施貴寶 (BMY) 2022 Q3 法說會逐字稿

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

您好，歡迎參加百時美施貴寶第三季業績電話會議。今天的會議正在錄製。

At this time, I would like to turn the conference over to Mr. Tim Power, Vice President of 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。先生，請繼續。

Thanks, Dennis, and good morning, everyone. Thanks for joining us this morning for our third quarter 2022 earnings call.

謝謝，丹尼斯，大家早安。感謝您今天上午參加我們的 2022 年第三季財報電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in today's call are Chris Boerner, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. As you'll note, we've posted slides to bms.com that you can follow along with for Giovanni and David's remarks.

今天早上與我一起發表準備好的發言的還有我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio)；以及我們的財務長David Elkins。參加今天電話會議的還有我們的首席商業化長 Chris Boerner；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。正如您所注意到的，我們已將幻燈片發佈到 bms.com，您可以關注 Giovanni 和 David 的演講。

But before we get going, I'll read our forward-looking statements. During this call, we 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.

但在我們開始之前，我會先讀我們的前瞻性聲明。在本次電話會議中，我們對公司未來計畫和前景所做的陳述構成了前瞻性陳述。由於各種重要因素（包括公司向美國證券交易委員會提交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有重大差異。

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.

這些前瞻性陳述代表我們截至今天的估計，不應被視為代表我們對任何未來日期的估計。我們明確表示不承擔更新前瞻性聲明的任何義務，即使我們的估計發生變化。

We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of certain 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。某些非 GAAP 財務指標與最具可比性的 GAAP 指標的對帳表可在 bms.com 上查閱。

With that, I'll hand it over to Giovanni.

說完這些，我就把它交給喬瓦尼。

Thank you, Tim, and good morning, everyone.

謝謝你，提姆，大家早安。

Starting on Slide 4. I'm pleased to share that we delivered another good quarter, and we continue to advance our strategy to position Bristol-Myers Squibb for sustainable growth.

從幻燈片 4 開始。

In the third quarter, our in-line and new product portfolio grew by 13% adjusting for foreign exchange, and we delivered non-GAAP EPS growth of 3%, while also making substantial progress advancing our promising pipeline.

第三季度，經外匯調整後，我們的現有產品和新產品組合成長了 13%，非公認會計準則每股收益成長了 3%，同時我們在推進有前景的產品線方面也取得了實質進展。

Highlights for the quarter included the approval of Sotyktu, our first-in-class TYK2 inhibitor for psoriasis, and closing of our Turning Point acquisition, which brings another product to our portfolio with repotrectinib expected to launch in the second half of next year.

本季度的亮點包括我們用於治療銀屑病的首創 TYK2 抑制劑 Sotyktu 獲得批准，以及我們完成對 Turning Point 的收購，這將為我們的產品組合帶來另一種產品，repotrectinib 預計將於明年下半年推出。

Overall, I am very pleased that we have significantly advanced the renewal of our portfolio. We have now launched 9 new medicines with 3 first-in-class products approved this year alone.

總體而言，我很高興我們顯著推進了產品組合的更新。我們現在已經推出了9種新藥，其中光是今年就有3種首創產品獲得批准。

Let me take a minute to discuss our new products on Slide 5. Our strategy is to accelerate a diversified portfolio of innovative medicines to market, to renew our business and grow the company during the period of Revlimid exclusivity loss and beyond.

讓我花一點時間討論一下幻燈片 5 上的新產品。

Supporting this strategy, we delivered 3 key new products this year: Opdualag, Camzyos and Sotyktu. Each is a first-in-class asset, and these products have the potential to contribute meaningfully to our growth.

為了支持這項策略，我們今年推出了 3 款主要新產品：Opdualag、Camzyos 和 Sotyktu。每一種都是一流的資產，這些產品都有可能為我們的成長做出有意義的貢獻。

Opdualag marks the second approved I-O combination that we delivered. Its strong launch continued during the quarter, furthering our leadership in delivering innovative cancer treatments to patients well into the next decade.

Opdualag 是我們交付的第二個經批准的 I-O 組合。本季度，該產品繼續保持強勁推出，進一步鞏固了我們在未來十年為患者提供創新癌症治療的領導地位。

We're also encouraged with the progress we have made towards building our foundation for Camzyos as a specialty cardiovascular medicine. We are seeing increasing numbers of patients initiating therapy, and their feedback has been very positive. David will provide more details on the launch in a moment.

我們也對在為 Camzyos 作為專業心血管藥物奠定基礎方面取得的進展感到鼓舞。我們看到越來越多的患者開始接受治療，他們的回饋非常積極。 David 稍後將提供有關此次發布的更多細節。

Sotyktu has been approved with a label that reflects its profile, and as an oral of choice medicine for moderate-to-severe plaque psoriasis. We are very encouraged by the early days of this launch and see significant benefit to these patients with this important new option.

Sotyktu 已獲批准，其標籤反映了其特性，並被批准作為治療中度至重度斑塊狀乾癬的首選口服藥物。我們對此次上市的初期感到非常鼓舞，並看到這一重要的新選擇為這些患者帶來了顯著的益處。

Combined with our other launch products, these approvals represent a significant milestone in the renewal of our portfolio, allowing multiple avenues for growth in the second half of the decade and beyond.

與我們其他已推出的產品結合，這些產品的核准代表著我們產品組合更新的一個重要里程碑，為未來五年及以後的成長提供了多種途徑。

Turning to our scorecard on Slide 6. During the quarter, we made great progress on our pipeline milestones. Abecma is now the first BCMA CAR T to have demonstrated superiority to standard regimens in relapsed and refractory multiple myeloma based on the positive top line results of KarMMa-3.

轉到幻燈片 6 上的記分卡。 Abecma 是目前第一個根據 KarMMa-3 的積極頂線結果證明在復發和難治性多發性骨髓瘤治療中優於標準方案的 BCMA CAR T。

We also presented exciting data for Milvexian, which has exhibited an approximate 30% relative risk reduction in recurrent symptomatic ischemic strokes on top of dual antiplatelet therapy. It has also shown a safety profile that is differentiated to existing anticoagulants.

我們也展示了 Milvexian 令人興奮的數據，該藥物在雙重抗血小板療法的基礎上，使復發性症狀性缺血性中風的相對風險降低了約 30%。它也表現出與現有抗凝血劑不同的安全性。

We believe this asset has great potential as a next-generation antithrombotic treatment, and we look forward to initiating Phase III trials soon. Samit can provide you with the scientific details during our Q&A.

我們相信該資產作為下一代抗血栓治療具有巨大潛力，我們期待很快啟動第三階段試驗。 Samit 可以在我們的問答過程中為您提供科學細節。

Turning to Slide 7. You can see several important pipeline catalysts ahead. These include key approvals as well as important registrational data readouts, including the COMMANDS study for Reblozyl.

翻到第 7 張投影片。其中包括關鍵批准以及重要的註冊資料讀數，包括 Reblozyl 的 COMMANDS 研究。

As you will recall, we've said that our early pipeline would generate multiple proof-of-concept data sets over time. Importantly, we are expecting proof-of-concept data for some exciting assets from our early pipeline in the near-term. This data could support transitions of early-stage assets over to full development, thereby strengthening our mid- to late-stage pipeline.

您可能還記得，我們​​說過，我們早期的管道將隨著時間的推移產生多個概念驗證資料集。重要的是，我們期待近期從我們的早期管道中獲得一些令人興奮的資產的概念驗證數據。這些數據可以支持早期資產向全面開發的過渡，從而加強我們的中後期管道。

Some examples include our BCMA T cell engager for multiple myeloma. We believe this could be a differentiated asset, and we expect to present the data at ASH in December. Our second-generation LPA1 agent for pulmonary fibrosis, the unmet need in this disease is very high and should Phase II data be supportive, this asset could move into Phase III trials next year.

一些例子包括我們用於治療多發性骨髓瘤的 BCMA T 細胞接合劑。我們相信這可能是一種差異化資產，我們預計將於 12 月在 ASH 上公佈數據。我們的第二代 LPA1 藥物用於治療肺纖維化，這種疾病的未滿足需求非常高，如果 II 期數據支持，該資產可能會在明年進入 III 期試驗。

Our androgen receptor degrader is generating some early promising data, and we hope to transition the asset to full development next year. This highlights the breadth of our protein homeostasis platform beyond cell modes, including in solid tumors.

我們的雄激素受體降解劑正在產生一些早期有希望的數據，我們希望明年將該資產轉變為全面開發。這凸顯了我們的蛋白質穩態平台超越細胞模式的廣度，包括實體腫瘤。

These examples demonstrate the power of our R&D engine with a new wave of innovative and differentiated medicines emerging, which have the potential to treat patients with high unmet medical needs. We look forward to updating you on our portfolio of mid-stage assets going forward.

這些例子證明了我們研發引擎的強大力量，新一波創新和差異化藥物正在湧現，這些藥物有可能治療高度未滿足的醫療需求的患者。我們期待向您通報我們今後中期資產組合的最新情況。

With this in mind, let me move to Slide 8 to give you a perspective on how we are thinking about our business moving forward. With continued strong performance of our in-line business, and our 9 launches now in full commercial execution, our priorities have not changed: delivering the full commercial value of the 9 launch products, expanding the opportunity for these assets through new indications, and advancing our mid-stage pipeline.

考慮到這一點，請允許我轉到投影片 8，向您介紹我們如何思考未來的業務發展。隨著我們的在研業務繼續保持強勁表現，以及我們 9 款產品現已全面投入商業化執行，我們的首要任務沒有改變：實現 9 款產品的全部商業價值，透過新的適應症擴大這些資產的機會，並推進我們的中期產品線。

Additionally, we will continue to leverage our financial strength and flexibility to prioritize business development opportunities. As we deliver on renewing our portfolio and transforming our company with a younger and more diversified business, I am confident in the future of Bristol-Myers Squibb.

此外，我們將繼續利用我們的財務實力和靈活性來優先考慮業務發展機會。隨著我們更新產品組合並向更年輕、更多元化的業務轉型，我對百時美施貴寶的未來充滿信心。

We now have critical mass across all 4 of our therapeutic areas. Each has foundational in-line brands, exciting new products and a broadening mid- to late-stage pipeline. This is important because we believe that this more diversified business of younger products, supported by constant innovation and focus in therapeutic areas where we have real expertise, best position us to navigate the changing U.S. environment.

如今，我們在所有四個治療領域都已達到臨界規模。每家公司都擁有基礎品牌、令人興奮的新產品和不斷擴大的中後期產品線。這一點很重要，因為我們相信，這種更加多樣化的年輕產品業務，加上不斷創新和專注於我們真正擅長的治療領域，最能讓我們應對不斷變化的美國環境。

Before I turn it over to David, I want to thank our employees for their relentless focus on delivering for the patients we serve. I am confident we will continue to deliver for patients and our shareholders.

在把時間交給戴維之前，我想感謝我們的員工不懈地致力於為病人提供服務。我相信我們將繼續為患者和股東提供服務。

I will now turn it over to David to walk you through the financials. David?

現在我將把話題交給 David，讓他向大家介紹財務狀況。戴維？

Thank you, Giovanni, and thanks again for joining our third quarter earnings call.

謝謝你，喬瓦尼，再次感謝您參加我們的第三季財報電話會議。

Let's turn to Slide 10 to discuss our top line performance. Unless otherwise stated, I will discuss sales performance growth rates on an underlying basis, which excludes the impacts of foreign exchange.

讓我們翻到投影片 10 來討論我們的頂線表現。除非另有說明，我將在基本基礎上討論銷售業績成長率，即不包括外匯的影響。

Revenues in the third quarter were approximately $11.2 billion, consistent with prior year. Our diversified in-line and new product portfolio grew strongly, up 13%, offsetting the impact of our recent LOEs.

第三季營收約112億美元，與去年同期持平。我們多元化的線上和新產品組合成長強勁，上漲了 13%，抵消了近期 LOE 的影響。

Now let me touch on our performance of our new product portfolio on Slide 11. Global revenues were over $550 million, up 66% versus prior year, driven by continued demand. Growth over prior quarter was also strong, up 16%. We continue to be very pleased with the performance of our new product portfolio and its future potential.

