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.

美好的一天，歡迎參加百時美施貴寶第三季度業績電話會議。今天的會議正在錄製中。

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

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

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

謝謝，丹尼斯，大家早上好。感謝您今天早上加入我們的 2022 年第三季度財報電話會議。

Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. 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.

今天早上和我一起準備發言的是我們的董事會主席兼首席執行官 Giovanni Caforio；和我們的首席財務官 David Elkins。我們的首席商業化官 Chris Boerner 也參加了今天的電話會議；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。正如您將注意到的，我們已將幻燈片發佈到 bms.com，您可以跟隨 Giovanni 和 David 的發言。

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，我將閱讀我們的前瞻性陳述。在本次電話會議中，我們就構成前瞻性陳述的公司未來計劃和前景發表聲明。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表明的結果存在重大差異。

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。即使我們的估計發生變化，我們也明確表示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 certain non-GAAP financial measures to the most comparable GAAP measures are available on bms.com.

我們還將把我們的評論集中在我們的非公認會計原則財務指標上，這些指標經過調整以排除某些特定項目。 bms.com 上提供了某些非 GAAP 財務指標與最具可比性的 GAAP 指標的對賬。

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

有了這個，我會把它交給喬瓦尼。

Thank you, Tim, and good morning, everyone.

謝謝蒂姆，大家早上好。

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。我很高興與大家分享，我們又實現了一個良好的季度，我們將繼續推進我們的戰略，以使 Bristol-Myers Squibb 實現可持續增長。

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.

在第三季度，我們的在線和新產品組合經外匯調整後增長了 13%，我們實現了 3% 的非公認會計原則每股收益增長，同時在推進我們有前途的管道方面也取得了實質性進展。

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 Sotyktu 的批准，我們的一流 TYK2 銀屑病抑製劑，以及我們的 Turning Point 收購的完成，這為我們的產品組合帶來了另一個產品，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.

總的來說，我很高興我們顯著推進了投資組合的更新。僅今年一年，我們就推出了 9 個新藥，其中 3 個一流產品獲批。

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.

讓我花一點時間在幻燈片 5 上討論我們的新產品。我們的戰略是在 Revlimid 排他性喪失期間及以後加速多元化的創新藥物組合上市，更新我們的業務並發展公司。

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.

為支持這一戰略，我們今年推出了 3 款關鍵新產品：Opdualag、Camzyos 和 Sotyktu。每一個都是一流的資產，這些產品有可能為我們的增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 標誌著我們交付的第二個獲批的 I-O 組合。它在本季度繼續強勁推出，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.

我們在為 Camzyos 作為專業心血管藥物奠定基礎方面取得的進展也讓我們感到鼓舞。我們看到越來越多的患者開始接受治療，他們的反饋非常積極。 David 將在稍後提供有關此次發布的更多詳細信息。

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 已獲批准貼有反映其特徵的標籤，並作為中度至重度斑塊狀銀屑病的首選口服藥物。我們對此次發布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巨大的好處。

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.

與我們的其他推出產品相結合，這些批准代表了我們產品組合更新的一個重要里程碑，為本世紀下半葉及以後的增長提供了多種途徑。

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。在本季度，我們在管道里程碑方面取得了很大進展。根據 KarMMa-3 的陽性頂線結果，Abecma 現在是第一個在復發和難治性多發性骨髓瘤中證明優於標準方案的 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.

我們還展示了 Milvexian 的令人興奮的數據，該數據顯示，在雙重抗血小板治療的基礎上，復發性症狀性缺血性卒中的相對風險降低了約 30%。它還顯示出與現有抗凝劑不同的安全特性。

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藥物具有巨大潛力，我們期待盡快啟動 III 期試驗。 Samit 可以在我們的問答環節為您提供科學細節。

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.

轉到幻燈片 7。您可以在前面看到幾個重要的管道催化劑。其中包括關鍵批准以及重要的註冊數據讀數，包括 Rebrozyl 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.

您會記得，我們曾說過，我們的早期管道將隨著時間的推移生成多個概念驗證數據集。重要的是，我們期待在短期內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多發性骨髓瘤的 BCMA T 細胞接合劑。我們認為這可能是一種差異化資產，我們預計將在 12 月的 ASH 上展示數據。我們用於肺纖維化的第二代 LPA1 藥物，這種疾病的未滿足需求非常高，如果 II 期數據得到支持，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有希望的早期數據，我們希望明年將資產過渡到全面開發。這突出了我們的蛋白質穩態平台在細胞模式之外的廣度，包括在實體瘤中。

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.

這些例子展示了我們研發引擎的力量，新一波的創新和差異化藥物正在湧現，這些藥物有可能治療有高度未滿足醫療需求的患者。我們期待在未來向您更新我們的中期資產組合。

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，讓我轉到幻燈片 8，讓您了解我們如何看待我們的業務向前發展。隨著我們在線業務的持續強勁表現，以及我們的 9 款產品現已全面商業執行，我們的優先事項沒有改變：提供 9 款上市產品的全部商業價值，通過新的適應症擴大這些資產的機會，並推進我們的中期管道。

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。隨著我們不斷更新我們的投資組合併通過更年輕、更多元化的業務轉型我們的公司，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.

我們現在在所有 4 個治療領域都有臨界質量。每個都有基礎的在線品牌、令人興奮的新產品和不斷擴大的中後期管道。這一點很重要，因為我們相信這種更多元化的年輕產品業務，在不斷創新和專注於我們擁有真正專業知識的治療領域的支持下，最能幫助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.

在我把它交給大衛之前，我要感謝我們的員工不懈地專注於為我們服務的患者提供服務。我相信我們將繼續為患者和我們的股東提供服務。

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

我現在將把它交給大衛，讓你了解財務狀況。大衛？

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

謝謝喬瓦尼，再次感謝您參加我們的第三季度財報電話會議。

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.

讓我們轉到幻燈片 10 來討論我們的頂線表現。除非另有說明，否則我將在不包括外匯影響的基礎上討論銷售業績增長率。

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.

