Legend Biotech Corp (LEGN) 2023 Q4 法說會逐字稿

Good day, and welcome to the Legend Biotech Reports Fourth Quarter Earnings Call. (Operator Instructions) As a reminder, this call is being recorded. I would now like to hand the call over to Jessie Yeung, Head of Investor Relations and Public Relations. You may begin.

美好的一天，歡迎參加傳奇生物科技第四季財報電話會議。 （操作員說明）謹此提醒，此通話正在錄音。我現在想將電話轉交給投資者關係和公共關係主管 Jessie Yeung。你可以開始了。

Good morning. This is Jessie Yeung, Head of Investor Relations and Public Relations at Legend Biotech. Thank you for joining our conference call today to review our fourth quarter and full year 2023 performance. Joining me on today's call are Ying Huang, the company's Chief Executive Officer; and Lori Macomber, the company's Chief Financial Officer. Following the prepared remarks, we will open up the call for a Q&A. We have Guowei Fang, Chief Scientific Officer; and Steve Gavel, Head of Commercial Development for the U.S. and Europe, joining the Q&A session.

早安.我是傳奇生物科技投資者關係和公共關係主管 Jessie Yeung。感謝您今天參加我們的電話會議，回顧我們第四季和 2023 年全年的業績。參加今天電話會議的還有該公司執行長黃英；以及公司財務長洛里·麥康伯 (Lori Macomber)。在準備好的發言之後，我們將開始問答環節。我們有方國偉，首席科學官；以及美國和歐洲商業發展主管 Steve Gavel 參加了問答環節。

During today's call, we will be making forward-looking statements, which are subject to risks and uncertainties that may cause our actual results to differ materially from those expressed or implied here within. These forward-looking statements are discussed in greater detail in our SEC filings, which we encourage you to read and can be found under the Investors section of our company website.

在今天的電話會議中，我們將做出前瞻性陳述，這些陳述存在風險和不確定性，可能導致我們的實際結果與此處明示或暗示的結果有重大差異。這些前瞻性陳述在我們的 SEC 文件中進行了更詳細的討論，我們鼓勵您閱讀這些文件，並且可以在我們公司網站的投資者部分找到這些文件。

Thank you. I will now turn the call over to Ying.

謝謝。我現在將電話轉給Ying。

Good morning, everyone. We're glad you could join us today because a lot has happened since our last earnings call. First, we're excited at the prospect of bringing our lead therapy, CARVYKTI to more multiple myeloma patients in Europe.

大家，早安。我們很高興您今天能加入我們，因為自上次財報電話會議以來發生了很多事情。首先，我們對將我們的主導療法 CARVYKTI 帶給歐洲更多多發性骨髓瘤患者的前景感到興奮。

As many of you have heard, CARVYKTI received a positive opinion from the Committee for Medicinal Products for Human Use to expand into earlier lines of treatment. CARVYKTI is the first CAR-T therapy to receive a positive CHMP opinion in the second-line setting for patients with relapsed and lenalidomide-refractory multiple myeloma.

正如你們許多人所聽說的，CARVYKTI 收到了人類用藥產品委員會的積極意見，將其擴展到早期的治療領域。 CARVYKTI 是第一個在二線治療復發性和來那度胺難治性多發性骨髓瘤患者中獲得 CHMP 積極意見的 CAR-T 療法。

The formal European Commission decision is expected in April. As for the approval of CARVYKTI in the United States in the second line, we are scheduled to meet with the FDA's Oncologic Drug Advisory Committee this Friday, the 15th. To answer any outstanding questions they have, we are preparing for a potential launch in this expanded indication on the PDUFA date of April 5, and we will, of course, keep you posted.

歐盟委員會預計四月做出正式決定。至於CARVYKTI在美國的二線獲批，我們定於本週五（15日）與FDA腫瘤藥物諮詢委員會會面。為了回答他們提出的任何懸而未決的問題，我們正在準備在 4 月 5 日的 PDUFA 日期發布此擴展適應症，當然，我們會及時通知您。

Now I'd like to turn to other achievements and activities since our last earnings call. Our work to bring CARVYKTI to more patients globally resulted in total net sales for the fourth quarter of 2023 of $159 million. For the full year, total sales for CARVYKTI were $0.5 billion. The increase in our fourth quarter performance versus the third quarter was a result of the ongoing launch of CARVYKTI and share gain from capacity expansion and manufacturing efficiencies.

現在我想談談自上次財報電話會議以來的其他成就和活動。我們致力於將 CARVYKTI 帶給全球更多患者，2023 年第四季的總淨銷售額達 1.59 億美元。 CARVYKTI 全年總銷售額為 5 億美元。第四季業績較第三季有所成長是由於 CARVYKTI 的持續推出以及產能擴張和製造效率帶來的份額成長。

We have now been in the market for 7, 4 quarters, and we are the fastest launched CAR-T therapy. We anticipate continued quarter-over-quarter growth throughout 2024 as well. We believe our cash balance of $1.3 billion provides us with financial runway through the end of 2025.

