線格局的演變提供高層次的觀點？

Mikael, why don't you take the flu question and then the oncology question will go to William.

Mikael，你為什麼不回答流感問題，然後腫瘤學問題將交給 William。

We are very pleased what we see so far, the totality date of our flu mRNA. As you know, we have reported out very high antibody type A, similar or possibly lower to the B antigen versus standard flu vaccines. But in contrast to standard flu vaccines, we have very nice T cell activity. And I think we are the only mRNA platform that has dosed CD4 and CD8 T cells of significance. We do think that could offer a unique profile for flu and the tolerability with our dose is very encouraging. So the trial is -- in the last leg for a readout. Hopefully, we'll be able later before to share an update. And we are very encouraged, and we are in parallel at risk investing in combination opportunities with recent COVID and RSV in various combination, as Albert earlier alluded to.

到目前為止，我們對我們所看到的流感 mRNA 的完整日期感到非常高興。如您所知，我們已經報告了非常高的 A 型抗體，與標準流感疫苗相比，與 B 抗原相似或可能更低。但與標準流感疫苗相比，我們的 T 細胞活性非常好。我認為我們是唯一一個對 CD4 和 CD8 T 細胞進行給藥的 mRNA 平台。我們確實認為這可以為流感提供獨特的概況，並且我們劑量的耐受性非常令人鼓舞。所以審判是——在最後一站進行讀數。希望我們稍後能夠分享更新。正如阿爾伯特早些時候提到的那樣，我們感到非常鼓舞，我們同時面臨著以各種組合方式投資於最近 COVID 和 RSV 的組合機會的風險。

Thank you, Mikael. And William, on the oncology front, how do you feel about?

謝謝你，米凱爾。威廉，在腫瘤學方面，你怎麼看？

Yes, sure. So again, this is a molecule for Seagen ADCETRIS, which is the CD30 ADC. It's already been approved in Hodgkin's lymphoma post-transplant and then in previously untreated Hodgkin's lymphoma now with chemotherapy, doxorubicin, vinblastine and dacarbazine. And it's already -- we anticipate actually later this year that the label will be updated for overall survival. Now the data you're talking about is from the SWOG S1826 study with nivo AVD versus ADCETRIS AVD, and I believe they'll be presenting PFS data, but this is a curable disease. And we believe that the OS update with the ADCETRIS label will show that ADCETRIS is the favorite product at this time.

是的，當然。同樣，這是 Seagen ADCETRIS 的分子，即 CD30 ADC。它已經被批准用於移植後的霍奇金淋巴瘤，然後用於以前未經治療的霍奇金淋巴瘤，現在使用化療、多柔比星、長春鹼和達卡巴嗪。而且它已經——我們實際上預計今年晚些時候標籤將針對整體生存進行更新。現在你談論的數據來自 SWOG S1826 研究，使用 nivo AVD 與 ADCETRIS AVD，我相信他們會提供 PFS 數據，但這是一種可治癒的疾病。並且我們相信帶有 ADCETRIS 標籤的操作系統更新將表明 ADCETRIS 是此時最受歡迎的產品。

Our next question will come from Colin Bristow with UBS.

我們的下一個問題將來自瑞銀的 Colin Bristow。

Maybe first on danuglipron on the upcoming data. Could you just walk us through what the key efficacy and safety thresholds you're looking to meet to move this forward. And sort of with regards to those thresholds, how you think about them in light of that, this is BID dosing? And how does that potentially impact the sort of commercial opportunity. And then just second, a quick one on your DMD Phase III CIFFREO trial. You previously guided to completion of recruitment in April of this year. Just could you give us a quick update here, and then how you view the opportunity and positioning in light of the fact that there's a potential competitor approval at the end of this month?

也許首先在即將發布的數據上使用達格列隆。您能否向我們介紹一下您希望達到哪些關鍵功效和安全閾值以推動這一進程。關於這些閾值，你如何看待它們，這是 BID 劑量？這對商業機會有何潛在影響。然後是第二個，關於您的 DMD III 期 CIFFREO 試驗的快速測試。您之前曾指導今年 4 月完成招聘。您能否在這裡給我們快速更新一下，然後根據本月底有潛在競爭對手批准的事實，您如何看待機會和定位？

Mikael?

米凱爾？

Yes. We are very excited about our 2 (inaudible) 1532 and danuglipron 1532 called lotiglipron and we are looking for a differentiated profile that will be a combination of rapid onset, high control of HbA1c, bringing it down and body weight loss at various doses to be very competitive and a more easily titrable drug that can optimize a preferred profile versus injectable when it comes to nausea and other well-known effects. So we look forward very much to data, maybe later this year or possibly early next year and cherry-pick the winner here. You also asked about DMD. Well, if there is an approval, it is based just on the surrogate markers. And in this area, I think it's very important to report out data when it comes to real patient benefit. And we expect possibly already late this year, alternatively next year to have data from the first randomized study that if positive could show favorable benefit for patients doing better according to the North Star scale. So we feel really positive about our own DMD program, and I think the entry will be competitive with the real data that patients need.

是的。我們對我們的 2（聽不清）1532 和 danuglipron 1532（稱為 lotiglipron）感到非常興奮，我們正在尋找一種差異化的特徵，它將快速起效、高度控制 HbA1c、降低 HbA1c 並在各種劑量下減輕體重非常有競爭力且更容易滴定的藥物，在涉及噁心和其他眾所周知的效果時，可以優化首選配置文件而不是注射劑。所以我們非常期待數據，可能在今年晚些時候或明年初，然後在這裡挑選獲勝者。您還詢問了 DMD。好吧，如果有批准，它只是基於替代標記。在這個領域，我認為當涉及到真正的患者利益時，報告數據非常重要。我們預計可能已經在今年晚些時候，或者明年獲得第一項隨機研究的數據，根據北極星量表，如果結果呈陽性，可能會對患者表現出更好的益處。所以我們對我們自己的 DMD 項目感到非常積極，我認為該項目將與患者需要的真實數據競爭。

Our next question will come from Geoff Meacham with Bank of America.