第三季度的收入約為 112 億美元，與去年同期持平。我們多元化的在線和新產品組合強勁增長，增長 13%，抵消了我們近期 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.

現在讓我談談我們在幻燈片 11 上新產品組合的表現。在持續需求的推動下，全球收入超過 5.5 億美元，比去年增長 66%。較上一季度的增長也很強勁，增長了 16%。我們繼續對我們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.

今年推出了 3 個新品牌，迄今為止年化收入超過 20 億美元，我們的投資組合在很大程度上被降低了風險，增強了我們對 2029 年產生超過 250 億美元非風險調整收入的潛力的信心。

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.

轉向幻燈片 12 討論我們的實體瘤產品組合的表現，在對我們新推出的核心適應症的需求的推動下，Opdivo 的全球銷售額繼續增長 13%。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.

由於對我們新的轉移性和輔助適應症的需求，我們繼續以兩位數增長，比去年增長 17%，部分被二線資格的下降以及 Opdualag 在一線黑色素瘤中的一些使用所抵消。

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.

在國際上，收入增長了 8%，主要是由於新適應症的增長，特別是一線肺癌和胃腸道癌。展望未來，我們繼續期待 Opdivo 的增長來自我們在早期和晚期癌症中新的和不斷擴大的適應症。

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.

現在讓我們轉到 Opdualag。我們對 Opdualag 的推出感到非常滿意。此次發布是一個良好的開端，是第一個與我們的 PD-1抑製劑 Opdivo 以固定劑量組合推出的 LAG-3抑製劑。本季度銷售額為 8400 萬美元，環比增長 45%，Opdualag 的銷售額已經年化至約 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.

在發布的這一點上，我們在一線黑色素瘤中的份額處於中高水平。正如預期的那樣，我們看到了來自 PD-1 單一療法和 Opdivo + Yervoy 組合的 Opdualag 的使用。

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.

在幻燈片 13 上繼續我們擴大的心血管產品組合。我們領先的 OAC 公司 Eliquis 又一個強勁的季度，同比增長 16%。在美國，銷售額同比增長 31%，主要受需求和有利的總淨額調整的推動。正如預期的那樣，隨著患者進入甜甜圈洞，我們每年都經歷了較高的總支付淨額支付的典型動態，從而推動了連續業績。

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 已成為眾多國家的領先 OAC。鑑於產品的成功，正如預期的那樣，定價壓力阻礙了增長。除了在英國和荷蘭有風險的仿製藥進入之外，定價措施也影響了本季度的增長。

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，這是一種治療阻塞性肥厚性心肌病基礎疾病的一流藥物。我們繼續對我們在將這種改變生活的藥物帶給患者方面所取得的進展感到高興。

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.

迄今為止，我們擁有超過 2,000 名獲得 REMS 認證的醫療保健專業人員，這是治療意向的良好指標。我們收到了來自醫生和患者的非常積極的反饋。我們還在大型 HCM 中心取得了進展，以確保它們能夠投入使用，從而為患者提供 Camzyos。截至第三季度末，有超過 1,100 名患者加入了我們的中心，並且每週都在增長。

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，新患者通常開始治療，作為他們定期安排的超聲心動圖的一部分。根據將患者轉變為商業配藥的時間，我們預計從第四季度開始以及進入 2023 年，收入將加速增長。克里斯可以在問答期間提供有關發布的更多細節，但我們對取得的進展感到滿意。

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.

轉到幻燈片 14 討論血液學的表現，從 Revlimid 開始。本季度銷售額約為 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 月份第二波仿製藥進入市場的速度低於預期。我們預計未來幾週通用侵蝕會逐漸增加。在這一點上，我們預計 Revlimid 的銷售額將在我們今年 90 億美元至 95 億美元範圍內的高端。

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 全球收入與上年相比增長 8%，主要是由於對早期三聯方案的需求，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.

轉移到 Rebrozyl，後者有另一個強勁的季度。本季度銷售額為 1.9 億美元，比去年同期增長 22%。在美國，收入增長受到上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.

排除去年的影響，銷售額將比上年增長約 25%。這是由提高患者依從性和延長治療時間的持續進展推動的。

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， Rebrozyl 在 MDS 和 β 地中海貧血相關貧血的需求的推動下繼續增長。迄今為止，我們已在 9 個國家/地區獲得報銷，未來我們將繼續確保在其他國家/地區獲得報銷。

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.

現在轉向我們的細胞治療資產 Abecma 和 Breyanzi。 Abecma 在本季度創造了 1.07 億美元的強勁收入。這意味著與上一年相比增長了 59%，或環比增長了 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，銷售增長受到強勁需求的推動，主要被患者輸液的時間所抵消，我們預計這將在第四季度實現。

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.

在美國以外的地區，由於特定市場的廣告位一次性增加，銷售額增加，預計在可預見的未來將維持在這一水平。

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.

我們對我們為確保 Abecma 獲得更多患者而取得的製造進展感到非常高興，同時我們將繼續努力進一步擴大我們的產能。當我們準備根據 KarMMa-3 的正讀數將 Abecma 移動到更早的行時。

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，在 Breyanzi，本季度的銷售額為 4400 萬美元，比去年同期增長 50%。需求依然強勁，我們將在明年繼續努力擴大產能，以惠及更多大 B 細胞淋巴瘤患者。正如我們過去所傳達的，我們預計第四季度的銷售額與第三季度的銷售額大致相似。

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.

現在轉向幻燈片 15 上我們擴展的免疫學產品組合。從 Zeposia 開始。本季度全球銷售額為 6900 萬美元，比去年同期增長 83%，主要是由於 Zeposia 在潰瘍性結腸炎中的擴張。

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.

隨後，在美國，銷售額受到上一季度有利的總淨額和批發商購買模式的影響，約為 2000 萬美元。我們繼續看到需求比上一季度增長 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.