我們現在已經上市7、4季了，我們是推出最快的CAR-T療法。我們預計 2024 年將持續實現季度環比成長。我們相信 13 億美元的現金餘額為我們提供了 2025 年底的財務跑道。

In order to serve more patients and meet our revenue targets, we have expanded our supply of lentiviral vectors significantly through a large reactor in Switzerland, operated by our partner, Johnson & Johnson. In addition, Johnson & Johnson has another factory under construction in the Netherlands.

為了服務更多患者並實現我們的收入目標，我們透過我們的合作夥伴強生公司營運的位於瑞士的大型反應器大幅擴大了慢病毒載體的供應。此外，強生公司在荷蘭還有另一家工廠正在興建中。

We also continued to expand our internal manufacturing capacity in partnership with Janssen. Our cell processing site in Ghent, Belgium, called Obelisc produced the first batches of CARVYKTI for clinical use in January 2024. We hope to start commercial production in the second half of the year. Construction progressed on our second manufacturing site, Tech Lane in Belgium and is expected to be complete at the end of the year.

我們也與楊森合作繼續擴大我們的內部製造能力。我們位於比利時根特的細胞加工基地 Obelisc 於 2024 年 1 月生產了第一批用於臨床的 CARVYKTI。我們希望在今年下半年開始商業化生產。我們位於比利時的 Tech Lane 的第二個生產基地的建設進展順利，預計今年年底完工。

We have increased capacity at our Raritan, New Jersey facility, doubling cell processing capacity since the beginning of 2023. The increases to our production capacity will help ensure we meet our target of supplying CARVYKTI to 10,000 patients by the end of 2025.

自 2023 年初以來，我們提高了新澤西州 Raritan 工廠的產能，使細胞處理能力增加了一倍。產能的增加將有助於確保我們實現到 2025 年底向 10,000 名患者供應 CARVYKTI 的目標。

I am excited to announce we have a new federal leader with more than 25 years of experience now overseeing our manufacturing sites. Our own Birk Vanderweeën has been promoted to Senior Vice President, Global Manufacturing and Technical Operations.

我很高興地宣布，我們有了一位擁有超過 25 年經驗的新聯邦領導人，負責監督我們的生產基地。我們自己的 Birk Vanderweeän 已晉升為全球製造和技術營運資深副總裁。

Our previous Head of Global Tech Ops, Liz Gosen has stepped aside from full-time work for personal reasons and is now serving as a senior adviser for us. Birk joined us in 2021 to start our European organization and the manufacturing facilities I just mentioned. The site in Ghent that has just came online and second one under construction. Before joining Legend, he served at Janssen, Teva and AstraZeneca.

我們的前全球技術營運主管 Liz Gosen 因個人原因辭去了全職工作，現在擔任我們的高級顧問。 Birk 於 2021 年加入我們，啟動我們的歐洲組織和我剛才提到的製造設施。根特的網站剛剛上線，第二個網站正在建設中。在加入 Legend 之前，他曾在 Janssen、Teva 和 AstraZeneca 任職。

Birk has earned the trust and respect of our global manufacturing teams, and he's already made a big impact. The increase in production capacity enabling us to meet growing patient demand comes in parallel with new data we presented at the American Society of Hematology meeting in December. In an oral presentation, we unveiled the data showing improvements in patient outcomes as early as second line treatment in our pivotal Phase III CARTITUDE-4 study.

Birk 贏得了我們全球製造團隊的信任和尊重，他已經產生了巨大的影響。產能的增加使我們能夠滿足不斷增長的患者需求，同時我們也在 12 月的美國血液學會會議上提交了新數據。在口頭報告中，我們公佈了關鍵的 III 期 CARTITUDE-4 研究中的數據，顯示早在二線治療時患者的治療結果就得到了改善。

The results demonstrated clinically meaningful improvement in health-related quality of life measures and reductions in symptoms following treatment with CARVYKTI compared to standard of care. In other deals from the fourth quarter, we continue to bring more hospitals online, and we now have a total of 65 U.S. hospitals certified to treat with CARVYKTI patients. Additionally, about 30% of patients are now administered in the outpatient setting.

結果表明，與標準護理相比，CARVYKTI 治療後健康相關生活品質指標得到臨床有意義的改善，症狀減少。在第四季度的其他交易中，我們繼續讓更多醫院上線，目前我們共有 65 家美國醫院獲得了可以治療 CARVYKTI 患者的認證。此外，大約 30% 的患者現在在門診接受治療。

Turning to the pipeline. We're investigating the potential of our cell therapies in blood cancers beyond multiple myeloma and also in solid tumors. We have started dosing patients in our DLL3-targeted program, the Phase I clinical trial LB2102 in lung cancer. The (inaudible) used in LB2102 can also be deployed in other pipeline programs if validated in the clinic.

