施貴寶 (BMY) 2020 Q2 法說會逐字稿

Good day, and welcome to the Bristol-Myers Squibb 2020 Second Quarter Results Conference Call. Today's conference is being recorded.

美好的一天，歡迎參加百時美施貴寶 2020 年第二季度業績電話會議。今天的會議正在錄製中。

At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead, sir.

現在，我想將會議交給投資者關係副總裁 Tim Power 先生。請繼續，先生。

Thanks, Orlando, and good morning, everyone. Thanks for joining us today for our second quarter 2020 earnings call.

謝謝奧蘭多，大家早上好。感謝您今天參加我們的 2020 年第二季度財報電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. And also participating on today's call are Chris Boerner, our Chief Commercialization Officer; and Nadim Ahmed, President, Hematology; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development.

今天早上與我一起發表準備好的講話的是我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio)；和我們的首席財務官大衛埃爾金斯。參加今天電話會議的還有我們的首席商業化官 Chris Boerner；納迪姆·艾哈邁德 (Nadim Ahmed)，血液學總裁；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。

As you know, we've posted slides to bms.com that you can follow along with -- for David and Giovanni's remarks. But before we get going, I'll read our forward-looking statements.

如您所知，我們已將幻燈片發佈到 bms.com，您可以觀看 David 和 Giovanni 的講話。但在我們開始之前，我將閱讀我們的前瞻性聲明。

During this call, we will make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements, even if our estimates change.

在本次電話會議中，我們將就公司的未來計劃和前景發表前瞻性聲明。由於各種重要因素（包括公司提交給美國證券交易委員會的文件中討論的因素），實際結果可能與這些前瞻性陳述所示的結果存在重大差異。這些前瞻性陳述代表了我們截至目前的估計，不應被視為代表我們截至未來任何日期的估計。即使我們的估計發生變化，我們特別不承擔任何更新前瞻性陳述的義務。

We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are available on bms.com.

我們還將重點關注我們的非公認會計準則財務指標，這些指標經過調整以排除某些特定項目。這些非 GAAP 財務指標與最具可比性的 GAAP 指標的調節表可在 bms.com 上找到。

And with that, I'll hand it over to Giovanni on Slide 3.

接下來，我將把幻燈片 3 上的內容交給 Giovanni。

Thank you, Tim, and good morning, everyone. I hope that everyone is remaining healthy and safe. As we continue to navigate the impact of the pandemic, I want to thank our colleagues around the world whose commitment to our mission and dedication to our patients has enabled us to continue delivering our medicines to those who are relying on us.

謝謝蒂姆，大家早上好。我希望每個人都保持健康和安全。在我們繼續應對這一流行病的影響時，我要感謝世界各地的同事，他們對我們使命的承諾和對患者的奉獻使我們能夠繼續向那些依賴我們的人提供藥物。

Before starting the call, let me briefly comment on yesterday's news on Eliquis. We believe the IP for this medicine reflects the innovation we have brought to help patients with AF and VTE. In this regard, we are very pleased by the court's decision to rule in our favor on both patents.

在開始通話之前，讓我簡要評論一下昨天有關 Eliquis 的新聞。我們相信該藥物的知識產權反映了我們為幫助 AF 和 VTE 患者帶來的創新。在這方面，我們對法院對這兩項專利作出有利於我們的裁決感到非常高興。

Let's turn to Slide 4. We have delivered another very strong quarter, with solid commercial performance, including a promising start with multiple launches, strong financial performance and the achievement of important clinical and pipeline milestones that reinforce our long-term potential.

讓我們轉向幻燈片 4。我們又交付了一個非常強勁的季度，具有堅實的商業業績，包括多次上市的良好開局、強勁的財務業績以及增強我們長期潛力的重要臨床和管道里程碑的實現。

Our ability to advance the business was enabled in part by our integration efforts. Our teams are working well across the organization. Our systems are coming together, and we are on track to deliver $2.5 billion in synergies by the end of '22. With a strong foundation, a broad and deep portfolio and pipeline and significant financial flexibility, I have never been more confident in the future of Bristol-Myers Squibb.

我們推動業務發展的能力部分歸功於我們的整合工作。我們的團隊在整個組織內運作良好。我們的系統正在整合，我們有望在 22 年底之前實現 25 億美元的協同效應。憑藉堅實的基礎、廣泛而深入的產品組合和產品線以及顯著的財務靈活性，我對百時美施貴寶的未來充滿信心。

Before I discuss our results, I will take a moment to talk about how our teams are coming back to the workplace and into the field. We are taking a thoughtful and phased approach to our return to the workplace. Our time lines and circumstances vary by market, and we are taking significant measures to protect the safety of our colleagues, while we continue to deliver medicines to patients and enhance our long-term competitive position as a company.

在討論我們的結果之前，我將花點時間談談我們的團隊如何重返工作場所並進入現場。我們正在採取深思熟慮、分階段的方式返回工作場所。我們的時間表和情況因市場而異，我們正在採取重大措施保護同事的安全，同時繼續向患者提供藥品並增強我們作為公司的長期競爭地位。

In locations where country restrictions permit, and we can ensure the safety of patients, providers and colleagues, we have resumed recruiting for our clinical trials. Our discovery researchers have returned to our laboratories to continue their vital work. Depending on local and regional conditions in the U.S. and globally, our sales and medical teams are continuing to effectively engage virtually and, where possible, returning to the field.

在國家限制允許的地區，並且我們可以確保患者、提供者和同事的安全，我們已經恢復了臨床試驗的招募。我們的發現研究人員已返回我們的實驗室繼續他們的重要工作。根據美國和全球的當地和地區情況，我們的銷售和醫療團隊將繼續有效地進行虛擬參與，並在可能的情況下返回現場。

We also continue to support the global COVID-19 response effort in a variety of areas, including working with researchers, the biopharma community and the broader life sciences industry on ways to accelerate therapies for COVID-19. While uncertainty remains with how the COVID-19 pandemic will evolve, we have plans in place to adapt and ensure that our business continues to operate well.

我們還繼續支持全球各個領域的 COVID-19 應對工作，包括與研究人員、生物製藥界和更廣泛的生命科學行業合作，探討加速 COVID-19 治療的方法。儘管 COVID-19 大流行將如何演變仍存在不確定性，但我們已製定計劃來適應並確保我們的業務繼續良好運營。

Now let me turn to the quarter on Slide 5. David will provide more details later in the call, so I'll take a moment to cover the highlights. First, I'm very encouraged by the resilience and strength of our business and the robust demand for our medicines, enabled by strong commercial execution. We posted $10.1 billion in sales. And while COVID-related inventory and demand dynamics had an impact on sales of our medicines in Q2, underlying dynamics remain very positive and fully aligned with our expectations.

現在讓我談談幻燈片 5 上的季度。David 將在稍後的電話會議中提供更多詳細信息，因此我將花點時間介紹重點內容。首先，我對我們業務的彈性和實力以及強大的商業執行力所帶來的對我們藥品的強勁需求感到非常鼓舞。我們公佈的銷售額為 101 億美元。儘管與新冠病毒相關的庫存和需求動態對我們第二季度的藥品銷售產生了影響，但潛在的動態仍然非常積極，並且完全符合我們的預期。

During the quarter, we also made important progress with our pipeline. We achieved 2 first-line lung cancer approvals for dual I-O therapy. We delivered positive pivotal Phase III results for ZEPOSIA in ulcerative colitis, which we look forward to discussing with health authorities and presenting at a future medical meeting. And we also made good progress with the regulatory process for our cell therapy medicines, particularly the submission of ide-cel.

本季度，我們的管道也取得了重要進展。我們的雙 I-O 療法獲得了 2 項一線肺癌批准。我們在 ZEPOSIA 治療潰瘍性結腸炎的 III 期臨床試驗中取得了積極的關鍵結果，我們期待與衛生當局討論並在未來的醫學會議上介紹這些結果。我們在細胞治療藥物的監管流程方面也取得了良好進展，特別是 ide-cel 的提交。

Also during the second quarter, we have launched several of our new medicines and new indications. And while we are clearly in the launch cycle -- early in the launch cycle, we are seeing encouraging initial performance. We are off to a very good start with our Opdivo + Yervoy launches in first-line lung, with encouraging initial feedback from physicians and good indications of early adoption. This supports our expectation that Opdivo will return to annual sales growth in 2021.

同樣在第二季度，我們推出了幾種新藥和新適應症。雖然我們顯然正處於發布週期的早期階段，但我們看到了令人鼓舞的初始表現。我們在一線肺部推出 Opdivo + Yervoy，這是一個良好的開端，醫生的初步反饋令人鼓舞，並且有良好的早期採用跡象。這支持了我們對 Opdivo 將在 2021 年恢復年度銷售增長的預期。

We have launched ZEPOSIA with a best-in-class S1P label in MS, and we are pleased with the feedback from customers, so far, including with respect to the ease of treatment initiation. And we're very encouraged by the adoption we've seen with REBLOZYL in MDS. Early demand trends support our view that this will be an important driver for patients and for the company. And we further strengthened our financial position with strong operating results and cash flow. The results we've delivered in the quarter provide a strong foundation for the future.

我們在 MS 領域推出了具有一流 S1P 標籤的 ZEPOSIA，到目前為止，我們對客戶的反饋感到滿意，包括關於開始治療的難易程度。 REBLOZYL 在 MDS 中的應用讓我們深受鼓舞。早期需求趨勢支持我們的觀點，即這將成為患者和公司的重要驅動力。我們憑藉強勁的經營業績和現金流進一步增強了我們的財務狀況。我們在本季度交付的業績為未來奠定了堅實的基礎。

So looking forward and turning to Slide 6, as we discussed during our investor series in June, we are executing on an unprecedented number of new launch opportunities. And across almost every one of our new products, we have the potential to build on our initial launch success, with additional new indications benefiting more patients and growing our business. We believe that the new products we're bringing to market provide us with an opportunity to renew our portfolio for the long term. In fact, we estimate that the new launches, together with their life cycle management opportunities, could deliver approximately $20 billion in peak revenue on a nonrisk-adjusted basis.

因此，展望並轉向幻燈片 6，正如我們在 6 月份的投資者係列中討論的那樣，我們正在執行數量空前的新發布機會。在我們幾乎每一款新產品中，我們都有潛力在最初推出的成功基礎上再接再厲，讓更多的新適應症惠及更多患者並發展我們的業務。我們相信，我們推向市場的新產品為我們提供了長期更新產品組合的機會。事實上，我們估計新推出的產品及其生命週期管理機會，在非風險調整的基礎上可以帶來約 200 億美元的峰值收入。

During the quarter, we began to realize this potential, having launched several new products and indications, and we also delivered key clinical data to potentially expand the use of ZEPOSIA. Later this year, we expect key data for our TYK2 inhibitor, which we believe is an asset with significant potential as a broad-based autoimmune medicine. In fact, we have recently received Phase II data for TYK2 in psoriatic arthritis, reinforcing this view. We look forward to presenting the data at an upcoming medical meeting and embarking on a Phase III program in this indication.