我們的戰略仍然專注於進一步擴大數量，以便我們能夠在 2023 年繼續改善訪問量，並且我們在提高訪問量的質量方面也取得了進展。

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，我們將繼續在確保其他市場的報銷方面取得進展，以使 Zeposia 惠及更多患有 MS 和潰瘍性結腸炎的患者。

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.

現在轉向我們最近推出的 Sotyktu，這是我們用於中度至重度斑塊型銀屑病患者的一流選擇性 TYK2 抑製劑。我們對基於強大數據的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.

在發布初期，我們從醫生那裡得到的反饋令我們深受鼓舞。我們的重點是確保盡可能多的患者獲得 Sotyktu，將這種藥物確立為首選口服藥物，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，我們也很高興在 9 月份獲得了日本的批准，我們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.

現在讓我們在幻燈片 16 上討論我們的第三季度損益表。我已經討論了收入，所以我現在將關注本季度其他關鍵的非 GAAP 項目。毛利率下降主要是由於產品組合，部分被外彙和相關對沖結算所抵消。

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.

不包括獲得的進行中的研發，運營費用與上一年基本一致，並受到支出時間的影響。本季度獲得的過程中研發費用為 3000 萬美元，與向 GentiBio 的預付款有關。這被本季度受益於 OI&E 的 7300 萬美元許可收入所抵消。

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.

受收益組合的推動，第三季度有效稅率為 16.9%。總體而言，我們實現了另一個季度的收益增長，非公認會計準則每股收益比去年增長了 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.

轉到幻燈片 17 上的資產負債表和資本分配。本季度運營現金流為 37 億美元。截至 9 月 30 日，該公司的資產負債表仍然強勁，手頭有大約 90 億美元的現金和有價證券，這也占我們為 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保持不變。業務發展仍然是重中之重，我們繼續執行這一戰略，最近完成了 Turning Point Therapeutics 收購。

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。在本季度，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。今年早些時候，我們執行了 50 億美元的 ASR，通過授權剩餘 95 億美元的股份，我們將繼續在股份回購方面投機取巧。

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.

現在轉向我們在幻燈片 18 上的 2022 年非公認會計原則指導。我們維持全年展望。我們繼續預計收入約為 460 億美元，我們的在線和新產品組合在低兩位數範圍內增長。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。我們繼續預計毛利率約為 79%，我們的運營費用（不包括已獲得的進行中研發）保持不變，主要受外匯市場的青睞以及成本紀律的推動，部分被包含在 Turning Point 收購中的費用所抵消.

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.

綜上所述，我們重申了我們的全年非公認會計原則每股收益指引，反映了我們基礎業務的實力，並吸收了 Turning Point 收購帶來的大約 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.

我現在將電話轉回給 Giovanni 和 Tim 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，我們可以回答第一個問題嗎？

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?

對我來說只有2個。我想，首先是在 Sotyktu 上。鑑於有利的標籤，你能談談你將在這裡追求的目標患者群體嗎？所以具體來說，你最初會主要關注 Otezla 的失敗嗎？我猜你會更多地關注開始全身治療的一線患者嗎？

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?

我知道你在這裡也談到了報銷動態。但是，在你暗示的這種 2024 年時間線之前，你有沒有做任何事情來加速這個過程？

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?

然後第二個快速的就在 Eliquis 上。我認為我們已經有幾個季度看到了積極的價格調整。我只是想知道，您是否可以詳細說明那裡的動態？這在本質上是不是一次性的並且會逆轉？或者這只是我們應該為業務考慮的一個新基礎，所以我們認為未來會有什麼樣的銷量增長？

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

謝謝你，克里斯。 Chris Boerner 將開始，然後 David 會給您一些關於 Eliquis 的評論。

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.

所以讓我們從 Sotyktu 開始。謝謝你的問題，克里斯。首先，我認為 Sotyktu 的推出是一個非常好的開始。我們對醫生的反饋感到非常滿意。我們已經看到該產品的每週加速非常好。

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.

我們現在獲得的大部分使用來自社區環境。這非常重要，因為克里斯，您可能知道，該環境中大約 80% 的音量將來自社區。

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。另外，請記住，該產品在發布之初在學術界的知名度非常高。因此，我們在此次發布之初就得到了來自社區的好評，這是一個很好的早期開始。

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.

就我們正在研究的患者群體而言，我們實際上將專注於該群體的動態部分，其中包括一線環境中的初始開始以及任何即將到來的失敗離開奧特茲拉。

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換，儘管這又是非常早期的日子。但我想說，這次發布的主要焦點仍然是 Otezla。我的意思是那些在沒有 TYK2 的情況下會繼續使用 Otezla 的患者，以及那些對該產品失敗或醫生決定轉換的患者，因為我們在 Sotyktu 上看到的療效概況。

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.

就我們在訪問方面看到的情況而言，我們的重點仍然是三重訪問：首先，消除市場——面對該領域所有新產品的新市場塊；其次，利用我們今天開放獲取的優勢，請記住，我們估計大約 10% 的患者在此次發布的初始階段擁有開放獲取；然後很明顯，這一切都是關於在發布的早期階段建立音量，然後利用這個音量。

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?

我們將盡一切努力加速在 2023 年進入更好的訪問位置。但我們當然覺得我們處於一個非常好的位置，並且有望在 2024 年處於一個良好的位置。大衛？

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 的回扣，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，我們預測基於所有付款人的產品組合的預期折扣。每個季度，我們都會進行調整，有些季度上漲，有些季度下跌。但最近兩個季度我們發布了一些版本，這就是真正的解釋。但全年沒有任何變化，真的。

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

您的下一個問題來自古根海姆證券公司的 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.

