施貴寶 (BMY) 2021 Q2 法說會逐字稿

Good day, and welcome to the Bristol-Myers Squibb 2021 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 2021 年第二季度業績電話會議。今天的會議正在錄製中。

And at this time, I'd 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, Catherine, and good morning, everybody. Thanks for joining us this morning for our second quarter 2021 earnings call. Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in the call today are Chris Boerner, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development.

謝謝，凱瑟琳，大家早上好。感謝您今天早上參加我們的 2021 年第二季度財報電話會議。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；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。

As you'll be aware, we've posted slides to bms.com that you can use to follow along with -- for David and Giovanni's his remarks, but before we get started, I'll read our forward-looking statement. During today's call, we'll 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 estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements even if our estimates change.

如您所知，我們已在 bms.com 上發布了幻燈片，您可以使用它們來觀看 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。在今天的電話會議中，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 those non-GAAP financial measures to the most comparable GAAP measures are available at 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.

這樣，我就把它交給喬瓦尼了。

Thank you, Tim, and good morning, everyone. I hope you're all staying safe and healthy.

謝謝蒂姆，大家早上好。我希望你們都安全健康。

Now turning to Slide 4. Let me start by saying I am very proud of our second quarter results and express my gratitude to our teams across the globe for their dedication and steadfast commitment to our patients. Through their work, we are continuing to make great progress to diversify and renew our portfolio and position Bristol-Myers Squibb for an even stronger future.

現在轉向幻燈片 4。首先我要說的是，我對我們第二季度的業績感到非常自豪，並對我們全球團隊的奉獻精神和對患者的堅定承諾表示感謝。通過他們的工作，我們將繼續取得巨大進展，實現產品組合的多元化和更新，並為百時美施貴寶打造更美好的未來。

During the second quarter, we delivered excellent results across the board, including strong sales growth due to solid commercial performance, positive clinical results in our mid- and late-stage pipeline, continued BD execution and strengthened our financial position. The strength of our commercial execution this quarter was underscored by the performance of our key medicines, including the return of Opdivo to growth and the uptake of our new launch portfolio. Over the last 18 months, we launched 5 new medicines with significant potential, and we are very encouraged by their performance to date. Clinically, we continue to deliver on the potential of our pipeline with significant mid- and late-stage clinical readouts and important regulatory actions across our therapeutic areas. The recent additions to our portfolio added diversification to our business and an opportunity to generate sustained growth over time.

第二季度，我們全面取得了優異的業績，包括由於穩健的商業業績而實現的強勁銷售增長、中後期產品線的積極臨床結果、持續的 BD 執行以及增強了我們的財務狀況。我們的關鍵藥物的表現凸顯了我們本季度商業執行的實力，包括 Opdivo 恢復增長和我們新推出的產品組合的採用。在過去 18 個月裡，我們推出了 5 種具有巨大潛力的新藥，它們迄今為止的表現令我們深受鼓舞。在臨床上，我們繼續通過重要的中後期臨床數據和整個治療領域的重要監管行動來發揮我們的管道的潛力。我們最近的投資組合增加了我們業務的多元化，並有機會隨著時間的推移實現持續增長。

From a financial perspective, we saw double-digit growth for both the top and bottom line, and we are reaffirming our full year revenue and non-GAAP EPS guidance. We continue to maintain a strong balance sheet and generate significant cash flow, allowing us to advance our disciplined capital allocation strategy. We remain focused on external business development opportunities to further strengthen our pipeline over the long term.

從財務角度來看，我們的收入和利潤都實現了兩位數的增長，並且我們重申了我們的全年收入和非公認會計準則每股收益指導。我們繼續保持強勁的資產負債表並產生大量現金流，使我們能夠推進嚴格的資本配置策略。我們仍然關注外部業務發展機會，以進一步加強我們的長期渠道。

This quarter, we executed 2 licensing deals, an anti-TIGIT bispecific antibody program with Agenus; and MORAb-202, a folate receptor alpha ADC with Eisai, both strategically aligned with our oncology franchise. Overall, I am extremely pleased with our progress in the quarter.

本季度，我們執行了 2 項許可協議，一項是與 Agenus 的抗 TIGIT 雙特異性抗體項目； MORAb-202，一種與衛材合作的葉酸受體 α ADC，兩者都與我們的腫瘤學特許經營戰略一致。總的來說，我對本季度的進展感到非常滿意。

Turning now to our execution scorecard on Slide 5. We have made tremendous progress year-to-date across our therapeutic areas. In oncology, we are strengthening our IO franchise and have returned Opdivo to growth through multiple clinical successes and excellent commercial execution. Earlier this year, we launched Opdivo in 3 additional indications, including first-line gastric cancer, where we are the first and only I-O agent. We anticipate additional launch opportunities and growth drivers for Opdivo to further accelerate the growth of the brand.

現在轉向幻燈片 5 上的執行記分卡。今年迄今為止，我們在治療領域取得了巨大進展。在腫瘤學領域，我們正在加強我們的 IO 特許經營權，並通過多項臨床成功和出色的商業執行使 Opdivo 恢復增長。今年早些時候，我們在另外 3 個適應症中推出了 Opdivo，其中包括一線胃癌，我們是第一個也是唯一一個 I-O 藥物。我們預計 Opdivo 將有更多的推出機會和增長動力，以進一步加速該品牌的增長。

We also see opportunities to expand our I-O portfolio through the fixed-dose combination of our LAG-3 inhibitor relatlimab with Opdivo. At ASCO last month, we announced impressive results for relatlimab, potentially the third I-O therapy for BMS, building on our leadership in the field and expanding the durability of our franchise. We have a broad development program underway in I-O to benefit more patients over time.

我們還看到了通過 LAG-3 抑製劑 relatlimab 與 Opdivo 的固定劑量組合來擴展 I-O 產品組合的機會。上個月在 ASCO 上，我們宣布了 relatlimab 的令人印象深刻的結果，這可能是 BMS 的第三種 I-O 療法，鞏固了我們在該領域的領導地位並擴大了我們特許經營權的持久性。我們正在 I-O 領域開展廣泛的開發計劃，以便隨著時間的推移讓更多患者受益。

Moving to hematology. We received approval in the U.S. for 2 cell therapies, Breyanzi and Abecma, and demand for these products has been strong. Physicians recognize the value of these treatments, and there is significant patient need.

轉向血液學。我們的兩種細胞療法 Breyanzi 和 Abecma 在美國獲得了批准，並且對這些產品的需求一直很強勁。醫生認識到這些治療的價值，並且患者有很大的需求。

Building on existing indications for Breyanzi, we announced the first ever positive Phase III top line data in second-line transplant-eligible large B-cell lymphoma last month. This is an important result. For the first time, we have shown that our cell therapy treatment is superior to a well-established standard of care. The positive results demonstrate that we can benefit patients early in their treatment journey. We look forward to sharing more details on these results later this year.

在 Breyanzi 現有適應症的基礎上，我們上個月宣布了符合二線移植資格的大 B 細胞淋巴瘤的第一個 III 期頂線陽性數據。這是一個重要的結果。我們首次證明我們的細胞療法優於既定的護理標準。積極的結果表明我們可以使患者在治療過程的早期受益。我們期待在今年晚些時候分享這些結果的更多細節。

We also have iberdomide Phase II data in-house, which we are very pleased with and look forward to discussing with health authorities. The data are potentially the first step toward the establishment of a new backbone of treatment in multiple myeloma, offering a better option to benefit patients. We have made tremendous progress expanding our immunology franchise. Deucravacitinib, a first-in-class selective TYK2 inhibitor, has the potential to be the oral agent of choice. We expect to launch this potential new medicine in psoriasis in the second half of 2022.

我們還擁有伊伯多胺二期臨床數據，我們對此非常滿意，並期待與衛生當局進行討論。這些數據可能是建立多發性骨髓瘤新治療支柱的第一步，為患者提供更好的選擇。我們在擴大免疫學業務方面取得了巨大進展。 Deucravacitinib 是一種一流的選擇性 TYK2 抑製劑，有潛力成為首選口服藥物。我們預計在 2022 年下半年推出這種治療銀屑病的潛在新藥。

We have initiated our Phase III program in psoriatic arthritis, and we also look forward to Phase II data in ulcerative colitis later this year and in Crohn's disease and lupus in 2022 to further expand the potential of this molecule. We initiated our Phase III program for cendakimab in eosinophilic esophagitis, and last month, in the U.S., we launched Zeposia in ulcerative colitis.

我們已經啟動了銀屑病關節炎的 III 期項目，我們也期待今年晚些時候獲得潰瘍性結腸炎的 II 期數據，以及 2022 年克羅恩病和狼瘡的 II 期數據，以進一步擴大該分子的潛力。我們啟動了 cendakimab 治療嗜酸性食管炎的 III 期項目，上個月，我們在美國推出了治療潰瘍性結腸炎的 Zeposia。

Finally, turning to CV. We are encouraged by the top line results we received this quarter for Milvexian, our Factor XIa inhibitor. We look forward to presenting the data at a medical meeting later in the year. Additionally, we are preparing to launch mavacamten for symptomatic obstructive HCM in the U.S. early next year. We are encouraged by the potential of these assets to strengthen the durability of our CV franchise.

最後，轉向簡歷。我們對本季度收到的 XIa 因子抑製劑 Milvexian 的營收結果感到鼓舞。我們期待在今年晚些時候的醫學會議上展示這些數據。此外，我們準備明年初在美國推出用於治療有症狀的梗阻性 HCM 的 mavacamten。我們對這些資產增強我們 CV 特許經營權持久性的潛力感到鼓舞。

In closing, on Slide 6. Our steadfast progress gives me great confidence that we are well positioned for growth. We are rapidly advancing a new launch portfolio of first-in-class or best-in-class medicines across therapeutic areas. We remain focused on driving inline product performance; executing on our launches; advancing early, mid- and late-stage pipeline opportunities; and continuing to take a disciplined approach to capital allocation.

最後，在幻燈片 6 上。我們堅定不移的進步讓我充滿信心，相信我們已經做好了實現增長的準備。我們正在快速推進跨治療領域的一流或一流藥物的新上市組合。我們仍然專注於提升內聯產品性能；執行我們的發布；推進早期、中期和後期管道機會；並繼續採取嚴格的資本配置方法。

Our strong clinical performance further derisks our launch portfolio. And as a result, our confidence in our ability to deliver the $20 billion to $25 billion in non-risk-adjusted revenue in 2029 continues to increase. Our continued strong financial performance and balance sheet enable us to diversify and strengthen our long-term prospects.