在本季度，我們開始意識到這一潛力，推出了多種新產品和適應症，並且我們還提供了關鍵的臨床數據，以潛在擴大 ZEPOSIA 的使用。今年晚些時候，我們預計將獲得 TYK2 抑製劑的關鍵數據，我們認為該抑製劑作為一種廣泛的自身免疫藥物具有巨大潛力。事實上，我們最近收到了 TYK2 治療銀屑病關節炎的 II 期數據，證實了這一觀點。我們期待在即將召開的醫學會議上展示這些數據，並開始針對該適應症的 III 期項目。

And finally, in the very near term, we are looking forward to the U.S. PDUFA dates for CC-486 in September and liso-cel in November. And of course, beyond our new launches, we have a pipeline full of promise.

最後，在不久的將來，我們期待 CC-486 的美國 PDUFA 日期為 9 月，liso-cel 的美國 PDUFA 日期為 11 月。當然，除了我們的新產品之外，我們還有一個充滿希望的產品線。

Turning to Slide 7. I am encouraged by the progress with the next wave of medicines that are emerging. Our pipeline includes more than 6 assets that have achieved proof-of-concept or are close to it, spanning multiple disease areas. In I-O, we have our LAG-3 inhibitor, relatlimab, with potential Phase III data later this year or early next year as well as bempeg partnered with Nektar. In multiple myeloma, we have 2 CELMoDs, iberdomide and CC-92480; and our BCMA T-cell engager. In cardiovascular disease, we see promise in our Factor XIa inhibitor. And finally, in immunology and GI, we are looking forward to taking cendakimab into Phase III trials in eosinophilic esophagitis. All of these agents could have significant commercial potential.

轉向幻燈片 7。我對下一波正在出現的藥物所取得的進展感到鼓舞。我們的產品線包括超過 6 個已實現或接近概念驗證的資產，涵蓋多個疾病領域。在 I-O 中，我們擁有 LAG-3 抑製劑 relatlimab，以及與 Nektar 合作的 bempeg，該藥物將於今年晚些時候或明年初獲得潛在的 III 期數據。在多發性骨髓瘤中，我們有 2 種 CELMoD，伊伯多胺和 CC-92480；以及我們的 BCMA T 細胞接合器。在心血管疾病方面，我們看到了 XIa 因子抑製劑的前景。最後，在免疫學和胃腸道方面，我們期待將 cendakimab 納入嗜酸性粒細胞性食管炎的 III 期試驗。所有這些藥物都可能具有巨大的商業潛力。

When I look at our portfolio, I'm confident that the opportunities we have with our new launches, life cycle management programs and earlier pipeline assets have the potential to strengthen our position in key therapeutic areas, such as expanding our franchise in hematology and sustaining a leadership position in multiple myeloma, broadening our presence in immunology with our TYK2 inhibitor and establishing a GI franchise starting ZEPOSIA and renewing our franchise in cardiovascular. Along with these opportunities, our financial flexibility enables the external sourcing of assets and innovation to complement our internal R&D efforts.

當我審視我們的投資組合時，我相信我們的新產品、生命週期管理計劃和早期管道資產所擁有的機會有可能加強我們在關鍵治療領域的地位，例如擴大我們在血液學方面的特許經營權並維持在多發性骨髓瘤領域佔據領導地位，通過 TYK2 抑製劑擴大我們在免疫學領域的業務，並建立胃腸道特許經營權，啟動 ZEPOSIA 並更新我們在心血管領域的特許經營權。除了這些機會之外，我們的財務靈活性還使資產和創新的外部採購能夠補充我們的內部研發工作。

Now moving to Slide 8. Our future has never been brighter. In the first half of the year, we've executed very well, realizing a number of important accomplishments, while integrating the company. These accomplishments all point to our opportunity to successfully renew our portfolio for the long term. None of this would be possible without the tireless efforts of our extraordinary teams around the globe. I'm very proud of our colleagues and thank them for their focus and dedication. We have incredible talent in the company, and it is our priority to continue to attract, retain and develop the best people.

現在轉到幻燈片 8。我們的未來從未如此光明。今年上半年，我們執行得很好，在整合公司的同時取得了一些重要成就。這些成就都表明我們有機會成功地長期更新我們的投資組合。如果沒有我們全球傑出團隊的不懈努力，這一切都是不可能實現的。我為我們的同事感到非常自豪，並感謝他們的專注和奉獻。我們公司擁有令人難以置信的人才，繼續吸引、留住和培養最優秀的人才是我們的首要任務。

Before I hand it over to David, let me provide our perspective on the recent executive orders in the U.S. We are supportive of increasing access to medicines and reducing the out-of-pocket cost of medicines for seniors. Actions like the rebate rule would help achieve these goals. However, the IPI would not. We, the industry, physicians and patient groups, are very concerned about and firmly disagree with the administration's decision to sign the executive order on IPI. We believe that IPI has the potential to impose price controls from countries where government run health care systems and price controls do not appropriately reward innovation and where, too often, patients do not even have access to new medicines. The policy of importing price controls from foreign countries, which the administration has described as having socialist health care systems, would have a significant impact on our industry in the U.S., starting with our ability to continue to invest in R&D and lead innovative research to treat disease at a time when we are leading the fight against COVID-19.

在我把它交給大衛之前，讓我談談我們對美國最近的行政命令的看法。我們支持增加老年人獲得藥物的機會並降低老年人的自付費用。諸如回扣規則之類的行動將有助於實現這些目標。然而，IPI 不會。我們行業、醫生和患者團體非常關注並堅決不同意政府簽署 IPI 行政命令的決定。我們認為，IPI 有可能對政府運營醫療保健系統的國家實施價格控制，而價格控制不能適當獎勵創新，而且患者常常無法獲得新藥。從外國進口價格控制政策（政府將其描述為擁有社會主義醫療保健系統）將對我們在美國的行業產生重大影響，首先是我們有能力繼續投資研發並領導創新研究來治療疾病在我們領導抗擊 COVID-19 的鬥爭之際。

I'll now hand it over to David to walk you through our financials for this quarter. David?

現在我將把它交給大衛，讓他向您介紹我們本季度的財務狀況。大衛？

Thank you, Giovanni. Hello, everyone, and thank you again for joining our call today. As Giovanni mentioned, I continue to be very impressed by the execution of our teams in the wake of COVID-19. Our exceptional second quarter and first half results depict the resiliency of our portfolio.

謝謝你，喬瓦尼。大家好，再次感謝您今天加入我們的電話會議。正如 Giovanni 提到的，我對我們團隊在 COVID-19 疫情之後的執行力仍然印象深刻。我們出色的第二季度和上半年業績體現了我們投資組合的彈性。

So now let's dig in a bit more on our recent performance, turning to Slide 10. We had a solid top line performance in the second quarter of $10.1 billion, including significant unwinding of the COVID-related stocking in the first quarter. On a pro forma basis, sales were flat year-over-year as inventory built in the first quarter reversed in the second. Importantly, if you look at our half year results, sales were strong at $20.9 billion, growing 6% year-over-year with growth across the vast majority of our prioritized brands.

現在讓我們更深入地了解一下我們最近的業績，轉向幻燈片 10。我們在第二季度實現了 101 億美元的穩健營收業績，其中包括在第一季度大幅減少了與新冠病毒相關的庫存。預計銷售額同比持平，因為第一季度建立的庫存在第二季度出現逆轉。重要的是，如果你看看我們的半年業績，就會發現銷售額強勁，達到 209 億美元，同比增長 6%，我們絕大多數優先品牌都實現了增長。

Now let's turn to our key brand performance, starting with Eliquis on Slide 11. Eliquis demand trends remain robust with double-digit TRx growth of 20% in the U.S. versus prior year. As mentioned, we saw significant favorable impact from channel and patient level stocking due to COVID in the first quarter, which, as expected, largely reversed in Q2. Second quarter global sales were approximately $2.2 billion, growing 6% versus prior year. If you look at the sales in the first half of the year and wash out the quarterly noise, sales were very strong, up 21% versus the first half of 2019.

現在讓我們轉向我們的關鍵品牌表現，從幻燈片 11 上的 Eliquis 開始。Eliquis 的需求趨勢仍然強勁，與去年相比，美國的 TRx 增長了 20% 的兩位數。如前所述，我們看到第一季度新冠疫情對渠道和患者庫存產生了顯著的有利影響，正如預期的那樣，這種影響在第二季度基本逆轉。第二季度全球銷售額約為 22 億美元，比去年同期增長 6%。如果你看看今年上半年的銷售情況，並消除季度噪音，你會發現銷售非常強勁，比 2019 年上半年增長了 21%。

We would like to remind you of second half dynamics related to the coverage gap of Eliquis. As we've explained in the past, we accrue our liability related to this patient population when they entered the donut hole, which reflects a substantially higher impact in the second half of the year. Recall that there's a step-up in the liability in 2019, where the manufacturer responsibility increased from 50% to 70%. Though this factor has not changed for the full year in 2020, there are additional drivers to keep in mind.

我們想提醒您有關 Eliquis 覆蓋範圍差距的下半年動態。正如我們過去所解釋的，當這些患者群體進入甜甜圈洞時，我們就累積了與他們相關的責任，這反映出下半年的影響要大得多。回想一下，2019 年的責任有所增加，製造商的責任從 50% 增加到 70%。儘管這個因素在 2020 年全年沒有改變，但還有其他驅動因素需要牢記。

First is our mix. Medicare is an increasingly large component of Eliquis. And second is the size of the coverage gap per patient that increased in 2020 compared to last year. This further increases the gross to net accrual in the third and fourth quarters. Because of these gross to net phasing dynamics, as we've seen before, we expect Eliquis net sales in the second half of the year to be lower than the first half of the year, despite the strong underlying demand growth.

首先是我們的組合。醫療保險是 Eliquis 的一個日益重要的組成部分。其次是 2020 年每位患者的保險覆蓋範圍與去年相比有所擴大。這進一步增加了第三和第四季度的總應計淨額。由於這些從總量到淨值的階段動態，正如我們之前所看到的，我們預計 Eliquis 下半年的淨銷售額將低於上半年，儘管潛在需求增長強勁。

From a COVID perspective, though we saw new brand levels unfavorably impacted, we are seeing positive recovery signals of patient access to health care providers and cardiologists from the lows we experienced in April and May.

從新冠疫情的角度來看，儘管我們看到新的品牌水平受到了不利影響，但我們看到患者獲得醫療保健提供者和心髒病專家的服務從 4 月和 5 月經歷的低點開始出現積極的複蘇信號。

Looking forward, we continue to expect significant future growth driven by Eliquis' #1 position among the NOAC class due to the coverage of total brand share to new brand share and continued erosion of warfarin.

展望未來，由於總品牌份額覆蓋新品牌份額以及華法林的持續侵蝕，我們繼續預計 Eliquis 在 NOAC 類別中排名第一的地位將推動未來的顯著增長。

Turning to Opdivo on Slide 12. In the U.S., we continue to see strong share across key indications, stabilization of I-O eligibility in second-line lung and strong share within the RCC market. With respect to COVID, we saw some demand pressures due to patient access to hospitals and infusion centers, which we estimate to be in the low to single-mid digits. We are starting to see recovery signals with patients' ability to access centers.