我們的下一個問題將來自美國銀行的 Geoff Meacham。

Just have 2. The first, Angela, on the I&I landscape, can you just talk about your expectations for category growth, just looking this year and next, just in light of the Humira and Stelara biosimilar to come. I'm asking just in the context for the etrasimod launch as well as (inaudible). And then Albert, I know this question has been asked, but a different way though. I know you expect this year for COVID to be a down year, but when you think about your scorecard outside the U.S. with payers, as you've transitioned to commercial, what's been the initial feedback from a -- sort of from a price and volume perspective. Obviously, that's a key to your assumptions in 2024 and beyond.

只有 2 個。首先，Angela，關於 I&I 領域，你能否談談你對類別增長的期望，看看今年和明年，就 Humira 和 Stelara 生物仿製藥的到來。我只是在 etrasimod 發布的背景下詢問以及（聽不清）。然後是艾伯特，我知道有人問過這個問題，但方式不同。我知道你預計今年 COVID 會是低迷的一年，但是當你考慮你在美國以外的記分卡時，當你已經過渡到商業時，最初的反饋是什麼——有點來自價格和體積的角度。顯然，這是您對 2024 年及以後的假設的關鍵。

Let me answer the COVID question, and then Angela will answer the I&I landscape. We expect to have commercialization in the U.S., I think, likely the U.S. government will stop purchasing outside the normal (inaudible) products. We do not expect that to be the case in most of the countries international. We think that most of the countries will continue having governmental practices. And most of them, we have already long-term contract. So I don't think there will be much fluctuation over there in the price given the longevity of the product. When the products -- the contracts expire, of course, prices also will be adjusted. Now let's move to the question about I&I and Angela, please.

讓我回答 COVID 問題，然後 Angela 將回答 I&I 景觀。我們希望在美國實現商業化，我認為美國政府可能會停止購買正常（聽不清）產品之外的產品。我們預計國際上大多數國家不會出現這種情況。我們認為大多數國家/地區將繼續採用政府做法。其中大多數，我們已經簽訂了長期合同。因此，考慮到產品的使用壽命，我認為價格不會有太大波動。當產品——合同到期時，當然價格也會隨之調整。現在讓我們轉到關於 I&I 和 Angela 的問題。

Sure. Well, I think to answer that question, you really have to look at each product and the specific disease that they're in. So let's start with etrasimod, which is UC. There, we believe that we have an advantage from a clinical profile perspective. We believe that we have the best-in-class S1B inhibitor, but there are also other great benefits such as the fact that it can be used steroid free, that we have convenient dosing. We also offer an oral option in a world that is very prevalent with injectables. And even with all of the assets out there, we still have 50% of people that have not achieved remission. So I think that the unmet need in UC is clear.

當然。嗯，我認為要回答這個問題，你真的必須看看每種產品和它們所患的特定疾病。所以讓我們從 etrasimod 開始，它是 UC。在那裡，我們相信從臨床概況的角度來看我們具有優勢。我們相信我們擁有一流的 S1B 抑製劑，但還有其他巨大的好處，例如它可以不含類固醇，我們可以方便地給藥。在註射劑非常普遍的世界中，我們還提供口服選擇。即使有所有的資產，我們仍然有 50% 的人沒有達到緩解。所以我認為加州大學未滿足的需求是顯而易見的。

And for us, in particular, given the profile of etrasimod, what we think is the greatest opportunity for us is in earlier lines of treatment, where there has not been as much advancement, right? There's a lot of anti-TNF. There's a lot of biosimilars, there's JAKs, there's other mechanisms. But in earlier lines of treatment, there really is not enough. And so that's where we think we have an opportunity to meet an underserved need today, and that's where we're going to be -- that's where we're going to be positioning etrasimod. Ritlecitinib is a different story. When you look at that particular indication for alopecia that is really an underdeveloped market.

特別是對我們來說，考慮到 etrasimod 的概況，我們認為對我們來說最大的機會是在早期的治療中，那裡沒有那麼大的進步，對吧？有很多抗腫瘤壞死因子。有很多生物仿製藥，有 JAKs，還有其他機制。但在早期的治療中，確實是不夠的。因此，這就是我們認為我們有機會滿足今天服務不足的需求的地方，這就是我們要去的地方——這就是我們將定位 etrasimod 的地方。 Ritlecitinib 是一個不同的故事。當您查看脫髮的特定跡象時，這確實是一個不發達的市場。

There's 3 million people today, there are no great options for adults. And there are absolutely no options for adolescents and children. And so the profile that we have with ritlecitinib is a -- it's the best-in-class JAK. It's the best JAK. And I think that we're going to compete well in addition to the fact that we're going to be the only JAK compared to ritlecitinib that has an indication for adolescents. So I think in this regard, because it's a new disease or a highly undeserved disease, I think education and awareness, education at the level of the prescriber, the patient but also with the payers is going to be key to our ability to access this market.

今天有 300 萬人，成年人沒有很好的選擇。青少年和兒童絕對沒有選擇。因此，我們對 ritlecitinib 的了解是——它是同類最佳的 JAK。這是最好的JAK。而且我認為，除了我們將成為唯一與 ritlecitinib 相比具有青少年適應症的 JAK 之外，我們還將進行良好的競爭。所以我認為在這方面，因為它是一種新疾病或一種非常不應得的疾病，我認為教育和意識，在處方者、患者以及付款人層面的教育將是我們獲得這種能力的關鍵市場。

Thank you. And of course, considering these all the time.

謝謝。當然，一直在考慮這些。

Our next question comes from Trung Huynh with Crédit Suisse.

我們的下一個問題來自瑞士信貸的 Trung Huynh。

Trung Huynh from Crédit Suisse. I have 2, if I can. So first one, a few days ago, you saw the FDA Advisory Committee vote on Lynparza's PROpel trial. In that, the committee voted against the approval in all comers. So for TALZENNA and TALAPRO-2, what's your expectations for your label here given the strength of your data. And could that affect your $1 billion peak sales number that you gave in December. And then for the RSV flu co-administration study, what flu vaccine did you test that with, is at the high dose or the low dose? And if it's the low dose, could you be approved for use with the high dose, which is more relevant today.