我們強大的臨床表現進一步降低了我們推出產品組合的風險。因此，我們對 2029 年實現 200 億至 250 億美元非風險調整收入的能力的信心持續增強。我們持續強勁的財務業績和資產負債表使我們能夠實現多元化並加強我們的長期前景。

As our sales force returns to the field and we welcome our remote teams back to the office, I'm excited by the opportunity to reconnect with our colleagues, stakeholders and patients. I believe we have the strongest pipeline and launch portfolio in BMS' history, and I am very excited about our future.

隨著我們的銷售人員返回現場並歡迎我們的遠程團隊回到辦公室，我很高興有機會與我們的同事、利益相關者和患者重新建立聯繫。我相信我們擁有 BMS 歷史上最強大的產品線和產品組合，我對我們的未來感到非常興奮。

With that, I'll turn it over to David to walk you through the financials. David?

接下來，我將把它交給 David，讓他帶您了解財務狀況。大衛？

Thank you, Giovanni, and thank you all for joining our call today. Let me start with our top line performance on Slide 8. I'm very pleased to discuss our strong double-digit growth this quarter, driven by increased demand for our key medicines across the globe.

謝謝喬瓦尼，也感謝大家今天加入我們的電話會議。讓我從幻燈片 8 上我們的頂線業績開始。我很高興討論本季度我們強勁的兩位數增長，這是由全球對我們關鍵藥品的需求增加推動的。

Looking at the first half of the year, which normalizes for most of the COVID-related buying patterns we experienced last year, commercial performance was strong, up 9% year-over-year or 7% excluding currency. This robust performance demonstrates both the strong execution of our commercial teams as well as increased demand for our products.

回顧今年上半年，我們去年經歷的大多數與新冠病毒相關的購買模式都已正常化，商業表現強勁，同比增長 9%，不包括貨幣因素則增長 7%。這種強勁的表現既證明了我們商業團隊的強大執行力，也證明了對我們產品的需求不斷增加。

I'll now provide additional color on the performance of our key brands and new launches, starting with Eliquis on Slide 9. This was another strong quarter for Eliquis, with global sales up 29% versus last year. Second quarter growth benefited from a favorable year-over-year comparison as prior year included the unwinding of COVID-related buying patterns. When looking at the first half to normalize for this dynamic, sales remained strong, up 18%.

現在，我將從幻燈片 9 上的 Eliquis 開始，對我們的主要品牌和新產品的表現提供更多信息。這是 Eliquis 的另一個強勁季度，全球銷售額比去年增長 29%。第二季度的增長受益於與去年同期相比有利的情況，包括與新冠病毒相關的購買模式的放鬆。上半年，這種動態趨於正常化，銷售額依然強勁，增長了 18%。

In the U.S., we saw strong demand with total prescription growth of 14% versus prior year, driven by market share gains. We continue to expect strong new-to-brand share growth to further translate to overall total prescription growth. As a reminder, when we look toward the third and fourth quarters, we expect similar dynamics from the Medicare coverage gap we've seen in previous years. Internationally, we had very strong demand across all key geographies as we further gained share as the #1 OAC in multiple markets and we continue to see additional room to grow. Overall, we remain very pleased with the execution of Eliquis around the world and expect to continue to grow Eliquis share within a growing class.

在美國，由於市場份額的增長，我們看到了強勁的需求，總處方量比去年增長了 14%。我們繼續預計新品牌份額的強勁增長將進一步轉化為總體處方量的增長。提醒一下，當我們展望第三季度和第四季度時，我們預計醫療保險覆蓋範圍缺口將出現與前幾年類似的動態。在國際上，隨著我們作為多個市場第一大 OAC 的份額進一步增加，我們在所有關鍵地區的需求都非常強勁，並且我們繼續看到額外的增長空間。總體而言，我們對 Eliquis 在全球的執行情況仍然非常滿意，並期望在不斷增長的類別中繼續增加 Eliquis 的份額。

Now turning to Opdivo on Slide 10. Let me start by saying we're very pleased to deliver return to growth this quarter, up 16% versus last year. While COVID recovery dynamics as well as approximately $40 million in U.S. inventory build contributed to this quarter's growth, the brand's performance was largely driven by strong demand for both our core and our newly launched indications. In the U.S., sales were up 13% year-over-year as well as 14% sequentially, driven by launches in lung, RCC and our upper GI cancers, which are all going well.

現在轉向幻燈片 10 上的 Opdivo。首先我要說的是，我們很高興本季度恢復增長，比去年增長 16%。雖然新冠疫情的複蘇動態以及約 4000 萬美元的美國庫存建設推動了本季度的增長，但該品牌的業績在很大程度上是由對我們的核心和新推出的適應症的強勁需求推動的。在美國，由於肺癌、腎細胞癌和上消化道癌症的上市進展順利，銷售額同比增長 13%，環比增長 14%。

In lung, share is in the low double digits with positive momentum, and we are seeing use across all histologies. In RCC, our Opdivo + cabo launch continues to do well, with Opdivo now the leading PD-1 first-line renal across both available regimens. In upper GI, we saw a very strong start with Opdivo plus chemo in first-line gastric cancer with CheckMate-649, which reached 25% to 30% share in just a few months, based upon the strength of our data. The adjuvant esophageal launch, while still in early days, is off to a great start. Overall, we see upper GI as an important opportunity for Opdivo, based on the breadth of offered indications and the fact that Opdivo is the only PD therapy approved for HER2-negative gastric cancer.

在肺部，份額處於低兩位數且呈積極勢頭，並且我們看到在所有組織學中都有使用。在 RCC 領域，我們的 Opdivo + cabo 推出繼續表現良好，Opdivo 目前是兩種可用治療方案中領先的 PD-1 一線腎臟藥物。在上消化道中，我們看到 Opdivo 聯合 CheckMate-649 化療在一線胃癌中取得了非常強勁的開端，根據我們的數據強度，在短短幾個月內就達到了 25% 至 30% 的份額。食管輔助治療雖然仍處於早期階段，但已經有了一個良好的開端。總的來說，我們認為上消化道是 Opdivo 的一個重要機會，因為 Opdivo 所提供的適應症很廣泛，而且 Opdivo 是唯一被批准用於 HER2 陰性胃癌的 PD 療法。

Outside the U.S., we had another strong quarter with sales up 13% excluding the impact of foreign currency versus last year. Growth was primarily driven by demand of our new launches in lung and renal cancer. Results also benefited from a favorable comparison due to COVID-related impact last year. All in all, we're very pleased with Opdivo's performance and future growth outlook based on positive momentum for our current launches, our future potential launches, including muscle-invasive bladder cancer and first-line esophageal as well as potential expansion opportunities from clinical trials that will read out over time.

在美國以外的地區，我們又經歷了一個強勁的季度，與去年相比，排除外彙的影響，銷售額增長了 13%。增長主要是由我們在肺癌和腎癌領域的新產品的需求推動的。由於去年新冠肺炎相關的影響，結果也受益於有利的比較。總而言之，我們對 Opdivo 的業績和未來增長前景感到非常滿意，因為我們當前的上市、未來潛在的上市（包括肌層浸潤性膀胱癌和一線食管癌）的積極勢頭以及臨床試驗的潛在擴展機會隨著時間的推移會讀出。

Now turning to Slide 11, regarding our inline multiple myeloma portfolio. Revlimid was up globally primarily driven by demand for triplet-based therapies and increasing treatment duration. In the U.S., we are encouraged to see prescriptions nearing pre-COVID levels. Pomalyst global sales were up 15%, driven by continued strong demand for triplet-based therapies and use in earlier lines.

現在轉向幻燈片 11，關於我們的內聯多發性骨髓瘤產品組合。 Revlimid 在全球範圍內的上漲主要是由於對三聯療法的需求和治療持續時間的延長。在美國，我們很高興看到處方接近新冠疫情前的水平。由於對三聯療法的持續強勁需求以及早期產品線的使用，Pomalyst 全球銷售額增長了 15%。

Now moving to our recent launches on Slide 12. We continue to be very pleased with our new launches. Beginning with Reblozyl, which generated $128 million in Q2 and increased 14% sequentially. As the bolus from the MDS launches continue to wind down, it's being replaced by underlying demand growth as expected. We continue to expect sustained growth in the second half of the year as we remain focused on treating new patients earlier in their treatment journey and ensuring they receive the most appropriate dose for sustained benefit.

現在轉到幻燈片 12 上我們最近發布的內容。我們仍然對我們的新發布感到非常滿意。首先是 Reblozyl，第二季度營收 1.28 億美元，環比增長 14%。隨著 MDS 的推出繼續減少，它正被預期的潛在需求增長所取代。我們繼續預計下半年的持續增長，因為我們仍然專注於在治療過程的早期治療新患者，並確保他們獲得最合適的劑量以獲得持續的益處。

Moving to Zeposia, which generated $28 million in the quarter. The MS launch continues to progress well, where Zeposia is the S1P of choice in terms of written prescriptions and where we continue to see high-intent-to-prescribe metrics. We have also seen an acceleration in the conversion time from written prescriptions to commercially supplied product. Looking forward, we see -- we continue to focus on establishing Zeposia not only as the S1P of choice, but also the oral treatment of choice for MS.

轉向 Zeposia，該季度創造了 2800 萬美元的收入。 MS 的推出繼續進展順利，就書面處方而言，Zeposia 是首選的 S1P，並且我們繼續看到高處方意願指標。我們還看到從書面處方到商業供應產品的轉換時間加快。展望未來，我們看到——我們繼續致力於將 Zeposia 打造為不僅是首選的 S1P，而且是 MS 的首選口服治療藥物。

Beyond MS, we launched Zeposia in ulcerative colitis in the U.S. in early June. While early in the launch, we are very encouraged by physician receptivity to the product so far. Our plan is to focus on step-wise process of building volume by establishing demand for this differentiated oral biologic-like medicine while maximizing access over time.

除了 MS 之外，我們於 6 月初在美國推出了治療潰瘍性結腸炎的 Zeposia。在推出初期，迄今為止醫生對該產品的接受度讓我們深受鼓舞。我們的計劃是通過建立對這種差異化口服生物類藥物的需求，同時隨著時間的推移最大限度地提高獲取量，重點關注逐步擴大產量的過程。

Turning to Onureg. The launch is also going well with double-digit demand growth over prior quarter. We continue to expand the user base with physicians recognizing Onureg as the first and only FDA-approved treatment for AML patients in first remission with a demonstrated OS benefit. Second quarter sales were impacted by reduced inventory, driven by our transition from bottles to blister cards. However, based upon the strength of the underlying demand trends, we expect to see sales rebound in the second half of the year. Remember that this is a new treatment segment where it will take time to shape and establish Onureg as a maintenance treatment. Looking at each of these products internationally, we are encouraged to see how these launches are going, and we look forward to driving growth through gaining access and reimbursement in additional markets over time.