轉向幻燈片 12 上的 Opdivo。在美國，我們繼續看到其在關鍵適應症中的強勁份額、二線肺部 I-O 資格的穩定以及 RCC 市場中的強勁份額。就新冠疫情而言，我們看到了由於患者前往醫院和輸液中心而產生的一些需求壓力，我們估計這種壓力在低至個位數之間。我們開始看到患者能夠進入中心的康復信號。

Internationally, COVID has impacted patient starts across tumors, with melanoma being the most impacted. Despite COVID impact, our I-O franchise has remained strong across all -- remained strong shares across all our key indications.

在國際上，新冠肺炎已經影響了各種腫瘤的患者開始治療，其中黑色素瘤受到的影響最大。儘管受到新冠疫情的影響，我們的 I-O 特許經營權在所有方面仍然保持強勁——在我們所有的關鍵指標上仍然保持強勁的份額。

Now moving to the frontline lung approvals for Opdivo + Yervoy in May based on CheckMate -227 and -9LA. We are very encouraged by how the launches are going. While it's still early days, we believe it's going well, if not better than expected, particularly in light of COVID and launching in a virtual environment. We have already achieved market share in the mid-single digits. For -227, we are seeing use of Opdivo + Yervoy across histologies and PD-L1 expression. What we're hearing from prescribers is they are impressed with the depth and durability of response as well as the long-term survival data. With respect to -9LA, this gives physicians another option in first-line setting, limiting the use of chemo and addressing the needs of patients with rapidly progressing disease. Based on these promising launches in the U.S., we expect Opdivo to return to annual sales growth in 2021.

現在將在 5 月份基於 CheckMate -227 和 -9LA 進行 Opdivo + Yervoy 的一線肺部批准。我們對發布的進展感到非常鼓舞。雖然現在還處於早期階段，但我們相信進展順利，即使沒有比預期更好，特別是考慮到新冠疫情以及在虛擬環境中推出。我們已經取得了中個位數的市場份額。對於 -227，我們看到 Opdivo + Yervoy 在組織學和 PD-L1 表達中的使用。我們從處方醫生那裡聽到的是，他們對反應的深度和持久性以及長期生存數據印象深刻。就-9LA而言，這為醫生在一線治療中提供了另一種選擇，限制化療的使用並滿足疾病快速進展患者的需求。基於這些在美國的有希望的上市，我們預計 Opdivo 將在 2021 年恢復年度銷售增長。

Moving on to our in-line multiple myeloma portfolio on Slide 13. Revlimid and Pomalyst continue to perform well, delivering strong year-over-year sales growth, up 6% and 21%, respectively. Growth was primarily driven by increased treatment duration due to demand for Revlimid and Pomalyst-based triple therapies. As previously mentioned, the impact of COVID on the brands is modest to the oral administration of Revlimid and Pomalyst. There was some stocking impact in the prior quarter x U.S. However, the REMS program in the U.S. resulted in limited stocking compared to other brands like Eliquis. When looking at our sales year-to-date, both Revlimid and Pomalyst grew double digits, up 10% and 20% -- 25%, respectively.

接下來是幻燈片 13 上我們的多發性骨髓瘤內線產品組合。Revlimid 和 Pomalyst 繼續表現良好，銷售額同比強勁增長，分別增長 6% 和 21%。增長主要是由於對基於 Revlimid 和 Pomalyst 的三聯療法的需求增加了治療持續時間。如前所述，新冠肺炎對口服 Revlimid 和 Pomalyst 品牌的影響不大。上一季度美國的庫存受到了一些影響。但是，與 Eliquis 等其他品牌相比，美國的 REMS 計劃導致庫存有限。從今年迄今的銷售額來看，Revlimid 和 Pomalyst 均實現了兩位數增長，分別增長了 10% 和 20% - 25%。

Now I'd like to take a moment to highlight some of the recent launches on Slide 14, starting with Reblozyl. We're extremely pleased with the virtual launch of Reblozyl post the approval in April for RS-positive MDS-associated anemia. Physician experience in beta thal and the MEDALIST data published in the New England Journal of Medicine in January led to substantial acknowledgment of the clinical value of Reblozyl and pent-up demand leading to the MDS launch, which contributed to the strong sales in the quarter. Physician feedback remains positive, with significant awareness of the approval. While still early, we are very pleased with the launch and patient retention of the product, where a majority of eligible patients have already received their second and third cycles of treatment. We have recently received approval in Europe, and we look forward to launching Reblozyl in the various markets across the world over the next 6 to 12 months.

現在我想花點時間重點介紹幻燈片 14 上最近發布的一些產品，首先是 Reblozyl。我們對 Reblozyl 在 4 月份獲得批准用於治療 RS 陽性 MDS 相關貧血症後的虛擬上市感到非常高興。醫生在 beta thal 方面的經驗以及 1 月份在《新英格蘭醫學雜誌》上發表的 MEDALIST 數據促使人們充分認識到 Reblozyl 的臨床價值以及導致 MDS 推出的被壓抑的需求，這促成了本季度的強勁銷售。醫生的反饋依然積極，人們對批准的認知度很高。雖然還為時尚早，但我們對該產品的推出和患者保留感到非常滿意，大多數符合條件的患者已經接受了第二和第三週期的治療。我們最近在歐洲獲得了批准，我們期待在未來 6 至 12 個月內在全球各個市場推出 Reblozyl。

Now turning to ZEPOSIA. We are also very pleased with our best-in-class S1P label in multiple sclerosis. And while very early in the launch, we are very encouraged on how things are progressing so far. We have already made great progress on the payer front with strong day 1 access, including Express Scripts. It is important to remember that MS market does not change over quickly, and it takes time to penetrate due to patients' long duration on their medicine. With that in mind, we are pleased with the initiation we've seen across multiple prescribers and centers.

現在轉向ZEPOSIA。我們對多發性硬化症領域一流的 S1P 標籤也感到非常滿意。雖然還處於發布初期，但我們對迄今為止的進展感到非常鼓舞。我們已經在付款人方面取得了巨大進展，擁有強大的第一天訪問權限，包括 Express Scripts。重要的是要記住，多發性硬化症市場不會很快發生變化，而且由於患者服藥時間較長，滲透需要時間。考慮到這一點，我們對多個處方醫生和中心的啟動感到滿意。

Now let's move to our balance sheet and the strength in our capital allocation on Slide 15. We continue to generate significant amount of cash flow from operations, with over $4 billion generated in the second quarter. We ended the quarter in a strong liquidity position, with approximately $22 billion in cash and marketable securities, reducing our net debt to $24 billion. Our capital allocation providers remain unchanged, deleveraging and achieving less than 1.5x debt to EBITDA ratio by the end of 2023. We've continued our commitment to our dividend and investing in future innovation through business development.

現在讓我們轉向幻燈片 15 上的資產負債表和資本配置優勢。我們繼續從運營中產生大量現金流，第二季度產生超過 40 億美元。本季度結束時，我們的流動性狀況良好，擁有約 220 億美元的現金和有價證券，將我們的淨債務減少至 240 億美元。我們的資本配置提供商保持不變，去槓桿化，到 2023 年底實現債務與 EBITDA 比率低於 1.5 倍。我們繼續致力於股息並通過業務發展投資於未來創新。

So now let's turn to Slide 16 and review the guidance. Last quarter, we provided assumptions around how we view the impact of COVID-19 crisis on our business. Our view today has not changed. As a reminder, we assume the peak impact would occur in the second quarter, with a return to a more stable business environment in Q3 and minimal impact in Q4. So far, the key factors we assumed are also playing out as we expected. Those were products that saw significant advanced buying at the end of Q1, we'll see that inventory work down during the rest of the year, mostly in Q2, which I described earlier. The remaining inventory will work its way out in the second half of the year. The second factor was the reduction in new-to-brand prescriptions and physician-administered products during Q2, recovery in Q3 and fully recovered in Q4. And lastly, we were planning to resume all clinical trial activities by year-end where restrictions have been lifted.

現在讓我們轉向幻燈片 16 並回顧一下該指南。上季度，我們就如何看待 COVID-19 危機對我們業務的影響提供了假設。我們今天的觀點沒有改變。提醒一下，我們假設影響峰值將出現在第二季度，第三季度將恢復到更加穩定的商業環境，第四季度影響最小。到目前為止，我們假設的關鍵因素也如我們預期的那樣發揮作用。這些產品在第一季度末出現了顯著的提前購買，我們將看到庫存在今年剩餘時間內下降，主要是在第二季度，正如我之前所描述的那樣。剩餘庫存將在下半年消耗殆盡。第二個因素是第二季度新品牌處方和醫生管理產品的減少，第三季度恢復，第四季度完全恢復。最後，我們計劃在年底前恢復所有已取消限制的臨床試驗活動。

Now based on the strength of our results in the first half of the year, we are narrowing our revenue range, updating our tax rate and, as a result, increasing our 2020 adjusted EPS guidance. We now expect revenue to be between $40.5 billion and $42 billion based on strong performance and currency improvement. We expect expenses to be at the high end of our range as we invest in our launch products and accelerate the resumption of clinical trial activities in the second half of the year. And we expect our tax rate to be between 16% and 17%, primarily driven by favorable post-close tax initiatives and earnings mix. With these changes, we are increasing our EPS range to $6.10 to $6.25. Our revenue guidance takes into account the donut hole effect affecting Eliquis in the second half of the year. And as I discussed earlier as well as the competitive dynamics associated with some of our established brands, remember, as I've mentioned earlier in the year, we project revenue from our established brand portfolio to decrease about 30% for the full year on a pro forma basis compared to 2019, which is mainly coming from our international business.

現在，根據我們上半年的強勁業績，我們正在縮小收入範圍，更新稅率，從而提高 2020 年調整後每股收益指導。基於強勁的業績和貨幣改善，我們現在預計收入將在 405 億美元至 420 億美元之間。隨著我們投資推出產品並加速下半年臨床試驗活動的恢復，我們預計費用將處於我們範圍的高端。我們預計我們的稅率將在 16% 至 17% 之間，這主要是受到有利的交割後稅收舉措和盈利組合的推動。通過這些變化，我們將 EPS 範圍提高到 6.10 美元至 6.25 美元。我們的收入指引考慮了下半年影響 Eliquis 的甜甜圈效應。正如我之前討論的以及與我們一些知名品牌相關的競爭動態，請記住，正如我在今年早些時候提到的，我們預計全年來自我們既定品牌組合的收入將減少約 30%與 2019 年相比，預計數據主要來自我們的國際業務。

Lastly, as Giovanni mentioned, we are on track to deliver the $2.5 billion of synergies by the end of 2022, with 1/3 of those expected to be delivered this year.

最後，正如 Giovanni 提到的，我們有望在 2022 年底之前實現 25 億美元的協同效應，其中 1/3 預計將在今年實現。

Before we move on to question and answer, I want to close out by saying how delighted I am with our robust execution in the first half of the year. I discussed a great deal about the financial strength of the company at our Investor Series a little over a month ago. Our performance in this global pandemic illustrates just how resilient our business remains as well as our ability to be agile in a changing environment. I, therefore, remain confident in our long-term outlook for the company.