現在，讓我談談第 11 張投影片上我們新產品組合的表現。與上一季相比，成長同樣強勁，達 16%。我們對我們的新產品組合的表現及其未來潛力感到非常滿意。

With 3 new launch brands this year and over $2 billion of annualized revenue so far, our portfolio has been largely derisked, increasing our confidence in the potential to generate greater than $25 billion of nonrisk-adjusted revenues in 2029.

今年我們推出了 3 個新品牌，迄今為止的年收入已超過 20 億美元，我們的投資組合風險已基本降低，這讓我們對 2029 年創造超過 250 億美元非風險調整收入的潛力更加有信心。

Turning to Slide 12 to discuss our performance of our solid tumor portfolio, Opdivo sales continue to grow globally, up 13%, driven by demand for our newly launched in core indications. In the U.S., sales were strong.

我們來看投影片 12，討論我們實體瘤產品組合的表現，Opdivo 的全球銷售額持續成長 13%，這得益於我們新推出的核心適應症產品的需求。在美國，銷售強勁。

We continue to grow double digits, up 17% versus prior year, driven by demand of our newer metastatic and adjuvant indications, partially offset by declining second-line eligibility as well as some use from Opdualag in first-line melanoma.

我們繼續保持兩位數的成長，較上年增長 17%，這主要得益於我們較新的轉移性和輔助適應症的需求，但二線治療合格率的下降以及 Opdualag 在一線黑色素瘤治療中的部分使用在一定程度上抵消了這一增長。

Internationally, revenues grew 8%, primarily due to growth from new indications, particularly first-line lung and GI cancers. Looking forward, we continue to expect growth of Opdivo from our new and expanding indications in both early and late-stage cancers.

在國際方面，收入增長了 8%，主要歸因於新適應症的增長，特別是一線肺癌和胃腸道癌。展望未來，我們繼續預期 Opdivo 將會因在早期和晚期癌症領域的新適應症和不斷擴大的適應症而實現成長。

Now let's move to Opdualag. We cannot be more pleased with the launch of Opdualag. The launch is off to a great start, being the first LAG-3 inhibitor to launch in fixed-dose combination with our PD-1 inhibitor, Opdivo. Sales in the quarter were $84 million, growing 45% sequentially, and sales of Opdualag are already annualizing to approximately $350 million.

現在讓我們前往奧普杜阿格。我們對 Opdualag 專案的啟動感到非常高興。此次上市開局良好，成為第一個與我們的 PD-1 抑制劑 Opdivo 以固定劑量組合形式推出的 LAG-3 抑制劑。本季銷售額為 8,400 萬美元，比上一季成長 45%，Opdualag 的年銷售額已達到約 3.5 億美元。

At this point in the launch, our share in first-line melanoma is in the mid- to high teens. And as expected, we are seeing use of Opdualag coming from PD-1 monotherapy and Opdivo + Yervoy combinations.

在目前的發布階段，我們在一線黑色素瘤領域的份額處於中高水平。如預期，我們看到 Opdualag 的使用來自 PD-1 單藥療法和 Opdivo + Yervoy 組合。

Moving on to our expanded cardiovascular portfolio on Slide 13. Our leading OAC, Eliquis, had another strong quarter, up 16% year-over-year. In the U.S., sales increased 31% versus prior year, driven primarily by demand and favorable gross-to-net adjustments. As expected, sequential performance was driven by the typical dynamics we experienced each year from higher gross-to-net payments, as patients enter the donut hole.

接下來是幻燈片 13 上我們擴展的心血管產品組合。在美國，銷售額較上年增長了 31%，主要原因是需求和有利的毛利與淨利調整。正如預期的那樣，隨著患者進入甜甜圈洞，連續表現受到我們每年經歷的典型動態的推動，即總支付額與淨支付額之間的比例增加。

Internationally, Eliquis has become a leading OAC across numerous countries. Given the success of the product, pricing pressures, as expected, impede growth. Pricing measures in addition to at-risk generic entry in the U.K., Netherlands, affected growth in the quarter.

在國際上，Eliquis 已成為許多國家領先的 OAC。鑑於該產品的成功，定價壓力正如預期的那樣阻礙了成長。除英國和荷蘭的仿製藥進入風險外，定價措施也影響了本季的成長。

Now turning to Camzyos, a first-in-class medicine to treat underlying disease of obstructive hypertrophic cardiomyopathy. We are continue to be pleased with the progress we are making to bring this life-changing medicine to patients.

現在轉向 Camzyos，一種治療阻塞性肥厚型心肌病變潛在疾病的同類首創藥物。我們為將這種改變生活的藥物帶給患者所取得的進展感到非常高興。

To date, we have over 2,000 REMS-certified health care professionals, which is a good indicator for intent to treat. And we've received extremely positive feedback from physicians and patients. We are also making progress at large HCM centers to ensure they are operationalized to make Camzyos available to patients. As of the end of Q3, there are over 1,100 patients enrolled in our hub and growing each week.

到目前為止，我們擁有超過 2,000 名 REMS 認證的醫療保健專業人員，這是意向治療的良好指標。我們收到了來自醫生和患者的非常正面的回饋。我們也在大型 HCM 中心取得進展，以確保它們能夠投入運營，讓患者能夠使用 Camzyos。截至第三季末，我們的中心已有超過 1,100 名患者登記，每週都在增加。

As expected, new patients are generally initiating treatment as part of their regularly scheduled echocardiograms. Based on the time to transition patients to commercially dispense medicine, we expect acceleration of revenue beginning in Q4 and as we move into 2023. Chris can provide more details on the launch during Q&A, but we are pleased with the progress we have made.

正如預期的那樣，新患者通常會在定期進行心臟超音波檢查的同時接受治療。根據患者過渡到商業化配藥的時間，我們預計從第四季度開始到 2023 年，收入將加速增長。

Turning to Slide 14 to discuss hematology's performance, starting with Revlimid. Sales in the quarter were approximately $2.4 billion. Sales were primarily impacted by generic entry, particularly in international markets.

轉到投影片 14 討論血液學的表現，從 Revlimid 開始。本季銷售額約為 24 億美元。銷售主要受到仿製藥進入的影響，尤其是在國際市場。

In the U.S., we saw slower than anticipated entry by second wave generics in September. We expect to see generic erosion progressively increasing in the coming weeks. And at this point, we expect Revlimid sales to be at the upper end of our $9 billion to $9.5 billion range for the year.

在美國，我們看到 9 月第二波仿製藥的進入速度比預期的要慢。我們預計未來幾週通用侵蝕將逐漸加劇。目前，我們預計 Revlimid 的年銷售額將達到 90 億至 95 億美元的上限。

Pomalyst global revenues grew 8% versus prior year, primarily driven by demand for triple-based regimens in earlier lines, extending the duration of treatment for patients.

Pomalyst 全球營收較前一年成長 8%，主要受早期三重方案需求推動，延長了患者的治療時間。

Moving to Reblozyl, which had another strong quarter. Sales were $190 million in the quarter, up 22% versus prior year. In the U.S., revenue growth was impacted by a onetime change in distribution model in the prior year.

轉向 Reblozyl，該公司又度過了一個強勁的季度。本季銷售額為 1.9 億美元，較上年成長 22%。在美國，收入成長受到前一年分銷模式一次性變化的影響。

Excluding the impact from last year, sales would have been approximately 25% versus prior year. This is being driven by continued progress in increasing patient adherence, and extending treatment duration.

除去去年的影響，銷售額將比前一年增長約 25%。這是由於在提高患者依從性和延長治療時間方面不斷取得進展所推動的。

Outside of the U.S., Reblozyl continues to grow driven by demand in both MDS and beta thalassemia associated anemia. To date, we are now reimbursed in 9 countries, and we'll continue to secure reimbursement in additional countries in the future.

在美國以外，Reblozyl 繼續成長，受到 MDS 和β地中海貧血相關貧血的需求所推動。到目前為止，我們已在 9 個國家獲得報銷，未來我們將繼續在其他國家獲得報銷。

Now turning to our cell therapy assets, Abecma and Breyanzi. Abecma generated strong revenues in the quarter of $107 million. This represents growth of 59% versus prior year or 22% sequentially.

現在來談談我們的細胞治療資產，Abecma 和 Breyanzi。 Abecma 本季的營收強勁，達到 1.07 億美元。這比去年同期增長了 59%，比上一季增長了 22%。

In the U.S., sales growth was driven by strong demand, offset primarily by timing of patient infusions, which we expect to materialize in Q4.

在美國，銷售成長主要受強勁需求推動，但主要受到患者輸液時間的影響，我們預計患者輸液時間將在第四季度實現。

Outside of the U.S., sales increased due to a onetime step-up of slots in select markets, which is expected to be sustained at this level for the foreseeable future.

在美國以外，由於特定市場的一次性提升，銷售額增加，預計在可預見的未來將維持在這個水平。

We are very pleased with the manufacturing progress we've made to ensure Abecma gets to more patients, while we continue to work on further expanding our capacity. As we prepare to move Abecma into earlier lines based upon the positive readout of KarMMa-3.

我們對所取得的生產進展感到非常滿意，這將確保 Abecma 能夠惠及更多患者，同時我們將繼續致力於進一步擴大我們的產能。我們準備根據 KarMMa-3 的積極讀數將 Abecma 移至早期線路。

Finally, on Breyanzi, sales in the quarter were $44 million, up 50% versus prior year. Demand remains strong, and we continue to work hard expanding capacity in the next year to benefit more patients with large B-cell lymphoma. As we communicated in the past, we expect Q4 sales to be largely similar to Q3 sales.

最後，Breyanzi 本季的銷售額為 4,400 萬美元，比上年增長 50%。需求依然強勁，我們將在明年繼續努力擴大產能，以造福更多大B細胞淋巴瘤患者。正如我們過去所傳達的那樣，我們預計第四季度的銷售額將與第三季的銷售額大致相同。

Now turning to our expanded immunology portfolio on Slide 15. Starting with Zeposia. Global sales in the quarter was $69 million, up 83% versus prior year, largely due to the expansion of Zeposia in ulcerative colitis.

現在轉到幻燈片 15 上我們擴展的免疫學產品組合。本季全球銷售額為 6,900 萬美元，較上年增長 83%，這主要歸功於 Zeposia 在潰瘍性結腸炎領域的擴張。

Sequentially, in the U.S., the sales were impacted by last quarter's favorable gross-to-net and wholesaler buying patterns of approximately $20 million. We continue to see demand growth of 12% over last quarter.

其次，在美國，上個季度有利的毛利與淨利以及批發商購買模式對銷售額產生了約 2000 萬美元的影響。我們繼續看到需求比上一季成長 12%。

Our strategy remains focused on further expanding volume so we can continue to improve access in 2023, and we made progress on improving the quality of access as well.

我們的策略仍然專注於進一步擴大數量，以便我們能夠在 2023 年繼續改善訪問，並且我們在提高訪問品質方面也取得了進展。

Internationally, we are continuing to make strides in securing reimbursement in additional markets to get Zeposia to more patients living with MS and ulcerative colitis.

在國際上，我們正​​在繼續努力爭取在其他市場獲得報銷，以便讓更多患有 MS 和潰瘍性結腸炎的患者能夠使用 Zeposia。

Now turning to our most recent launch, Sotyktu, our first-in-class selective TYK2 inhibitor for patients with moderate-to-severe plaque psoriasis. We're extremely pleased with the U.S. label based upon the strong data.

現在來談談我們最近推出的產品 Sotyktu，這是我們的首創選擇性 TYK2 抑制劑，適用於中度至重度斑塊狀乾癬患者。基於強有力的數據，我們對美國標籤感到非常滿意。

While early in the launch, we are very encouraged by the feedback we are getting from physicians. Our focus is to ensure many patients as possible get Sotyktu, establishing this medicine as the oral of choice allowing us to secure broader formulary position in 2024.

雖然還處於發布初期，但我們對來自醫生的回饋感到非常鼓舞。我們的重點是確保盡可能多的患者能夠獲得 Sotyktu，將這種藥物確立為首選口服藥物，從而使我們能夠在 2024 年獲得更廣泛的處方地位。

Internationally, we are also pleased to have received Japanese approval in September, and we look forward to European approval next year.