轉向奧努雷格。此次發布也進展順利，需求較上一季度實現兩位數增長。我們繼續擴大用戶群，醫生認為 Onureg 是 FDA 批准的第一個也是唯一一個用於首次緩解的 AML 患者的治療方法，並已證明具有 OS 益處。第二季度的銷售受到庫存減少的影響，這是由於我們從瓶子轉向吸塑卡的推動。然而，根據潛在需求趨勢的強勁程度，我們預計下半年銷售將出現反彈。請記住，這是一個新的治療領域，需要時間來塑造和建立 Onureg 作為維持治療。縱觀國際上的每一款產品，我們很高興看到這些產品的推出進展如何，我們期待著隨著時間的推移，通過在更多市場獲得准入和報銷來推動增長。

Now I'd like to turn to Slide 13 and discuss cell therapy. Demand for our 2 new differentiated cell therapy products has been strong. Starting with Breyanzi. We were pleased with our launch progress with Q2 sales of $17 million driven by strong execution and rapid site activation, with more than 65 sites activated to date. Messages around our differentiated profile and outpatient utilization are resonating well with high awareness among CAR-T treaters.

現在我想轉到幻燈片 13 來討論細胞療法。對我們兩種新型差異化細胞治療產品的需求一直很強勁。從布雷揚齊開始。我們對我們的發布進展感到滿意，在強大的執行力和快速的網站激活的推動下，第二季度銷售額達到 1700 萬美元，迄今為止已激活超過 65 個網站。關於我們的差異化形象和門診利用率的信息與 CAR-T 治療人員的高度認識產生了良好的共鳴。

Next, as it relates to Abecma, our first-in-class BCMA CAR-T, it had sales of $24 million in the quarter, led by very strong demand. We were able to leverage the site footprint of Breyanzi to accelerate site onboarding, an advantage of launching 2 CAR-T medicines simultaneously. Based on the significant unmet demand and differentiated profile, we have seen robust demand for this product beyond our current capacity, and we are looking hard to increase capacity over time. Looking forward, we continue to see meaningful long-term potential with our cell therapy franchise across both Breyanzi and Abecma as evidenced by the recent demand we've seen.

接下來，與我們一流的 BCMA CAR-T Abecma 相關，在非常強勁的需求帶動下，該季度的銷售額為 2400 萬美元。我們能夠利用 Breyanzi 的網站足跡來加速網站上線，這是同時推出 2 種 CAR-T 藥物的優勢。基於顯著的未滿足需求和差異化特徵，我們發現對該產品的強勁需求超出了我們當前的產能，並且我們正在努力隨著時間的推移增加產能。展望未來，我們繼續看到 Breyanzi 和 Abecma 的細胞治療專營權具有有意義的長期潛力，正如我們最近看到的需求所證明的那樣。

Now turning to the next slide. A few points as we think about our launch portfolio overall. First, we are very encouraged with how each of these products are progressing at this point in the launch cycle. Together, they have already contributed $225 million this quarter and are approaching $1 billion run rate. Importantly, we review these products as having significant future potential. This gives us great confidence in our ability to diversify and renew our portfolio as we look forward.

現在轉到下一張幻燈片。當我們思考我們的整體發布組合時，有幾點。首先，我們對這些產品在發布週期的此時此刻的進展感到非常鼓舞。他們本季度已總共貢獻了 2.25 億美元，運轉率接近 10 億美元。重要的是，我們認為這些產品具有巨大的未來潛力。這讓我們對未來多元化和更新投資組合的能力充滿信心。

Now let me take you through a few line items on our P&L on Slide 15. Since we've already covered strong sales for the quarter, I'll focus on a couple of other key line items. First, gross margin decreased versus prior year, which is primarily due to foreign exchange and product mix.

現在讓我帶您瀏覽幻燈片 15 上損益表中的幾個項目。由於我們已經介紹了本季度的強勁銷售情況，因此我將重點介紹其他幾個關鍵項目。首先，毛利率較上年下降，這主要是由於外彙和產品結構的影響。

Operating expenses were higher than last year particularly in MS&A due to higher launch and prelaunch investments across therapeutic areas as well as foreign exchange, which were partially offset by our realized synergies. Remember that at the same time period last year, our spend levels were lower than normal due to the initial wave of COVID. Effective tax rate was 16.9%, primarily driven by our earnings mix. And overall non-GAAP EPS increased significantly year-over-year, primarily driven by our strong top line performance.

運營費用高於去年，特別是在管理和收購方面，這是由於治療領域的啟動和啟動前投資以及外匯增加，但我們實現的協同效應部分抵消了這一支出。請記住，去年同期，由於第一波新冠疫情，我們的支出水平低於正常水平。有效稅率為 16.9%，主要是由我們的盈利組合推動的。整體非公認會計原則每股收益同比顯著增長，這主要是由我們強勁的營收業績推動的。

Now switching gears to the balance sheet and our capital allocation on Slide 16. Our liquidity position remains strong with over $13 billion in cash and marketable securities and strong cash flow from operations of $3.1 billion in the quarter. Our capital allocation priorities remain unchanged.

現在轉向幻燈片 16 上的資產負債表和資本配置。我們的流動性狀況依然強勁，現金和有價證券超過 130 億美元，本季度運營產生的現金流強勁，達 31 億美元。我們的資本配置重點保持不變。

During the quarter, we continued to strengthen the balance sheet while renewing and diversifying our portfolio through business development. As Giovanni mentioned, we executed 2 deals during the quarter that both complement and diversify our oncology portfolio with Agenus and Eisei.

本季度，我們繼續強化資產負債表，同時通過業務發展更新和多元化我們的投資組合。正如 Giovanni 提到的，我們在本季度執行了 2 筆交易，既補充了我們與 Agenus 和 Eisei 的腫瘤學產品組合，又使其多樣化。

As it relates to continued debt reduction, a $4 billion tender offer and additional $1.5 billion in maturities in the first half of the year demonstrate our commitment to strong investment-grade rating. As it relates to our share repurchases, of the planned buyback of $3 billion to $4 billion this year, we have already bought back $3 billion to date, and we'll remain opportunistic as the year progresses.

由於與持續削減債務相關，今年上半年 40 億美元的要約收購和額外 15 億美元的到期債務表明了我們對強勁投資級評級的承諾。由於這與我們的股票回購有關，今年計劃回購 30 億至 40 億美元，迄今為止我們已經回購了 30 億美元，隨著時間的推移，我們將保持機會主義。

Now turning to our 2021 guidance on Slide 17. Following this quarter's performance, we are reaffirming our top and bottom line non-GAAP guidance for the year, which reflects significant growth over last year. From a full year revenue perspective, we continue to expect growth in the high single digits.

現在轉向幻燈片 17 上的 2021 年指引。繼本季度的業績之後，我們重申了今年的非 GAAP 營收和利潤指引，這反映了去年的顯著增長。從全年收入的角度來看，我們繼續預計高個位數的增長。

In terms of phasing for the remainder of the year, due to Eliquis' coverage gap and an unwinding of Opdivo inventory that I noted earlier, we expect Q3 global revenues to be similar to Q2. However, we are encouraged by the strength in the business and expect full year sales at the higher end of our guidance. We have updated our gross margin assumption to 80% for the full year primarily due to product mix and the impact of foreign exchange.

就今年剩餘時間的分階段而言，由於 Eliquis 的覆蓋範圍差距和我之前提到的 Opdivo 庫存的減少，我們預計第三季度的全球收入將與第二季度相似。然而，我們對該業務的實力感到鼓舞，並預計全年銷售額將達到我們指導的較高水平。我們已將全年毛利率假設更新為 80%，主要是由於產品結構和外匯影響。

Moving to operating expenses. We are maintaining our full year guidance on MS&A of low single-digit increase and on R&D of mid-single-digit increase. In terms of phasing for OpEx, we expect it to increase quarter-over-quarter at a similar pace to the first half of the year.

轉向運營費用。我們維持對 MS&A 低個位數增長和研發中個位數增長的全年指引。就運營支出的分階段而言，我們預計其環比增長速度將與上半年相似。

Based on that and the strength of the business, we are reaffirming non-GAAP diluted EPS of $7.35 to $7.55 for 2021. This quarter, we remain pleased not just with our performance but also with the considerable progress we've made in executing our launches and advancing our pipeline.

基於這一點和業務實力，我們重申 2021 年非 GAAP 攤薄後每股收益為 7.35 美元至 7.55 美元。本季度，我們不僅對我們的業績感到滿意，而且對我們在執行產品發布方面取得的巨大進展感到滿意並推進我們的管道。

I'll now turn the call back over to Tim and Giovanni for Q&A.

我現在將把電話轉回蒂姆和喬瓦尼進行問答。

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

謝謝，大衛。凱瑟琳，我們可以回答第一個問題嗎？

We'll take the first question from Chris Schott at JPMorgan.

我們將回答摩根大通的克里斯·肖特提出的第一個問題。

I guess the first one for me was on Opdivo and maybe just a 2-parter here. First of all, good to see that return to growth. But what are you seeing for Opdivo in terms of the COVID impact? I know you've talked in the past about some lingering kind of headwinds, but just want to get the latest. As we moved through June, July, is that business still depressed? Or are we starting to see a more normalized environment?

我想我的第一個是 Opdivo，也許只是這裡的 2 部分。首先，很高興看到經濟恢復增長。但您對 Opdivo 的新冠疫情影響有何看法？我知道您過去曾談論過一些揮之不去的逆風，但只是想了解最新情況。到了六月、七月，生意還低迷嗎？或者我們是否開始看到一個更加正常化的環境？

And then the second one on Opdivo was just a little bit more color on the rollout in gastric in terms of where we stand today in terms of penetration rates. And then my final question was just on the competitive environment for mavacamten in light of some of the recent competitor data. I just want to see -- kind of more broadly speaking, has there been any change in view or confidence in that asset at all?

然後，就我們今天的滲透率而言，Opdivo 的第二個產品在胃病方面的推出稍微有點色彩。然後我的最後一個問題是根據最近的一些競爭對手數據來了解 mavacamten 的競爭環境。我只是想看看——更廣泛地說，對該資產的看法或信心有任何變化嗎？

Thank you, Chris. Let me ask Chris Boerner to answer your question about Opdivo, and then Samit will make some comments on the profile of mavacamten.