所以幾個快速的問題。所以第一個只是在潰瘍性結腸炎中不斷發展的競爭格局上。你們能否讓我們了解一下 Zeposia 在 MS 與 UC 中的發布情況？當我們查看腳本的分離時，您在這一點上具體看到的患者百分比是多少？您如何看待隨著醫生和 IL-23 興趣的增加而演變的競爭格局，甚至可能將 IL-23 與生物仿製藥 Humira 的組合作為該類別潛在的新突破？只是想知道，你們在最近的會議上也在想什麼。

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。只是想了解一下你們預計何時會看到處方或收入的有意義的變化。這是我們應該期待在第四季度看到有意義的增長嗎？還是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。所以 Chris 和 Samit 將解決您關於 UC 的問題，然後 Chris 將評論 Camzyos。

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。謝謝你的問題，Seamus。關於 Zeposia，我想說 Zeposia 繼續表現良好。我們在本季度看到了不錯的兩位數需求增長。大部分增長繼續來自潰瘍性結腸炎。所以我想說的是，如果你看看到今年年底這項資產的增長將發生在哪裡，當然當我們進入明年時，大部分患者將來自加州大學.

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.

我們在 MS 中 Zeposia 的市場份額繼續保持穩定。 S1Ps 中超過 50% 的份額來自 Zeposia。我們對自己所處的位置感覺非常好。顯然，正如我們之前談到的，MS 的口腔市場受到 IV 的一些壓力。但儘管如此，我們在 MS 人群中保持一致的份額。

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.

我們的重點仍然是 UC。我們相信，這是我們擁有最強地位和最大增長機會的地方。我想說的是，我認為從競爭的角度來看，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 的引入，RINVOQ 的增長在很大程度上並沒有以犧牲 Zeposia 為代價。事實上，儘管引入了這項新資產，我們仍保持了我們在該市場的地位。顯然，有許多動態將繼續發揮作用，但我們對我們作為 UC 市場上第一個 S1P 的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，Zeposia 的重點是建立音量，然後將該音量轉換為更強大的訪問位置。我們確實在 10 月份在訪問方面獲得了非常重要的早期勝利，CBS, Inc. 現在以 0 步編輯覆蓋 Zeposia。這很重要，因為如果您將其與其他計劃相加 - 涵蓋 Zeposia 的較小計劃，我們現在擁有約 3000 萬受保人的生命，並且隨著我們進入其他 PBM，我們將處於有利位置2023 年。

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

也許我會讓 Samit 解決這個問題的另一部分，然後我會繼續討論 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，Seamus，我們認為潰瘍性結腸炎患者未滿足的醫療需求仍然很高。當然，需要新藥。如您所知，我們有自己的與 Sotyktu 治療潰瘍性結腸炎的臨床開發計劃。 2023 年，CD 和 UC 的兩個試驗將從概念驗證的角度宣讀，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導致未來的發展，以及組合是否將成為未來護理標准或新療法的可能性。還有更多，但我們需要先查看數據。

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.

然後回答你關於 Camzyos 的問題，我只想說，我們對 Camzyos 的推出感到非常高興。我們在下半年看到這款產品的加速非常好。

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，我們談到了認證醫師的重要性。截至第二季度末，我們現在擁有超過 2,000 名獲得 REMS 認證的醫生。我們看到一周比一周的健康增長。 David 提到，截至第三季度末，我們有 1,100 名患者接受了 Camzyos 處方。這也看到了不錯的每週增長。

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.

我認為我們在上一季度的電話會議中提到了一個重點領域是幫助一些大型機構建立基礎設施以支持該產品的使用。最近幾週，我們已經看到了非常顯著的改善。我們看到的新開始的步伐與這些賬戶一致，尤其是組織起來。

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在通過我們的 Camzyos 患者中心，這非常重要，因為這將有助於讓患者接受治療並繼續接受治療。而且我認為值得注意的是，到目前為止，在進行過多次分配的患者中，沒有人退出治療，這是該中心運作情況的一個很好的指標。

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.

我認為關於我們將以多快的速度看到收入加速的問題與訪問問題有關。正如預期的那樣，訪問並沒有成為此次發布的障礙。我們現在有大約 50% 的計劃涵蓋 Camzyos。所有報導 Camzyos 的患者都被 [PA-ed] 到標籤上，這是一個強有力的位置的良好指標。

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，截至第三季度末，這 1,100 名患者中約有 1/3 已轉換為商業藥物。僅在 10 月，我們看到的商業分配數量幾乎是第三季度的兩倍。因此，我們對此次發布的速度以及我們在下半年看到的情況感到非常滿意，並且很高興隨著此次發布的繼續以及我們進入第四季度電話會議提供額外的顏色。

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

您的下一個問題來自花旗銀行的 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 Rebrozyl。我只是好奇，關於 Onureg 的相同主題。鑑於該藥物作為口服替代品的吸引力，我很驚訝它並沒有做得更好，也許您可以概述一下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，對於 200 毫克劑量的 milvexian，療效不如安慰劑。關於在特定劑量開始期間 COVID 是否會影響血栓栓塞事件的發生率，有一些討論。我想知道你是否有試驗來描述試驗的特定劑量臂？

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 Samit 會回答關於 Rebrozyl 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 關於我們所看到的一些障礙的問題。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。如您所知，這裡一線環境中的這些動態正在繼續發展。我們已經看到美國主要是繼續接受強化化療的患者比例有所下降。請記住，該標籤適用於接受強化化療並獲得完全反應的患者。

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。目前的維護份額約為 50% 至 60%。我們認為隨著時間的推移有機會繼續擴大維護市場。

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、獲得完全反應、繼續維持治療的患者，選擇需要是 Onureg。所以這是我們對美國團隊的重要關注。

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.

然後我們繼續看到在美國以外的德國和法國等市場推出的早期階段，早期的吸收情況很好。

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，謝謝你關於 milvexian 的問題。是的，當然，我們研究了圍繞 COVID 的假設，而 200 毫克的劑量似乎並沒有通過那裡。但我們正在繼續探索該團隊為何脫穎而出。但我認為，要帶回家的一點仍然是，我們有八倍的劑量範圍可供我們選擇與 III 期試驗的正確劑量結合，我們正處於我們現在期待啟動在接下來的幾個月中，該計劃將在第三階段進行，其中包含我們之前在 AF、ACS 和 SSP 中談到的 3 個跡象。

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?