在國際上，我們也很高興9月獲得了日本的批准，並期待明年獲得歐洲的批准。

Let's now discuss our third quarter P&L on Slide 16. The I've already discussed revenues, so I'll now focus on other key non-GAAP items in the quarter. Gross margins decreased primarily due to product mix, partially offset by foreign exchange and related hedging settlements.

現在讓我們討論幻燈片 16 上的第三季損益表。毛利率下降主要由於產品結構下降，部分被外匯和相關避險結算所抵銷。

Excluding acquired in-process R&D, operating expenses were broadly in line with prior year, and affected by the timing of spend. Acquired in-process R&D charges in the quarter were $30 million related to an upfront payment to GentiBio. This was offset by $73 million of licensing income benefiting OI&E in the quarter.

除收購的在研發外，營業費用與去年大致持平，並受到支出時間的影響。本季發生的在研發費用為 3,000 萬美元，與向 GentiBio 支付的預付款有關。但該季度 OI&E 獲得了 7,300 萬美元的許可收入，抵消了這一差額。

The third quarter effective tax rate was 16.9%, driven by earnings mix. And overall, we delivered another quarter of earnings growth with non-GAAP earnings per share growing 3% versus prior year.

受獲利組合的影響，第三季有效稅率為 16.9%。整體而言，我們又實現了一個季度的獲利成長，非公認會計準則每股收益較上年增長 3%。

Moving to the balance sheet and capital allocation on Slide 17. Cash flow from operations in the quarter were $3.7 billion. The company's balance sheet remains strong with approximately $9 billion in cash and marketable securities on hand as of September 30, which also accounts for the $3.3 billion we paid for Turning Point Therapeutics.

前往投影片 17 上的資產負債表和資本配置。該公司的資產負債表仍然強勁，截至 9 月 30 日，庫存現金和有價證券約為 90 億美元，也佔了我們為 Turning Point Therapeutics 支付的 33 億美元。

Our capital allocation priorities remain unchanged. Business development continues to be a top priority, and we continue to execute on this strategy with the closing of Turning Point Therapeutics acquisition as a recent example.

我們的資本配置重點維持不變。業務發展仍然是我們的重中之重，我們將繼續執行這項策略，最近完成對 Turning Point Therapeutics 的收購就是一個例子。

We remain committed to continued debt reduction. In the quarter, we repaid $2.8 billion of debt, and we remain committed to returning capital to shareholders. We executed a $5 billion ASR earlier this year, and have $9.5 billion remaining in our share via authorization, and we will continue to be opportunistic on share repurchases.

我們仍然致力於繼續減少債務。本季度，我們償還了 28 億美元的債務，我們仍然致力於向股東返還資本。我們今年稍早執行了 50 億美元的 ASR，並且透過授權剩餘 95 億美元的股份，我們將繼續抓住機會進行股票回購。

Now turning to our 2022 non-GAAP guidance on Slide 18. We are maintaining our full year outlook. We continue to expect revenues to be approximately $46 billion with our in-line and new product portfolio growing in the low double-digit range. Our recent LOE guidance and Revlimid guidance remain unchanged.

現在轉到第 18 張投影片上的 2022 年非 GAAP 指引。我們繼續預計收入將達到約 460 億美元，其中我們的現有產品和新產品組合將以低兩位數的速度成長。我們最近的 LOE 指導和 Revlimid 指導保持不變。

However, as mentioned earlier, we expect Revlimid sales to be in the upper end of the $9 billion to $9.5 billion range. We continue to expect gross margin to be approximately 79%, and our operating expenses, excluding acquired in-process R&D remain unchanged, primarily driven by favorability in FX as well as cost discipline, partially offset by the inclusion of expenses from the Turning Point acquisition.

然而，如前所述，我們預計 Revlimid 的銷售額將在 90 億美元至 95 億美元之間。我們繼續預期毛利率約為 79%，而我們的營業費用（不包括收購的在研研發）保持不變，這主要受到外匯有利因素以及成本控制的推動，但被 Turning Point 收購費用納入其中所部分抵銷。

Putting everything I just mentioned together, we are reaffirming our full year non-GAAP EPS guidance, reflecting the strength of our underlying business and absorbing the approximate $0.06 impact from Turning Point acquisition.

綜合我剛才提到的所有內容，我們重申全年非 GAAP 每股收益指引，這反映了我們基礎業務的實力，並吸收了 Turning Point 收購帶來的約 0.06 美元的影響。

Before we move over to Q&A session, I want to express my gratitude to our employees for the performance in the quarter and their continued commitment to our patients.

在我們進入問答環節之前，我想對我們的員工在本季度的表現以及他們對患者的持續承諾表示感謝。

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

現在我將把電話轉回喬瓦尼和提姆進行問答環節。

Great. Thanks very much, David. Dennis, can we go to the first question, please?

偉大的。非常感謝，大衛。丹尼斯，我們可以開始第一個問題嗎？

The first question comes from the line of Chris Schott with JPMorgan.

第一個問題來自摩根大通的 Chris Schott。

Just 2 for me. I guess, first on Sotyktu. Given the favorable label, can you just talk about the target patient population you're going to be going after here? So specifically, are you going to be looking mostly at Otezla failures initially? Are you going to focus more, I guess, on first-line patients starting on systemic therapy?

對我來說只要 2 個。我想，首先是 Sotyktu。鑑於這個有利的標籤，您能談談您將要針對的目標患者群體嗎？那麼具體來說，您最初會主要關注 Otezla 的失敗嗎？我想，您會更關注開始全身治療的第一線患者嗎？

I know you've talked a little bit also here about reimbursement dynamics. But is there anything you do to accelerate this process prior to this kind of 2024 time line that you've been kind of alluding to?

我知道您在這裡也談論了一些有關報銷動態的問題。但是，在您提到的 2024 年時間表之前，您是否採取了什麼措施來加速這一進程？

And then the second quick one was just on Eliquis. I think we've had a few quarters now where we're seeing kind of a positive price adjustment. I just was wondering, if you can elaborate a little bit on the dynamics there? And is this something that's more onetime in nature and will reverse? Or is this kind of just a new base we should think about for the business, so we think what kind of volume growth going forward?

然後第二個快速問題是有關 Eliquis 的。我認為我們已經有幾個季度看到了某種積極的價格調整。我只是想知道，您是否可以詳細說明那裡的動態？這是否是本質上一次性的事情並且會逆轉？或者這只是我們應該為業務考慮的一種新基礎，那麼我們思考未來的數量會有什麼樣的成長？

Thank you, Chris. Chris Boerner will start and then David will give you some comments on Eliquis.

謝謝你，克里斯。首先由 Chris Boerner 主持，然後 David 會對 Eliquis 發表一些評論。

So let's start with Sotyktu. Thanks for the question, Chris. First, I think the launch of Sotyktu is off to an very good start. We're extremely happy with what we're hearing back from physicians. We've seen a very nice week-over-week acceleration of this product.

那麼讓我們從 Sotyktu 開始。謝謝你的提問，克里斯。首先，我認為Sotyktu的推出有一個很好的開始。我們對醫生的回饋感到非常高興。我們看到該產品的周環比增長非常強勁。

The majority of the use right now that we're getting is coming from the community setting. That's really important because, Chris, as you may know, about 80% of the volume in the setting is going to be in the community.

目前，我們獲得的大部分使用都來自社區環境。這真的很重要，因為克里斯，你可能知道，大約 80% 的設定量將發生在社區中。

And so to see that level of uptake there early on is nice to see. Also, remember that the awareness of this product in the academic community going into the launch was very high. So the fact that we've got good uptake early in the days of this launch coming from the community is a good early start.

因此，很高興看到早期的吸收水平如此之高。另外，請記住，該產品在發佈時學術界的認知度非常高。因此，我們在發布初期就得到了社區的積極回應，這是一個很好的開始。

In terms of the patient population that we're looking at, we're actually going to be focused on the dynamic portion of this population, which includes both initial starts in the first-line setting as well as any of those failures who were coming off of Otezla.

就我們關注的患者群體而言，我們實際上將重點關注該群體的動態部分，其中包括一線治療中的初始患者以及任何停止使用 Otezla 治療並失敗的患者。

We're also seeing some early switching, though that's again very early days. But I would say that the primary focus of this launch continues to be squarely on Otezla. I mean that would be patients who would have gone on to Otezla in the absence of TYK2 as well as for those patients who have either failed that product or physicians decide to switch given the efficacy profile that we're seeing with Sotyktu.

我們也看到了一些早期的轉變，儘管這還處於早期階段。但我想說，此次發布的重點仍然放在 Otezla 上。我的意思是，這些患者將在沒有 TYK2 的情況下繼續使用 Otezla，以及那些對該產品無效的患者，或者醫生根據 Sotyktu 的療效情況決定改用該產品的患者。

In terms of what we're seeing on the access side, our focus continues to be threefold on access: first, removing the market -- new-to-market blocks that face all new products in this space; second, taking advantage of where we have open access today, and remember, we estimate that about 10% of patients have open access at the initial stages of this launch; and then obviously, it's all about building volume during the early phases of the launch and then leveraging that volume.

就我們在進入方面看到的情況而言，我們的重點仍然是三方面的：首先，消除市場——該領域所有新產品面臨的新市場障礙；第二，利用我們今天的開放取用優勢，記住，我們估計在啟動初期大約有 10% 的患者可以開放取用；顯然，這一切都是為了在發布的早期階段建立銷量，然後利用該銷量。

We're going to do everything we can to accelerate getting into a better access position in 2023. But we certainly feel like we're in a very good position and on track to be in a good position in 2024. David?

我們將竭盡全力，加快在 2023 年進入更好的訪問位置。

Yes. On the Eliquis rebates, remember, this is a very large product over $10 billion in revenue. And based upon the product mix, we forecast what the anticipated discounts will be based upon the product mix across all the payers. And each quarter, we adjust that, some quarters are up and some quarters are down. But the last 2 quarters we had some releases, and that's what really explains it. But nothing changes for the full year, really.

是的。關於 Eliquis 折扣，請記住，這是一個收入超過 100 億美元的非常大的產品。根據產品組合，我們預測所有付款人的產品組合將會帶來多少折扣。每個季度我們都會進行調整，有些季度上升，有些季度下降。但最近兩個季度我們發布了一些產品，這才是真正的原因。但實際上，全年並沒有什麼改變。

Your next question is from the line of Seamus Fernandez with Guggenheim Securities.

您的下一個問題來自古根漢證券公司的 Seamus Fernandez。

So a couple of quick questions. So the first one is just on the competitive landscape that's evolving in ulcerative colitis. Can you guys just give us a sense of how the launch of Zeposia is tracking in MS versus UC? And what percentage of patients are you seeing specifically at this point as we look at the sort of separation of scripts? And how you're thinking about the competitive landscape evolving with the increasing interest from physicians and IL-23, perhaps even the combination of IL-23s with biosimilars Humira as a potential new breakthrough in the category? Just wondering, what you guys were thinking coming out of the most recent meeting as well.

我有幾個簡單的問題。第一個問題是關於潰瘍性結腸炎的競爭格局演變。你們能否向我們介紹一下 Zeposia 在 MS 和 UC 上的發布情況？當我們考慮處方分離時，您目前具體接待了多少比例的患者？隨著醫生對 IL-23 的興趣日益增加，您如何看待競爭格局的變化，甚至 IL-23 與生物相似藥 Humira 的結合是否可能成為該類別的一個新突破？只是想知道，你們在最近的會議中想到了什麼。

And then just the last second question is on the Camzyos launch. Just trying to get a sense of when you guys anticipate seeing a meaningful inflection in prescriptions or revenue. Is this something where we should anticipate seeing a meaningful uptick in the fourth quarter? Or is it potentially with the new indication in the middle of next year?

最後一個問題是關於 Camzyos 的發布。只是想了解你們預計何時會看到處方或收入的有意義的變化。我們是否應該預期第四季會出現有意義的上漲？或者是否有可能在明年年中出現新的跡象？

Thanks, James. So Chris and Samit will address your question on UC, and then Chris will comment on Camzyos.