謝謝你，克里斯。讓我請Chris Boerner回答您關於Opdivo的問題，然後Samit將對mavacamten的簡介發表一些評論。

Sure. Thanks for the question, Chris. So let me start with the COVID impact. We have seen a recovery in the I-O market really coming out of Q1 and into Q2. And I would say that is a recovery on multiple parameters. First, we've seen new patient claims, while they still lag pre-COVID levels, they've certainly improved quarter-over-quarter. I-O demand continues to recover versus the pre-COVID levels and in fact, grew about 5% quarter-over-quarter.

當然。謝謝你的提問，克里斯。讓我從新冠疫情的影響開始吧。我們看到 I-O 市場從第一季度到第二季度確實出現了復甦。我想說這是多個參數的恢復。首先，我們看到了新的患者索賠，雖然仍然落後於新冠疫情前的水平，但季度環比確實有所改善。與新冠疫情爆發前的水平相比，I-O 需求繼續恢復，事實上，季度環比增長了約 5%。

And importantly, we've seen an increase in in-person engagement. Oncology still lags other therapeutic areas, but increasingly, our field teams are able to engage live with our customers. And that's going to be really important given the competitive nature of a number of these markets like first-line lung cancer. So I would say, in general, COVID continues to be dynamic really across markets, and certainly, that's true in oncology. But I would say there's been a general improvement as we exited Q1 and into Q2.

重要的是，我們看到面對面的參與度有所增加。腫瘤學仍然落後於其他治療領域，但我們的現場團隊越來越能夠與客戶進行實時互動。考慮到許多此類市場（例如一線肺癌）的競爭性質，這將非常重要。所以我想說，總的來說，新冠疫情在整個市場上仍然充滿活力，當然，在腫瘤學領域也是如此。但我想說，隨著我們退出第一季度並進入第二季度，總體有所改善。

As for how things are going in gastric cancer, I would say the gastric launch continues to go really very well. As you know, we have multiple indications now in gastric cancer. And I would say that in general, the first-line metastatic launch is going quite well. Our share is roughly 35%. That's being led really by the gastric segment that we see really good utilization of Opdivo plus chemo in both GEJ and EAC as well.

至於胃癌的進展情況，我想說，胃部的發射繼續進行得非常順利。如您所知，我們現在有多種胃癌適應症。我想說的是，總的來說，一線轉移性藥物的上市進展順利。我們的份額大約是35%。這實際上是由胃部分引領的，我們看到 Opdivo 聯合化療在 GEJ 和 EAC 中的使用都非常好。

And we're seeing use across all CPS levels. As you would expect, the majority is in the greater than 10%, but we are seeing strong uptake in less than 10% as well. And I would say execution has been very good, and in fact, we have the #1 share of voice. And we continue to build new trials, which is important at this stage in the launch. So overall, very happy with the performance in gastric.

我們看到它在所有 CPS 級別上都有使用。正如您所料，大多數人都超過 10%，但我們也看到不到 10% 的人也有強勁的使用率。我想說，執行力非常好，事實上，我們擁有第一的話語權。我們繼續建立新的試驗，這在發布的現階段很重要。總的來說，對胃部的表現非常滿意。

Thanks, Chris. And Chris, I'll just take on the mavacamten question that you asked. And I guess the question is emerging from the REDWOOD data that we recently shared through a press release. And while it's truly an apples-to-oranges comparison, if we were to indulge in that, I would say that we don't see a differentiation as might have been perceived.

謝謝，克里斯。克里斯，我將回答您提出的 mavacamten 問題。我想這個問題是從我們最近通過新聞稿分享的 REDWOOD 數據中浮現出來的。雖然這確實是蘋果與橘子的比較，但如果我們沉迷於這一點，我想說我們並沒有看到人們可能認為的差異。

And the reason for that is, if you look at it from an efficacy perspective, the measures were at a different time point, first of all, 10 weeks versus a 30-week trial for EXPLORER. Secondly, the differences -- or the primary endpoints that were measured were at rest and with Valsalva maneuver in the REDWOOD trial versus doing exercise. So if you were to compare those apples to apples, there is no differentiation that we see.

原因是，如果從功效的角度來看，這些措施是在不同的時間點進行的，首先，EXPLORER 的試驗是 10 週，而不是 30 週。其次，差異——或者說測量的主要終點是在 REDWOOD 試驗中休息時和 Valsalva 動作與運動時進行的。因此，如果你將這些蘋果與蘋果進行比較，我們看不到任何差異。

From a safety perspective as well, when we talk about decreasing the ejection fraction, if you start with a higher ejection fraction, of course, you will not see as big of a decrease below 50%, which was the case in the REDWOOD trial. We had patients enrolled in our EXPLORER study with a lower ejection fraction of 55% or lower. And therefore, when we compare apples to apples again, in fact, if anything, we could turn out to be better.

同樣從安全角度來看，當我們談論降低射血分數時，如果你從較高的射血分數開始，當然，你不會看到低於 50% 的大幅下降，就像 REDWOOD 試驗中的情況一樣。我們的 EXPLORER 研究中招募了射血分數為 55% 或更低的患者。因此，當我們再次進行同類比較時，事實上，如果有的話，我們可能會變得更好。

At the end of it all, I would say we need to wait to see the data in the Phase III trial for the competitor molecule. We already have our Phase III data. We've already submitted and look forward to bringing it to patients with a PDUFA date in January.

最後，我想說我們需要等待查看競爭對手分子的 III 期試驗數據。我們已經有了第三階段的數據。我們已經提交並期待將其提供給 PDUFA 日期為 1 月份的患者。

We'll now take the next question of Geoff Meacham of Bank of America.

現在我們將回答美國銀行傑夫·米查姆的下一個問題。

Congrats on the quarter. I just had a few. On the cell therapy launches, you guys had a good quarter out of the gate. So I wanted to ask you what the drivers of the next few quarters are. Is it signing up more accounts? Is it establishing better reimbursement? And maybe just help us with kind of if you had any manufacturing bottlenecks. I know you guys have talked about that previously.

恭喜本季度。我只吃了一些。在細胞療法的推出方面，你們已經度過了一個不錯的季度。所以我想問您未來幾個季度的驅動因素是什麼。是否要註冊更多帳戶？是否建立了更好的報銷機制？如果您遇到任何製造瓶頸，也許可以幫助我們解決。我知道你們之前已經討論過這個問題。

And then on deucravacitinib, maybe just help us with kind of how you're thinking about what success looks like in ulcerative colitis. And also, any additional thoughts that you've had? I know there's been a lot of discussion about potential labeling and differentiation versus JAK. And maybe as you've had time to digest the recent data, can you just give some updated thoughts on that?

然後，關於 deucravacitinib，也許只是幫助我們了解一下您如何看待潰瘍性結腸炎的成功。另外，您還有什麼其他想法嗎？我知道有很多關於潛在標籤和與 JAK 的差異化的討論。也許您已經有時間消化最近的數據，您能就此給出一些最新的想法嗎？

Thank you, Geoff. So let's start with cell therapy. Let me just say first, really exciting. And the launch is off to a great start. It really demonstrates that our decision to invest in this technology and the differentiated nature of our 2 products is paying off. There is a lot of excitement. Let me ask Chris to give you more details, and then Samit will give you his perspective on deucravacitinib. Chris?

謝謝你，傑夫。那麼讓我們從細胞療法開始吧。我先說一下，真的很興奮。這次發布有了一個良好的開端。這確實表明我們投資這項技術的決定以及我們兩種產品的差異化性質正在得到回報。有很多興奮。讓我請 Chris 向您提供更多詳細信息，然後 Samit 將向您介紹他對 deucravacitinib 的看法。克里斯？

Yes. So I would just reiterate what Giovanni just said. The commercial and medical launches for both products continues to be very strong. We've seen good execution across the teams.

是的。所以我只想重申喬瓦尼剛才所說的話。這兩種產品的商業和醫療發布仍然非常強勁。我們看到了各個團隊的良好執行力。

Importantly, for both Abecma and Breyanzi, the profiles for these products are resonating well with customers, in the case of Abecma as a first-in-class BCMA-targeted cell therapy and for Breyanzi as a best-in-class. One of the things we've seen across both products is there's significant unmet need. That's particularly true in the case of Abecma just given the fact that there are no other opportunities, in many cases, for these patients, and as a result, we've seen very strong demand for both products.

重要的是，對於 Abecma 和 Breyanzi 來說，這些產品的簡介與客戶產生了良好的共鳴，Abecma 是一流的 BCMA 靶向細胞療法，Breyanzi 是一流的。我們在這兩種產品中看到的一件事是，存在大量未滿足的需求。對於 Abecma 來說尤其如此，因為在許多情況下，這些患者沒有其他機會，因此，我們看到對這兩種產品的需求非常強勁。

What I would say for Breyanzi, the focus continues to be on ensuring that sites know how to manage these patients well, continuing to sell the best-in-class profile that we have with Breyanzi. And we're increasingly seeing interest in patients being referred to clinical trial sites. So we're managing that well with Breyanzi.

對於 Breyanzi，我想說的是，重點仍然是確保網站知道如何很好地管理這些患者，繼續銷售我們在 Breyanzi 上擁有的一流的資料。我們越來越多地看到人們對將患者轉診至臨床試驗地點的興趣。所以我們與 Breyanzi 的合作很好。

For Abecma, I would say the focus there continues to be engaging with customers around manufacturing capacity. As we had said previously, this is a space where, because of the significant unmet need and because we are the first BCMA-targeted cell therapy in the space, the demand for this product has outstripped our current capacity to manufacture. What I would say is the sole focus that we have there is on steadily increasing manufacturing capacity.

對於 Abecma，我想說，重點仍然是圍繞製造能力與客戶進行互動。正如我們之前所說，由於需求未得到滿足，而且我們是該領域第一個 BCMA 靶向細胞療法，因此對該產品的需求已經超出了我們目前的製造能力。我想說的是，我們唯一的重點是穩步提高製造能力。

We have a very strong team that's in place focused on this. We're engaging obviously internally and externally with third parties, including regulators, to increase the number of slots that we have available for patients, and that's going to be the main focus on that product for the coming months.

我們有一支非常強大的團隊專注於此。我們顯然正在與包括監管機構在內的第三方進行內部和外部接觸，以增加我們為患者提供的插槽數量，這將是未來幾個月該產品的主要焦點。

Thanks. And maybe I can take on the deucrava question. In terms of ulcerative colitis for deucrava, as you know, with a TYK2 inhibitor, we know that downstream effect is the inhibition of IL-12 and IL-23 pathway. These mechanisms are already proven to be effective in ulcerative colitis, so we are truly looking forward to seeing the data at the end of the year from our Phase II study where we will get to see the induction data comparing deucrava versus placebo.