來自瑞士信貸的 Trung Huynh。如果可以的話，我有 2 個。所以首先，幾天前，你看到 FDA 諮詢委員會對 Lynparza 的 PROpel 試驗進行了投票。就此而言，委員會投票反對所有參與者的批准。因此，對於 TALZENNA 和 TALAPRO-2，鑑於您的數據強度，您對此處標籤的期望是什麼。這會影響您在 12 月給出的 10 億美元的銷售峰值嗎？然後對於 RSV 流感聯合給藥研究，你用什麼流感疫苗進行了測試，是高劑量還是低劑量？如果是低劑量，你能否獲准與高劑量一起使用，這在今天更為相關。

Thank you very much. William, would you like to take the TALAPRO part question?

非常感謝。 William，您想回答 TALAPRO 零件問題嗎？

Yes, sure. So thanks for the question. So as Mikael said, the study showed with enzalutamide plus TALAPRO -- TALZENNA versus enza, we showed a 37% reduction in the radiographic progression-free survival. Notably, in the same presentation, we also showed a hazard ratio in the HR deficient population of 0.48, a significant p-value. And then in the HRR non-deficient unknown population, HR of 0.7 with the p-value of 0.004. So we remain confident about our data in the all-comer population. Obviously, we can't compare to PROpel. Notably, in TALAPRO-2, we had prospective testing for HRR deficiencies, including BRCA1 and 2. I also want to point out that our control arm of XTANDI reaffirms XTANDI is best-in-class NHT for the indication with a radiographic PFS of 22 months. And in the treatment on the TALA, our PFS was not reached. So we expect that the HR population, which is 25% will be compelling with the data. And we'll also continue to present additional data in the HR subpopulation at ASCO in 2023. And notably, we did get priority review, and we're currently in registration.

是的，當然。所以謝謝你的問題。正如 Mikael 所說，該研究表明，恩雜魯胺加 TALAPRO——TALZENNA 與 enza 相比，我們發現放射學無進展生存期降低了 37%。值得注意的是，在同一演示文稿中，我們還顯示 HR 缺陷人群的風險比為 0.48，這是一個顯著的 p 值。然後在 HRR 非缺陷未知人群中，HR 為 0.7，p 值為 0.004。因此，我們對所有人群中的數據仍然充滿信心。顯然，我們無法與 PROpel 相提並論。值得注意的是，在 TALAPRO-2 中，我們對 HRR 缺陷進行了前瞻性測試，包括 BRCA1 和 2。我還想指出，我們的 XTANDI 控制臂重申 XTANDI 是同類最佳的 NHT，用於放射學 PFS 為 22 的適應症個月。在 TALA 的治療中，我們的 PFS 沒有達到。因此，我們預計 25% 的 HR 人口將對數據具有吸引力。我們還將在 2023 年繼續在 ASCO 的 HR 亞群中提供更多數據。值得注意的是，我們確實獲得了優先審查，我們目前正在註冊中。

Thank you, William. And Mikael, about RSV and flu.

謝謝你，威廉。 Mikael，關於 RSV 和流感。

Yes. We are extremely excited about the RSV vaccine, and we'll provide data on co-administration of that vaccine with adjuvanted flu. We expect it to be available and generalized to all flu vaccines. And then when it comes to longer term, we also are already in combination study with our RSV and using our internal portfolio of COVID and mRNA flu. So we see this as a developing a very strong portfolio this year with core administration opportunities next year, possibly our own flu vaccine and then combination thereof. So stay tuned.

是的。我們對 RSV 疫苗感到非常興奮，我們將提供該疫苗與佐劑流感共同給藥的數據。我們希望它能夠適用於所有流感疫苗。然後，從長遠來看，我們也已經在與我們的 RSV 結合研究，並使用我們內部的 COVID 和 mRNA 流感產品組合。因此，我們認為這是今年開發非常強大的產品組合，明年有核心管理機會，可能是我們自己的流感疫苗，然後是它們的組合。敬請期待。

Next question will come from Andrew Baum with Citi.

下一個問題將來自花旗銀行的 Andrew Baum。

Just coming back to the -- your oral GLP-1 portfolio. Lilly has called out an anticipated weight loss at 32 weeks from memory of around 14%, 15%. And they hesitate to give baseline. Given the competitive nature of the field, you're late to market and the cost of running CVOT trials in this setting. Where does the relative weight loss need to be from your Phase II for you to advance given the benchmark that Lilly seems to be setting?

剛剛回到——你的口服 GLP-1 產品組合。禮來（Lilly）根據記憶預測 32 週時體重減輕約 14%、15%。他們不願給出基線。考慮到該領域的競爭性質，您的產品上市時間較晚，並且在此設置中運行 CVOT 試驗的成本較高。考慮到 Lilly 似乎正在設定的基準，你的第二階段的相對體重減輕需要從哪裡開始？

That's a good question for Mikael. Mikael?

這對 Mikael 來說是個好問題。米凱爾？

Yes. No, we agree completely with you that we should have an ambitious profile, and we have certainly seen in patients up to 15% weight loss depending on different dose regimens. So for obesity, that's a really good ambition to have up to 15%. And for diabetes patients, of course, it's about having a very strong HbA1c lowering, maybe 2% or even more, so we think it's feasible with orals, and we think that will open up a very large place, and we think that pending data readout that we may have a differentiated profile for our full agonists.

是的。不，我們完全同意你的看法，我們應該有一個雄心勃勃的形象，而且我們確實看到患者根據不同的劑量方案減輕了高達 15% 的體重。所以對於肥胖來說，達到 15% 是一個非常好的目標。對於糖尿病患者，當然，它是關於 HbA1c 的非常強烈的降低，可能是 2% 甚至更多，所以我們認為口服是可行的，我們認為這將打開一個非常大的空間，我們認為待定的數據讀出我們可能對我們的完全激動劑有不同的描述。

Thank you, Mikael. So we are waiting to see the data that I will speak.

謝謝你，米凱爾。所以我們在等著看我要講的數據。

Next, we have Chris Schott with JPMorgan.