在我們開始提問和回答之前，我想最後說一下，我對我們上半年的強勁執行力感到非常高興。一個多月前，我在投資者係列活動中大量討論了該公司的財務實力。我們在這場全球大流行中的表現說明了我們的業務保持了多大的彈性，以及我們在不斷變化的環境中保持敏捷的能力。因此，我對公司的長期前景仍然充滿信心。

I'll now turn the call back over to Tim and Giovanni for the question and answer.

現在我將把電話轉回蒂姆和喬瓦尼進行問答。

Thanks, David. Orlando, could we go to our first question, please?

謝謝，大衛。奧蘭多，我們可以回答第一個問題嗎？

(Operator Instructions) And we'll take our first question from Geoff Meacham with Bank of America.

（操作員說明）我們將回答美國銀行傑夫·米查姆 (Geoff Meacham) 提出的第一個問題。

Just had a few quick ones. On Opdivo, based on demand trends you've seen so far in lung, does that change your view of growth looking to 2021? Maybe it'd just be helpful to get a little bit more detail of a commercial view looking to what happened in 2Q from lung. And then just with respect to the pipeline, TYK2 will be, obviously, a big growth driver in a category you have some experience with. When you look to that brand, maybe just help us with the opportunities that you see for TYK2 for differentiation and what investments commercially that you have to make to really maximize the value there.

剛剛吃了幾個快點。關於 Opdivo，根據您迄今為止在肺部看到的需求趨勢，這是否會改變您對 2021 年增長的看法？也許從肺部角度了解第二季度發生的情況的商業觀點的更多細節會有所幫助。然後就管道而言，TYK2 顯然將成為您有一定經驗的類別中的重要增長動力。當您關注該品牌時，也許只是幫助我們了解您所看到的 TYK2 的差異化機會，以及您必須進行哪些商業投資才能真正實現價值最大化。

Thank you, Geoff. So 2 important questions. And as I mentioned in my remarks, we feel good about both with the opportunity for Opdivo and the remarks we've made about the first-line launch so far and TYK2, particularly as we've now seen a second Phase II study in psoriatic arthritis. But let me just ask Chris to give you more color on both Opdivo and TYK2.

謝謝你，傑夫。所以有兩個重要的問題。正如我在發言中提到的，我們對 Opdivo 的機會以及我們迄今為止對一線產品和 TYK2 的評論感到滿意，特別是因為我們現在已經看到了針對銀屑病的第二項 II 期研究關節炎。但我請 Chris 為您提供有關 Opdivo 和 TYK2 的更多信息。

Sure. So thanks for the question, Geoff. Let me start with first-line lung because I think that's probably on a number of folks' mind. The lung launches are going very well and, in fact, are tracking at or maybe even a bit ahead of our expectations. And let me highlight just a few things. From a share standpoint, it's still very early days, but share is currently in the mid-single digits, and we've seen very good momentum in the uptake here. Importantly, we've seen uptake across all PD-L1 segments as well as across histology. And the uptake has been particularly good, I would say, in the PD-L1, 1 to 49 segment. As expected, given the timing of approval and the relative immaturity of the data, the uptake of the -9LA regimen has lagged -227. However, in recent weeks, we've even seen an uptake in the use of dual I-O with chemo. And again, this appears to be across subgroups. So good momentum on utilization.

當然。謝謝你的提問，傑夫。讓我從一線肺部開始，因為我認為這可能是很多人的想法。肺部發射進展順利，事實上，正在跟踪甚至可能有點超出我們的預期。讓我強調幾件事。從份額的角度來看，現在還處於早期階段，但份額目前處於中個位數，而且我們已經看到了非常好的增長勢頭。重要的是，我們已經看到所有 PD-L1 片段以及整個組織學的吸收。我想說的是，在 PD-L1、1 至 49 細分市場中，採用率特別好。正如預期的那樣，考慮到批准的時間和數據的相對不成熟，-9LA 方案的採用率落後於 -227。然而，最近幾週，我們甚至看到雙 I-O 與化療的結合使用有所增加。同樣，這似乎是跨子群體的。使用勢頭良好。

Execution has been particularly good, especially given the dynamics of COVID. Most of the engagements remain virtual, but we're seeing very good engagement between the sales force, even in a remote environment, with key customers. Physician reaction has largely been aligned with expectations in our previous conversations with depth and durability of response of these agents with a manageable safety profile being the primary message. So what I would say is it's still early days, but we're very happy with the utilization that we're seeing. We've got good execution. Physician reaction continues to be positive. And we're very pleased that, in spite of entering first-line lung as the third company to market, our shares now after 8 weeks are putting us as having the second most widely used regimens in the space.

執行情況特別好，特別是考慮到新冠疫情的動態。大多數互動仍然是虛擬的，但我們看到銷售人員與主要客戶之間的互動非常好，即使是在遠程環境中。醫生的反應在很大程度上與我們之前的對話中的預期一致，這些藥物的反應深度和持久性與可管理的安全性是主要信息。所以我想說的是，現在還處於早期階段，但我們對所看到的利用率非常滿意。我們有很好的執行力。醫生的反應仍然是積極的。我們非常高興的是，儘管作為第三家上市公司進入一線肺病領域，但八週後我們的股價使我們成為該領域使用第二廣泛的治療方案。

And as it relates to the growth, as Giovanni mentioned, we still see Opdivo as a growth brand going forward. The fundamentals of the business today continue to be relatively strong. We've got a relatively stable base of business in the U.S. The second-line lung dynamics continue to play out, as we had expected, both in the U.S. and x U.S. The early launch in lung is performing well, and we've got good fundamentals x U.S. And then if you think about 2021 with the strong 9ER data that we talked about in the last quarter, we feel really good about the growth opportunities that we see for Opdivo starting in 2021.

正如喬瓦尼提到的，由於它與增長有關，我們仍然將 Opdivo 視為一個未來的增長品牌。如今，該業務的基本面仍然相對強勁。我們在美國擁有相對穩定的業務基礎。正如我們預期的那樣，二線肺部業務的動態繼續發揮作用，無論是在美國還是在美國。肺部業務的早期推出表現良好，我們已經良好的基本面 x 美國 然後，如果您考慮 2021 年，並考慮到我們在上個季度談到的強勁 9ER 數據，我們對 Opdivo 從 2021 年開始的增長機會感到非常滿意。

With respect to TYK2, very excited, obviously, about the data that we have already presented with Phase II in psoriasis. The psoriatic arthritis Phase II data is, we think, if it plays out in the Phase III, going to be compelling. Remember, this is a disease area that's large. Over 2 million people are diagnosed in the U.S., EU5 and Japan with psoriatic arthritis, and there's still significant unmet need here. 2/3 of the patients, for example, who are stable on DMARDs continue to have disease activity, and there's considerable dissatisfaction with existing oral agents when you look at the totality of the profile, both efficacy and safety. So obviously, early days, but we're excited about what we're seeing there.

關於 TYK2，顯然，我們對銀屑病 II 期臨床數據已經提供了非常興奮的信息。我們認為，銀屑病關節炎第二階段的數據如果在第三階段發揮作用，將會令人信服。請記住，這是一個很大的疾病領域。美國、歐盟五國和日本有超過 200 萬人被診斷患有銀屑病關節炎，而且這裡仍有大量未滿足的需求。例如，使用 DMARD 治療後病情穩定的患者中有 2/3 仍處於疾病活動狀態，從總體情況來看，無論是療效還是安全性，人們對現有口服藥物都相當不滿意。顯然，還處於早期階段，但我們對在那裡看到的東西感到興奮。

And we'll move on to our next question from Terence Flynn with Goldman Sachs.

我們將繼續回答高盛特倫斯·弗林提出的下一個問題。

Great. Maybe just 2 for me as well. Just was wondering if you can give us an update on the timing of some of your Opdivo adjuvant studies. I know 816 from new adjuvant lung and -274 for bladder or potentially expected later this year. So just wondering any update on timing and how you're thinking about those opportunities. And then the second I had is -- I didn't see any mention of 2021 guidance in the release. Just wanted to confirm that there were no changes on that front.

偉大的。也許對我來說也只有2個。只是想知道您是否可以向我們提供一些 Opdivo 輔助研究的最新時間安排。我知道 816 來自新的肺輔助，-274 來自膀胱或可能預計在今年晚些時候。所以只是想知道有關時間安排的最新消息以及您如何看待這些機會。然後我遇到的第二個問題是——我在新聞稿中沒有看到任何提及 2021 年指導的內容。只是想確認這方面沒有任何變化。

Thank you, Terence. Let me just briefly comment on guidance, and then I'll ask Samit to give you perspective on the adjuvant readouts.

謝謝你，特倫斯。讓我簡要評論一下指導意見，然後我將請薩米特向您提供對輔助讀數的看法。

So based on where we stand today, we are reaffirming the guidance for '21. There's really nothing that has changed. The assumptions for COVID are playing out as we thought. The business is strong. We've given you some comments on early positive indicators. Of course, there is a number of considerations that we discussed last quarter. They remain very valid today. We've made a number of assumptions regarding COVID, particularly the end of the year and into next year. I think we'll have to see how those play out. And obviously, as you know, there is significant variability there. And at this point, we've not really included any impact from U.S. health care reform in our assumptions because there, again, it's early days and difficult to understand what an impact may be. So -- but when you look at our assumptions and the strength of our business, we're reaffirming the guidance for '21 at this point. Samit?

因此，基於我們今天的立場，我們重申 21 世紀的指導方針。確實沒有什麼改變。對新冠病毒的假設正在如我們所想的那樣發生。生意很強勁。我們已經向您提供了有關早期積極指標的一些評論。當然，我們上季度討論了許多考慮因素。它們在今天仍然非常有效。我們對新冠病毒做出了一些假設，特別是在今年年底和明年。我想我們得看看結果如何。顯然，如您所知，那裡存在顯著的變化。目前，我們還沒有真正將美國醫療改革的任何影響納入我們的假設中，因為現在還處於早期階段，很難理解可能產生的影響。所以，但是當你看看我們的假設和我們的業務實力時，我們此時重申了 21 世紀的指導。薩米特？

Yes. Thank you, Giovanni. And thanks. To answer the answer for adjuvant , certainly, many opportunities in front of us beyond the still available opportunities in metastatic setting. We're looking forward to a few readouts within the overall holistic program that we have across several tumor types. The ones that we're looking forward to in 2020 would be melanoma, CheckMate -915 potentially reading out towards the end of this year. And then, of course, muscle-invasive bladder cancer, Checkmate -274 is the other one. And then you already mentioned a potential PCR endpoint readout for non-small cell lung cancer at the end of this year. And then in 2021, we're looking forward to the readout for esophageal cancer as well and then others come in 2022 and beyond.

是的。謝謝你，喬瓦尼。謝謝。為了回答佐劑的答案，當然，我們面前有許多機會，超出了轉移環境中仍然可用的機會。我們期待在我們針對多種腫瘤類型的整體整體計劃中獲得一些讀數。我們在 2020 年期待的將是黑色素瘤，CheckMate -915 可能會在今年年底讀出。當然，另一種是肌肉浸潤性膀胱癌，Checkmate -274。然後您已經提到了今年年底非小細胞肺癌的潛在 PCR 終點讀數。然後在 2021 年，我們也期待食道癌的讀數，然後其他讀數將在 2022 年及以後公佈。

We'll take our next question from Chris Schott with JPMorgan.