謝謝。也許我可以回答 deucrava 問題。就 deucrava 的潰瘍性結腸炎而言，如您所知，使用 TYK2 抑製劑，我們知道下游作用是抑制 IL-12 和 IL-23 通路。這些機制已被證明對潰瘍性結腸炎有效，因此我們非常期待在今年年底看到 II 期研究的數據，我們將看到比較 deucrava 與安慰劑的誘導數據。

So we know what success would look like because there is proven mechanisms out there. We know the efficacy that we would be looking for in a Phase II study to initiate our Phase III program. And the good news is we also have the Crohn's disease study ongoing, which will read out in next year. So a broad program that we will be able to take forward to really get the Phase III data to impact the second half of the decade following the Zeposia launch right now in that disease.

所以我們知道成功會是什麼樣子，因為有經過驗證的機制。我們知道我們在啟動我們的 III 期項目的 II 期研究中所尋求的功效。好消息是我們還在進行克羅恩病研究，該研究將於明年公佈。因此，我們將能夠推進一項廣泛的計劃，以真正獲得 III 期數據，以影響 Zeposia 目前在該疾病中推出後的十年後五年。

We'll now take the next question from Terence Flynn at Goldman Sachs.

現在我們將回答高盛特倫斯·弗林提出的下一個問題。

Congrats on the progress with the new products. Maybe 2 for me. Just one follow-up on Abecma. I was wondering if you could give us any guidance in terms of number of patients you can currently serve from your manufacturing facility that you have right now.

祝賀新產品取得進展。也許對我來說是2個。只是 Abecma 的一項後續行動。我想知道您是否可以就您目前擁有的製造工廠可以服務的患者數量向我們提供任何指導。

And then remind us of timing to bring on additional capacity as, again, I think you guys are building out some further capacity there. So any update on timing?

然後提醒我們增加額外容量的時機，因為我認為你們正在那裡建立更多的容量。那麼時間方面有更新嗎？

And then a question for Samit on the Factor XIa program. I know we talked about this last month. You have the data in-house. But any more perspective on how to think about starting up a trial in the AFib setting? Or is that really contingent on seeing data from the second Phase II trial?

然後向 Samit 提出一個關於 XIa 因子計劃的問題。我知道我們上個月討論過這個問題。您擁有內部數據。但對於如何考慮在 AFib 環境中啟動試驗還有更多觀點嗎？或者這真的取決於第二次二期試驗的數據嗎？

Thanks, Terence. Chris, do you want to start on Abecma?

謝謝，特倫斯。 Chris，你想開始使用 Abecma 嗎？

Sure. So as I said in the previous question, our focus continues to be to increase the available capacity that we have for this product. As I think we've discussed previously, we had increased the number of slots that were available for patients through August, and so we were able to increase to meet the demand in August.

當然。正如我在上一個問題中所說，我們的重點仍然是增加該產品的可用容量。正如我認為我們之前討論過的那樣，我們增加了 8 月份可供患者使用的時段數量，因此我們能夠增加以滿足 8 月份的需求。

At the same time, we continue to see a shortage of vector. That is something that's been affecting multiple cell therapy products, and so we're keeping an eye on that. And what I would say, Terence, is that the situation on vector supply continues to be fairly dynamic.

與此同時，我們繼續看到載體的短缺。這已經影響了多種細胞治療產品，因此我們正在密切關注。特倫斯，我想說的是，載體供應的情況仍然相當動態。

And so with respect to when supply will ramp significantly, I would say that rather than put out a date that would likely shift, I'll just say that this continues to be a top priority for us. Our sole focus continues to be on increasing the supply to meet the near-term anticipated commercial demand. And then, obviously, we have a longer-term focus on ensuring more stable long-term supply for vector that would be available to support both of these products. But that's where the situation sits for Abecma.

因此，關於供應何時大幅增加，我想說的是，我不會提出一個可能會發生變化的日期，而是說這仍然是我們的首要任務。我們唯一的重點仍然是增加供應以滿足近期預期的商業需求。然後，顯然，我們的長期重點是確保更穩定的長期載體供應，以支持這兩種產品。但這就是 Abecma 的處境。

And Terence, for Milvexian, our factor XIa inhibitor, what I would say is that what we've seen thus far from the total knee replacement study, we are very pleased with that. The trial showed exactly what we anticipated it to show. And we do believe, along with our collaborator Janssen, that we do need this second trial data as, collectively, the 2 trials will form the basis for the clinical development plan.

Terence，對於 Milvexian，我們的因子 XIa 抑製劑，我想說的是，迄今為止我們從全膝關節置換研究中看到的情況，我們對此非常滿意。試驗完全符合我們的預期。我們和我們的合作者楊森一起相信，我們確實需要第二次試驗數據，因為這兩項試驗將共同構成臨床開發計劃的基礎。

Remember, in the first study, in the TKR study, we only have about 2 weeks of dosing with a single agent Factor XIa inhibitor, whereas in the second trial, in the secondary stroke prevention, we have the background therapy of doublet anti-platelet therapy as well with up to 3 months of dosing. And so that longevity will be important to understand the overall safety profile, and that will obviously then be able to go into Phase III program, not only just AF but we are thinking of other indications as well.

請記住，在第一項研究中，在 TKR 研究中，我們只有約 2 週的單一藥物 XIa 因子抑製劑給藥時間，而在第二項試驗中，在二級中風預防中，我們有雙藥抗血小板的背景治療治療以及長達 3 個月的給藥。因此，壽命對於了解整體安全狀況非常重要，顯然，這將能夠進入第三階段計劃，不僅是 AF，我們也在考慮其他適應症。

We'll now take the next question of Andrew Baum at Citi.

現在我們將回答花旗銀行安德魯·鮑姆的下一個問題。

A couple of questions. First, we don't hear so much about your earlier generation of immuno-oncology programs before the transaction. There's been a number of papers out on the importance of Treg depletion and ADCC as a part of CTLA-4 mechanism. And I know you have your A2-postulated molecule in a fairly large trial. Could you update us on when we might expect to see some results and just your general level of enthusiasm on that approach for validated target?

有幾個問題。首先，在交易之前，我們並沒有聽說太多有關你們早期一代免疫腫瘤學項目的信息。已有多篇論文闡述了 Treg 耗竭和 ADCC 作為 CTLA-4 機制一部分的重要性。我知道您已經在相當大的試驗中獲得了 A2 假定分子。您能否向我們介紹一下我們預計何時會看到一些結果以及您對這種驗證目標方法的總體熱情程度？

And then second, in light of the Aduhelm approval and particularly the biomarker, how is this thinking influencing your assets in neurodegenerative disease? Obviously, you've been investing historically in that space. Is this a catalyst for Bristol to reenter that segment?

其次，鑑於 Aduhelm 的批准，特別是生物標誌物，這種想法如何影響您在神經退行性疾​​病領域的資產？顯然，您一直在該領域進行投資。這是布里斯托爾重新進入該領域的催化劑嗎？

Thanks, Andrew. Let me make just a couple of very high-level comments, and then Samit will take both of your questions. So first of all, with respect to I-O, I think we're really excited about the opportunity to launch our third I-O agent potentially soon, which is relatlimab in metastatic melanoma. And that really shows how we are progressing and extending, in fact, the strength of our I-O franchise.

謝謝，安德魯。讓我發表一些非常高級別的評論，然後薩米特將回答你們的兩個問題。首先，就 I-O 而言，我認為我們對可能很快推出第三種 I-O 藥物的機會感到非常興奮，它是治療轉移性黑色素瘤的 relatlimab。事實上，這確實表明了我們如何取得進步並擴展我們的 I-O 特許經營權的實力。

With respect to the CNS, again, Samit will address your question in more detail. From my perspective, what I'd like to say is this is a research area that we committed to, in fact, as part of the Celgene research strategy a few years ago. We are really excited to have a number of early programs that are continuing to advance that's primarily driven by a really interesting set of external partnerships.

關於中樞神經系統，薩米特將再次更詳細地回答你的問題。從我的角度來看，我想說的是，這是我們幾年前致力於的一個研究領域，實際上是 Celgene 研究戰略的一部分。我們非常高興有許多早期項目正在繼續推進，這些項目主要是由一組非常有趣的外部合作夥伴推動的。

So let me ask Samit to give you more detail on both of those topics.

因此，讓我請薩米特為您提供有關這兩個主題的更多詳細信息。

Andrew, I think from a CTLA-4 perspective, as you know, we have 3 molecules in development in the back of CTLA-4 probody non-fucosylated and fucosylated molecules. The trials are ongoing, as you've said, very well, and we are actually looking forward to see the data towards the end of the year as well as in early part of next year. That will certainly pave the way for new trials looking at combinations with our pipeline, with Opdivo as well as other molecules that you just heard from Giovanni. We have relatlimab and then new additions to our pipeline with TIGIT as well as with the ADC that we recently acquired. Those clinical development plans are being formulated, and appropriate indications are yet to be chosen based on the activity that we will see from these trials.

Andrew，我認為從 CTLA-4 的角度來看，如您所知，我們在 CTLA-4 探針體非岩藻糖基化和岩藻糖基化分子的後面有 3 個分子正在開發中。正如您所說，試驗正在進行中，進展順利，我們實際上期待在今年年底和明年初看到數據。這肯定會為新的試驗鋪平道路，研究與我們的管道、Opdivo 以及您剛剛從 Giovanni 聽到的其他分子的組合。我們有 relatlimab，還有 TIGIT 以及我們最近收購的 ADC 的新產品。這些臨床開發計劃正在製定中，並且尚未根據我們從這些試驗中看到的活動來選擇適當的適應症。

To your second question on the recent approval on Alzheimer's disease and then how to see that data and what to do with that, we do believe, as Giovanni said, that our focus on neurology and neurodegenerative disease has continued to be there, and we'll continue actually to increase from there onwards. The way we look at that data is now that the threshold has been set from a regulatory perspective -- it was hard to gauge before what endpoints to really shoot for and what was the threshold. Now that we know what the threshold is, it is now probably going to be better or easier to develop studies because there is a regulatory path forward. As you recall, we recently had announced our collaboration with Prothena and looking forward to make our way into the clinical studies with that TAU inhibitor with a differentiated mechanism that we'll be able to take forward. More to follow in the future.