接下來，我們有來自摩根大通的 Chris Schott。

Just 2 questions for me. Maybe first on the capital allocation comments. I guess the more balanced capital allocation post the SGEN delevering. Just on that front, where do we need to see leverage go to before we can think about that balanced allocation? And in the meantime, what is the capacity and appetite for further deals? So can we think about kind of Biohaven size deals while you're delevering from Seagen, or is it really smaller transactions? And then my second question was just one on RSV market development. Just how quickly do you see this market developing? I guess I'm just trying to get my hands around how much education this require, and do you worry at all about vaccine fatigue, I guess, just given all the boosters that this population, I guess, received during the pandemic, does that slow at all the uptake versus kind of a normalized environment?

只問我兩個問題。也許首先是關於資本分配的評論。我猜 SGEN 去槓桿後資本配置會更加平衡。就在這方面，在我們考慮平衡分配之前，我們需要在哪裡看到槓桿作用？與此同時，進一步交易的能力和意願如何？那麼，當你從 Seagen 去槓桿化時，我們能否考慮 Biohaven 規模的交易，或者它真的是更小的交易？然後我的第二個問題只是關於 RSV 市場發展的問題。您認為這個市場發展的速度有多快？我想我只是想弄清楚這需要多少教育，你是否擔心疫苗疲勞，我想，只要考慮到這個人口在大流行期間接受的所有助推器，就可以了嗎？與某種規範化環境相比，吸收速度是否緩慢？

Good questions, Chris. Dave, capital allocation.

問得好，克里斯。戴夫，資本配置。

Yes. So thank you, Chris, for the question. Obviously, we have invested heavily back into our business here's all with the focus of growing our business from -- both from a top line perspective, but importantly, from a bottom line perspective. And I think now as we begin to cycle into I'll say, post the peak of this reinvestment in the business, we should begin to harvest, if you will, some of the cash flows coming out of the investments that we made and capitalize, if you will, on the returns that we expect out of these investments.

是的。克里斯，謝謝你提出這個問題。顯然，我們已經對我們的業務進行了大量投資，重點是從頂線角度，但重要的是，從底線角度發展我們的業務。我認為，現在我們開始進入循環，我會說，在業務再投資達到頂峰之後，我們應該開始收穫，如果你願意的話，我們所做的投資產生的一些現金流，並將其資本化，如果你願意的話，關於我們期望從這些投資中獲得的回報。

So having said that, we expect, because of that, we should get ourselves back more balanced into the 3 pillars, again, reinvesting back in our business, growing our dividend and doing value-enhancing share repurchases. From a leverage perspective, obviously, we want to maintain our high investment-grade rating in access to Tier 1 commercial paper, that would say that we would probably be in the low 3x levered ZIP code from that perspective. And then from an M&A perspective, we're still active in the M&A market. Obviously, first and foremost, on our objective now is to close and begin to integrate Seagen, so that's priority #1. Having said that, we will still look at the M&A marketplace, understand if there's assets that meet our criteria to supplement our business and we could theoretically execute against that given our capital structure. Having said that, in the near term, those will probably be smaller, little tuck-in type deals given our leverage ratio in the very near term.

話雖如此，我們預計，因此，我們應該讓自己在三大支柱中更加平衡，再次投資於我們的業務，增加股息和進行價值提升的股票回購。從槓桿的角度來看，顯然，我們希望在獲得一級商業票據方面保持我們的高投資級評級，也就是說，從這個角度來看，我們可能處於低 3 倍的槓桿郵政編碼中。然後從併購的角度來看，我們仍然活躍在併購市場。顯然，首要的是，我們現在的目標是關閉並開始整合 Seagen，因此這是第一要務。話雖如此，我們仍將關注併購市場，了解是否有符合我們標準的資產來補充我們的業務，理論上我們可以根據我們的資本結構執行。話雖如此，在短期內，考慮到我們在短期內的槓桿率，這些交易可能會是規模較小的、小規模的交易。

Thank you, Dave. Angela, what about RSV and the educational efforts that the market would mean.

謝謝你，戴夫。安吉拉，關於 RSV 和市場意味著的教育努力呢？

Well, with all launches, education is really important. And that's why we've already begun our unbranded disease education with physicians, laying the groundwork for the importance of vaccinating with or vaccinating for RSV. But of course, with all launches and with all new diseases and education is important to consumers, it's important to caregivers, to payers. And so on all of those fronts, those discussions have either begun or are beginning, and we plan to obviously implement a robust market development plan like we do for all of our vaccines. However, I think that the biggest advantage here is in the synergies of RSV together with our other adult vaccines, right? We have not 20 adults. We've had COVID. We -- all of these vaccines follow a very similar pattern in terms of the commercial needs that they have.

好吧，對於所有發布，教育都非常重要。這就是為什麼我們已經開始對醫生進行無品牌疾病教育，為 RSV 疫苗接種或疫苗接種的重要性奠定基礎。但是，當然，隨著所有產品的推出和所有新疾病的出現，教育對消費者、護理人員和付款人都很重要。因此，在所有這些方面，這些討論已經開始或正在開始，我們顯然計劃實施一個強有力的市場開發計劃，就像我們對所有疫苗所做的那樣。但是，我認為這裡最大的優勢在於 RSV 與我們其他成人疫苗的協同作用，對嗎？我們沒有 20 個成年人。我們有 COVID。我們——所有這些疫苗在商業需求方面都遵循非常相似的模式。

And I think that we have the opportunity to quickly and seamlessly bring RSV on into our portfolio and use the very same approaches and mechanisms and the same conversations that whether it's with a retailer, whether it's a payer, whether it's with our point of vaccinations to bring RSV on. So actually, I think that this is a very exciting time, and we feel very confident about the ability to seamlessly introduce RSV as another vaccine in our respiratory portfolio.

而且我認為我們有機會快速無縫地將 RSV 引入我們的產品組合，並使用與零售商、付款人、我們的疫苗接種點完全相同的方法和機制以及相同的對話帶來RSV。所以實際上，我認為這是一個非常激動人心的時刻，我們對將 RSV 作為我們呼吸道產品組合中的另一種疫苗無縫引入的能力感到非常有信心。

Our next question comes from David Risinger with SVB Securities.