我們將回答摩根大通的克里斯·肖特 (Chris Schott) 提出的下一個問題。

Great. I guess, first for me was on TYK2. Can you just elaborate a little bit more on the safety profile of the product that you saw in the psoriatic arthritis study? Is there anything, I guess, new to report relative to what you saw with psoriasis? Or is it a similar kind of profile that you saw there?

偉大的。我想，對我來說，第一個是 TYK2。您能否詳細說明一下您在銀屑病關節炎研究中看到的產品的安全性？我想，與您所看到的牛皮癬相關的情況，有什麼新的情況需要報告嗎？或者是您在那裡看到的類似的個人資料嗎？

And then my second question was coming back to Opdivo in first-line lung. Just any comments of where you think you can get to from a share perspective given the strong initial launch. And then when you think about the x U.S. opportunity here, do we just compare and contrast how you're thinking about that versus the U.S. given the lack of a -- 227 label x U.S.?

然後我的第二個問題是回到 Opdivo 在一線肺部治療中的應用。鑑於首次推出的強勁表現，您可以從分享的角度發表任何評論。然後，當您在這裡考慮 x 美國的機會時，我們是否只是將您的想法與美國（考慮到缺乏 -- 227 標籤 x 美國）進行比較和對比？

Thank you, Chris. Samit, why don't you start on TYK2, and then Chris can provide some update on Opdivo.

謝謝你，克里斯。 Samit，您為什麼不開始使用 TYK2，然後 Chris 可以提供有關 Opdivo 的一些更新。

Sure. Thanks. Chris, thank you for the question. For TYK2, as already alluded to a little bit by Giovanni and then Chris earlier, really excited for TYK2 overall. And we've seen the profile, as you saw in psoriasis in the Phase II study, and we see similar results in terms of trending, in terms of safety, and really looking forward to presenting this data in the next medical conferences. Overall, as we've said, we are excited about the data to be able to now plan the Phase III program in psoriatic arthritis and looking forward to the readout towards the end of the year for the psoriasis program for the first study and then the second study in the first quarter of next year. So nothing to report as a differentiation at this time from what we've already known from a safety perspective. So Chris, do you want to take over the Opdivo question?

當然。謝謝。克里斯，謝謝你的提問。對於 TYK2，正如 Giovanni 和 Chris 之前提到的那樣，總體而言，我們對 TYK2 感到非常興奮。我們已經看到了該概況，正如您在第二階段研究中在銀屑病中看到的那樣，我們在趨勢、安全性方面看到了類似的結果，並且非常期待在下一次醫學會議上展示這些數據。總的來說，正如我們所說，我們對這些數據感到興奮，現在能夠規劃銀屑病關節炎的 III 期項目，並期待在今年年底公佈第一項研究的銀屑病項目，然後是明年第一季度進行第二次研究。因此，目前從安全角度來看，沒有什麼可以報告為與我們已知的差異。克里斯，你想接手 Opdivo 的問題嗎？

Sure. Thanks for the question, Chris. So one of the things that we're most pleased about with respect to what we're seeing in the early dynamics in the U.S. is that, as we had suspected, physicians are not pigeonholing the dual I-O regimen to a specific patient type. In fact, as I mentioned before, we're actually seeing good uptake of the -227 regimen and really across segments, across PD-L1 expression levels as well as across histologies.

當然。謝謝你的提問，克里斯。因此，我們在美國的早期動態中看到的最令我們高興的事情之一是，正如我們所懷疑的那樣，醫生並沒有將雙重 I-O 方案歸為特定的患者類型。事實上，正如我之前提到的，我們實際上看到 -227 方案的良好吸收，並且確實跨區段、跨 PD-L1 表達水平以及跨組織學。

What I would say with respect to the patients that have gone on therapy, thus far, within the 1 to 49 segment, the patients are generally those who are requesting non-chemo options or they may be frail patients who can't tolerate chemotherapy. We are seeing some utilization in the greater than 50% population for patients who want or maybe need a more aggressive option than single-agent PD-1. And then with the 9LA regimen, we're seeing patients who are young. Maybe they're fit patients with severe disease, but they're motivated to have a more aggressive option. So those are the types of patients that we're seeing right now.

對於目前已經接受治療的患者，我想說的是，在1至49段內，患者通常是那些要求非化療方案的患者，或者他們可能是無法耐受化療的虛弱患者。我們發現超過 50% 的患者希望或可能需要比單藥 PD-1 更積極的選擇。然後通過 9LA 方案，我們看到了年輕的患者。也許他們是患有嚴重疾病的健康患者，但他們有動力做出更積極的選擇。這些就是我們現在看到的患者類型。

Importantly, as I think about the opportunity to continue to grow here, again, I think we're going to continue to emphasize the opportunity for dual I-O patient -- dual I-O therapy across all patient subtypes. We have not seen as much utilization yet in the PD-L1 negative, unknown or untested segment. That's an area where I-O is generally underpenetrated, so that's obviously an opportunity with the 9LA regimen. So we think we have a number of opportunities where we can continue to drive utilization across patient segment types in the U.S.

重要的是，當我再次考慮在這裡繼續增長的機會時，我認為我們將繼續強調雙重 I-O 患者的機會——所有患者亞型的雙重 I-O 治療。我們尚未看到 PD-L1 陰性、未知或未經測試的部分有如此多的利用率。這是 I-O 通常滲透不足的領域，因此這顯然是 9LA 方案的一個機會。因此，我們認為我們有很多機會可以繼續推動美國跨患者細分類型的利用率。

Outside of the U.S., obviously, we won't have -227 on label. However, I'd say a couple of things. First of all, the data will be publicly available. And obviously, as appropriate, our medical teams will be engaging on that. The 9LA data by the time we launch will obviously continue to mature. That data does provide us an [entry] into the PD-L1 negative. So those are some of the dynamics that, I think, will be at play as we get into the x U.S. market. But again, I think we'll continue to update you as we get closer to the timing of that approval.

顯然，在美國之外，我們的標籤上不會有 -227。不過，我想說幾件事。首先，數據將公開。顯然，我們的醫療團隊將酌情參與其中。到我們推出時，9LA 數據顯然會繼續成熟。該數據確實為我們提供了 PD-L1 陰性的[入口]。我認為，這些是我們進入美國市場時將發揮作用的一些動力。但我想再次強調，隨著批准時間的臨近，我們將繼續向您通報最新情況。

And next, we'll hear from Tim Anderson with Wolfe Research.

接下來，我們將聽取沃爾夫研究公司蒂姆·安德森的說法。

I have a question on the Eliquis patent ruling. Your press release last night said you expect generics sometime after 2026, but before 2031. I think everyone on the analyst side expects generics around mid-2027. Does that mean you get pediatric exclusivity? But I'm wondering if that exclusivity could actually extend beyond that based on that press release language. You've done settlements with lots of generic challengers. You've never made any of those terms public. So is there a reasonable possibility that generics don't arrive until something like 2028 or maybe even later? And then on ozanimod in ulcerative colitis from the True North trial, will there be something differentiating in the data relative to the current in-market competitors besides this just being a different mechanism?

我對 Eliquis 專利裁決有疑問。你們昨晚的新聞稿稱，你們預計仿製藥會在 2026 年之後、2031 年之前的某個時間出現。我認為分析師方面的每個人都預計仿製藥會在 2027 年中期左右出現。這是否意味著您獲得了兒科專營權？但我想知道這種排他性是否真的可以超出基於新聞稿語言的範圍。你已經與許多普通挑戰者達成了和解。您從未公開過任何這些條款。那麼仿製藥是否有可能要到 2028 年甚至更晚才會出現？然後，對於來自 True North 試驗的潰瘍性結腸炎的奧扎尼莫德，除了機制不同以外，相對於當前市場競爭對手的數據是否會有一些差異？

Thank you, Tim. Let me start on Eliquis, and then Samit will provide some comments on True North.

謝謝你，蒂姆。讓我從 Eliquis 開始，然後 Samit 將對 True North 提供一些評論。

So first of all, let me say, we've always been confident in the strength of the IP for Eliquis. And as you alluded to, and just as a background, the IP covering Eliquis is a composition of matter patent, which expires in November of '26 with the potential pediatric extension to May '27 and a formulation patent, which expires in '31. And we're very pleased with the outcome when the strength of both patent has been confirmed yesterday. So this does mean that there is potentially some extension beyond the 2026 composition of matter patent, obviously, if we are successful at maintaining the formulation patent upon appeal. And you are right that we've settled with a number of companies, and the terms of those settlements are confidential.

首先，我要說的是，我們一直對 Eliquis 的知識產權實力充滿信心。正如您所提到的，作為背景，涵蓋 Eliquis 的知識產權是一項物質組合物專利，該專利將於 26 年 11 月到期，兒科可能會延長至 27 年 5 月，還有一項製劑專利，該專利將於 31 年到期。當昨天這兩項專利的強度得到證實時，我們對結果感到非常滿意。因此，這確實意味著，如果我們在上訴中成功維持配方專利，那麼顯然，2026 年物質組合物專利可能會有一些延期。你說得對，我們已經與多家公司達成和解，並且這些和解的條款是保密的。

Giovanni, thank you. I'll take on the ozanimod question. Thanks for the question, Tim. I think a couple of things to note.

喬瓦尼，謝謝你。我將回答奧扎尼莫德的問題。謝謝你的提問，蒂姆。我認為有幾點需要注意。

Number one, the current treatment pattern for patients with ulcerative colitis primarily is dependent on biologics. And I think there is still an underserved patient population because of the need for additional treatments. And a therapy that is safe, effective and can actually be delivered orally is going to be important. And then if you recall, the trial actually enrolled patients both who were biologic-naive as well as biologic pretreated. So there is an opportunity over here for patients to be treated in the prebiologic setting as well.

第一，目前潰瘍性結腸炎患者的治療模式主要依賴於生物製劑。我認為由於需要額外的治療，仍然有一些患者得不到充分的服務。安全、有效且實際上可以口服的療法將非常重要。然後，如果你還記得的話，該試驗實際上招募了未接受過生物製劑治療以及接受過生物製劑治療的患者。因此，患者也有機會在前生物環境中接受治療。

ZEPOSIA, as you've seen from the MS table, is a best-in-class safety profile with the absence of the first dose monitoring, both for the cardiovascular aspect of it and the lack of required broad-based ocular testing in this drug. Now from the Phase III UC trial perspective, as we look at ZEPOSIA and, obviously, the data will be presented at a future medical meeting, but it has not only met the primary endpoint, but we see very important, very significant results in the secondary endpoints as well, including the improvements in the endoscopic findings, which is very uncommon for many of the drugs out there, and these are very stringent definitions that have been used in the trial. So overall, what I would say is from a safety perspective as well as from the efficacy perspective, you will see that this drug, which can be given orally, is differentiated. And we are looking forward to the dialogue with the health authorities and agencies for submission. Chris, I wonder if you would like to comment as well.