如果我可以問一個問題，您如何看待多發性骨髓瘤環境中的動態，特別是 CAR T 療法之間的相互作用以及雙特異性藥物作為一種選擇的預期到來。您能否談談您在 2023 年看到的動態？

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，在 Opdualag 上，那裡的收入表現不錯。您能否提醒我們，您擴大這些標籤機會的策略是什麼，以及我們何時能夠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。謝謝你，克里斯，這個問題。對於多發性骨髓瘤，我認為出發點是，無論已經開發出多少療法並可用，這種疾病目前仍未治愈。因此，有機會繼續為這些患者帶來更具變革性、更有效和安全的治療方法。

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.

在這方面，當然，細胞療法在讓患者完全緩解方面確實帶來了一些轉變。希望這些都是非常持久的。

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.

Bispecific，正如今天在美國 - 或昨天在美國，當然在歐盟也被批准的那樣，是一種新的軍備庫。肯定會帶來很好的療效。但是，正如您從已提供的數據中看到的那樣，有機會繼續改善安全狀況，高 CRS 發生率將是一個問題，因為您還看到了思想領袖發表的一些聲明，那就是差異化將需要繼續發生。

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 上為一位 T 細胞參與者展示我們自己的數據，你會看到的。我認為另一種看待它的方式是多發性骨髓瘤的整體發展，我們也在開發現在啟動的 3 個 CELMoD 的 III 期試驗。未來可能看起來像是 T 細胞接合劑或細胞療法的組合方法，以及如何將 CELMoDs 添加到這些方法中。

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，我們有一種治療多發性骨髓瘤的整體方法，並試圖讓越來越多的患者獲得非常長、持久的完全反應，並在某一天得到治愈。你想補充點什麼嗎，克里斯？

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。也許我會補充一點，雖然雙特異性藥物和 CAR T 在這種情況下共享 BCMA 的目標，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徵，包括產品的可用性、持續時間治療，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.

而且我認為最終，正如我們反复說過的那樣，BCMA CAR T 和雙特異性藥物的效用對於每個患者和我們所處的環境都是獨一無二的。我們預計這些不同的患者因素將變得越來越對確定如何治療患者很重要。

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.

然後，也許在我將 Opdualag 的擴展交給 Samit 之前，我只想說，一開始，我們仍然對 Opdualag 的強勁表現印象深刻。我們的重點一直是並將繼續以 PD-1 單藥治療人群為目標。

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.

我認為正如大衛所暗示的那樣；從今天開始，我們看到使用 Opdivo + Yervoy 患者的轉換以及 PD-1 單一療法來推動這種使用。但當我們考慮到這一資產未來的增長時，請記住，我們今天所處的位置，PD-1 單一療法仍佔一線轉移性黑色素瘤的 20% 左右。這就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繼續增長這一資產的機會。

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.

而且我認為除了克里斯剛才所說的之外，顯然還有許多其他的試驗正在進行中。在 III 期環境中，我們進行了黑色素瘤研究、輔助環境以及二線和 MSS 結直腸癌環境中的 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.

然後研究繼續註冊 III 期部分——或非小細胞肺癌隨機部分的 II 期部分，以及與研究人員合作正在進行的 2 項 HCC 研究和多項其他信號尋求研究。

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

很明顯，隨著數據的出現，我們可以將該計劃推進到多個其他跡象。

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

下一個問題來自沃爾夫研究公司的蒂姆安德森。

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.

回到溫和的。我只是想了解為什麼我們還沒有看到 III 期試驗開始。您已經獲得了數月的心房顫動等數據。您沒有運行第二階段，因此沒有專門在該設置中分析的數據。你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呢？這幾乎讓你想知道 FDA 是否阻止你前進。是否有顧慮或類似的事情。

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.

然後第二個問題只是 Samit 的一般管道問題。這是 2022 年一個相當大的積極消息流。我認為有一種觀點認為，你會在 2023 年進入更多類似催化劑的時期。

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，在您看來，接下來的 2 或 3 個最重要的臨床催化劑是什麼，比如說，在接下來的 12 個月裡？

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

謝謝你，蒂姆。讓我請 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，正如我在講話中提到的，我認為真正令人興奮的是，實際上中期管道開始加速，催化劑的數量非常重要。這就是為什麼我們在我的發言中強調了這一點，我們期待著繼續在那裡更新你。

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.

蒂姆，謝謝你的提問。我很高興您和我們一樣對啟動第三階段計劃感到興奮。一旦試驗宣讀，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，然後我們可以通過將方案提交給 IRB、倫理委員會、他們的機構來啟動計劃必須通過才能真正招收病人。

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.

所以所有這些都在解決。我們有我們的合作夥伴楊森和我們。我們正在非常勤奮、非常密切地工作以啟動該計劃。在接下來的幾個月裡，您將聽到 milvexian 第三階段計劃的啟動。

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，明年或第二年的新催化劑是什麼？我之前談過它，幸運的是，我們的管道非常充實，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。當我們考慮未來幾年進行的嗜酸性食管炎研究中的 cendakimab 時，我認為 Giovanni 在他的開場白中談到了 LPA1 概念驗證研究。如果讀取出來，並且從功效的角度來看，如果數據與我們幾年前在 2018 年看到的 [國際象棋] 出版物相似，那麼如果安全狀況得到妥善管理，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.