謝謝，詹姆斯。因此 Chris 和 Samit 將解答您關於 UC 的問題，然後 Chris 將對 Camzyos 發表評論。

Sure. Thanks for the question, Seamus. With respect to Zeposia, I would say Zeposia continues to perform well. We saw a nice double-digit demand growth in the quarter. The majority of that growth is continuing to come from ulcerative colitis. So I would say that the majority of patients, if you look at where the growth of this asset is going to occur through the end of this year, and certainly as we get into next year, the majority of that's going to be coming from UC.

當然。謝謝你的提問，Seamus。對於 Zeposia，我想說 Zeposia 繼續表現良好。本季我們看到了兩位數的良好需求成長。其中大部分的增長仍源自潰瘍性結腸炎。因此我想說的是，如果您觀察今年年底這項資產的成長情況，以及進入明年的情況，您會發現大多數患者都將來自 UC。

The market share that we have for Zeposia in MS continues to remain stable. Above 50% of the share in S1Ps is coming to Zeposia. We feel very good about the position that we're in there. Obviously, as we've talked about previously, the oral market in MS is under some pressure from IV. But in spite of that, we're maintaining a consistent share in the MS population.

Zeposia 在多發性硬化症 (MS) 市場的佔有率持續保持穩定。 S1P 中 50% 以上的份額流向了 Zeposia。我們對自己所處的地位感到非常滿意。顯然，正如我們之前談到的，多發性硬化症的口服藥物市場受到了來自靜脈注射的一些壓力。但儘管如此，我們在 MS 人口中仍然保持著穩定的比例。

The big focus that we have continues to be on UC. We believe that's where we have the strongest position as well as the biggest opportunities for growth. And I would say that there, I think that from a competitive standpoint, so far, the position for Zeposia continues to be strong. Obviously, it is a very competitive marketplace.

我們的重點依然是 UC。我們相信，這是我們最強的地位以及最大的成長機會。我想說的是，從競爭的角度來看，到目前為止，Zeposia 的地位仍然很強。顯然，這是一個競爭非常激烈的市場。

But for example, with the introduction of RINVOQ, the growth of RINVOQ has not largely come at the expense of Zeposia. In fact, we've maintained our position in that market in spite of the introduction of that new asset. Clearly, there are a number of dynamics that are going to continue to play out, but we feel pretty good about our competitive position as the first S1P in this market for UC.

但例如，隨著 RINVOQ 的推出，RINVOQ 的成長並沒有很大程度上以犧牲 Zeposia 為代價。事實上，儘管引入了新資產，我們仍然保持了在該市場的地位。顯然，有許多動態因素將繼續發揮作用，但作為 UC 市場上第一款 S1P，我們對自己競爭地位感到非常滿意。

The only other thing that I would note is that obviously, as we've said, the big focus we have with Zeposia is to build volume and then convert that volume into a stronger access position. We did get a very important early win on the access side in October with CBS, Inc. now covering Zeposia with 0 step edits. That's important because if you add that with the other plans that -- smaller plans that have covered Zeposia, we now have about 30 million covered lives and we're well on track to be in a good position with the other PBMs as we go into 2023.

我唯一要注意的另一件事是，顯然，正如我們所說的那樣，我們對 Zeposia 的重點是建立數量，然後將該數量轉化為更強大的訪問地位。 10 月份，我們確實在訪問方面取得了非常重要的早期勝利，CBS, Inc. 現在以 0 步驟編輯的方式報道了 Zeposia。這很重要，因為如果將其與其他計劃（已涵蓋 Zeposia 的小型計劃）相加，我們現在已覆蓋約 3000 萬人，並且我們有望在 2023 年與其他 PBM 一起處於良好地位。

And maybe I'll let Samit address the other part of that question, and then I'll pick up on Camzyos.

或許我會讓薩米特 (Samit) 來回答這個問題的另一部分，然後我再來談談 Camzyos。

Very briefly, Seamus, the way we think about it is that unmet medical need still remains very high in patients with ulcerative colitis. And certainly, new medicines are needed. As you know, we have our own clinical development plan ongoing with Sotyktu in ulcerative colitis. Two of the trials will read out from a proof-of-concept perspective in 2023 for CD and UC, UC would be in the second half of the year.

簡而言之，西莫斯，我們的想法是，潰瘍性結腸炎患者的未滿足的醫療需求仍然很高。當然，我們需要新的藥物。如您所知，我們正在與 Sotyktu 合作開展潰瘍性結腸炎的臨床開發計劃。其中兩項試驗將於 2023 年從概念驗證的角度針對 CD 和 UC 進行，而 UC 將在下半年進行。

And we will continue to explore if those trials then lead to future development as well as if combinations are going to be the possibilities of the future with standard of care or novel therapies. So more to come, but we need to first see the data.

我們將繼續探索這些試驗是否會帶來未來的發展，以及組合療法是否將成為未來標準治療或新療法的可能性。接下來還有更多內容，但我們首先需要查看數據。

And then picking back up on your question on Camzyos, I would just say at the outset, we are very pleased with the launch of Camzyos. We're seeing a really nice acceleration for this product in the second half.

然後回到你關於 Camzyos 的問題，我首先要說的是，我們對 Camzyos 的推出感到非常高興。我們看到這款產品在下半年呈現非常好的加速成長。

A few elements or color around that. First, we've talked about the importance of certified physicians. We now have over 2,000 REMS-certified physicians as of the end of the second quarter. We're seeing a nice healthy increase in that week-over-week. David referenced that as of the end of the third quarter, we had 1,100 patients who had been prescribed Camzyos. That's also seeing nice week-over-week increases.

周圍的一些元素或顏色。首先，我們討論了認證醫生的重要性。截至第二季末，我們目前擁有 2,000 多名 REMS 認證醫生。我們看到，週復一周，這一數字呈現良好的成長動能。大衛提到，截至第三季末，我們已有 1,100 名患者被處方 Camzyos。這也顯示出每週都有良好的成長。

I think we had referenced on the previous quarterly call that a big focus area has been helping some of the larger institutions build the infrastructure to support the use of this product. We've seen very significant improvement on that in recent weeks. And the pace of new starts that we're seeing is consistent with those accounts, in particular getting organized.

我想我們在上次季度電話會議上提到過，一個重點關注的領域是幫助一些較大的機構建立基礎設施來支援該產品的使用。最近幾週我們看到了非常顯著的改善。我們看到的新起點的步伐與這些帳戶一致，特別是組織起來的步伐。

Nearly all of the patients that we are seeing are going through our Camzyos patient hub, and that's really important because that will facilitate getting patients onto therapy and staying on therapy. And I think it's notable that of the patients who have had multiple dispenses thus far, none of them have dropped out therapy, which is a nice indicator of how well that hub is working.

我們看到的幾乎所有患者都會通過我們的 Camzyos 患者中心，這非常重要，因為這將有助於患者接受治療並堅持治療。我認為值得注意的是，到目前為止，在已經多次配藥的患者中，沒有一人放棄治療，這很好地表明了該中心的運作情況。

I think the question with respect to how fast we're going to see an acceleration of revenue kind of speaks to this question of access. Access, as anticipated, has not been a barrier with this launch. We now have about 50% of plans covering Camzyos. All of the patients who are covering Camzyos are being [PA-ed] to the label, which is a good indicator of a strong position.

我認為，有關我們將以多快的速度看到收入成長的問題，在某種程度上說明了這個訪問問題。正如預期的那樣，訪問並未成為這次發布的障礙。我們現在有大約 50% 的計劃涵蓋 Camzyos。所有使用 Camzyos 的患者都已通過 PA-ed 認證，這是強勢地位的良好指標。

And you will have seen on the slides that as of the end of the third quarter, about 1/3 of those 1,100 patients had converted to commercial drug. In October alone, we've seen an almost doubling of the number of commercial dispense that we saw in Q3. So we feel very good about the pace of this launch and what we're seeing in the second half, and happy obviously to provide additional color as this launch continues and we get into the fourth quarter call.

您會在幻燈片上看到，截至第三季末，這 1,100 名患者中約有 1/3 已轉用商業藥物。光是在十月份，我們就看到商業分送的數量幾乎是第三季的兩倍。因此，我們對此次發布的步伐以及下半年的前景感到非常滿意，並且很高興能夠在此次發布繼續進行以及進入第四季度電話會議時提供更多細節。

Your next question is from the line of Andrew Baum with Citi.

您的下一個問題來自花旗的 Andrew Baum。

You addressed Reblozyl in your prepared comments. I'm just curious, same topic on Onureg. Given the attractiveness of the drug as an oral alternative, I'm surprised it's not doing better, perhaps you could outline what are the barriers here and some of the key catalysts ahead?

您在準備好的評論中提到了 Reblozyl。我只是好奇，Onureg 上有同樣的話題。鑑於該藥物作為口服替代品的吸引力，我很驚訝它沒有表現得更好，也許你可以概述這裡的障礙是什麼以及未來的一些關鍵催化劑？

And then second, in relation to milvexian, the 200-milligram dose, the efficacy was inferior to placebo. There was some discussion about whether COVID could have impacted the rate of thromboembolic events during the initiation of that particular dosage. I wonder whether you had trial to characterize that particular dosing arm of the trial?

其次，與 milvexian 相比，200 毫克劑量的療效不如安慰劑。有人討論 COVID 是否會影響在開始服用特定劑量期間血栓栓塞事件的發生率。我想知道您是否進行過試驗來描述該試驗的特定劑量組？

Thanks, Andrew. Chris, why don't you start on Onureg and then Samit will answer the question on Reblozyl.

謝謝，安德魯。克里斯，你為什麼不從 Onureg 開始，然後薩米特會回答有關 Reblozyl 的問題。

Sure. The question on Onureg around some of the barriers that we're seeing. I would say that the biggest challenge with Onureg continues to be the proportion of patients who are getting intensive chemotherapy. As you know, those dynamics in the first-line setting here are continuing to evolve. We've seen a decrease in the U.S. mainly of the percentage of patients who go on to get intensive chemotherapy. And remember, the label is for patients who receive intensive chemotherapy and get a complete response.

當然。 Onureg 上的問題涉及我們所看到的一些障礙。我想說，Onureg 面臨的最大挑戰仍然是接受強化化療的患​​者比例。如你們所知，這裡一線環境中的動態正在持續發展。我們發現美國接受強化化療的患​​者比例下降。請記住，該標籤適用於接受強化化療並獲得完全緩解的患者。

Having said that, focus with Onureg continues to be on ensuring that we maximize the opportunity for maintenance. The maintenance share right now is about 50% to 60%. We think there's opportunity to continue over time to expand that maintenance market.

話雖如此，Onureg 的重點仍然是確保我們最大限度地利用維護機會。目前維護份額約50%到60%。我們認為，隨著時間的推移，維護市場仍有機會繼續擴大。

And for those patients who get intensive chemotherapy, get a complete response, go on to maintenance, the choice needs to be Onureg. So that's been the significant focus we have for the U.S. team.

對於那些接受強化化療、獲得完全緩解、持續維持治療的患者來說，需要選擇 Onureg。所以這是我們對美國隊關注的重點。

And then we continue to see very early stages of launch outside of the U.S. in markets like Germany and France, and the early uptake there has been good.

然後，我們繼續看到該技術在美國以外的德國和法國等市場處於非常早期的推出階段，而這些市場的早期採用情況良好。

And Andrew, thank you for the question on milvexian. Yes, certainly, we looked at the hypothesis around COVID, and the 200-milligram dose doesn't seem to be driven through there. But we are continuing to explore why the group stood out. But the point to be taken home, I think, remains that we have an eightfold dose range that is available to us for picking the right dose bond to Phase III trials, and we are in that place where we are now looking forward to initiation of the program in the next few months on the Phase III side with the 3 indications that we've spoken about before in AF, ACS and SSP.

安德魯，感謝您關於 milvexian 的問題。是的，當然，我們研究了有關 COVID 的假設，200 毫克的劑量似乎無法解決這個問題。但我們仍在繼續探索該團體脫穎而出的原因。但我認為，需要注意的一點仍然是，我們擁有八倍劑量範圍，可用於選擇與 III 期試驗相結合的正確劑量，我們現在正處於這個階段，我們期待在未來幾個月啟動 III 期試驗項目，其中包括我們之前談到的 AF、ACS 和 SSP 三種適應症。

The next question is from the line of Chris Shibutani with Goldman Sachs.