正如您從 MS 表中看到的，ZEPOSIA 具有一流的安全性，無需首次劑量監測，無論是心血管方面還是該藥物缺乏所需的廣泛眼部測試。現在從 III 期 UC 試驗的角度來看，當我們觀察 ZEPOSIA 時，顯然，數據將在未來的醫學會議上公佈，但它不僅達到了主要終點，而且我們看到了非常重要、非常顯著的結果次要終點也是如此，包括內窺鏡檢查結果的改善，這對於許多藥物來說非常罕見，並且這些是試驗中使用的非常嚴格的定義。所以總的來說，我想說的是，從安全角度以及功效角度來看，你會發現這種可以口服的藥物是有區別的。我們期待與衛生當局和機構進行對話以提交。克里斯，我想知道你是否也想發表評論。

Sure. The only thing I would add to what you said, Samit, is that, remember, and you see the unmet need here is really for oral options with efficacy that's comparable to biologics, but with a better safety profile than you see with existing biologic agents and JAK inhibitors. There's, obviously in this space, a lot of competitive noise, and the data are going to evolve. And clearly, we need to wait for the full True North data set to be presented. But based on what we know today, and the data that we've seen, we feel very good about the ZEPOSIA profile. In UC, the efficacy appears to be in line with biologics, but with better safety. And specifically, we're not seeing either here or in the MS profile the rates of serious infections or thrombosis or malignancies that have led to black box warnings for a number of the TNF inhibitors and JAK.

當然。薩米特，我對你所說的唯一要補充的是，記住，你看到這裡未滿足的需求實際上是口服選擇，其功效與生物製劑相當，但比現有生物製劑具有更好的安全性和 JAK 抑製劑。顯然，這個領域存在很多競爭噪音，而且數據也會不斷變化。顯然，我們需要等待完整的真北數據集的呈現。但根據我們今天所了解的情況以及我們所看到的數據，我們對 ZEPOSIA 配置文件感覺非常好。對於 UC，其療效似乎與生物製劑一致，但安全性更好。具體來說，我們在這里或 MS 概況中都沒有看到嚴重感染或血栓形成或惡性腫瘤的發生率，這些發生率導致對許多 TNF 抑製劑和 JAK 發出黑框警告。

So given the chronic nature of this disease, we think ZEPOSIA is going to have a role to play. It's an oral agent. As you noted, Tim, in your question, it has a unique mechanism of action, which actually is important given the chronic nature of this disease. And it offers a better benefit risk profile potentially than existing agents.

因此，考慮到這種疾病的慢性性質，我們認為 ZEPOSIA 將發揮作用。這是一種口服製劑。正如您所指出的，蒂姆，在您的問題中，它具有獨特的作用機制，考慮到這種疾病的慢性性質，這實際上很重要。與現有代理商相比，它可能提供更好的收益風險狀況。

And we'll go to Steve Scala with Cowen.

我們將和考恩一起去史蒂夫·斯卡拉（Steve Scala）。

If I can ask 3 follow-up questions. First, on Eliquis, are the settlement dates fixed now, although undisclosed? Or in some way, are they dependent on the 2031 patent?

如果我可以問 3 個後續問題。首先，在 Eliquis 上，雖然尚未公開，但結算日期現在已經確定了嗎？或者在某種程度上，它們是否依賴於 2031 年專利？

Secondly, you've said many times that Opdivo is likely to return to growth in 2021. Can you clarify, is that for the full year, the second half of '21, the fourth quarter of '21? And is it dependent on adjuvant lung approval?

其次，您多次說過Opdivo可能會在2021年恢復增長。您能否澄清一下，是全年、21年下半年、21年第四季度嗎？它是否取決於輔助肺的批准？

And then lastly, on ide-cel, has the FDA indicated that they still plan to review ide-cel in an 8-month review cycle? Or have they not said that one way or the other?

最後，關於 ide-cel，FDA 是否表示他們仍計劃以 8 個月的審查週期對 ide-cel 進行審查？或者他們沒有這樣說過嗎？

Thank you, Steve. Let me maybe take the 3 very quickly. So as I mentioned, the details of those settlements with our -- which are complete, are confidential. And again, as I said, there is clearly potential for some extension beyond '26, I would say, in between '26 and '31 depending on the outcome of the appeal. And I don't think there's anything more than we can say about that.

謝謝你，史蒂夫。也許讓我很快就拿3。正如我所提到的，與我們達成和解的詳細信息是完整的、保密的。而且，正如我所說，顯然有可能在 26 年之後進行一些延期，我想說的是，在 26 年和 31 年之間，具體取決於上訴的結果。我認為對此我們無話可說。

With respect to Opdivo, what we've commented on is that the brand has an opportunity to grow in 2021. We're not really providing quarterly breakdowns of that -- of the growth, but we feel really good about where we are based on the strength of the current business and what Chris has mentioned earlier about first-line lung and the approval potential in first-line renal based on 9ER, and this would be the main driver.

關於 Opdivo，我們評論的是該品牌有機會在 2021 年實現增長。我們並沒有真正提供增長的季度細目，但我們對我們的基礎感到非常滿意當前業務的實力以及 Chris 之前提到的關於一線肺和基於 9ER 的一線腎的批准潛力，這將是主要驅動力。

I think the only thing we can say for ide-cel is what we've already communicated. We have requested a priority review, but it's obviously the agency's decision to make that comment. Samit, anything?

我認為我們對 ide-cel 唯一能說的就是我們已經溝通過的內容。我們已要求進行優先審查，但顯然是該機構決定發表此評論。薩米特，有什麼事嗎？

Yes. I think in addition to that, we have a breakthrough therapy designation as well. So overall, the agency will take a look at the data itself, which we are very excited about and then, of course, the overall status of the program that we have.

是的。我認為除此之外，我們還有突破性的療法名稱。因此，總的來說，該機構將查看數據本身，我們對此感到非常興奮，當然還有我們所擁有的計劃的總體狀態。

Chris, anything to add on Opdivo?

Chris，關於 Opdivo 有什麼需要補充的嗎？

No, I think you've covered Opdivo well. What we said is that the trajectory of the growth will be determined by the adjuvant indications, but we feel very good about the growth opportunities starting in 2021 based on the dynamics I mentioned.

不，我認為您已經很好地報導了 Opdivo。我們所說的是增長軌跡將由輔助適應症決定，但根據我提到的動態，我們對 2021 年開始的增長機會感到非常好。

And we'll hear from Kushal Patel with Guggenheim Securities.

我們將聽取古根海姆證券公司庫沙爾·帕特爾 (Kushal Patel) 的發言。

On behalf of Seamus, so in terms of the reaffirmation of the 2021 EPS guidance, I was just wondering in relation to that how the integration efforts and just expense management in the P&L was progressing and how that might play through in 2021, especially with R&D increasing as trials ramp up presumably. Just push and pulls for, I guess, the synergies there. And then potentially your comments in regard to the elections. And then the second question just with the cash pile building up, wondering how the team is thinking about deals in the future, maybe bolt-ons. Just any color there would be nice.

因此，就 2021 年 EPS 指導的重申而言，我代表 Seamus，想知道損益表中的整合工作和公正的費用管理進展如何，以及在 2021 年將如何發揮作用，特別是在研發方面隨著試驗的增加，可能會增加。我想，只要推拉就能產生協同效應。然後可能還有您對選舉的評論。然後是第二個問題，隨著現金儲備的增加，想知道團隊如何考慮未來的交易，也許是補充交易。只要有任何顏色都會很好。

Thank you. David?

謝謝。大衛？

Yes. So thank you for the question on the integration and synergies. Look, as Giovanni and I both said on the integration side of things, we're really pleased with how quickly everything has gone. And we're very fortunate to get the vast majority of people in the roles over 90% prior to COVID situation hitting us, which was very fortunate because everybody knew their roles and their reporting relationships, and that really enabled everyone to come together. I think also just having a crisis like this, everyone's working remotely and getting through it. And the way everyone's reacted to focus on meeting patient needs and making sure we're getting product at the door has really -- I think the cultural integration has sped up. And we've seen that through the surveys we've done from an employee engagement perspective.

是的。感謝您提出有關整合和協同作用的問題。看，正如喬瓦尼和我在集成方面所說的那樣，我們對一切進展得如此之快感到非常滿意。我們非常幸運，在新冠疫情爆發之前，90% 以上的人就已經擔任了這些角色，這非常幸運，因為每個人都知道自己的角色和報告關係，這確實使每個人都能走到一起。我認為，面對這樣的危機，每個人都在遠程工作並度過難關。每個人都專注於滿足患者需求並確保我們將產品送到家門口的反應方式確實 - 我認為文化融合已經加速。通過從員工敬業度角度進行的調查，我們已經看到了這一點。

You also know, on the integration side of things, we mentioned before that we announced all of the major sites around the world and there was a high overlap there, so people know where they're going to be working. So again, that helps from a cultural aspect.

您還知道，在集成方面，我們之前提到過，我們宣布了世界各地的所有主要站點，並且那裡有很高的重疊度，因此人們知道他們將在哪里工作。再說一次，這從文化方面有所幫助。

On the synergy side, as I said in my call, things are going very well. We're going to achieve 1/3 of those next year. I think the team is doing an amazing job within a couple of weeks after us closing the deal. We've got all of our major suppliers together. And we saw about $1 billion of the $2.5 billion coming from third party -- from third parties. And we feel very, very confident in how we're executing against those synergies.

在協同方面，正如我在電話中所說，一切進展順利。明年我們將實現其中的 1/3。我認為在我們完成交易後的幾週內，團隊的工作做得非常出色。我們所有的主要供應商都聚集在一起。我們看到 25 億美元中約有 10 億美元來自第三方。我們對如何實現這些協同效應感到非常非常有信心。

Yes. With respect to capital allocation, you had a question, nothing really -- nothing really has changed with respect to capital allocation. And what I would say is that as we've said in the past, our priority for capital allocation and the central pillar of that has always been to continue to source external innovation through business development. So that's very much a priority for us. And as you know, we look at business development from the perspective of deals that are sort of aligned strategically with the therapeutic areas we know well where there is a potential for breakthrough science. And obviously, we're disciplined from a financial perspective.

是的。關於資本配置，你有一個問題，實際上什麼都沒有——資本配置方面什麼都沒有真正改變。我想說的是，正如我們過去所說，我們資本配置的優先事項和核心支柱始終是繼續通過業務發展來獲取外部創新。所以這對我們來說是一個非常重要的優先事項。如您所知，我們從交易的角度來看待業務發展，這些交易在戰略上與我們熟知的有突破性科學潛力的治療領域保持一致。顯然，我們從財務角度來看是有紀律的。

So we're very active looking at potential deals across the board to strengthen our discovery platform, increase the number of collaborations we have and pretty much across the board. So you are right that our financial positions continue to strengthen, and business development remains an area of focus for us.

因此，我們非常積極地全面尋找潛在交易，以加強我們的發現平台，增加我們的合作數量，而且幾乎是全面的。因此，您說得對，我們的財務狀況繼續增強，業務發展仍然是我們關注的重點領域。

We'll hear from Andrew Baum with Citi.

我們將聽取花旗銀行安德魯·鮑姆 (Andrew Baum) 的來信。

A couple of questions, please. Firstly, to Giovanni, could you give us the true level of concern in the industry, but also in Bristol regarding the President's executive order on the state of nation's IPI that you've referred to in your opening comments? Extensively, it would seem that the requirement for having a favorable CBO score and the HHS being able to validate that is a requirement, which doesn't seem likely given what happened last time. So what is the real risk that, that changes and therefore, this proposal has lags? I'm just trying to understand how real the threat is and whether something has changed, and we shouldn't be quite as relaxed as we are given the last time around.