以類似的方式，我們的 repotrectinib 將被註冊，並有望在明年下半年用於患有 RAS 突變的非小細胞肺癌患者。隨著數據的出現，2023 年也可能發生一些從早期發展到晚期發展的轉變，例如雄激素受體滯後獨立降解劑或 alnuctamab。然後，當然，還有我們期待 Rebrozyl 的 COMMANDS 試驗的讀數。因此，2023 年還有多種其他催化劑正在醞釀之中。

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

下一個問題來自 Stephen M Scala 和 Cowen 的觀點。

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 繼續超出預期，大概為 2023 年創造了一個艱難的比較。所以我只是想知道，在這一點上，你對尋求布里斯托爾明年整體增長的共識感到滿意嗎？我知道 2023 年指南將於明年 2 月發布。但是，如果您能告訴我們此時您是否願意發表評論，那將很有幫助。

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，在 branebrutinib 上，3 個項目被終止，只有 RA 仍然存在。為什麼其他項目被終止而 RA 繼續？如果是毒，能具體說一下是不是肝毒嗎？

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。我想請大衛從 Revlimid 和 Outlook 開始，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，斯蒂芬。關於 Revlimid，正如我們在我的講話中所說，我們仍然預計全年 Revlimid 將在 90 億美元至 95 億美元之間，更多地位於該範圍的上半部分。但正如我們一直所說的那樣，我們將根據我們的通用量如何進入市場以及季度與季度的時間安排來實現季度間的變化。

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.

從廣義上講，我們仍然符合我們之前提供的預測。至於 2023 年的指引，基礎業務，我們繼續排除外幣。正如我們今年所看到的，我們繼續能夠發展業務，我們將像通常在第四季度電話會議上所做的那樣，提供有關 '23 指南的更新。

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。只是，史蒂夫，在 branebrutinib 方面，這肯定不是毒性。我們為將分子帶入後期開發設定了高標準，但我們沒有達到這些適應症的高標準。 RA 的指示仍在繼續，我們將看到數據讀出的內容。然後根據這些數據，我們將決定是否應該繼續。

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

您的下一個問題來自 Luisa Hector 和 Berenberg 的台詞。

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?

也許只是為了再次嘗試 2023 年的前景。關於 Revlimid 還有什麼要說的嗎？你已經得到了每年 20 億到 25 億美元侵蝕的指導。這是你對明年的期待嗎？

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與您對 IPR&D 的陳述部分相關的許可收入，但當我們在其他營業收入中查看該線時，特許權使用費，許可收入似乎在第三季度有所增加。所以我只是想知道，這可能是由未來特別好的阿斯特拉糖尿病驅動的嗎？第三季度的產品線中是否有一次性的項目，或者我們應該考慮向前發展的更可持續的項目？

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。所以讓我重申一下。就我們的前景而言，與 2023 年相比，沒有什麼真正改變，這包括我們繼續看到 Revlimid 下降約 25 億美元的事實。但大衛可以讓你對第二個問題有更多的見解。

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。一是我們對 PD-1和糖尿病的特許權使用費繼續 - 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繼續增長。

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.

其他幾件事，如果你只考慮我們現金餘額的利率，利息收入正在增加。但如您所知，我們一直在下台並償還債務，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，您將所有這 4 個因素放在一起，這就是我們看到 OI&E 隨著時間的推移而取得更好進展的方式。回想一下，從長遠來看，與特許權使用費收入有關，這些特許權使用費率將在 23 年和未來以及 24 年對 PD-1 降低我們的糖尿病特許經營權。因此，當我們對第四季度電話會議進行指導時，我們將向您更新該指導。

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 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?

對我來說可能是 2 個。我只是想知道，首先是關於 Camzyos，也許只是對 Chris 的澄清。您提到與上一季度相比，本季度的商業准入正在改善。我想你說的是加倍。那麼這是否意味著我們應該考慮 1000 萬美元範圍內的第四季度銷售額？

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。我知道如果你確信你現在有一個前進劑量並且你看到的 CRS 比你在 IV 製劑中看到的要少，並且如果你希望與 teclistamab 競爭，我知道你在那裡將配方更改為 subcu，後者剛剛獲得強生的批准？

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

謝謝你。克里斯，你為什麼不從 Camzyos 開始，然後是 Samit。

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，謝謝你的問題。讓我澄清幾件事。首先，雖然我們不會為第四季度提供具體的產品級別指導。我要說的是，我們對使用 Camzyos 的患者轉化和越來越多地轉化為商業藥物感到非常高興。

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，當您考慮此次發佈時，您需要在有多少醫生獲得 REMS 認證的背景下考慮它。然後，我們將這些醫生轉化為讓患者進入診所並接受治療的能力，如果您願意的話，就進入漏斗頂部的患者而言，我們看到每週都有很好的增長。因為他們要進入我們的中心，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，現在我們正在以更快的速度將這些患者轉變為商業藥物，我認為這是一個非常好的跡象，表明這一推出在第四季度繼續加速。唯一要記住的另一件事是，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任何上訴程序，這些患者將免費服用大約 7 到 8 週的藥物。隨著我們在今年年底和明年初正式做出 PBM 覆蓋決策，該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.

但這就是你應該如何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。反饋一直很好。我們看到頂部患者的每週增加，並且我們看到繼續使用商業藥物的患者的轉化率顯著增加。我們預計這種情況會持續下去。

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.

Terence，對於 T 細胞參與者，我們當然不會深入了解數據的細節。但是您還記得，使用 IV 製劑，我們已經看到了非常好的療效，但毒性特徵是不可接受的，這就是我們更換皮下的原因。並且將呈現數據。所以當然，在展示數據之後，我們很高興就數據是什麼以及我們如何看待它們進行對話。

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

下一個問題來自於 Barclays 的 Carter Gould。

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

偉大的。感謝 Camzyos 上的所有顏色。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，第三階段發布了。只是想知道 - 但是關於你如何考慮在設置中滴定的細節非常稀疏，因為這裡完成的第二階段工作更多地依賴於藥物濃度。顯然，REMS 更依賴於迴聲。那麼您是如何考慮在非阻塞性環境中進行滴定的呢？

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?

然後在 [224] 上，您如何看待這個問題？我們是否應該將其視為 Camzyos 的備份？或者您是否認為這種共存可能存在於不同的適應症中，例如 HFpEF 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。讓我先從非手術肥厚型心肌病中的 Camzyos 開始。我們期待在 III 期研究中開始招募患者。

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.