關於你的第二個問題，即最近批准阿爾茨海默病，以及如何查看這些數據以及如何處理這些數據，正如喬瓦尼所說，我們確實相信，我們對神經病學和神經退行性疾​​病的關注仍然存在，而且我們”從那時起，實際上將繼續增加。我們現在看待這些數據的方式是從監管角度設定閾值——之前很難衡量真正要達到的終點以及閾值是什麼。現在我們知道了門檻是什麼，現在可能會更好或更容易地開展研究，因為有一條前進的監管道路。您還記得，我們​​最近宣布了與 Prothena 的合作，並期待著以我們能夠推進的差異化機制進入 TAU 抑製劑的臨床研究。未來還會有更多內容。

We'll now take the next question from Seamus Fernandez of Guggenheim.

現在我們將回答古根海姆的謝默斯·費爾南德斯提出的下一個問題。

Great. So first, on Abecma, just wanted to get a better sense of where capacity could potentially go to and if there's any visibility on the vector dynamics and perhaps when that might release. Is that entirely reflective of -- is that more reflective of the situation in terms of vector manufacturing and capabilities at Bluebird? Or is it a global market dynamic associated with the sort of use of nucleic acid targeted therapies? Just wanted to get a sense of what the impacts are there.

偉大的。因此，首先，在 Abecma 上，只是想更好地了解產能可能流向何處，以及矢量動態是否有任何可見性，以及何時可能釋放。這是否完全反映了——這是否更能反映藍鳥矢量製造和能力方面的情況？或者這是與核酸靶向療法的使用相關的全球市場動態？只是想了解一下有什麼影響。

And then what would the hope for expansion of capacity capabilities be in 2022 relative to 2021? And do you have any sense of timing improvement for the vectors as it relates to a Abecma?

那麼相對於2021年，2022年產能擴張的希望是什麼呢？您對與 Abecma 相關的向量的時序改進有什麼感覺嗎？

Second question, just wanted to get a little bit of a better sense of the ongoing strategy, the number of targets that you guys are pursuing. Specifically in multiple myeloma, you have a huge number of programs ongoing there. Just wanted to have you guys talk a little bit about prioritization in that regard and where you see the most opportunity for new products in that space, whether it be the CELMoDs or bispecific, the T cell engager. Just wondering where we're going to see some acceleration in those programs there.

第二個問題，只是想更好地了解正在進行的戰略，以及你們正在追求的目標數量。特別是在多發性骨髓瘤方面，有大量正在進行的項目。只是想讓你們談談這方面的優先順序，以及您認為該領域新產品最有機會的地方，無論是 CELMoD 還是雙特異性 T 細胞接合器。只是想知道我們將在哪裡看到這些項目的加速。

Thanks, Seamus. So on Abecma, let me just say, to your question, the supply chain of -- globally, the supply chain for vector is very dynamic. We don't look at this as a specific issue but rather a really complex issue across the industry. I'll ask Chris to -- whether there's anything he wants to add.

謝謝，西莫。關於 Abecma，我只想說，對於你的問題，全球範圍內，載體的供應鍊是非常動態的。我們並不認為這是一個具體問題，而是整個行業的一個非常複雜的問題。我會問克里斯——他是否有什麼要補充的。

And then we'll talk with Samit about our strategy in multiple myeloma. As I mentioned, excited to have the iberdomide Phase II data in-house, which is a really important step forward for us. Chris, anything to add on Abecma?

然後我們將與 Samit 討論我們在多發性骨髓瘤方面的策略。正如我所提到的，很高興能夠獲得伊伯多胺二期臨床數據，這對我們來說是向前邁出的非常重要的一步。 Chris，關於 Abecma 有什麼要補充的嗎？

Yes. The only thing I would add, Seamus, is there are sort of 2 dynamics at play with Abecma. One is the significant demand that we're seeing in the marketplace, which is, I would say, a function of the fact that there's significant unmet need, the profile of Abecma is very strong and the fact that you've seen a bolus of patients who have been really reserved for these therapies and this therapy in particular when it launched. So there's very strong demand, and so obviously, there's an internal focus on increasing our ability to supply that demand, which has exceeded the supply that we anticipated having to deliver into the marketplace.

是的。 Seamus，我唯一要補充的是，Abecma 有兩種動力在發揮作用。一是我們在市場上看到的巨大需求，我想說，這是因為存在大量未滿足的需求，Abecma 的形象非常強大，並且您已經看到了大量的事實那些真正保留接受這些療法的患者，尤其是在該療法推出時。因此，需求非常強勁，很明顯，內部重點是提高我們滿足需求的能力，這已經超出了我們預期必須交付給市場的供應量。

The second thing I would say is this broader global issue around vector supply. That's something we've been hearing from customers. That's impacting multiple cell therapy products. And obviously, as we think about our strategy, not only through the end of this year but really as we get into next year, our focus is going to be ensuring a more stable long-term supply of vector. And that's something we'll be happy to update on as we have more details to provide you. Samit?

我要說的第二件事是圍繞載體供應的更廣泛的全球問題。這是我們從客戶那裡聽到的。這正在影響多種細胞治療產品。顯然，當我們考慮我們的戰略時，不僅是在今年年底，而且在進入明年時，我們的重點將是確保載體的長期穩定供應。我們很樂意為您更新這一點，因為我們有更多詳細信息可以提供給您。薩米特？

Seamus, from a multiple myeloma perspective, we certainly remain the leaders in multiple myeloma and want to continue to progress on that path. And we have a very strong pipeline, as you very well mentioned. There are 3 pillars to the multiple myeloma strategy: number one, the CELMoDs. And we intend to use these CELMoDs as the future backbones, replacing the IMiDs that are currently out there.

Seamus，從多發性骨髓瘤的角度來看，我們無疑仍然是多發性骨髓瘤領域的領導者，並希望繼續在這條道路上取得進展。正如您所提到的，我們擁有非常強大的渠道。多發性骨髓瘤策略有 3 個支柱：第一，CELMoD。我們打算使用這些 CELMoD 作為未來的骨幹，取代目前的 IMiD。

In that regard, the strategy is 2-pronged. One is a single agent entering in the late line of therapy. The first data, we've seen with iberdomide already. And then next year, we'll see the data for CC-480, the second CELMoD which is more potent.

在這方面，該戰略是雙管齊下的。一種是進入後期治療的單一藥物。我們已經看到了伊伯多胺的第一個數據。明年，我們將看到 CC-480 的數據，這是第二個更強大的 CELMoD。

And then progressing them further up the line in terms of combinations. You might see on clinicaltrials.gov we've already announced and are initiating a trial in patients who have received 2 to 3 prior lines of therapy as a combination of iberdomide with daratumumab and dexamethasone compared to VELCADE, daratumumab and dexamethasone. And that strategy will continue as we go further up the line with the CELMoDs.

然後在組合方面進一步提升它們。您可能會在 ClinicalTrials.gov 上看到，我們已經宣布並正在針對先前接受過 2 至 3 種療法的患者啟動一項試驗，將伊伯多胺與達雷木單抗和地塞米松聯合治療與 VELCADE、達雷木單抗和地塞米松進行比較。隨著我們與 CELMoD 的合作進一步推進，這一戰略將繼續下去。

The second pillar is the BCMA-targeted therapies, first of which is already approved, that is Abecma. And the idea for Abecma will be to, again, move further up the line for eligible patients who can receive cell therapies. KarMMA-3 is currently enrolling, looking at patients who have received 3 prior lines of therapy. And then intention would be to go further up the line, again, for the right patient population.

第二個支柱是BCMA靶向療法，其中第一個已經獲得批准，即Abecma。 Abecma 的想法將是再次為符合條件的可以接受細胞療法的患者提供進一步的服務。 KarMMA-3 目前正在招募，研究之前接受過 3 種治療的患者。然後，我們的目的將是再次針對合適的患者群體進一步推進。

Now not all patients can get cell therapy because of comorbidities or other reasons, and therefore, other BCMA-directed therapies are going to be important. And that's where the T cell engagers and the ADC come into play. But they are very early in development right now, in Phase I studies. And so more to follow on that. Our prioritization -- our belief remains very strong that patients with multiple myeloma still are not cured, and we will require combination therapies in the future with multiple targets and multiple modalities and we'll progress accordingly.

現在，由於合併症或其他原因，並非所有患者都能接受細胞治療，因此其他 BCMA 導向的療法將變得很重要。這就是 T 細胞接合者和 ADC 發揮作用的地方。但它們目前還處於開發的早期階段，處於第一階段的研究中。還有更多後續內容。我們的優先事項——我們仍然堅信多發性骨髓瘤患者仍未治愈，未來我們將需要多靶點和多種方式的聯合治療，我們將相應取得進展。

We'll now take the next question from Tim Anderson at Wolfe Research.

現在我們將回答沃爾夫研究中心蒂姆·安德森提出的下一個問題。

Eliquis continues to do well. Of course, one thing that could derail would be an appeals court ruling overturning the lower court. Can you just give us your expectation for a time line on an appeals court ruling?

Eliquis 繼續表現出色。當然，可能導致脫軌的一件事是上訴法院推翻下級法院的裁決。您能否告訴我們您對上訴法院裁決的時間表的期望？

And then second question on just mavacamten. It feels like there's a kind of a back story on the regulatory front why you guys got the standard review. Because at the time of that deal, you did expect and you had it in your slides and we thought you'd get a second half 2021 launch. So a fair amount of time has elapsed since you got the standard review, and I'm wondering if you can share what concerns the agency may have. It seems like there may be some concerns about not having long enough cardiovascular duration in terms of efficacy [that might be important] for a new filing.

然後是關於 mavacamten 的第二個問題。感覺監管方面有一個背景故事，為什麼你們得到了標準審查。因為在達成該交易時，您確實期望並且您已將其包含在幻燈片中，我們認為您將在 2021 年下半年發布。自您獲得標準審查以來已經過去了相當長的時間，我想知道您是否可以分享該機構可能存在的擔憂。似乎對於新申請的療效[這可能很重要]，可能有人擔心心血管持續時間不夠長。

Yes. Thanks, Tim. Samit, do you want to start with the second question?

是的。謝謝，蒂姆。 Samit，你想從第二個問題開始嗎？

Sure, absolutely. For mavacamten, Tim, we've already filed for mavacamten. The FDA has already accepted the file. We have a PDUFA date. So those concerns, I think, are relieved. And our -- we are really looking forward to bringing these exciting data as well as the medicine to patients with obstructive hypertrophic cardiomyopathy. As you know, with mavacamten, we have other plans that are already ongoing and in execution in other disease types as well. So we don't see it as a showstopper in any which way and looking forward to really the readout on the regulatory side and also bringing it globally to other parts of the world.