我們的下一個問題來自 SVB Securities 的 David Risinger。

First, could you discuss the PAXLOVID private market sales potential in China after March 31 that isn't included in your PAXLOVID guidance for the year? And also, could you comment on the late-stage competitive threats from Sanofi's 21-valent pneumococcal conjugate vaccine in adults and infants and Merck's 21-valent in adults.

首先，您能否討論一下 3 月 31 日之後 PAXLOVID 在中國私募市場的銷售潛力，這沒有包含在您當年的 PAXLOVID 指導中？此外，您能否評論一下賽諾菲成人和嬰兒 21 價肺炎球菌結合疫苗以及默克成人 21 價肺炎球菌結合疫苗的後期競爭威脅。

Thank you. Angela, PAXLOVID equity in private market in China?

謝謝。 Angela, PAXLOVID 在中國私募市場的股權？

Sure. So after April, we are -- we continue to have PAXLOVID available, and -- but it will be accessed through an out-of-pocket payment mechanism. So if you're a private patient, you can get it, if you're a public patient, you can get it, you just need to be able to pay out of pocket for it. And we intend to continue to work with the public and with the Chinese government to ensure its access.

當然。因此，在 4 月之後，我們將繼續提供 PAXLOVID，並且——但將通過自付費用機制訪問它。所以如果你是私人病人，你可以得到它，如果你是公共病人，你可以得到它，你只需要能夠自掏腰包就可以了。我們打算繼續與公眾和中國政府合作，以確保其訪問。

We can't give now guidance for a particular product in a particular country. So but -- Angela explained the dynamics. Mikael, very quickly on the competition of pneumococcal.

我們現在無法針對特定國家/地區的特定產品提供指導。所以但是—— Angela 解釋了動態。 Mikael，很快就參加了肺炎球菌的比賽。

Yes, I mean, we are extremely excited about the PCV20 recent pediatric approval with a stellar labor, reflecting the strength of our data. We monitor carefully competitor activity, as you alluded to and are planning ourselves to enter next year, further expanded PCV vaccines, followed by additional expansion a few years later, including optimization of the conjugation procedures, including different carriers and possibly for the adult also adjuvants that we think could be useful. So this is a market where we have been the leaders. We have a unique platform. And we monitor and feel very confident that we are going to have a bright future, although you mentioned competitor which is a nature of markets that are becoming, of course, more saturated like the adult market. But there, we also hope to benefit from our broader portfolio of respiratory vaccines from COVID flu RSV that cannot be matched by others at the moment.

是的，我的意思是，我們對 PCV20 最近獲得兒科批准感到非常興奮，並取得了出色的成果，這反映了我們數據的實力。我們仔細監測競爭對手的活動，正如您提到的併計劃在明年進入，進一步擴大 PCV 疫苗，然後在幾年後進一步擴大，包括優化結合程序，包括不同的載體，可能還包括成人佐劑我們認為可能有用。所以這是一個我們一直處於領先地位的市場。我們有一個獨特的平台。我們監控並非常有信心我們將擁有光明的未來，儘管您提到了競爭對手，這是市場的本質，當然，市場正在變得像成人市場一樣更加飽和。但在那裡，我們也希望從我們更廣泛的 COVID 流感 RSV 呼吸道疫苗產品組合中獲益，這些疫苗目前是其他產品無法比擬的。

Our next question will come from Steve Scala with Cowen.

我們的下一個問題將來自 Steve Scala 和 Cowen。

I have 2 follow-ups. First, on pneumococcal vaccine. So Pfizer just started a study of a vaccine, including a new ingredient. Is the new ingredient an adjuvant? Is it more valent, or is it something else? And then a follow-up on the OPDIVO versus ADCETRIS study. Can you say whether you are aware of the data at the time of announcing the Seagen acquisition? And why should we not view this as a significant risk.

我有 2 個跟進。首先，關於肺炎球菌疫苗。因此，輝瑞公司剛剛開始研究一種疫苗，其中包括一種新成分。新成分是佐劑嗎？它更有價值，還是別的什麼？然後是 OPDIVO 與 ADCETRIS 研究的後續行動。您能說一下您是否知道在宣布收購 Seagen 時的數據嗎？為什麼我們不應該將其視為重大風險。

Thank you. Mikael, what is the secret ingredient?

謝謝。 Mikael，秘方是什麼？

The secret sauce in this particular trial is a new adjuvant that we think could play a potential nice role in the PCV adult market as you go to increasing valency in this space. As I said before, in parallel, we are working on -- looking at different carriers, different chemistries and we'll shortly reveal for next year a start of a broader expanded PCV vaccine that will incorporate all these learnings. So stay tuned.

這個特殊試驗的秘訣是一種新的佐劑，我們認為它可以在 PCV 成人市場發揮潛在的良好作用，因為你會在這個領域提高效價。正如我之前所說，與此同時，我們正在研究不同的載體、不同的化學物質，我們將很快在明年公佈一個更廣泛的擴展 PCV 疫苗的開始，該疫苗將結合所有這些知識。敬請期待。

And William, on the -- again, on the OPDIVO study.

威廉，再次，關於 OPDIVO 研究。

Yes, sure. So again, on the OPDIVO study, that SWOG study has been ongoing for a while. We were not aware of the data that's going to be presented at ASCO. I would reiterate again, it's early PFS data from what we can see and the most important measure of activity in Hodgkin's lymphoma would be overall survival. And again, we expect Seagen to get an updated label showing overall survival benefit in first-line Hodgkin's lymphoma.

是的，當然。因此，在 OPDIVO 研究中，SWOG 研究已經進行了一段時間。我們不知道將在 ASCO 上展示的數據。我要再次重申，這是我們所看到的早期 PFS 數據，霍奇金淋巴瘤最重要的活動衡量標準是總生存期。再一次，我們希望 Seagen 獲得更新的標籤，顯示一線霍奇金淋巴瘤的總體生存益處。

Our next question will come from Kerry Holford with Berenberg.