我們已經在第二階段看到的數據非常有希望，著眼於對生物標誌物的影響，甚至是對該試驗的長期隨訪。我目前無法向您提供有關滴定的細節，當然也無法用於未來的討論。一旦我們開始試驗，我們就可以談論更多。

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.

如您所知，對於 MYK-224，我們總是希望有多個鏡頭。這是我們正在開發的一種新分子。當然，您可能會看到的第一個試驗也將關注阻塞性肥厚性心肌病。原因是我們有 Camzyos 數據。我們以我們想要比較試驗的方式擁有內部數據——比較藥物並查看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，當我們從開發的角度展望未來時，我們將定義我們希望使用 MYK-224 追求哪些適應症，以及我們希望使用 Camzyos 複製哪些適應症。我們還沒有定義和決定我們將如何開發 224。當然，當我們有了這個時，我們也會進行對話。

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

下一個問題來自 Matthew Phipps 和 William Blair。

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?

對我來說只是一個快速的。 Samit，今年 EoE 出現了幾次失敗，其中 II 期可能是組織學終點，但不是消化不良終點。也許您可以就您認為 IL-13 更適合 EoE 第三階段中的這兩個端點的 IL-13 給我們任何評論？

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——您可能正在談論的是我們昨天或前一天為 EoE 看到的那個。請記住，那裡的作用機制是 IL-5 抑制，而不是 cendakimab，後者是 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.

該差異化特徵還與其他一些已獲批准或已顯示數據的藥物進行了比較。這是一種 IL-13 的直接抑製劑，具有抑制 R1 和 R2 受體的下游作用。

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.

我們認為，兩者的抑制不僅對減少炎症很重要，而且對重塑和逆轉纖維化也很重要。我們在前一段時間為 cendakimab 提出的 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，我們也會在這次試驗中研究這個比率。因此，在試驗宣讀的幾年內，我們希望能夠複製和改進 II 期研究的結果。

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 的快速跟進。您之前談到了通過某種免費藥物或橋接計劃來對抗老牌競爭對手的策略。您能否就您在那裡所做的工作提供一些更具體的細節，以幫助我們思考銷售軌蹟的進展？

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，我們應該特別期待在 ASH 上看到關於 iberdomide 和 mezigdomide 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 Samit 將使用 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，當我們考慮 Sotyktu 的進展時，我認為您先從幾件事開始。一是藥物的概況。我們已經詳細討論過，我們在這裡有一個非常乾淨的標籤這一事實，它使我們能夠講述關於 2 項 III 期研究的非常有力的故事，這些研究直接顯示出相對於現有護理標準的療效改善。

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.

所以我們有一個很好的功效信息要告訴，良好的安全性，這個資產的價值是非常清楚的。我們看到了這一點，到目前為止，我們從醫生那裡收到的所有反饋都與此一致。

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.

下一個重要的一點是，我們擁有一支經驗豐富的團隊。他們很了解這個空間。因此，我們已經能夠深入了解這些患者中絕大多數的位置，也就是社區環境中。所以我們對此感覺很好。這個空間的訣竅，因為它是一個管理繁重的空間，我們將做一些非常好的事情。

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.

最初，我們必須刪除新的市場塊。這些模塊適用於這個領域的每一個新產品，這是我們現在的一個重點。然後，我們必須利用開放訪問的位置。正如我之前在回答上一個問題時所說，這大約是 10% 的患者。因此，我們正在盡我們所能。

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，重點是建立容量，然後利用該容量與 PBM 協商，讓您盡快進入更有利的處方位置。

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.

由於這次發布的時機，我們肯定錯過了今年的談判窗口。重點將放在談判 24 訪問。儘管為了回應 Chris 之前的問題，我們將盡一切努力加快這一進程。

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.

所以這確實是我們的重點。我們有一套強大的患者服務，可以提供給患者，讓他們接受治療。我們向他們提供初始免費試用優惠和過渡計劃，我們預計該過渡計劃的大量使用將引導我們進入何時我們擁有更有利的處方位置。

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。一般來說，您將在那裡看到的一件事是美西多胺擴張臂與地塞米松聯合用於五線加患者群體的數據呈現。但總的來說，對於多發性骨髓瘤，我們還將展示我們的下一個 CAR T 的數據，該 CAR T 是針對 GPRC5D 的，以及 KarMMa-2 的數據，其中一個臂正在研究移植後的概念證明治療設置。除了 T 細胞接合劑 alnuctamab 之外，該數據還將在 ASH 上提供。

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?

一個關於 Abecma。您能否提供一些關於我們何時可以看到 KarMMa-2 數據的顏色？我知道 270 新聞稿遲到了——一個醫學會議，我看到你的近期催化劑上有一個綠色的複選標記？

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?

然後更廣泛地說，當您考慮 BCMA CAR T 領域的演變時，您如何定位 Abecma 與競爭對手，尤其是即將出現的 Carvykti 數據？

Thank you. Samit?

謝謝你。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。我將從這個開始，埃文。從 KarMMa-2 數據呈現的角度來看，當然，正如我之前所說，這些數據將作為概念證明，並在 ASH 會議上進行更長時間的跟進。當然，我們已經討論過基於這些數據啟動下一次試驗的內容——我認為這就是我談到的 270 Bio，我們打算如何在早期環境中啟動試驗。這是一種不同的看待它的方式。當我們在試驗設計和我們的思考方式方面實際啟動試驗時，將提供更多詳細信息。

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.

就 Abecma 與 Carvykti 的數據進行比較而言。再一次，正如 Chris 之前所說，我們確實相信 Abecma 從安全性角度來看仍然是一個非常差異化的資產，也是第一個具有隨機 III 期試驗數據的 CAR-T，顯示優於當前的護理標準。因此，該配置文件將繼續增長，並且該配置文件將有望繼續改善。這就是為什麼我們正在考慮在移植後環境中啟動早期線試驗。

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?