當然，絕對。對於 mavacamten，蒂姆，我們已經申請了 mavacamten。 FDA 已經接受了該文件。我們有一個 PDUFA 日期。所以我認為這些擔憂都得到了緩解。我們非常期待將這些令人興奮的數據以及藥物帶給梗阻性肥厚型心肌病患者。如您所知，對於 mavacamten，我們還有其他計劃正在進行中，並正在針對其他疾病類型執行。因此，我們不認為它會以任何方式成為攪局者，並期待監管方面的真正結果，並將其帶到全球其他地區。

Thank you, Samit. And with respect to your first question, Tim, on the IP litigation for Eliquis, first of all, as you know, we're very pleased with the decision that was made by the court in past summer, which really confirms the strength of not only the composition of matter patent but also our formulation patent. And as you mentioned, there is an appeal that has been filed, and the hearing is scheduled in September. So we look forward to hearing the result of that process.

謝謝你，薩米特。關於你的第一個問題，蒂姆，關於 Eliquis 的知識產權訴訟，首先，正如你所知，我們對去年夏天法院做出的決定感到非常高興，這確實證實了不不僅是物質成分專利，還有我們的配方專利。正如您提到的，已經提出上訴，聽證會定於 9 月舉行。因此，我們期待聽到該過程的結果。

We'll now take the next question from Carter Gould at Barclays.

現在我們將回答巴克萊銀行卡特·古爾德提出的下一個問題。

Congrats on the results so far. Maybe just first on Reblozyl. Can you talk about sort of the headwinds you're still seeing from COVID? And also, as you think about ex U.S. kind of ramping over the second half of the year, any color on expectations or additional countries you expect to launch in?

恭喜到目前為止的結果。也許首先是 Reblozyl。您能談談您仍然看到的新冠疫情帶來的不利因素嗎？另外，當您考慮下半年美國以外的市場增長時，您對預期或您希望在其他國家/地區推出的產品有什麼看法嗎？

And then maybe coming back to iberdomide. Samit, you talked about the combination study that got posted on clinicaltrials.gov. Can you just talk a little bit more around just sort of demonstrating clinical meaningfulness in the setting where, obviously, you're going to have generic IMiDs in the not-too-distant future? And you're still -- in the study, you're comparing against -- there's no IMiD in the comparison. So just really kind of driving home that the importance of CELMoDs in this setting would be helpful.

然後也許會回到伊伯多胺。 Samit，您談到了發佈在 ClinicalTrials.gov 上的聯合研究。您能否再多談一點，以證明在不久的將來您將擁有通用 IMiD 的臨床意義？而且你仍然——在研究中，你正在比較——比較中沒有IMiD。因此，讓我們明白 CELMoD 在這種情況下的重要性會很有幫助。

Yes. Thanks for the questions. There's really good dynamics on Reblozyl. Let me ask Chris to give you a better perspective before we cover iberdomide with Samit.

是的。感謝您的提問。 Reblozyl 的動態非常好。在我們與 Samit 討論伊伯多胺之前，請讓 Chris 給您一個更好的視角。

Yes. Thanks for the question, Carter. So with respect to COVID, I would say it's very similar to the answer I gave previously on COVID. I think the dynamics in that market are still evolving. We've not yet seen a full return to normal. But what I would say is, in the quarter, we also there saw an improvement both with respect to new patients entering the clinic and being given access to therapy as well as, importantly, again, our field team's ability to interact with customers. And that's going to be really important here because you've got to continue to push on an urgency to treat these patients, many of whom have been treated for a considerable time on ESAs. So those dynamics, we think, are very favorable and bode well for continued growth opportunities for us as we go into the second half of the year.

是的。謝謝你的提問，卡特。因此，關於新冠病毒，我想說這與我之前就新冠病毒給出的答案非常相似。我認為該市場的動態仍在不斷發展。我們尚未看到完全恢復正常。但我想說的是，在本季度，我們還看到了新患者進入診所和獲得治療的機會以及重要的是我們的現場團隊與客戶互動的能力方面的改善。這在這裡非常重要，因為你必須繼續推動治療這些患者的緊迫性，其中許多人已經接受了 ESA 治療相當長的時間。因此，我們認為，這些動態非常有利，並且預示著我們在進入下半年時將有持續增長的機會。

And with respect to the ex-U.S. launches, I'd say it's still very early days, but what we've seen is very good customer reception in early launch markets like Germany. The execution in those markets have been good. As COVID continues to improve there and we're able to engage with customers more, we see those dynamics continuing to improve over the course of the year. And then we have, of course, additional launches as access is secured, most notably with Belgium, The Netherlands, France and Italy in the coming months.

就前美國而言發布，我想說現在還處於早期階段，但我們看到在德國等早期發布市場中客戶反響非常好。這些市場的執行情況良好。隨著新冠疫情的持續改善，我們能夠與客戶進行更多的接觸，我們看到這些動態在這一年中持續改善。當然，隨著准入的獲得，我們還會推出更多產品，尤其是在未來幾個月內與比利時、荷蘭、法國和意大利合作。

Thanks, Chris. And for iberdomide, the way I look at it is there is a progression of how we move forward and how we move up the line. If you recall, over the last couple of meetings at ASCO as well as ASH, we've been able to show the overall profile for iberdomide. Because of its tolerability, the combinability is good. So we've been able to combine with dara. We've been able to combine with Kyprolis as well as with VALCADE.

謝謝，克里斯。對於伊伯多胺，我的看法是，我們如何前進以及如何向上發展是一個循序漸進的過程。如果您還記得，在 ASCO 和 ASH 的最近幾次會議上，我們已經能夠展示伊伯多胺的整體概況。由於其耐受性好，因此組合性良好。所以我們已經能夠與dara結合了。我們已經能夠與 Kyprolis 以及 VALCADE 結合。

So this is just one of the first studies that we have launched in the Phase III setting in the randomized trials. As you know, there's a Phase II study that is also ongoing, doing a head-to-head comparison of Revlimid versus iberdomide in Europe through [E&M]. And we will get to see the data that will form the basis of the future Phase III trial there. And there will be other studies that will be coming through where you'll start to see the comparisons versus the IMiDs as well.

因此，這只是我們在隨機試驗的 III 期環境中啟動的首批研究之一。如您所知，一項 II 期研究也在進行中，通過 [E&M] 在歐洲對來那度胺 (Revlimid) 與伊伯多胺 (iberdomide) 進行頭對頭比較。我們將在那裡看到構成未來第三階段試驗基礎的數據。並且還會有其他研究進行，您將開始看到與 IMiD 的比較。

We'll now take the next question from Luisa Hector at Berenberg.

現在我們將回答貝倫貝格 (Berenberg) 的路易莎·赫克托 (Luisa Hector) 提出的下一個問題。

I wanted to come back to deucravacitinib. You talked about a potential launch in the second half of next year. Is that a delay?

我想回到 deucravacitinib。您談到了明年下半年可能推出的產品。這是延遲嗎？

And I know previously, you've commented on your plans to build out your dermatology sales force towards the end of this year. Is that still the plan? Or does that shift slightly into next year?

我知道之前，您曾評論過在今年年底前建立皮膚科銷售隊伍的計劃。這仍然是計劃嗎？或者這種情況會稍微轉移到明年嗎？

Thanks, Luisa. Let me say we're really excited getting ready for deucrava. There is no delay. But I'll ask Samit to give you more perspective, and then Chris will talk about commercial preparation.

謝謝，路易莎。讓我說，我們真的很興奮為 deucrava 做好準備。沒有延遲。但我會請薩米特給你更多的觀點，然後克里斯將談論商業準備。

Sure. Thanks, Giovanni. And Luisa, thanks for your question as well. There is one thing that we need to remember, that this is an NDA, not an sNDA and certainly, 2 very large studies. This is a priority for the company. We are certainly looking forward to launching in the second half of next year. And certainly, we will share the acceptance of the file as the file is validated by the regulatory agencies. There is no other way to say it, we are excited about the data with the efficacy and the safety that we've shared before.

當然。謝謝，喬瓦尼。路易莎，也謝謝你的提問。我們需要記住一件事，這是一項 NDA，而不是 sNDA，當然，這是兩項非常大的研究。這是公司的首要任務。我們當然期待在明年下半年推出。當然，當文件經過監管機構驗證時，我們將分享該文件的接受情況。沒有其他方式可以說，我們對我們之前分享的有效性和安全性數據感到興奮。

Yes. And what I would say in terms of the commercial and medical build-out is that's well underway. We feel very good about where we are and the quality of the teams that we've been able to put in place. Medical has been in place for a number of months, and I would say those teams have very deep dermatology experience. We obviously have our key internal roles that have been filled and are in the process of building out launch planning.

是的。我想說的是，商業和醫療建設正在順利進行。我們對自己所處的位置以及我們所組建的團隊的質量感到非常滿意。醫療已經到位好幾個月了，我想說這些團隊擁有非常深厚的皮膚科經驗。顯然，我們的關鍵內部角色已經填補，並且正在製定啟動計劃。

Our plan is and has been to build out the sales teams in the second half of this year. We feel very good about where we are in that timing. And our anticipation is that we're going to be ready for launch whenever the approval comes. And so really no change in how we're thinking about building out the commercial teams.

我們的計劃是並且一直是在今年下半年建立銷售團隊。我們對當時所處的位置感覺非常好。我們的預期是，只要獲得批准，我們就準備好發布。因此，我們對建立商業團隊的思考方式確實沒有改變。

We'll now take the next question from Steve Scala of Cowen.

現在我們將回答 Cowen 的 Steve Scala 提出的下一個問題。

I have a few questions. Regarding the Factor XIa BTE total knee replacement Phase II data, Samit, you said that the trial showed exactly what was expected. Can you remind us of what you expected? For instance, did you expect 0 bleeds?

我有幾個問題。關於因子 XIa BTE 全膝關節置換術 II 期數據，Samit，您說試驗完全符合預期。您能提醒我們您的期望嗎？例如，您期望 0 流血嗎？

Second, has the FDA asked any questions on deucravacitinib CV risk? And if so, what was the nature of those questions? And then lastly, do you expect an FDA panel for mavacamten?

其次，FDA 是否詢問過有關 deucravacitinib CV 風險的問題？如果是這樣，這些問題的本質是什麼？最後，您是否期望 FDA 設立 mavacamten 小組？

Thank you, Steve. Let me ask Samit to address all 3 of your questions.

謝謝你，史蒂夫。讓我請薩米特回答您的所有 3 個問題。

Yes. So for Factor XIa, Steve, what -- when I say we got what we wanted, it was a multi-arm study where we looked at single daily dose as well as BID, and it was a dose range. What we wanted from the study is to give us an inkling on: number one, the safety profile that we were observing; as well as to see what is the dose that we should take to Phase III. And that's what we intended from the study, and that's what we got.