我們的下一個問題將來自 Kerry Holford 和 Berenberg。

Two questions on the RSV vaccine, please. Firstly, on the older adult vaccine. On Slide 22, you note emerging mid-second season data supporting durable efficacy. I wonder if you can elaborate a little more here on patent you have in hand today, and you want to act to get that second-season data in front of the FDA approval. And assuming you do see protection into that second season, how might that imply your pricing in the U.S.? And then secondly, on the maternal vaccine, you have had launched schedule in Q4 on Slide 6 and it implies that, that may not happen until the first quarter of next year. So could you just provide more clarity on when you could launch a maternal vaccine.

請回答兩個關於 RSV 疫苗的問題。首先，關於老年人疫苗。在幻燈片 22 上，您注意到新出現的第二季中期數據支持持久療效。我想知道你是否可以在這裡詳細說明你今天手頭的專利，你想在 FDA 批准之前採取行動獲得第二季的數據。假設你確實看到了第二季的保護，這對你在美國的定價有何影響？其次，關於母體疫苗，您已經在幻燈片 6 的第四季度啟動了時間表，這意味著這可能要到明年第一季度才會發生。那麼，您能否更清楚地說明何時可以推出孕產婦疫苗。

Yes. Mikael, what about the RSV vaccine?

是的。 Mikael，RSV 疫苗怎麼樣？

Yes. We were very pleased to get our first data chunk from second season, mid-season data for older adults, and it clearly shows that robust data that we shared, for example, we shared high 80% reduction in lower respiratory tract infections with 3 symptoms. We see also on this and similar on other end point a very robust, very meaningful protection also in the second season. Now as you know, at the same time, we are preparing for the future combination vaccines, and we think, in general, that you will see an evolution in the adult market with simplified vaccination schedule, annual revaccination of COVID flu RSV. For those that, for some reason, (inaudible) vaccination, we think, the second season data will be very good. On the maternal, we are preparing for an advisory committee, we think we have great data. We are the only one that have been able to conclude a maternal vaccination. We're the only one that we're able to construct an RSV vaccine without using an adjuvant, and we think it's a differentiated product. And I assume it will be soon after a potential approval and opportunity for Angela to launch to a very eagerly awaiting community of increasingly attentive pregnant women and maternal clinics to protect the newborn.

是的。我們很高興獲得第二季的第一個數據塊，即老年人的季中數據，它清楚地表明我們共享的可靠數據，例如，我們共享了 3 種症狀的下呼吸道感染減少了 80% .我們在第二個賽季也看到了這一點和其他類似的非常強大、非常有意義的保護。現在如您所知，與此同時，我們正在為未來的聯合疫苗做準備，我們認為，總的來說，您會看到成人市場的演變，簡化的疫苗接種計劃，每年重新接種 COVID 流感 RSV。對於那些出於某種原因（聽不清）接種疫苗的人，我們認為，第二季的數據會非常好。在產婦方面，我們正在籌備一個諮詢委員會，我們認為我們有很好的數據。我們是唯一能夠完成產婦疫苗接種的人。我們是唯一能夠在不使用佐劑的情況下構建 RSV 疫苗的公司，我們認為這是一種差異化產品。而且我認為，在潛在的批准和機會之後不久，安吉拉將進入一個非常熱切等待的社區，該社區由越來越細心的孕婦和孕產婦診所組成，以保護新生兒。

Thank you, Mike. As we said -- as we have in our slide, we expect to be approved in this year in the last quarter. So good launch. We expect the publication of the MMWR likely to happen at the beginning of the next year. So that plays also a key role in the uptake of the vaccine. But keep in mind, the launch of vaccine starts before the approval, right? We have done a lot of educational efforts and there are a lot of investments that we are doing in that field. So in that aspect, the launch already has started from our side at least.

謝謝你，邁克。正如我們所說 - 正如我們在幻燈片中所說的那樣，我們預計將在今年最後一個季度獲得批准。這麼好的發射。我們預計 MMWR 可能會在明年年初發布。因此，這在疫苗的使用中也起著關鍵作用。但請記住，疫苗的推出在批准之前就開始了，對吧？我們在教育方面做了很多努力，我們在該領域進行了大量投資。所以在這方面，至少已經從我們這邊開始了。

Next question will come from Carter Gould with Barclays.

下一個問題將來自巴克萊銀行的卡特古爾德。

I guess first on the decision to establish a new operating segment and specifically launched this Pfizer Ignite offering. Can you talk about what drove that? And if there's sort of like an aspirational target and how meaningful of a driver that could be? And then secondly, sort of on the decision to divest BAVENCIO. Did that reflect sort of a signal you got from FTC or a proactive move in your mind? Or are there other factors we should think about and the fact that we haven't seen other divestments to that, should that reinforce our confidence that you think that the deal can go through without other issues?

我想首先是決定建立一個新的運營部門，並專門推出了輝瑞 Ignite 產品。你能談談是什麼推動了那件事嗎？如果有點像一個理想的目標，那對司機來說有多大意義？其次，關於剝離 BAVENCIO 的決定。這是否反映了您從 FTC 獲得的某種信號或您心中的主動行動？或者還有其他我們應該考慮的因素以及我們還沒有看到其他撤資的事實，這是否會增強我們的信心，您認為交易可以在沒有其他問題的情況下進行？

Thank you very much. On the Bavencio question, the discussions to return the rights for royalties -- in exchange for royalties had started well before Seagen, so it has nothing to do with the acquisition of Seagen. It was something that was ongoing between us and [Exelon] for the benefit of the product and for simplest (inaudible), just was completed after we announced the deal shortly after, but it had started way, way before. Aamir, would you like also to explain the Ignite business?

非常感謝。在Bavencio問題上，關於返還特許權使用費的權利——換取特許權使用費的討論早在Seagen之前就開始了，所以這與收購Seagen無關。為了產品的利益和最簡單的（聽不清），這是我們和 [Exelon] 之間正在進行的事情，在我們宣布交易後不久就完成了，但它已經開始了。 Aamir，你也想解釋一下 Ignite 業務嗎？

Yes, Carter, thanks for the question. I think you've seen us collaborate with the biotech ecosystem in lots of different ways, and Pfizer Ignite is another way in which we can effectively do that. Frankly, there's a lot of interest and demand on the part of particularly Biotechs for working with us to access some of our distinctive research and clinical development capabilities, and we think Ignite gives us a platform to do that, to work with these companies, get closer to the science, which overtime also then improves our ability to access at science and make determinations about what we would like to bring in-house. So we think this is an excellent way for us to continue to collaborate with the biotech ecosystem and add to our growing and compelling pipeline overtime.