請教幾個問題。首先，Giovanni，您能否告訴我們業界以及布里斯托爾對您在開場白中提到的總統關於國家 IPI 狀況的行政命令的真正關注程度？從廣義上講，擁有良好的 CBO 分數並且 HHS 能夠驗證這一點似乎是一項要求，但考慮到上次發生的情況，這似乎不太可能。那麼，這種變化導致該提案滯後的真正風險是什麼？我只是想了解威脅有多真實以及事情是否發生了變化，我們不應該像上次那樣放鬆。

Second, perhaps Samit could talk to some of the forthcoming data at ESMO. You have a deep tranche of immuno-oncology agents, CCR2/CCR5, IL8, among others. What data will we see at ESMO?

其次，也許 Samit 可以談談 ESMO 即將發布的一些數據。您擁有大量免疫腫瘤藥物，如 CCR2/CCR5、IL8 等。我們將在 ESMO 上看到哪些數據？

And then finally, just on the COVID impact for Eliquis x U.S., particularly in Europe where, obviously, there's a delay in reimbursement. How much scope do you see for NOAC market share increases as a function of COVID and trying to keep patients out of medical centers from getting that INR measures?

最後，關於新冠疫​​情對 Eliquis x 美國的影響，特別是在歐洲，顯然，報銷存在延遲。您認為 NOAC 市場份額隨著新冠疫情的影響而增加多大範圍，並試圖阻止患者進入醫療中心獲取 INR 測量值？

Sure. So let me start on government-related issues. Samit will cover ESMO, and then Chris maybe can give you some insights into your question on demand.

當然。那麼讓我從與政府相關的問題開始。 Samit 將介紹 ESMO，然後 Chris 也許可以根據需要為您的問題提供一些見解。

So first of all, let me say, Andrew, I think it's really early to provide any more granular assessment. As you know, we have not seen the IPI executive order yet. And so with respect to that, there is some level of uncertainty with respect to really what is in the order and what a path to implementation may be. I want to say again what I said in my opening remarks. We feel very strongly that it is not the right direction for the U.S. to go. I think our view is shared not just across the industry, but providers and patients associations and other policy stakeholders are aligned with our view. I think the solution to patient affordability issues in the U.S. is to work on patient affordability issues. It is really not to import models and pricing levels that are not working internationally into the U.S. And quite frankly, the IPI doesn't do as much for patients as we should be doing for patients.

首先，安德魯，我認為現在提供更細緻的評估還為時過早。如您所知，我們尚未看到 IPI 行政命令。因此，就這一點而言，命令中的內容以及實施路徑可能是什麼，存在一定程度的不確定性。我想再說一遍我在開場白中所說的話。我們強烈認為這不是美國的正確方向。我認為我們的觀點不僅在整個行業得到認同，而且醫療服務提供者和患者協會以及其他政策利益相關者也與我們的觀點保持一致。我認為解決美國患者負擔能力問題的方法是解決患者負擔能力問題。這實際上並不是要將在國際上行不通的模式和定價水平引入美國。坦率地說，IPI 並沒有為患者做太多我們應該為患者做的事情。

So our industry continues to be really open to discussing different types of solutions with the administration that would help patients more, but also would enable us to continue to invest in innovation. I think that's really important at a time in which everybody understands the importance of our industry, which, quite frankly, is primarily a U.S. industry in fighting disease.

因此，我們的行業繼續持開放態度與政府討論不同類型的解決方案，這不僅可以為患者提供更多幫助，而且還使我們能夠繼續投資於創新。我認為這非常重要，因為每個人都了解我們行業的重要性，坦率地說，我們的行業主要是美國抗擊疾病的行業。

The impact of IPI in the version, at least, we knew would be extremely significant on our industry and the ability to continue to invest in innovation. And we hope that we are able to move into directions that are better for patients in the U.S.

至少我們知道，IPI 在該版本中的影響將對我們的行業以及繼續投資創新的能力產生極其重大的影響。我們希望我們能夠朝著對美國患者更好的方向發展。

From our perspective, when you think about our portfolio, it's clearly much more differentiated today than it was in the past across multiple segments. And when you look at our sales, it's about 40% internationally and 60% in the U.S. In the U.S., Part B, just as a reference point, it's about 15% of our business.

從我們的角度來看，當你考慮我們的投資組合時，今天的多個細分市場顯然比過去更加差異化。當你看看我們的銷售額時，你會發現，國際銷售額約佔 40%，美國銷售額約佔 60%。在美國，B 部分，僅作為參考點，約占我們業務的 15%。

With respect to your question about the rebate rule, I think we would have to see how HHS goes about really thinking about the various sort of implications of a rebate rule and assess what the cost of that would be versus the benefit. So I'm not sure I can really speculate on how that would be certified and whether the issues that were raised in the previous version would even be an issue at all at this point. I think that's as much as I know at this point. Samit?

關於你關於回扣規則的問題，我認為我們必須看看美國衛生與公眾服務部如何真正考慮回扣規則的各種影響，並評估其成本與收益之間的關係。因此，我不確定我是否可以真正推測如何進行認證，以及先前版本中提出的問題此時是否會成為問題。我想這就是我目前所知道的。薩米特？

Thank you. Thanks, Andrew, for the question on ESMO. I think the way to look at it is there are several presentations or data that are being presented at ESMO, primarily from the Phase I studies and some updates. But the most important one to focus on would be CheckMate 9ER for renal cell cancer because that certainly is a differentiating therapy. And as Chris mentioned earlier as well as you heard in the other comments in earlier presentations, inclusive of all subtypes or both, and inclusive of the favorable risk population, which is currently not covered to our data in the dual I-O setting, there will also be that update on the dual I-O with a 4-year follow-up for that study. So those 2 are going to be key as they provide a better way to look at treatment for patients with renal cell cancer with the dual I-O. And then, of course, we're looking at potentially getting the 9ER approval later. And so that will certainly provide an additional way to treat these patients from a safe and effective medicines perspective.

謝謝。感謝 Andrew 提出有關 ESMO 的問題。我認為看待這個問題的方法是，ESMO 上正在展示一些演示或數據，主要來自第一階段研究和一些更新。但最值得關注的是用於腎細胞癌的 CheckMate 9ER，因為這無疑是一種差異化療法。正如克里斯之前提到的以及您在之前的演示中聽到的其他評論，包括所有亞型或兩者，並包括有利的風險人群，目前我們在雙 I-O 設置中的數據未涵蓋這些人群，也將是雙 I-O 的更新以及該研究的 4 年隨訪。因此，這兩者將成為關鍵，因為它們提供了一種更好的方法來研究雙 I-O 腎細胞癌患者的治療方法。當然，我們正在考慮稍後獲得 9ER 批准的可能性。因此，這肯定會提供一種從安全有效的藥物角度治療這些患者的額外方法。

There was a third question on...

還有第三個問題……

Yes, yes. So thanks, Andrew, for the question on Eliquis. So let me just say at the outset that fundamentals for Eliquis remain very strong, both in the U.S. and x U.S. We're the #1 OAC in 12 markets now globally. We're the #2 in 5 additional markets. And the fundamentals, again, are very strong.

是的是的。謝謝安德魯提出有關 Eliquis 的問題。因此，我首先要說的是，Eliquis 的基本面仍然非常強勁，無論是在美國還是在美國。我們現在是全球 12 個市場中排名第一的 OAC。我們在另外 5 個市場中排名第二。而且基本面再次非常強勁。

With respect to COVID impact, there are really 2 things that are at play. As David mentioned, there's an inventory work down of the inventory build that we saw in Q1. That's the largest COVID impact that we've seen for the quarter. That's mainly been in the U.S., though not exclusively, but the main impact was in the U.S. And then there's been a smaller impact on demand, and that's reflective of the fact that the OAC market has been impacted by new patient volumes that have come down. The negative impact was most significant in April. It's begun to recover. We've really not seen an impact on total patient volumes. As you note, one of the potential upsides for Eliquis has been -- first of all, that Eliquis has been disproportionately unaffected by COVID relative to other players.

關於新冠疫​​情的影響，實際上有兩件事在起作用。正如大衛提到的，我們在第一季度看到的庫存建設正在進行庫存工作。這是本季度我們看到的最大的新冠疫情影響。這主要是在美國，雖然不是全部，但主要影響是在美國。然後對需求的影響較小，這反映了 OAC 市場受到新患者數量下降的影響這一事實。負面影響在四月份最為顯著。已經開始恢復了我們確實沒有看到對患者總數的影響。正如您所指出的，Eliquis 的潛在優勢之一是——首先，與其他公司相比，Eliquis 不受新冠疫情影響的程度不成比例。

And then secondarily, we have seen, as you alluded to, in a number of markets, the desire to try to keep patients out of hospitals and institutions, and that's impacted warfarin share. So we've seen a decrease in warfarin share from about 16% at the end of the first quarter to about 14% in June, and that's reflective of, we think, new patients initiating on DOACs as opposed to warfarin. As you alluded to, unlike warfarin, DOACs don't require extensive monitoring or dose adjustments. And so as a result, we've seen some IDNs and a number of governments seek to reduce exposure of those patients. And Eliquis has disproportionately picked up that share loss. So that's certainly been an opportunity coming out of COVID.

其次，正如您提到的，我們在許多市場看到了試圖讓患者遠離醫院和機構的願望，這影響了華法林的份額。因此，我們看到華法林的份額從第一季度末的約 16% 下降到 6 月份的約 14%，我們認為這反映了新患者開始使用 DOAC 而不是華法林。正如您所提到的，與華法林不同，DOAC 不需要廣泛的監測或劑量調整。因此，我們看到一些 IDN 和一些政府正在尋求減少這些患者的暴露。 Eliquis 承擔了不成比例的份額損失。所以這無疑是新冠疫情帶來的一個機會。

And we'll hear from Navin Jacob with UBS.

我們將聽取瑞銀集團 (UBS) 納文·雅各布 (Navin Jacob) 的發言。

Can you hear me okay?

你能聽到我說話嗎？

Yes. Yes, Navin.

是的。是的，納文。

Perfect. Just a few, if I may. On REBLOZYL, a strong quarter. Wondering how much inventory build there was relative to demand. And if you could remind us about the timing of the first-line MDS study readout. Are there any interim analyses that could happen earlier than the final look? And then also the timing of the MS study, please?

完美的。如果可以的話，就幾個。 REBLOZYL 是一個強勁的季度。想知道相對於需求而言，庫存增加了多少。您能否提醒我們一線 MDS 研究讀數的時間？在最終外觀之前是否有可能發生的臨時分析？還有 MS 研究的時間安排，好嗎？

And then just a question on your early-stage pipeline. I think you recently moved your Lp(a) antagonist into Phase II for IPF. Wondering if you could discuss any kind of activity that you may have seen in Phase Ib that moved that decision to move that asset into Phase II.