下一個問題來自高盛的 Chris Shibutani。

If I could ask a question about how you see dynamics in the multiple myeloma setting, particularly the interplay between CAR T therapies and with the anticipated arrival of bispecifics as an option. Could you perhaps talk about where you see the dynamics playing out in 2023?

我可以問一個問題，您如何看待多發性骨髓瘤的動態，特別是 CAR-T 療法之間的相互作用以及預期會出現的雙特異性抗體作為一種選擇。您能否談談您認為 2023 年的發展動態？

Secondly, on Opdualag, there has been a good revenue performance there. Can you remind us, what your strategy is for broadening those label opportunities, and when we might be able to see data to help build confidence in continued growth for that asset?

其次，奧普杜拉格盆地的收益表現良好。您能否提醒我們，您擴大這些標籤機會的策略是什麼，以及我們何時可以看到數據以幫助建立對該資產持續增長的信心？

Thank you, Chris. Samit?

謝謝你，克里斯。薩米特？

Sure. Thank you, Chris, for the question. On multiple myeloma, I think the starting point is that no matter how many therapies have been developed and become available, the disease remains uncured at this time. So there is an opportunity to continue to bring more transformative, more effective and safe therapies to these patients.

當然。謝謝克里斯提出的問題。關於多發性骨髓瘤，我認為起點是無論已經開發出多少種治療方法並可供使用，這種疾病目前仍無法治癒。因此，我們有機會繼續為這些患者帶來更具變革性、更有效和更安全的治療方法。

And in that regard, certainly, cell therapies have really brought in some transformation in terms of getting patients into a complete remission. And hopefully, those are very long lasting.

從這個方面來看，細胞療法確實在使患者完全緩解方面帶來了一些轉變。希望這些能夠持久。

Bispecific, as one has been approved today in the U.S. -- or yesterday in the U.S. and certainly in the EU as well, is a new armamentarium. Certainly brings a good efficacy. However, as you saw from the data that have been presented, there are opportunities to continue to improve on the safety profile, high rates of CRS are going to be problematic, as you also saw some of the statements made by thought leaders, and that's where differentiation will need to continue to occur.

雙特異性抗體如今已在美國獲得批准——或者昨天在美國獲得批准，當然在歐盟也同樣如此，它是一種新的武器。確實帶來了良好的功效。然而，正如您從已呈現的數據中看到的那樣，仍有機會繼續改善安全性，高 CRS 率將會帶來問題，正如您也看到的一些思想領袖所發表的言論，而這正是需要繼續進行差異化的地方。

We will be presenting our own data at ASH this year for a T cell engager, and you'll see that. I think the other way to look at it is the holistic development in multiple myeloma where we are also developing now initiated 3 Phase III trials with CELMoDs. And the future probably will look like a combination approaches of T cell engagers or cell therapies and how CELMoDs can be added to those.

我們將在今年的 ASH 上展示我們自己的 T 細胞接合劑數據，您將會看到這一點。我認為從另一個角度來看，多發性骨髓瘤的整體發展也正在與 CELMoD 合作進行，目前已啟動 3 個 III 期試驗。未來可能將會採用 T 細胞接合劑或細胞療法的組合方法以及如何將 CELMoD 添加到其中。

So we have a holistic approach of treating multiple myeloma and trying to get more and more patients into very long, durable complete responses and at some point, someday getting to a cure. Do you want to add something, Chris?

因此，我們採用整體方法來治療多發性骨髓瘤，並試圖讓越來越多的患者獲得非常長期、持久的完全緩解，並在某一天獲得治癒。克里斯，你還有什麼要補充嗎？

Sure. Maybe I'll just add that while bispecifics and CAR T both share, in this case, the target of BCMA, I think it's important to keep in mind they offer very different characteristics for patients, including the availability of the products, the duration of treatment, adverse event profile.

當然。我可能只想補充一點，雖然雙特異性抗體和 CAR-T 都以 BCMA 為目標，但我認為重要的是要記住它們為患者提供了非常不同的特性，包括產品的可用性、治療持續時間、不良事件概況。

And I think ultimately, as we've said repeatedly, the utility of BCMA CAR T and bispecifics is going to be unique to each patient and the setting that we're in. And we anticipate that these various patient factors are going to become increasingly important in determining how patients are treated.

我認為最終，正如我們反覆說過的那樣，BCMA CAR T 和雙特異性抗體的效用對於每個患者和我們所處的環境來說都是獨一無二的。

And then maybe before I turn it over to Samit about the expansion of Opdualag, let me just say, at the outset, we continue to be very impressed with the strong performance of Opdualag out of the gate. Our focus has been and will continue to be to target that PD-1 monotherapy population.

在我將奧普杜拉格監獄的擴張事宜轉交給薩米特之前，我想先說一下，首先，我們對奧普杜拉格監獄的強勁表現印象深刻。我們的重點一直是並將繼續是針對 PD-1 單一治療族群。

I think as David alluded to; we're seeing use of conversion of both Opdivo + Yervoy patients as well as PD-1 monotherapy to drive that use as of today. But as we think about the growth of this asset going forward, remember, where we sit today, PD-1 monotherapy is still about 20% of first-line metastatic melanoma. And that's the target for our commercial launch, and so we see continued opportunity to grow this asset through the end of this year and well into next year.

我認為正如大衛所提到的；截至目前，我們看到 Opdivo + Yervoy 患者以及 PD-1 單藥療法的轉化使用推動了這項使用。但是，當我們思考這項資產未來的成長時，請記住，目前的情況是，PD-1單一療法仍然佔一線轉移性黑色素瘤的20%左右。這是我們商業發布的目標，因此我們看到了在今年年底和明年之前繼續發展這項資產的機會。

And I think in addition to what Chris has just spoken about, there are obviously many other trials that are ongoing. In the Phase III setting, we've got the melanoma study, in the adjuvant setting as well as the CRC trial in the second line plus setting in MSS colorectal cancer.

我認為除了克里斯剛才談到的之外，顯然還有許多其他試驗正在進行中。在 III 期治療中，我們進行了黑色素瘤研究、輔助治療研究以及二線及 MSS 大腸直腸癌的 CRC 試驗。

And then looking into the continued enrollment in the Phase III portion -- or Phase II portion of non-small cell lung cancer randomized portion as well as the 2 studies ongoing in HCC and multiple other signal-seeking studies ongoing with our collaboration with investigators.

然後研究非小細胞肺癌隨機部分的 III 期或 II 期部分的持續招募情況，以及 HCC 中正在進行的 2 項研究和我們與研究人員合作進行的多項其他訊號搜尋研究。

So obviously, as the data emerges, we can take that program forward to multiple other indications.

因此顯然，隨著數據的出現，我們可以將該計劃推廣到其他多個領域。

The next question is from the line of Tim Anderson with Wolfe Research.

下一個問題來自 Wolfe Research 的 Tim Anderson。

Going back to mildexian. I'm just trying to understand why we haven't seen Phase III trial start yet. You've had the data for a number of months in something like atrial fibrillation. You didn't run Phase II, so there's no data specifically in that setting to analyze. You're in a race with other companies. So why haven't we seen anything posted yet? It's almost makes you wonder if FDA preventing you from advancing yet. And are there concerns or something like that.

回到米爾德西安。我只是想知道為什麼我們還沒有看到第三階段試驗開始。您已經獲得了數月有關心房顫動等疾病的數據。您沒有運行第二階段，因此沒有專門在該設定下的資料可供分析。您正在與其他公司競爭。那麼為什麼我們還沒有看到任何發布的內容？這幾乎讓你懷疑 FDA 是否會阻止你前進。是否存在擔憂或類似的事情。

And then second question is just a general pipeline one for Samit. It's been a pretty big positive news flow in 2022. I think there's the view that you go into more of a catalyst like period in 2023.

第二個問題對 Samit 來說只是一個一般的問題。 2022 年的利多消息相當多。

So Samit, what are the next 2 or 3 most important clinical catalysts coming up, let's say, over the next 12 months in your view?

那麼 Samit，您認為未來 12 個月內出現的最重要的 2 到 3 個臨床催化劑是什麼？

Thank you, Tim. Let me ask Samit to answer your question both on milvexian and the pipeline.

謝謝你，提姆。讓我請薩米特 (Samit) 回答您關於 milvexian 和管道的問題。

I just want to say, with respect to the pipeline, Tim, as I mentioned in my remarks, I think what's really exciting is that actually the mid-stage pipeline is beginning to accelerate and the number of catalysts there are really important. And that's why we highlighted that in my remarks, and we look forward to continuing to update you there.

我只想說，關於管道，蒂姆，正如我在發言中提到的那樣，我認為真正令人興奮的是，實際上中期管道正在開始加速，並且那裡的催化劑數量確實非常重要。這就是我們在我的發言中強調這一點的原因，我們期待繼續向你們通報最新情況。

And Tim, thank you for the question. I'm glad that you are as excited as us in terms of initiation of the Phase III program. Once the trial reads out, we have to get in touch with the health authorities, agree on the dose, agree on the overall trial design and then we can initiate the plans by submitting the protocols to IRBs, to ethics committees, to the institutions they have to go through before we can actually enroll patients.

提姆，謝謝你的提問。我很高興你們和我們一樣對第三階段計畫的啟動感到興奮。一旦試驗結果出來，我們必須與衛生當局取得聯繫，就劑量達成一致，就總體試驗設計達成一致，然後我們可以通過向IRB、倫理委員會和他們必須審查的機構提交方案來啟動計劃，然後我們才能真正招募患者。

So all of that is being worked through. We have our partner, Janssen and us. We're working very diligently, very closely to get the program started. In the next few months, you'll get to hear the initiation of the Phase III program for milvexian.

所以所有這些都在努力解決。我們有我們的合作夥伴 Janssen 和我們。我們正在非常勤奮、緊密地工作以啟動該計劃。在接下來的幾個月裡，您將會聽到 milvexian 第三階段計畫的啟動訊息。

In terms of the pipeline and what's the new catalyst in the next year or 2? I've talked about it before, and I think our pipeline is fortunately very full and each of the therapeutic areas has multiple opportunities beyond milvexian.

就管道而言，未來一兩年的新催化劑是什麼？我之前談過這個，我認為我們的產品線非常豐富，並且每個治療領域都有超越 Milvexian 的多個機會。

For example, in cardiovascular space that we've spoken about, I think we are looking forward to some of the readouts in the immunology space. as we think about cendakimab over the next couple of years for the ongoing eosinophilic esophagitis study as well as, I think Giovanni spoke about in his opening remarks, LPA1 proof-of-concept study. If that reads out and if the data's are similar to, from an efficacy perspective, what we saw a couple of years ago in 2018, the [Chess] publication, that could open up the doors if the safety profile is well managed.

例如，在我們談到的心血管領域，我認為我們期待免疫學領域的一些讀數。我們考慮在未來幾年內使用 cendakimab 進行正在進行的嗜酸性食道炎研究，以及我認為 Giovanni 在開幕詞中提到的 LPA1 概念驗證研究。如果結果正確，並且從功效的角度來看數據與我們幾年前在 2018 年看到的 [Chess] 出版物相似，那麼如果安全性得到良好的管理，這可能會打開大門。

In a similar way, we have repotrectinib that will be registered and hopefully available in the second half of next year for patients with non-small cell lung cancer with RAS mutations. And as the data emerges, there are a few transitions that could occur in 2023 as well from early to late development such as androgen receptor lag independent degrader or alnuctamab. And then, of course, there is the readout for the COMMANDS trial that we are anticipating for Reblozyl as well. So there are multiple other catalysts that are coming through in the pipeline in 2023.

類似地，我們的雷帕替尼也即將註冊，預計在明年下半年為 RAS 突變的非小細胞肺癌患者提供治療。隨著數據的出現，2023 年也可能會出現一些從早期到後期開發的轉變，例如雄激素受體滯後獨立降解劑或 alnuctamab。當然，我們也期待 Reblozyl 的 COMMANDS 試驗的讀數。因此，2023 年還會出現多種其他催化劑。

The next question is from the line of Stephen M Scala with Cowen.