是的，卡特，謝謝你的提問。我想你已經看到我們以許多不同的方式與生物技術生態系統合作，而輝瑞 Ignite 是我們可以有效地做到這一點的另一種方式。坦率地說，特別是生物技術公司對與我們合作以獲取我們一些獨特的研究和臨床開發能力有很大的興趣和需求，我們認為 Ignite 為我們提供了一個平台來做到這一點，與這些公司合作，獲得更接近科學，加班也提高了我們接觸科學的能力，並決定我們想把什麼帶進內部。因此，我們認為這是我們繼續與生物技術生態系統合作並增加我們不斷增長和引人注目的管道加班的絕佳方式。

Our next question will come from Chris Shibutani with Goldman Sachs.

我們的下一個問題將來自高盛的 Chris Shibutani。

On PAXLOVID, the U.S. commercial opportunity, can you update us on any framing of what you're thinking in terms of pricing and when we will know that. And in particular, with the commercial availability, are you anticipating much in the way of sort of payer engagements in terms of thinking about how that process will unfold utilization management wise. And then on the business development front, if we go to the $30 billion that you had outlined for a while now and think about what is remaining from that unadjusted target in terms of 2030 revenues let's say, approximately $5 billion is left. As we're thinking about how you guys are contemplating what areas to go into in terms of verticals or therapeutic areas or modalities, would it be fair to expect that at this stage, a consideration might be to minimize the extent that you would have to rebuild or sort of refurbish on the SI&A front, given your margin objectives longer term?

關於美國商業機會 PAXLOVID，您能否向我們更新您在定價方面的想法以及我們何時知道的任何框架。特別是，隨著商業可用性，您是否在考慮該過程將如何明智地展開利用管理方面，以付款人參與的方式期待很多。然後在業務發展方面，如果我們達到您現在概述的 300 億美元，並考慮到 2030 年收入方面未調整的目標還剩下什麼，比方說，大約還剩下 50 億美元。當我們考慮你們如何考慮在垂直或治療領域或模式方面進入哪些領域時，期望在這個階段是否公平，一個考慮因素可能是盡量減少你必須考慮到您的長期利潤目標，在 SI&A 方面重建或某種翻新？

Angela, on PAXLOVID commercialization.

Angela，關於 PAXLOVID 的商業化。

Sure. So Chris, yes, we're preparing for launch now. But as we've said, we've shared before, the date of launch and exactly how that's going to happen is still very much subject to our discussions with the U.S. government. So we're going to align with guidance from them in terms of how that's going to happen. Of course, in the meantime, we are preparing for the commercialization of PAXLOVID and payer discussions around the world is critical. So those have begun. Obviously, it's too early for me to share the price of PAXLOVID. But suffice to say that the price ranges that we have brought to our payers together with the value argument that we have been able to develop through robust real-world evidence from the number of hospitalizations, the number of deaths that we've been able to avert through the treatment with PAXLOVID is very much supportive of the pricing ranges that we're talking about. So I think very soon, we'll be able to share more.

當然。克里斯，是的，我們現在正在準備發布。但正如我們之前所說，我們之前已經分享過，發射日期以及具體將如何發生仍然在很大程度上取決於我們與美國政府的討論。因此，我們將就如何實現這一點與他們的指導保持一致。當然，與此同時，我們正在為 PAXLOVID 的商業化做準備，全球範圍內的付款人討論至關重要。所以那些已經開始了。顯然，現在分享 PAXLOVID 的價格還為時過早。但足以說明的是，我們為付款人提供的價格範圍以及我們能夠通過住院人數、死亡人數等可靠的現實證據得出的價值論證通過使用 PAXLOVID 治療的避免非常支持我們正在談論的定價範圍。所以我想很快，我們就能分享更多。

And Aamir, about -- what is the profile of (inaudible) activities?

Aamir，關於 - （聽不清）活動的概況是什麼？

Yes, Chris, as you mentioned, we have a goal of $25 billion in risk-adjusted revenue by 2030. And I should remind everyone that is a 2030 goal. We -- with the deals that we've done, have a remaining balance of less than $5 billion against that goal. And I think our strategy to pursue that is going to be consistent with what we have employed to date. First and foremost, it's going to be about compelling science that we can add value to. That's also going to contribute growth in the 25 to 30 period and take lots of things into consideration, including the impact on the P&L profile. So that will continue to be our focus, and we'll continue to be disciplined in the opportunities that we look for. And as Dave mentioned earlier, our priority right now is ensuring that we close out and successfully integrate the Seagen [contraction] as well as drive value from the other deals that we've done, and we'll continue to actively look for opportunities.

是的，克里斯，正如你提到的，我們的目標是到 2030 年實現 250 億美元的風險調整後收入。我應該提醒大家，這是 2030 年的目標。我們——通過我們已經完成的交易，實現該目標的剩餘餘額不到 50 億美元。我認為我們追求這一目標的戰略將與我們迄今為止採用的戰略保持一致。首先也是最重要的，這將是關於我們可以為其增加價值的引人注目的科學。這也將有助於 25 至 30 歲期間的增長，並考慮很多因素，包括對損益表的影響。因此，這將繼續成為我們的重點，我們將繼續在我們尋找的機會上保持紀律。正如 Dave 之前提到的，我們現在的首要任務是確保我們關閉並成功整合 Seagen [contraction] 以及從我們已經完成的其他交易中獲得價值，我們將繼續積極尋找機會。

Thank you, and we are a bit out of time, so last question, please.

謝謝，我們有點沒時間了，所以請問最後一個問題。

Our last question will come from Tim Anderson with Wolfe Research.