祝賀本季度取得的成果和進展。兩個對我來說很容易。首先，Opdualag 的推出進展順利。展望 2023 年，我認為仍然存在一些關於與 Opdivo 相關的黑色素瘤環境中潛在的蠶食問題，因為華爾街仍預計 Opdivo 明年將有相當強勁的增長。您能否評論一下隨著 Opdualag 的推出開始逐漸成熟時您所看到的情況，以及您的期望是否會對 Opdivo 在黑色素瘤環境中的利用產生有限的影響？

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

其次，一個簡單的問題，你期待明年 Camzyos 的 EMBARK 結果嗎？還是被推到2024年？

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

謝謝你，戴恩。克里斯，你為什麼不開始？

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

也許我會從 Opdualag 開始，然後把它交給 Samit。

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為了確定我們在 Opdualag 發佈時所處的位置。我們從 PD-1 單藥療法中採購了大約 50% 到 60% 的業務，從 Opdivo 和 Yervoy 的組合中採購了大約 40% 到 50% 的業務。這比我們預期預發布的第三季度 Opdivo + Yervoy 的蠶食率略高。但我們預計這種情況會穩定下來，並且我們會繼續預計，今後 Opdualag 的大部分業務將來自 PD-1 單藥治療。

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.

請記住，正如我之前所說，目前在市場上，PD-1 單一療法的市場份額約為 20%。這在 Opdivo 和 KEYTRUDA 之間大致平分。所以我對 Opdualag 發展的看法是，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，該資產的絕大多數使用應繼續來自 PD-1 單藥治療。其中一些將來自 Opdivo，其中一些將來自競爭對手。當我想到增長軌跡時，20% 的份額是我們 PD-1 單一療法的目標。這就是我們認為我們應該獲得業務的地方。事實上，我們仍有 20% 的市場份額讓我們有信心在 2023 年繼續發展這一整體業務。

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

僅根據 EMBARK 的結果，預計將在 2024 年出現。

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，請澄清一個問題，並提出一個問題。關於 Camzyos，Chris，我想你提到過 1/3 的 Camzyos 患者是商業化的。但後來你提到，在 10 月份，我們看到這一數字翻了一番。您能否澄清一下這裡的翻倍是什麼，商業患者的數量或 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?

然後問題的第二部分是關於 milvexian。您提到的適應症，SSP 和 ACS，這似乎是一種急性類型的適應症。所以是的，患者人數很多，但治療時間可能更短。我認為這只是中風後一個月左右的時間。所以只是想了解，我們應該如何考慮在急性類型的環境中的機會？

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。也許我會從 Camzyos 的問題開始。所以讓我澄清一下1/3。在 1,100 名患者中，我們截至年底的大約 1,100 名患者中，有 1/3 的患者已經降級為商業藥物，超出商業藥物。

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 10 月的前 3 週，我們看到整個第三季度的商業分配數量幾乎翻了一番。因此，這說明了該產品的商業銷售軌蹟的一個重要考慮因素，即我們開始看到接受治療的患者數量和這些患者轉變的速度都在加速到商業藥品。

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，雖然說的是急性冠脈綜合徵，但這並不意味著治療只在急性期進行，甚至用於中風的二級預防。例如，患者實際上會在長期治療期間長期接受抗血小板治療。因此，以類似的方式，預計 milvexian 將用於慢性環境——這意味著治療時間長，而不僅僅是急性期。

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?

我猜2對我來說。第一。關於 Rebrozyl，我們聽到了——我只是想知道治療的持續時間。我們在您的（聽不清）中有一些軼事評論，一些患者仍然充滿了很多疲勞，所以他們會在藥物真正起作用之前停止。所以你能評論一下你在治療期間看到的情況嗎？如果你認為這會改變？

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，在 deucra 上，我注意到您正在開發一個局部配方。你能談談你的策略可能在那裡嗎？顯然，主題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跡象？

Thank you. Chris, and then Samit.

謝謝你。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。所以我認為你是對的，我們對 Rebrozyl 的一個主要關注領域仍然是治療持續時間。然而，我們預計能夠推動治療持續時間的方式是繼續關注劑量滴定。

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.

我們現在看到的是大約 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您在實際環境中的臨床計劃中看到的益處。因此，大約 50% 的患者在第一步進行劑量滴定。相比之下，這一比例約為 80%，這是我們在臨床研究中看到的。

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調整，患者將獲得 Rebrozyl 的全部益處，我們預計，這種全部益處將轉化為更長的治療持續時間。

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.

所以我認為你所聽到的與我們關注該產品的持續增長是一致的，繼續確保 Rebrozyl 是二線標籤人群的護理標準，擴大該人群我們可以通過減少患者在 ESA 中的時間，然後通過專注於適當的劑量滴定來確保他們獲得 Rebrozyl 的全部益處，我們預計這將增加治療的持續時間。

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。並且非常簡短地介紹了 Sotyktu。看，我認為局部治療的整體潛力正在評估中，我們將不得不在適當的時候通知您，因為隨著針對輕度人群或輕度人群的多種療法的出現，情況正在繼續發展。我們已經獲得了中重度斑塊狀銀屑病的批准，以及輕度人群適應症，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.

所以謝謝大家。最後，在過去 3 年推出了 9 款新產品，我想花點時間回顧一下我們取得的所有進展。

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.

我們已經通過強大的臨床、商業和財務執行大大降低了我們的投資組合的風險，並且我們正在將我們的業務轉變為一家更加多元化和有彈性的公司。我期待著我們的新產品組合和我們的中期管道即將到來的催化劑。

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.

有了這個，再次感謝您今天抽出時間加入我們的電話會議。與往常一樣，我們的 IR 團隊將隨時為您解答任何後續問題。謝謝你，有一個美好的一天。

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

謝謝你。今天的電話會議到此結束。我們非常感謝您的參與。此時，您現在可以斷開連接。