是的。因此，對於 XIa 因子，史蒂夫，當我說我們得到了我們想要的東西時，這是一項多臂研究，我們研究了單日劑量和 BID，這是一個劑量範圍。我們希望從這項研究中獲得一些線索：第一，我們觀察到的安全狀況；以及看看我們應該在第三階段服用多少劑量。這就是我們研究的目的，也是我們得到的結果。

And plus, we wanted to see the therapeutic index, overall what dose range one can use in the future programs. And that's what we got. Now of course, you'll hear more as the data are presented later this year, but this is where we started off in the TKR study, and that's what we got.

另外，我們希望了解治療指數，以及在未來的項目中可以使用的總體劑量範圍。這就是我們得到的。當然，隨著今年晚些時候公佈的數據，您會聽到更多信息，但這就是我們 TKR 研究的起點，也是我們得到的結果。

On the deucrava study that you asked about, what -- the cardiovascular risk question, et cetera, from the regulatory agencies, of course, we will not comment on our conversations with the regulatory agencies. Having said that, you've seen the data. We've shown what -- the nonexistence of the cardiovascular risk in the follow-up that we have for deucravacitinib, and we are very pleased with the profile that we currently have, which is very differentiated.

關於您詢問的德烏克拉瓦研究，監管機構提出的心血管風險問題等等，當然，我們不會評論我們與監管機構的對話。話雖如此，你也看到了數據。我們已經證明，在 deucravacitinib 的隨訪中不存在心血管風險，我們對目前的情況非常滿意，這是非常差異化的。

On the mavacamten side, once again, not commenting on the regulatory strategies and regulatory conversations. But we continue to look forward to the PDUFA date in January, and we are certainly very excited with the data on that side as well.

在 mavacamten 方面，再次不對監管策略和監管對話發表評論。但我們仍然期待 1 月份的 PDUFA 日期，我們當然也對這方面的數據感到非常興奮。

We'll now take the next question from Matthew Harrison at Morgan Stanley.

現在我們將回答摩根士丹利的馬修·哈里森提出的下一個問題。

Great. I guess 2 for me, following up on a couple of questions from before. On Factor XI, can you just maybe put the secondary stroke trial into context? What is a good outcome from that study when we see the results later this year? And then second, on the CELMoDs, especially now that you have some data in-house, what do you see as the quickest sort of regulatory plan to get that to market?

偉大的。我猜對我來說是 2，跟進之前的幾個問題。關於因素 XI，您能否將二次中風試驗放在背景中？當我們今年晚些時候看到結果時，這項研究的良好結果是什麼？其次，關於 CELMoD，特別是現在您擁有一些內部數據，您認為將其推向市場的最快監管計劃是什麼？

Thanks, Matthew. Let me ask Samit to address both of your questions.

謝謝，馬修。讓我請薩米特回答你的兩個問題。

Thank you, Matt. For Factor XIa, from the secondary stroke prevention, the aim of the trial is to be able to see if Factor XIa can be combined with a background therapy of anti-platelet agents. And that's what we are looking forward to. Because, as you recall, Factor Xa inhibitors that are out there have a higher risk of bleeding when they are combined with anti-platelet therapy. So that's what a good outcome would look like, if we can actually manage that risk profile that is there. And that will then pave the way for taking it forward into indications that are to be discussed with our partners and of course, with the agencies in the future.

謝謝你，馬特。對於因子XIa，從卒中二級預防來看，試驗的目的是看看因子XIa是否可以與抗血小板藥物的背景治療相結合。這就是我們所期待的。因為，正如您所記得的，現有的 Xa 因子抑製劑與抗血小板治療聯合使用時出血的風險更高。如果我們能夠真正管理那裡的風險狀況，那麼這就是一個好的結果。這將為將其轉化為與我們的合作夥伴以及未來各機構討論的跡象鋪平道路。

For CELMoD, as Giovanni already shared with -- in his prepared remarks, we've seen the data from the Phase II trial of iberdomide. We are looking forward to having those conversations with the health agencies based on the overall response rate data and the overall profile that we have for iberdomide. And then that will pave the way for seeing if we can bring the drug to market with these data or not. And we'll share those as we know more.

對於 CELMoD，正如 Giovanni 在他準備好的發言中所分享的那樣，我們已經看到了伊伯多胺 II 期試驗的數據。我們期待根據總體響應率數據和我們對伊伯多胺的總體概況與衛生機構進行這些對話。然後，這將為我們是否可以利用這些數據將藥物推向市場鋪平道路。當我們了解更多時，我們將分享這些內容。

Let me just say that with CELMoDs, we have been discussing the progress with this platform for some time. And I think it's really good to be seeing now that we have 4 -- 5 of those agents in the clinic. And the iberdomide data is really the beginning of looking at really important proof-of-concept data on a number of assets. And I'm really pleased that this platform is progressing so well. I think it's going to be really important for us going forward.

我只想說，對於 CELMoDs，我們已經討論這個平台的進展有一段時間了。我認為現在看到我們診所有 4 - 5 種這樣的藥物真是太好了。伊伯多胺數據實際上是研究許多資產的非常重要的概念驗證數據的開始。我真的很高興這個平台進展順利。我認為這對我們的未來非常重要。

We'll take the next question from Matt Phipps at William Blair.

我們將回答威廉·布萊爾的馬特·菲普斯提出的下一個問題。

Another Factor Xa -- or XIa question. Do you have any thoughts on the recent antibody results in total knee arthroplasty that were published in New England Journal of Medicine last week? Obviously saw a nice VTE prevention but no real difference in bleeding rates, which might be expected given that was a smaller size study.

另一個因素 Xa 或 XIa 問題。您對上週發表在《新英格蘭醫學雜誌》上的全膝關節置換術中的抗體結果有何看法？顯然，VTE 的預防效果很好，但出血率沒有真正的差異，考慮到這是一項規模較小的研究，這可能是預料之中的。

And then I guess just any general thoughts on antibody versus small molecule approach? And then lastly, can you just confirm if any additional clinical studies for deucra, whether it be a longer follow-up or any healthy participant data with BDI or anything, is needed prior to submission?

然後我想對抗體與小分子方法有什麼一般性的想法嗎？最後，您能否確認在提交之前是否需要對 deucra 進行任何額外的臨床研究，無論是更長的隨訪時間還是 BDI 或其他任何健康參與者數據？

Thank you. Samit?

謝謝。薩米特？

Let me start on the Factor XIa. I will hold myself from commenting on anybody else's studies. But certainly, there is the specificity of the antibodies that we have to keep in mind. On the other hand, you have to keep in mind the oral versus IV aspect of things and oral versus subcutaneous, which will be very important in the future development and the patient burden as well as the health care system. So we'll need to continue to monitor that. And then we'll compare the results when full results are available for our program and then other programs as well as we take into account Phase III development.

讓我從 XIa 因子開始。我不會評論任何人的研究。但當然，我們必須牢記抗體的特異性。另一方面，你必須記住口服與靜脈注射以及口服與皮下注射，這對於未來的發展、患者負擔以及醫療保健系統都非常重要。因此我們需要繼續監控這一情況。然後，當我們的項目獲得完整結果時，我們將比較結果，然後與其他項目以及我們考慮到第三階段的開發進行比較。

For deucravacitinib, as we have previously talked about, we are looking forward to the approval in the second half of next year. So we are not waiting for additional studies from that perspective unless, of course, they become a part of the conversations with the health agencies.

對於deucravacitinib，正如我們之前談到的，我們期待明年下半年獲得批准。因此，我們不會等待從這個角度進行更多研究，當然，除非它們成為與衛生機構對話的一部分。

We'll now take the next question from Dane Leone at Raymond James.

現在我們將回答 Raymond James 的 Dane Leone 提出的下一個問題。

Appreciate the updates across the portfolio. Just one quick one, to wrap things up, on Factor XIa. How do you see the program evolving? Obviously, you seem -- you sound encouraged by the results you have in-house that will be presented later on TKR. But are you going to take additional compounds into the clinic? You recently published a paper on 724296 that looked promising. Just thinking about your competitors and the multipronged approach they're taking versus how you see that program expanding over time.

感謝整個產品組合的更新。就 XIa 因子而言，我只是簡單地總結一下。您如何看待該計劃的發展？顯然，您似乎對稍後將在 TKR 上公佈的內部結果感到鼓舞。但是您打算將其他化合物帶到診所嗎？您最近在 724296 上發表了一篇看起來很有前途的論文。只需考慮您的競爭對手以及他們正在採取的多管齊下的方法，以及您如何看待該計劃隨著時間的推移而擴展。

Thank you for the question. For Factor XIa, we are pleased with the profile that we have thus far for Factor XIa that is in the clinic already, the Milvexian molecule. We do have a backup, but that is progressing, as one would always have a backup plan, at its own pace. We are not accelerating that. We are looking forward to seeing the data for the secondary stroke prevention study early next year, and that would then pave the way for a Phase III program. Nothing more to add from that perspective at this time.

感謝你的提問。對於因子 XIa，我們對迄今為止已在臨床中使用的因子 XIa（Milvexian 分子）的概況感到滿意。我們確實有一個備份，但這正在取得進展，因為人們總是會按照自己的節奏制定備份計劃。我們並沒有加速這一進程。我們期待明年初看到二級中風預防研究的數據，這將為第三階段計劃鋪平道路。從這個角度來看，目前沒有什麼可補充的。

Thank you, Samit, and thank you all for joining us today. As we've discussed throughout the call, we had a very successful quarter. We delivered strong results consistent with our strategy by continuing to grow revenue, execute on new launches and advance our pipeline.

謝謝薩米特，也感謝大家今天加入我們。正如我們在整個電話會議中所討論的那樣，我們度過了一個非常成功的季度。通過繼續增加收入、執行新產品發布並推進我們的產品線，我們取得了符合我們戰略的強勁業績。

I'm proud of what our team have accomplished so far this year, including the attainment of several important milestones. And I'm really encouraged by what we are doing for patients. I believe we're very well positioned for the future.

我對我們的團隊今年迄今為止所取得的成就感到自豪，包括實現了幾個重要的里程碑。我們為患者所做的一切讓我深受鼓舞。我相信我們已經為未來做好了充分的準備。

I'd like to thank everybody for participating in the call. And of course, our team is available to answer any additional questions you may have. Thank you, and have a good day.

我要感謝大家參與這次電話會議。當然，我們的團隊可以回答您可能有的任何其他問題。謝謝你，有一個美好的一天。

That concludes today's call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。