下一個問題來自 Cowen 的 Stephen M Scala。

Revlimid continues to exceed expectations, presumably creating a tough compare for 2023. So I'm just wondering, at this point, are you comfortable with consensus looking for growth for Bristol overall next year? I know 2023 guidance will be issued next February. But if you could tell us whether you're comfortable or not willing to comment at this point, that would be helpful.

Revlimid 繼續超越預期，可能會為 2023 年帶來艱難的比較。 所以我只是想知道，在這一點上，您是否對明年布里斯托爾整體增長的共識感到滿意？我知道 2023 年指導方針將於明年 2 月發布。但如果您可以告訴我們您是否願意或不願意在此時發表評論，那將會很有幫助。

And then secondly, on branebrutinib, 3 programs were discontinued only RA remains. Why were the other programs discontinued and RA continues? If it was due to tox, can you specifically tell us whether it was liver tox?

其次，關於 branebrutinib，3 個項目已停止，僅剩下 RA 項目。為什麼其他專案都停止了，而 RA 仍繼續進行？如果是因為中毒引起的，您能具體告訴我們是否是肝毒嗎？

Thank you, Steve. I wanted to ask David to start on Revlimid and outlook, and then Samit will answer your question.

謝謝你，史蒂夫。我想請 David 開始討論 Revlimid 和前景，然後 Samit 會回答你的問題。

Thanks, Stephen. On Revlimid, as we said in my remarks, we still anticipate for the full year Revlimid to be in that $9 billion to $9.5 billion, more in the upper half of that range. But as we said all along, we're going to have quarter-to-quarter variability based upon how our generic volumes enter the market and timing from quarter-to-quarter.

謝謝，史蒂芬。關於 Revlimid，正如我們在評論中所說，我們仍然預計 Revlimid 全年銷售額將達到 90 億至 95 億美元，更接近該範圍的上半部分。但正如我們一直所說的那樣，根據仿製藥量進入市場的方式和季度間時間的變化，我們的季度間變化將存在。

So broadly, we're still in line with the forecast that we had provided before. As far as 2023 guidance, underlying business, we continue excluding foreign currency. As we see this year, we continue to be able to grow the business, and we'll provide an update on '23 guidance as we normally do on the Q4 call.

因此總體而言，我們仍然符合先前提供的預測。就 2023 年指引和基礎業務而言，我們將繼續排除外幣。正如我們今年所看到的，我們繼續能夠發展業務，並且我們將像往常在第四季度電話會議上一樣提供有關 23 年指引的更新。

Thanks, David. And just, Steve, on the branebrutinib side, it is certainly not the toxicity. We've set ourselves high bars for taking molecules into late-stage development, and we did not meet the high bar for those indications. The indication for RA is continuing, and we'll see what the data reads out. And based on that data, then we'll make a decision whether that should continue or not.

謝謝，大衛。史蒂夫，就 branebrutinib 方面而言，肯定不是毒性問題。我們為分子進入後期開發階段設定了很高的標準，但我們並未達到這些適應症的高標準。 RA 的跡象仍在繼續，我們將看看數據讀出什麼。根據這些數據，我們再決定是否要繼續。

Your next question is from the line of Luisa Hector with Berenberg.

您的下一個問題來自 Berenberg 的 Luisa Hector。

Maybe just to try again on the outlook for 2023. Is there anything more to say on Revlimid? You've had the guidance of $2 billion to $2.5 billion of erosion each year. Is that what you're expecting for next year?

也許只是為了再試一次 2023 年的前景。您的指導價格是每年 20 億到 25 億美元的侵蝕。這就是您對明年的期望嗎？

And then I wanted to try and clarify on some of the license income partly connected to your statements on IPR&D, but also when we look at that line within other operating income, royalties, license income does seem to be a step-up in Q3. So I'm just wondering, is that driven perhaps by the diabetes with Astra that's going particularly well on to future? Is there a one-off item within the line in Q3 or something a bit more sustainable that we should think about going forward?

然後，我想嘗試澄清一些授權收入，這部分與您關於智慧財產權與發展的聲明有關，但當我們查看其他營業收入、特許權使用費、授權收入中的那條線時，在第三季度似乎確實有所增加。所以我只是想知道，這是否可能是由阿斯特拉（Astra）治療糖尿病的未來前景特別好所致？第三季的產品線中是否存在一次性產品，或者是否存在一些更永續、值得我們考慮的產品？

Thank you, Luisa. So let me just reiterate. Nothing really changes with respect to 2023 in terms of our outlook, and that includes the fact that we continue to see approximately $2.5 billion of decline for Revlimid. But David can give you more insights into the second question you had.

謝謝你，路易莎。因此，請讓我重申。就我們的前景而言，2023 年沒有什麼真正變化，其中包括我們繼續看到 Revlimid 的銷售額下降約 25 億美元。但大衛可以對您的第二個問題提供更多見解。

Yes. On OI&E, it's a good question. A couple of good things that are going on there. One is that our royalties on PD-1 and diabetes continue to -- as those businesses grow, the royalties that we receive on those businesses continue to grow.

是的。關於 OI&E，這是一個很好的問題。那裡正在發生一些好事。一是我們在 PD-1 和糖尿病方面的特許權使用費持續增長——隨著這些業務的增長，我們從這些業務中獲得的特許權使用費也持續增長。

A couple of other things, if you just think about interest rates with our cash balance, interest income is increasing. But as you know, we've been stepping down and paying down our debt, so our interest expense has been declining. And some of our licensing income that we've seen come through has also improved.

另外，還有幾件事，如果你只考慮我們的現金餘額的利率，利息收入就會增加。但正如你所知，我們一直在減少並償還債務，因此我們的利息支出一直在下降。我們看到的一些許可收入也有所增加。

So you put all 4 of those factors together, and that's how we see the OI&E progressing better over time. Just to recall, there longer term as it relates to that royalty income, those royalty rates will step down on our diabetes franchise in '23 and going and '24 for PD-1. So we'll update you on that guidance when we do guidance on the fourth quarter call.

因此，將這 4 個因素放在一起，我們將看到 OI&E 隨著時間的推移而不斷取得更好的進展。回想一下，從長期來看，就特許權使用費收入而言，我們糖尿病特許經營權的特許權使用費率將在'23年下降，而 PD-1 的特許權使用費率將在'24年下降。因此，當我們對第四季度電話會議做出指引時，我們會向您更新該指引。

The next question is from the line of Terence Flynn with Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯弗林 (Terence Flynn)。

Maybe 2 for me. I was just wondering, first on Camzyos, just a clarification maybe for Chris. You mentioned that commercial access is improving this quarter relative to last quarter. I think you said something about doubling. So does that mean we should think about sales for 4Q in the $10 million range?

對我來說也許應該是 2。我只是想知道，首先關於 Camzyos，也許可以為 Chris 澄清一下。您提到本季的商業准入相對於上一季有所改善。我覺得您說過一些關於加倍的事情。那麼這是否意味著我們應該考慮第四季的銷售額在 1000 萬美元左右？

And then your T cell engager, the data we're going to see at ASH, maybe you could just remind us. I know you changed the formulation to a subcu there if you're confident you now have a go-forward dose and you're seeing less CRS than maybe you saw with the IV formulation, and if you expect to be competitive with teclistamab, which was just approved from J&J?

然後是您的 T 細胞接合劑，我們將在 ASH 上看到的數據，也許您可以提醒我們一下。我知道您將配方改為皮下注射，如果您有信心現在有了可用的劑量，並且您看到的 CRS 比使用 IV 配方時看到的要少，並且您預計與剛從強生公司批准的 teclistamab 具有競爭力？

Thank you. Chris, why don't you start on Camzyos and then Samit.

謝謝。克里斯，為什麼不先從 Camzyos 開始，然後再從 Samit 開始呢？

Sounds good. So Terence, thanks for the question. Let me clarify a few things. First, while we're not going to give specific product level guidance for the fourth quarter. What I would say is that we are very happy with the conversion and increasing conversion of patients on Camzyos to commercial drug.

聽起來不錯。所以，特倫斯，謝謝你的提問。讓我澄清一些事情。首先，我們不會給出第四季度具體的產品水準指引。我想說的是，我們對使用 Camzyos 的患者轉變為使用商業藥物的情況以及日益增多的情況感到非常高興。

Remember, as you think about this launch, you need to think about it in the context of how many physicians are REMS-certified. Our ability to then translate those physicians into getting patients into clinics and getting on therapy, we're seeing a nice increase week-over-week in terms of patients coming in at the top of the funnel, if you will. Because they're going into our hub, they're staying on therapy.

請記住，當您考慮這次發佈時，您需要考慮有多少醫生獲得了 REMS 認證。然後，我們就可以將這些醫生轉化為將患者帶到診所並接受治療的能力，如果你願意的話，我們可以看到，進入漏斗頂端的患者數量每週都在大幅增加。因為他們會進入我們的中心，所以他們會繼續接受治療。

And the fact that now we're converting those patients to commercial drug at a faster clip, I think it's a very good sign that this launch continues to accelerate in the fourth quarter. The only other thing to keep in mind is that because most patients will take some time to initiate therapy as well as work through the benefits verification and any appeals process, those patients are going to be on free drug for roughly 7 to 8 weeks. That time will decrease over time as we get PBM coverage decisions formally through the end of this year and into early next year.

事實上，我們現在正在以更快的速度將這些患者轉化為商業藥物，我認為這是一個非常好的跡象，表明這項發布將在第四季度繼續加速。唯一需要記住的是，由於大多數患者需要一些時間來開始治療以及完成福利驗證和上訴程序，因此這些患者將免費使用藥物約 7 到 8 週。隨著我們在今年年底至明年年初正式做出 PBM 覆蓋決定，這個時間將隨著時間的推移而減少。

But that's how you should think about the flow of patients and the sequence of patients. The really good news, though, is that we continue to see physician interest in this product. The feedback has been good. We're seeing week-over-week increases in patients at the top, and we're seeing a nice increase in conversion of patients going on to commercial drug. And we anticipate that continuing.

但您應該這樣考慮病人的流動和病人的順序。不過，真正的好消息是，我們繼續看到醫生對該產品感興趣。反饋很好。我們看到頂級患者的數量每週都在增加，而且我們看到使用商業藥物的患者轉換率也在大幅增加。我們預計這種情況將會持續下去。

And Terence, for the T cell engager, certainly we'll not get into the specifics of the data. But as you recall, with the IV formulation, we had very good efficacy that we had seen, but the toxicity profile was not acceptable and that's why we switched the subcutaneous. And the data will be presented. So certainly, after the presentation of the data, we are happy to get into dialogue as to what the data are and how we perceive them as we go forward.

特倫斯，對於 T 細胞接合器，我們當然不會深入討論數據的具體細節。但您還記得，採用靜脈注射劑型，我們看到了非常好的療效，但毒性是不可接受的，這就是我們改用皮下注射的原因。並會呈現數據。因此，在呈現數據之後，我們當然很樂意就數據是什麼以及我們今後如何看待數據展開對話。

The next question is from the line of Carter Gould with Barclays.

下一個問題來自巴克萊銀行的卡特·古爾德。

Great. And thanks for all the color on Camzyos. I have 2 more on that front, though, for Samit.

偉大的。並感謝 Camzyos 的所有色彩。不過，在這方面我還有 2 個給 Samit。

I guess, first off, we saw the nonobstructive trial design, the Phase III got posted. Just wonder -- but it's pretty sparse on details on how you're thinking about titration in the setting, given the Phase II work that was done here was more drug concentration dependent. Obviously, the REMS is more echo dependent. So just how you're thinking about titration in the nonobstructive setting?

我想，首先，我們看到了非阻塞性試驗設計，第三階段已經發布。只是好奇——但考慮到這裡進行的第二階段工作更多地依賴藥物濃度，您對如何考慮滴定設定的細節了解得相當少。顯然，REMS 更加依賴迴聲。那麼您如何考慮在非阻塞環境下進行滴定呢？

And then also on [224], how do you think about this? Should we be thinking about this as a backup to Camzyos? Or do you see this coexisting maybe in a different set of indications like HFpEF, et cetera?