我們的最後一個問題將來自 Wolfe Research 的 Tim Anderson。

A couple of questions. The first is, how much of your future COVID vaccine revenue forecast are tied to the ability to have the combination product if something like mRNA flu ends up not being viable and knocked out of flu COVID combo, would that impact your anticipated uptake in 2025 and beyond? Or can you get to those longer-term guidance levels, regardless of whether you have any combos or not. And then last question, Albert, I'm guessing there's some frustration among management with what the stock has been doing a tough 2023, 2022 wasn't a great year. This is despite Pfizer helping lead the world out of the pandemic, which was a remarkable accomplishment, even today be consensus, stock is down a little bit. So as you talk to analysts and investors, what are you hearing are the biggest concerns that you think could explain this? And what do you think analysts, investors are missing or misunderstanding?

幾個問題。首先是，如果像 mRNA 流感這樣的東西最終不可行並被流感 COVID 組合淘汰，那麼你未來的 COVID 疫苗收入預測中有多少與擁有組合產品的能力有關，這會影響你在 2025 年的預期攝入量嗎？超過？或者，無論您是否有任何組合，您能否達到那些長期指導水平。最後一個問題，阿爾伯特，我猜管理層對股票在 2023 年的艱難表現感到有些沮喪，2022 年並不是一個好年頭。儘管輝瑞公司幫助引領世界擺脫了大流行病，這是一項了不起的成就，但即使在今天達成共識，庫存仍略有下降。因此，當你與分析師和投資者交談時，你聽到的最大擔憂是什麼，你認為可以解釋這一點？您認為分析師、投資者遺漏或誤解了什麼？

Thank you, Tim. Let me start with the first one. We do expect that if there are successful combinations with flu, that will drive utilization of the COVID vaccine much higher. As you know, we now our estimation should we expect, for example, in the U.S. around 24%, 25% in the next few years of, call it, the vaccine. The flu right now utilization around 50%. So there is a big gap. So that's why we believe that the combination between flu and COVID will arise also to the COVID and eventually potentially we can call the way up to the same utilization like flu, particularly given that there are no copays approved and recommended vaccines. Now as regards to the frustration, for the 2023, clearly, I believe that the stock price right now does not reflect the value that Pfizer has.

謝謝你，蒂姆。讓我從第一個開始。我們確實希望，如果與流感成功結合，那將大大提高 COVID 疫苗的利用率。如你所知，我們現在的估計應該是，例如，在美國，在未來幾年，疫苗的使用率約為 24%、25%。流感目前使用率在50%左右。所以差距很大。因此，這就是為什麼我們相信流感和 COVID 之間的組合也會出現在 COVID 上，最終我們可能會像流感一樣使用相同的方法，特別是考慮到沒有批准和推薦的共付額疫苗。現在關於挫敗感，對於 2023 年，很明顯，我認為目前的股價並沒有反映輝瑞的價值。

The fact that we are so proud because of our contribution in saving the world, I don't think, but we expect the stock price increases because of that. We did it because it was the right thing to do. And I think we are very, very proud of that. But we expect to see stock price increases as we are executing our plan, which is to create sustainable top line revenue growth that will allow us to leverage the bottom line, that will grow faster than the top line. And I think we articulated the plan about that and that plan was to invest in acquiring good scientific substrate that will allow us to launch products that will give us $25 billion revenues by year 2030, and we have done tremendous progress on that by having already according to our calculation of $20 billion.

我不認為我們會因為我們為拯救世界所做的貢獻而感到自豪，但我們預計股價會因此而上漲。我們這樣做是因為這是正確的做法。我認為我們為此感到非常非常自豪。但我們預計在執行我們的計劃時會看到股價上漲，這是為了創造可持續的收入增長，這將使我們能夠利用底線，這將比收入增長更快。我認為我們已經闡明了這方面的計劃，該計劃是投資於獲得良好的科學基礎，這將使我們能夠推出到 2030 年為我們帶來 250 億美元收入的產品，並且我們已經在這方面取得了巨大進展，已經根據根據我們計算的 200 億美元。

We are also invested in R&D in the last -- in the past few years, and we have now an unprecedented launch of new products. And I think the world is expecting to see how those launches will evolve. Clearly, I think there is over hand -- over the COVID revenues. There is uncertainty if the COVID revenues will materialize. We don't have any precedents to show that we know how to predict it well. So our predictions are based on meteorological science. And based on trends that we are testing with market people. So I think that from my perspective, what I said, we are very committed to creating value for the shareholders. We know that everything we do, we do it with their money. It's not our money. And we want to be very good stewards of that. So it's not enough to save the world, I think also, we need to increase the pricing. We are highly committed to do that. We are explaining, better the strategy more importantly, executing on it.

在過去的幾年裡，我們也在研發方面進行了投資，現在我們推出了前所未有的新產品。我認為全世界都期待看到這些發射將如何演變。顯然，我認為 COVID 收入已經過剩。 COVID 收入是否會實現存在不確定性。我們沒有任何先例表明我們知道如何很好地預測它。所以我們的預測是基於氣象科學。並基於我們正在與市場人士一起測試的趨勢。所以我認為，從我的角度來看，正如我所說，我們非常致力於為股東創造價值。我們知道我們所做的一切，都是用他們的錢做的。這不是我們的錢。我們希望成為這方面的好管家。所以僅僅拯救世界是不夠的，我認為我們還需要提高定價。我們非常致力於這樣做。我們正在解釋，更重要的是更好地執行戰略。

So with that, I think it gave me also seem a good segue to close. In summary, we believe that, that was a solid quarter. We delivered on our commitments. We exceeded actual expectations from the street. And we will continue doing so with the compass, but we will create serious value for patients. And that we are certainly will translate into value for shareholders. We are executing our plan, and we will remain very committed to doing that.

因此，我認為它也給了我一個很好的結束語。總之，我們認為這是一個穩健的季度。我們兌現了承諾。我們超出了街道的實際期望。我們將繼續使用指南針這樣做，但我們將為患者創造重要的價值。而且我們肯定會轉化為股東的價值。我們正在執行我們的計劃，我們將繼續致力於這樣做。

Thank you very much to all, and have a nice day.

非常感謝大家，祝你有美好的一天。

Thank you, ladies and gentlemen. This does conclude today's teleconference, and we appreciate your participation. You may disconnect at any time, and have a wonderful day.

謝謝你們，女士們，先生們。今天的電話會議到此結束，感謝您的參與。您可以隨時斷開連接，祝您度過美好的一天。