然後是關於您的早期管道的問題。我認為您最近將 Lp(a) 拮抗劑轉移到 IPF 的 II 期。想知道您是否可以討論您在 Ib 階段中可能看到的任何類型的活動，這些活動促使您決定將該資產轉移到第二階段。

Thank you, Navin. Why don't we ask Nadim to start, and then Samit will cover a couple of your pipeline-related questions.

謝謝你，納文。我們為什麼不請 Nadim 開始，然後 Samit 將回答您的幾個與管道相關的問題。

Great. Navin, thanks for your question. So one thing I do want to reiterate that you heard earlier. Overall, we're very encouraged by the launch of REBLOZYL and especially the ability of our commercial teams to pivot to a virtual launch. And we have seen good early adoption so far, especially -- and I think the key factors here are the significant unmet need in MDS, especially in ESA refractory patients, the unique mechanism of action of Reblozyl. And of course, our field teams that have very good experience and knowledge of MDS and the relationships of MDS prescribers has allowed us to get that access. And we have good access with payers now that we have a permanent J-Code since July.

偉大的。納文，謝謝你的問題。所以我想重申你之前聽到的一件事。總的來說，我們對 REBLOZYL 的推出感到非常鼓舞，尤其是我們的商業團隊轉向虛擬發布的能力。到目前為止，我們已經看到了良好的早期採用，尤其是——我認為這裡的關鍵因素是 MDS 的顯著未滿足需求，特別是在 ESA 難治性患者中，Reblozyl 的獨特作用機制。當然，我們的現場團隊擁有豐富的 MDS 經驗和知識，以及與 MDS 處方者的關係，使我們能夠獲得這種訪問權限。自 7 月起我們就擁有了永久的 J 代碼，因此我們可以與付款人進行良好的接觸。

So coming back to a question, Navin, there are some kind of short-term dynamics here, partly COVID and the impact of blood shortage. On your specific question about inventory, this is a product that's shipped directly to our customers and sites, so that isn't really in play here. The one area that it could be a little bit in play here is, of course, of a new treatment addressing a significant unmet need, you do get a pent-up demand with new oncology agents. So there likely is somewhat of a bolus effect going on.

納文，回到問題上來，這裡存在某種短期動態，部分是新冠疫情和血液短缺的影響。關於您有關庫存的具體問題，這是一種直接運送到我們的客戶和網站的產品，因此這裡並沒有真正發揮作用。當然，它可能在這裡發揮一點作用的一個領域是一種新的治療方法，解決重大的未滿足的需求，你確實會得到對新腫瘤藥物的被壓抑的需求。因此，可能存在某種推注效應。

But as I said, we're very pleased with the progress so far, and the team is focused on both new patient initiation as well as patient persistence, and what we're seeing is encouraging. We're seeing new patients continue to initiate, and we're seeing most patients go on to receive their second and third treatment. Customer feedback remains very good. Brand awareness is high driven by our field teams. So we are encouraged. But as you -- as I said earlier, there is a little bit of a bolus effect, too. So we'll see how that dynamic continues to play out through the rest of the year. But very pleased with the progress so far. Samit?

但正如我所說，我們對迄今為止的進展感到非常滿意，團隊專注於新患者的啟動和患者的堅持，我們所看到的令人鼓舞。我們看到新的患者繼續開始治療，並且我們看到大多數患者繼續接受第二次和第三次治療。客戶的反饋仍然非常好。在我們的現場團隊的推動下，品牌知名度很高。所以我們受到鼓舞。但正如我之前所說，也有一點推注效應。因此，我們將看看這種動態在今年剩餘時間內如何繼續發揮作用。但對迄今為止的進展感到非常滿意。薩米特？

Yes. Thank you. From the COMMANDS study perspective, it's a Phase III study, as you know, in the first-line setting, which includes both RS-negative and RS-positive patients, and that study is currently enrolling. We're looking at readout coming in 2022 -- late 2022 time frame.

是的。謝謝。從 COMMANDS 研究的角度來看，如您所知，這是一項一線治療的 III 期研究，其中包括 RS 陰性和 RS 陽性患者，該研究目前正在招募中。我們正在考慮 2022 年——2022 年末的時間框架內公佈的數據。

The myelofibrosis study is just starting off, so that will take a little while to get going, and we'll obviously provide the time lines, again, 2022 and beyond.

骨髓纖維化研究才剛剛開始，因此需要一段時間才能開始，我們顯然會再次提供時間表，2022 年及以後。

For the interstitial pulmonary fibrosis side, as you are aware, we had presented the data and published the data in IPF as well, where we've seen interesting results, where the side effects were there for the blood pressure effects as well. So we are now investigating the -- in the Phase II study, looking at seeing what we can do in terms of management of the side effect. And the molecule is going to be investigated there, which we'll then decide how we proceed further with that molecule into the later-stage trials. But we have to wait to see the data when it reads out.

對於間質性肺纖維化方面，如您所知，我們已經在 IPF 中提供了數據並發表了數據，在那裡我們看到了有趣的結果，其中也存在血壓影響的副作用。因此，我們現在正在研究第二階段的研究，看看我們可以在管理副作用方面做些什麼。該分子將在那裡進行研究，然後我們將決定如何進一步將該分子帶入後期試驗。但我們必須等待數據讀出時才能看到。

And we'll get that question from Matt Phipps with William Blair.

我們將從馬特·菲普斯和威廉·布萊爾那裡得到這個問題。

Just ahead of the ESMO presentation of the 9ER data, can you remind us on your positioning of that regimen in RCC? Do you think you can meaningfully grow Opdivo total sales in RCC? Or is it really more going to just shore up Opdivo across the different regimens?

在 ESMO 展示 9ER 數據之前，您能否提醒我們您對該方案在 RCC 中的定位？您認為 Opdivo 在 RCC 的總銷售額能夠實現有意義的增長嗎？或者它真的只是在不同的治療方案中支持 Opdivo 嗎？

And then just a quick second one. With some of the COVID-related impacts on infusion center access, have you all thought about accelerating time launch for subcutaneous Opdivo? Looks like you recently started another trial that combines subcu Opdivo and Yervoy.

然後是快速的第二個。鑑於與新冠病毒相關的一些對輸液中心通道的影響，你們是否考慮過加快皮下注射 Opdivo 的上市時間？看起來您最近開始了另一項結合 subcu Opdivo 和 Yervoy 的試驗。

Thank you, Matt. Chris?

謝謝你，馬特。克里斯？

Sure. Yes. Sorry, Giovanni. Yes, maybe I'll start with renal cell. So just the baseline of where the business is today, Matt, is that market share is roughly unchanged from the last quarter. Our overall share of Opdivo, Yervoy in first-line renal is between 30% and 35%, on the upper end of that for our labeled indication. And then importantly, we are underpenetrated, as you would expect, in the favorable patient population, which is currently off-label. And the way we're thinking about 9ER is, first of all, we're very happy with the data that we've seen, both on OS and PFS. We're also very encouraged by the safety profile. And so as we think about positioning this agent, while it's still early days and we need to see the full data set being presented, we think these provide -- these data provide a very compelling opportunity with respect to existing I-O/TKI options. So there's a clear opportunity, we think, to drive share from existing I-O/TKI regimens in this space.

當然。是的。對不起，喬瓦尼。是的，也許我會從腎細胞開始。因此，馬特，目前業務狀況的基線是，市場份額與上季度相比大致沒有變化。我們 Opdivo 和 Yervoy 在一線腎臟治療中的總體份額在 30% 到 35% 之間，處於我們標籤適應症的上限。然後重要的是，正如您所期望的那樣，我們在目前處於適應證外的有利患者群體中滲透不足。我們考慮 9ER 的方式是，首先，我們對所看到的 OS 和 PFS 數據非常滿意。我們也對安全狀況感到非常鼓舞。因此，當我們考慮定位該藥物時，雖然現在還處於早期階段，我們需要看到完整的數據集，但我們認為這些數據為現有的 I-O/TKI 選項提供了非常引人注目的機會。因此，我們認為，有一個明顯的機會來推動該領域現有 I-O/TKI 方案的份額。

Second, TKI monotherapy is still a fairly sizable percentage of first-line use. It's about 30% in first line today, mostly in the favorable population. We think that's an opportunity for us as well because, remember, 9ER was conducted across risk status as well as included -- it included the favorable patient population. So we think there's a real opportunity for us to continue to drive share in that population as well.

其次，TKI 單藥療法在一線用藥中仍佔相當大的比例。如今，大約有 30% 的人處於一線，主要是在有利人群中。我們認為這對我們來說也是一個機會，因為請記住，9ER 是在不同風險狀態下進行的，並且涵蓋了有利的患者群體。因此，我們認為我們也有真正的機會繼續提高該人群的份額。

And so I think that the last thing I would say about the opportunity we have here is if you remember our position in renal cell, we have both monotherapy in the second-line setting, we have Opdivo and Yervoy in first line. And this gives us another option with IO plus TKI. In fact, we'll be the only company with that many different modalities at play. And so we think we're going to have a very strong position with 9ER in first line. It's going to be an important opportunity for us to continue to grow the brand starting in 2021 when it's approved.

因此，我認為關於我們在這裡的機會，我要說的最後一件事是，如果你還記得我們在腎細胞領域的地位，我們在二線環境中都有單一療法，我們在一線有 Opdivo 和 Yervoy。這為我們提供了 IO 加 TKI 的另一種選擇。事實上，我們將是唯一一家擁有如此多不同模式的公司。因此，我們認為 9ER 將在一線佔據非常有利的地位。從 2021 年獲得批准開始，這將是我們繼續發展該品牌的重要機會。

Yes. Thank you, Chris. And when it comes to subcu development, so we are continuously working on that and making good progress on that and looking forward to the readouts of the Phase I study, where we're looking at the PK parameters, where we'll be able to then compare it to the IV parameters and then plan on the next stage of development in concert with our communications with the health agencies.

是的。謝謝你，克里斯。當談到 subcu 開發時，我們正在不斷努力，並取得良好進展，並期待第一階段研究的結果，我們正在研究 PK 參數，我們將能夠然後將其與 IV 參數進行比較，然後根據我們與衛生機構的溝通來規劃下一階段的發展。

Thank you, and thanks, everyone. Thanks for participating in the call. In closing, let me just say, again, we had a very successful quarter. I'm very proud of our teams have executed, despite the challenges of the pandemic. We advanced our pipeline. We delivered strong commercial execution. We've continued to supply our medicines to patients, and we are very well positioned for the future. Our pipeline has increased potential to transform patients' lives through our science.

謝謝你們，也謝謝大家。感謝您參與通話。最後，我再次強調，我們度過了一個非常成功的季度。儘管面臨大流行的挑戰，我對我們的團隊所執行的工作感到非常自豪。我們推進了我們的管道。我們提供了強大的商業執行力。我們繼續向患者提供藥物，並且我們為未來做好了充分的準備。我們的產品線通過我們的科學增加了改變患者生活的潛力。

Thanks, everyone, for participating in the call. And as always, our team will be available to answer any other questions you may have. Thank you.

感謝大家參與此次通話。與往常一樣，我們的團隊將隨時回答您可能遇到的任何其他問題。謝謝。

And ladies and gentlemen, that does conclude today's call. We thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。我們感謝您的參與。您現在可以斷開連接。