然後還有[224]，您怎麼看待這一點？我們是否應該將其視為 Camzyos 的備份？或者您認為這兩種症狀可能共存於不同的症狀中，例如 HFpEF 等等？

Sure. Let me start with Camzyos first in the nonoperative hypertrophic cardiomyopathy. We are looking forward to initiation in terms of enrollment of patients in that Phase III study.

當然。讓我先從非手術性肥厚型心肌病變的 Camzyos 開始。我們期待著開始招募第三階段研究的患者。

The data that we had seen already in the Phase II are quite promising, looking at the impact on biomarkers and even in the longer-term follow-up of that trial. I can't give you the specifics on the titration at this time and certainly for future discussions. Once we have initiated the trial, we'll be able to talk more about it.

從對生物標記的影響，甚至對該試驗的長期追蹤來看，我們在第二階段已經看到的數據非常有希望。我現在無法向您提供有關滴定的具體信息，當然也不知道以後會如何討論。一旦我們開始試驗，我們就能進一步討論它。

For MYK-224, as you know, that we always want to have multiple shots. And this is a new molecule that we are developing. Certainly, the first trial that you'd probably see is going to be looking also at obstructive hypertrophic cardiomyopathy. And the reason for that is because we've got Camzyos data. We have in-house data the way we would want to compare the trial -- compare the drug and see what differentiation features that drug carries.

對於 MYK-224，如您所知，我們總是希望進行多次注射。這是我們正在開發的一種新分子。當然，您可能看到的第一個試驗也將研究阻塞性肥厚型心肌病變。原因是我們獲得了 Camzyos 數據。我們擁有內部數據，可以用它來比較試驗——比較藥物，看看該藥物具有哪些差異化特徵。

And then as we look to the future from a development perspective, we'll define which indications we want to pursue with MYK-224, which indication we want to replicate with Camzyos. We have not defined and decided yet on how we will develop 224. And certainly, when we have that, we'll get into that dialogue as well.

然後，當我們從發展的角度展望未來時，我們將確定我們想要用 MYK-224 追求哪些適應症，以及我們想要用 Camzyos 複製哪些適應症。我們尚未定義和決定如何開發 224 當然，當我們確定了這一點之後，我們也會開始對話。

The next question is from the line of Matthew Phipps with William Blair.

下一個問題來自威廉布萊爾的馬修菲普斯。

Just a quick one for me. Samit, there's been a couple of failures this year in EoE, where maybe the Phase II is a histological endpoint, but not the dyspepsia endpoint. Just maybe you can give us any comments on why you think IL-13 would be better suited to IL-13 both of those endpoints in your EoE Phase III?

對我來說這只是一個快速步驟。薩米特，今年 EoE 已經有幾次失敗了，其中 II 期可能是一個組織學終點，但不是消化不良終點。也許您可以給我們一些評論，說明為什麼您認為 IL-13 更適合您的 EoE III 期中的這兩個終點？

Sure. We can certainly -- the one that you're probably talking about is the one that we saw yesterday or day before for the EoE. Remember, the mechanism of action over there is the IL-5 inhibition as opposed to cendakimab, where it is the IL-13 inhibition.

當然。我們當然可以 - 您可能談論的是我們昨天或前天看到的 EoE。請記住，那裡的作用機制是 IL-5 抑制，而 cendakimab 則是 IL-13 抑制。

The differentiating feature also compared to some of the other drugs that are approved or have shown data. This is a direct inhibitor of IL-13 with a downstream effect of inhibition of both R1 and R2 receptors.

此差異特徵也與其他一些已獲批准或已顯示數據的藥物進行了比較。這是 IL-13 的直接抑制劑，具有抑制 R1 和 R2 受體的下游效應。

And we believe that the inhibition of both is important not only for decreasing the inflammation, but also for remodeling and reversing the fibrosis. We have seen this in the Phase II trial that was presented a while back for cendakimab, and that was the basis of taking this into a Phase III trial. And certainly, we'll be looking at this ratio in this trial as well. So in a couple of years when the trial reads out, we are hoping to be able to replicate and improve on the results of the Phase II study.

我們相信，抑制這兩種物質不僅對減少發炎很重要，而且對重塑和逆轉纖維化也很重要。我們在不久前針對 cendakimab 進行的 II 期試驗中看到了這一點，這是將其納入 III 期試驗的基礎。當然，我們也將在這次試驗中關注這個比例。因此，幾年後，當試驗結束時，我們希望能夠複製並改善第二階段研究的結果。

Next question is from the line of Colin Bristow with UBS.

下一個問題來自瑞銀的 Colin Bristow。

Maybe just a quick follow-up on Sotyktu. You previously talked about the strategy to build volume against established competitors with sort of free drug or bridging programs. Could you just give us some more specific details on what you are doing there just to help us think about the progression of the sales trajectory?

也許只是對 Sotyktu 的一個快速跟進。您之前談到利用免費藥物或過渡計劃來擴大銷量以對抗現有競爭對手的策略。您能否為我們提供一些更具體的細節，說明您在那裡做了哪些工作，以幫助我們思考銷售軌跡的發展？

And then just secondly, on the next-generation IMiD portfolio, what should we specifically expect to see at ASH with regards to iberdomide and mezigdomide?

其次，在下一代 IMiD 產品組合中，我們應該具體期待在 ASH 上看到有關伊伯多胺和美齊格胺的哪些內容？

Thanks, Colin. Chris, why don't you start on Sotyktu, and then Samit will take the IMiD.

謝謝，科林。克里斯，你為什麼不從 Sotyktu 開始，然後薩米特將接管 IMiD。

Sure. So as we think about the progression of Sotyktu, I think you start with a couple of things upfront. One is the profile of the drug. We've talked about that at some length that the fact that we have a very clean label here, it gives us the ability to tell a very strong story about 2 Phase III studies that directly show an efficacy improvement against the existing standard of care.

當然。因此，當我們思考 Sotyktu 的發展時，我認為您應該先考慮幾件事。一是藥品概況。我們已經詳細討論過這一點，事實上，我們在這裡有一個非常乾淨的標籤，它使我們能夠講述一個關於 2 個 III 期研究的非常有力的故事，這些研究直接顯示了相對於現有治療標準的療效改善。

So we've got a great efficacy message to tell, good safety profile, the value of this asset is very clear. We saw that coming into this launch, and all of the feedback that we've received from physicians thus far is consistent with that.

因此，我們得到了很好的功效訊息要傳達，良好的安全性，這項資產的價值非常明確。我們在這次發布會上看到了這一點，並且迄今為止我們從醫生那裡收到的所有反饋也與此一致。

The next important point is that we've got a very experienced team. They know this space well. So we've been able to penetrate where the vast majority of these patient sits, which is in the community setting. So we feel very good about that. The trick with this space because it is a heavily managed space is going to be that we do a few things really well.

下一個重點是我們擁有一支經驗豐富的團隊。他們非常熟悉這個地方。因此，我們已經能夠深入了解絕大多數患者所處的境況，即社區環境。因此我們對此感到非常高興。由於這個空間是嚴格管理的空間，因此這個空間的訣竅在於我們可以很好地完成一些事情。

Initially, we've got to remove new-to-market blocks. Those blocks are put in place for every new product in this space, and that's a big focus for us right now. We then have to take advantage of where access is open. And as I said earlier in response to the previous question, that's about 10% of patients. And so we're doing everything we can there.

首先，我們必須掃除新進入市場的障礙。這個領域中的每個新產品都配備了這些模組，這是我們目前的重點。然後我們必須充分利用開放的管道。正如我之前回答上一個問題時所說，這大約佔患者的 10%。所以我們正在盡一切努力。

But for the majority of patients, the focus is on building volume and then leveraging that volume to negotiate with PBMs to get you into a more favorable formulary position as soon as feasible.

但對於大多數患者來說，重點是增加數量，然後利用該數量與 PBM 進行協商，以盡快讓您獲得更有利的處方地位。

Because of the timing of this launch, we certainly missed the window by and large for negotiations this year. The focus will be on negotiating for 24 access. Though in response to Chris' earlier question, we're going to do everything we can to accelerate that.

由於此次發布的時間安排，我們顯然錯過了今年談判的大部分機會。重點將放在爭取 24 小時訪問權的談判上。不過，在回答克里斯之前的問題時，我們會盡一切努力來加快這一進程。

So that's really the focus that we have. We have a robust set of patient services that we can offer to patients to get them onto therapy. We give them both of initial free trial offer as well as a bridge program, and we would anticipate significant use of that bridge program to guide us into when we have a more favorable formulary position.

這確實是我們關注的重點。我們為患者提供一系列強大的服務，幫助他們接受治療。我們為他們提供了初始免費試用以及橋樑計劃，我們預計該橋樑計劃將廣泛使用，以指導我們何時獲得更有利的處方地位。

Yes. And just talking about ASH. In general, one of the things that you will be seeing over there is the presentation of the data for the expansion arm of mezigdomide in combination with dexamethasone in fifth line plus patient population. But in general, from multiple myeloma, we will also be presenting the data for our next CAR T, which is GPRC5D-targeted as well as for KarMMa-2, one of the arms which is looking at proof of concept in the post-transplant treatment setting. That data will also be presented at ASH in addition to alnuctamab, which is the T cell engager.

是的。只是談論 ASH。總的來說，您將在那裡看到的一件事是美齊多胺與地塞米松聯合用於第五線以上患者人群的擴展組的數據展示。但總的來說，對於多發性骨髓瘤，我們還將展示下一個 CAR T 的數據，該 CAR T 是針對 GPRC5D 的，也是針對 KarMMa-2 的，其中一個部門正在研究移植後治療環境中的概念驗證。除了 T 細胞接合劑 alnuctamab 以外，該數據也將在 ASH 上展示。

Next question is from the line of Evan Seigerman with BMO Cap.

下一個問題來自 BMO Cap 的 Evan Seigerman。

One on Abecma. Can you provide just some color as to when we may see the KarMMa-2 data? I know that the 270 press release late -- a medical meeting, and I see that there's now a green checkmark on your near-term catalysts?

一篇關於 Abecma 的文章。您能否提供一些關於我們何時可以看到 KarMMa-2 數據的詳細資訊？我知道 270 新聞稿已晚——一場醫學會議，我看到您的近期催化劑上現在有一個綠色複選標記？

And then also more broadly speaking, when you think about the evolution in the BCMA CAR T space, what do you -- how do you position Abecma versus, say, the competitors, especially with say, the Carvykti data on the horizon as well?

然後從更廣泛的角度來看，當您考慮 BCMA CAR T 領域的發展時，您會如何定位 Abecma 與競爭對手，尤其是考慮到 Carvykti 數據即將出現？

Thank you. Samit?

謝謝。薩米特？

Sure. I will start with that, Evan. And from a KarMMa-2 data presentation perspective, certainly, as I said earlier, those data will be there as a proof of concept with a longer follow-up at ASH meeting. And certainly, we've talked about what the initiation of the next trial based on those data would be with -- and that's what I think 270 Bio I talked about, how we intend to initiate a trial in the earlier setting. It is a differentiated way of looking at it. And more details will be available when we actually do launch the trial in terms of trial design and how we have thought about it.

當然。我先從這個開始，埃文。從 KarMMa-2 資料呈現的角度來看，正如我之前所說，這些資料將作為概念證明，並在 ASH 會議上進行更長期的追蹤。當然，我們已經討論了基於這些數據的下一次試驗的啟動方式——我想這就是我之前談到的，我們打算如何在早期環境中啟動一項試驗。這是一種差異化的觀察方式。當我們實際啟動試驗時，將會提供有關試驗設計和思考方面的​​更多詳細資訊。

In terms of the comparison of Abecma versus the data from Carvykti. Once again, as Chris has spoken about earlier, we do believe that Abecma remains a very differentiated asset from a safety profile perspective as well as the first CAR-T that has data as a randomized Phase III trial showing superiority to current standard of care. So that profile will continue to grow, and that profile will continue to improve hopefully. And that's why we are thinking of initiation of that early line trial in the post-transplant setting.

關於 Abecma 與 Carvykti 數據的比較。再一次，正如克里斯之前所說的那樣，我們確實相信，從安全性角度來看，Abecma 仍然是一種非常差異化的資產，同時也是第一個在隨機 III 期試驗中顯示出優於目前治療標準的 CAR-T。因此，該形象將會繼續成長，並且有望繼續改善。這就是為什麼我們考慮在移植後環境中啟動早期試驗。

Your next question is from the line of Dane Leone with RJF.

您的下一個問題來自 RJF 的 Dane Leone。

Congratulations on the results and progress this quarter. Two easy ones for me. Firstly, the launch of Opdualag has been going quite well. And looking into 2023, I think there's still some questions about the cannibalization potentially within the melanoma setting relative to Opdivo as the Street still expecting quite robust growth of Opdivo into next year. Could you just comment around what you're seeing as the launch starts to mature a little bit with Opdualag and whether your expectations are that's going to have limited impact in the utilization of Opdivo in the melanoma setting?

恭喜本季的業績和進展。對我來說兩個很容易。首先，Opdualag 計畫的啟動進展順利。展望 2023 年，我認為對於 Opdivo 在黑色素瘤領域的潛在蠶食仍存在一些疑問，因為華爾街仍然預計 Opdivo 在明年將實現相當強勁的成長。您能否評論一下隨著 Opdualag 的推出而開始逐漸成熟，您看到的情況，以及您是否預期這對 Opdivo 在黑色素瘤治療中的應用將產生有限的影響？

And then secondly, an easy one, are you expecting EMBARK results for Camzyos next year? Or is that being pushed to 2024?

第二，一個簡單的問題，您是否期待明年 Camzyos 的 EMBARK 結果？或是被延後到 2024 年？

Thank you, Dane. Chris, why don't you start?

謝謝你，丹恩。克里斯，你為什麼不開始呢？

Maybe I'll start with Opdualag and turn it over to Samit.

也許我會從奧普杜拉格開始，然後把它交給薩米特。

So what we're seeing right now, just to set sort of where we are with the Opdualag launches. We are sourcing roughly 50% to 60% of this business from PD-1 monotherapy and about 40% to 50% from Opdivo and Yervoy combination. That's slightly higher Opdivo + Yervoy cannibalization in the third quarter we had anticipated prelaunch. But we expect that to stabilize, and we would continue to expect that going forward, the majority of Opdualag business is going to come from PD-1 monotherapy.

所以我們現在看到的只是大致說明了 Opdualag 發射的情況。我們的業務中大約 50% 到 60% 來自 PD-1 單一療法，大約 40% 到 50% 來自 Opdivo 和 Yervoy 組合。這比我們在上市前預期的第三季 Opdivo + Yervoy 蠶食情況略高。但我們預計這種情況將會穩定下來，並且我們將繼續預計，未來 Opdualag 的大部分業務將來自 PD-1 單一療法。

Remember, in the market right now, as I said earlier, we've got about 20% market share for PD-1 monotherapy. That's roughly evenly split between Opdivo and KEYTRUDA. So the way I would think about the progression of Opdualag is, first and foremost, you will see some cannibalization of Opdivo and some of Yervoy as well.

記住，正如我之前所說，在目前的市場上，我們在 PD-1 單一療法中佔有約 20% 的市場份額。 Opdivo 和 KEYTRUDA 的份額大致相等。因此，我對 Opdualag 進展的看法是，首先，你會看到 Opdivo 和 Yervoy 的一些蠶食。

However, the vast majority of the use of this asset in the long run should continue to come from PD-1 monotherapy. Some of that will be Opdivo, some of that will be from a competitor. And as I think about the growth trajectory, that 20% share is the target for us of PD-1 monotherapy. That's where we think we should be getting the business. And the fact that we still have 20% of this market to go gives us confidence we can continue to grow this overall business going into 2023.

然而，從長遠來看，該藥物的絕大部分用途仍應來自 PD-1 單一療法。其中一些是 Opdivo，一些來自競爭對手。當我思考成長軌跡時，20% 的份額是我們 PD-1 單一療法的目標。我們認為我們應該從那裡開展業務。事實上，我們仍有 20% 的市佔率可供開發，這讓我們有信心在 2023 年繼續發展整體業務。

And just on EMBARK results, those are projected to be in 2024.

僅根據 EMBARK 的結果，預計這些將在 2024 年實現。

Your next question is from the line of Mohit Bansal with Wells Fargo.

您的下一個問題來自富國銀行的 Mohit Bansal。

So one clarification and one question, if I may. On Camzyos, Chris, I think you mentioned that 1/3 of the patients who are prescribed Camzyos are on commercial. But then you mentioned that in October, we have seen doubling of that. Can you please clarify what is doubling here, number of commercial patients or the funnel or prescribed prescription for Camzyos?

因此，如果可以的話，我想澄清一點並提出一個問題。關於 Camzyos，Chris，我想你有提到過，1/3 被處方 Camzyos 的病人是商業用藥。但您提到，十月份，我們看到這一數字翻了一番。您能否澄清一下這裡的倍增是指商業患者數量還是 Camzyos 的漏斗或處方？

And then the second part of the question is regarding milvexian. The indications you have mentioned, SSP and ACS, this seems to be a little bit of acute type of indications. So yes, the patient number are high, but duration of treatment may be smaller. I think that is only for a month or so after a stroke. So just trying to understand, how should we think about the opportunity in the acute type of settings?

問題的第二部分是關於 milvexian 的。您提到的適應症，SSP 和 ACS，這似乎是一些急性類型的適應症。所以是的，患者數量很高，但治療時間可能較短。我認為這只適用於中風後一個月左右的時間。所以只是想了解，我們該如何看待急性環境的機會？

Sure. Maybe I'll start on the Camzyos question. So let me just clarify the 1/3. Of the 1,100 patients, roughly 1,100 patients that we had as of the end, a 1/3 of those patients had dropped down to commercial drug, beyond commercial drug.

當然。也許我應該開始討論 Camzyos 的問題。因此，讓我澄清一下 1/3。在我們最終接診的 1,100 名患者中，大約有 1/3 的患者已經轉而使用商業藥物，甚至不再使用商業藥物。

And what I was referencing was in the first 3 weeks of October, we've seen an almost doubling of the number of commercial dispenses that took place through all of the third quarter. So that illustrates an important consideration for the trajectory of commercial sales here for this product, which is that we're starting to see an acceleration both in terms of the number of patients coming on to therapy and the pace at which those patients are converting down to commercial drug.

我指的是，在十月的前三週，我們看到整個第三季的商業發行數量幾乎翻了一番。這說明了對於該產品商業銷售軌蹟的一個重要考慮，即我們開始看到接受治療的患者數量和這些患者轉化為商業藥物的速度都在加速。

And on the milvexian side, although the words say acute coronary syndrome, but it doesn't mean that the treatment is only done in the acute setting or even for the secondary stroke prevention. Patients actually stay on antiplatelet regimens, for example, for a very long time on a chronic treatment period. And so in a similar way, milvexian is anticipated to be used in a chronic setting rather -- meaning the long duration of treatment rather than only in the acute phase.

而在 milvexian 方面，雖然字面上說的是急性冠狀動脈綜合徵，但這並不意味著治療僅在急性情況下進行，甚至不是為了二級中風預防。例如，患者實際上在慢性治療期間需要長期接受抗血小板治療。因此，類似地，預計 milvexian 將被用在慢性環境中——這意味著長期治療而不是僅在急性期使用。

The next question is from the line of Robyn Karnauskas with Truist Securities.

下一個問題來自 Truist Securities 的 Robyn Karnauskas。

I guess 2 for me. Number one. On Reblozyl, we're hearing -- I was just wondering about duration of therapy. We've got some anecdotal comments in your (inaudible) some patients still fill a lot of fatigue, and so they'll stop before the drug is actually working. So could you comment on like what you're seeing for duration of therapy and if you think that will change?

我想對我來說是 2。第一。關於 Reblozyl，我們聽說——我只是想知道治療持續時間。我們在您的（聽不清楚）中得到了一些軼事評論，一些患者仍然感到非常疲勞，因此他們會在藥物真正起作用之前停止用藥。那麼您能否評論一下您所看到的治療持續時間以及您認為這是否會改變？

And then second, on deucra, I noticed that you have a topical formulation that's being developed. Can you talk a little bit about what your strategy might be there? Obviously, the topicals are becoming a growing market segment, and maybe what different indications you might be pursuing?

其次，關於 deucra，我注意到你們正在開發一種外用配方。能否稍微談談您的策略？顯然，外用藥物正在成為一個不斷增長的細分市場，也許您可能會追求哪些不同的適應症？

Thank you. Chris, and then Samit.

謝謝。克里斯，然後是薩米特。

Sure. So I think you're right that a big focus area for us on Reblozyl continues to be on duration of therapy. The way we anticipate being able to drive that duration of therapy, though, is to continue to focus on dose titration.

當然。因此我認為您說得對，我們對 Reblozyl 的重點關注領域仍然是治療時間。然而，我們預期能夠延長治療時間的方法是繼續專注於劑量滴定。

What we're seeing right now is about 50% of patients are dose titrating. And remember, you need to have 2 dose titrations to get the benefit that you saw in the clinical program in the real-world setting. And so about 50% of patients are dose titrating with the first step. And that compares to about 80%, which is what we saw in the clinical study.

我們現在看到大約 50% 的患者正在調整劑量。請記住，您需要進行 2 次劑量滴定才能獲得在現實環境中的臨床計劃中看到的益處。因此大約 50% 的患者在第一步中進行劑量滴定。相較之下，我們在臨床研究中看到的結果約為 80%。

And if we can get that dose titration, patients will get the full benefit of Reblozyl, and we anticipate that, that full benefit will translate into a longer duration of therapy.

如果我們能夠進行劑量滴定，患者將獲得 Reblozyl 的全部益處，我們預計，這種全部益處將轉化為更長的治療時間。

So I think that what you're hearing is consistent with the focus that we have the continued growth of this product, continue to make sure that Reblozyl is the standard of care in the second-line on-label population, expand that population as much as we can by decreasing the time that patients are in ESAs and then ensuring they get the full benefit of Reblozyl by focusing on appropriate dose titration, which we anticipate will increase the duration of therapy.

因此，我認為您所聽到的與我們關注的重點是一致的，即持續增長該產品，繼續確保 Reblozyl 是二線標籤人群的護理標準，通過減少患者使用 ESA 的時間來盡可能地擴大該人群，然後通過關注適當的劑量滴定來確保他們獲得 Reblozyl 的全部益處，我們預計這將延長治療時間。

Yes. And just very briefly on Sotyktu. Look, I think the overall potential for topical therapy is being evaluated and we'll have to inform you in due course because landscape is continuing to evolve with multiple therapies coming for the milder population or mild population. We already have the approval for moderate-to-severe plaque psoriasis, and the mild population indication, we'll need to continue to explore.

是的。我簡單介紹一下 Sotyktu。看，我認為局部治療的整體潛力正在接受評估，我們必須在適當的時候通知您，因為前景不斷發展，針對較輕人群或輕度人群的多種治療方法正在出現。我們已經獲得了針對中度至重度斑塊狀乾癬的批准，對於輕度人群的適應症，我們還需要繼續探索。

So thanks, everyone. In closing, with 9 new product launches in the last 3 years, I want to take a moment to reflect on all of the progress we have made.

謝謝大家。最後，我們在過去 3 年內推出了 9 款新產品，我想花點時間回顧我們所取得的所有進展。

We have significantly derisked our portfolio with strong clinical, commercial and financial execution, and we are well underway to transform our business into a more diversified and resilient company. I look forward to the coming catalysts ahead from our new product portfolio and our mid-stage pipeline.

我們透過強大的臨床、商業和財務執行大大降低了我們投資組合的風險，並且我們正在順利地將我們的業務轉變為更多元化和有彈性的公司。我期待著我們的新產品組合和中期產品線未來的催化劑。

With that, thanks again for taking the time to join our call today. And as always, our IR team will be available for any follow-up questions you may have. Thank you, and have a good day.

最後，再次感謝您抽出時間參加我們今天的電話會議。像往常一樣，我們的 IR 團隊將隨時解答您的任何後續問題。謝謝您，祝您有美好的一天。

Thank you. That does conclude today's teleconference. We do appreciate your participation. At this time, you may now disconnect.

謝謝。今天的電話會議到此結束。我們非常感謝您的參與。此時，您可以斷開連線。