轉向管道。我們正在研究細胞療法在多發性骨髓瘤以外的血癌以及實體腫瘤的潛力。我們已經開始在 DLL3 標靶計畫（肺癌 I 期臨床試驗 LB2102）中給予病人用藥。如果在臨床中得到驗證，LB2102 中使用的（聽不清楚）也可以部署在其他管道項目中。

After Phase I, Novartis will take over and conduct any further development including manufacturing and commercial activities. To sum up 2023, we closed the year with accomplishments on several fronts. Now I would like to turn the call over to Lori to walk you through the financials for 2023. Lori?

第一階段結束後，諾華將接管並進行任何進一步的開發，包括製造和商業活動。總結 2023 年，我們在多方面取得了成就，為這一年畫上了圓滿的句號。現在我想將電話轉給 Lori，讓您了解 2023 年的財務狀況。Lori？

Thank you, Ying, and good morning, everyone. As Ying mentioned, we generated approximately $159 million in total net sales for CARVYKTI during the fourth quarter, an increase of 189% year-over-year, driven by the progress we have made with ongoing market launches, expanding market share and capacity improvements. As a reminder, we share equally in all profits and losses of CARVYKTI ex-China with our partner, Janssen. Turning to our revenue.

謝謝你，Ying，大家早安。正如應提及的，在我們不斷推出市場、擴大市場份額和提高產能方面取得的進展的推動下，我們第四季度 CARVYKTI 的總淨銷售額約為 1.59 億美元，同比增長 189%。謹此提醒，我們與我們的合作夥伴楊森公司平等分享 CARVYKTI 除中國以外的所有利潤和損失。轉向我們的收入。

Total revenues for the fourth quarter were $79.5 million, consisting almost entirely of collaboration revenue from the sale of CARVYKTI. Net loss for the quarter ended December 31, 2023, was $144.8 million or a loss of $0.40 per share compared to a net loss of $135.9 million or a loss of $0.41 per share for the same period last year. For the year ended December 31, 2023, net loss was $518.3 million or a loss of $1.47 per share compared to a net loss of $446.3 million or a loss of $1.40 per share for the year ended December 31, 2022.

第四季總收入為 7,950 萬美元，幾乎全部來自出售 CARVYKTI 的合作收入。截至 2023 年 12 月 31 日的季度淨虧損為 1.448 億美元，即每股虧損 0.40 美元，而去年同期淨虧損為 1.359 億美元，即每股虧損 0.41 美元。截至2023年12月31日止年度，淨虧損為5.183億美元，或每股虧損1.47美元，而截至2022年12月31日止年度，淨虧損為4.463億美元，或每股虧損1.40美元。

Moving on to expenses. Collaboration cost of revenue for the fourth quarter 2023 was $32.5 million compared to $23 million for the same period last year. These are Legend's portion of collaboration cost of sales in connection with the collaboration revenue under the Janssen Agreement, along with expenditures to support the manufacturing capacity expansion.

繼續討論支出。 2023 年第四季的協作收入成本為 3,250 萬美元，而去年同期為 2,300 萬美元。這些是聯想在與楊森協議下的合作收入相關的合作銷售成本中的一部分，以及支持製造能力擴張的支出。

Research and development expenses for the fourth quarter 2023 were $105.7 million compared to $80.8 million for the same period last year. The increase of $24.9 million for the 3 months ended December 31, 2023, compared to 3 months ended December 31, 2022, was due to primarily due to continuous research and development activities in cilta-cel including higher patient enrollment for Phase III clinical trials for cilta-cel, and an increase in research and development activities for other pipeline items.

2023 年第四季的研發費用為 1.057 億美元，而去年同期為 8,080 萬美元。與截至2022年12月31日止三個月相比，截至2023年12月31日止三個月增加了2,490萬美元，主要是由於cilta-cel的持續研發活動，包括更多患者參加III期臨床試驗cilta-cel，以及其他管道項目的研發活動的增加。

Administrative expenses for 3 months ended December 31, 2023, were $28.7 million compared to $26.7 million for the same period last year. The increase of $2 million year-over-year is primarily due to the expansion of administrative functions to facilitate continuous business growth and continuing investment in building Legend Biotech's global information technology infrastructure.

截至 2023 年 12 月 31 日止 3 個月的管理費用為 2,870 萬美元，而去年同期為 2,670 萬美元。年比增加200萬美元主要是由於行政職能的擴大以促進業務持續增長以及持續投資建設傳奇生物的全球資訊技術基礎設施。

Selling and distribution expense for 3 months ended December 31, 2023, was $33.7 million compared to $25.8 million for the same period last year. The increase of $7.9 million year-over-year due to costs associated with the commercialization of CARVYKTI.

截至 2023 年 12 月 31 日止 3 個月的銷售和分銷費用為 3,370 萬美元，而去年同期為 2,580 萬美元。由於 CARVYKTI 商業化相關成本，年增 790 萬美元。

To summarize, our spending remains on track, and we continue to maintain a strong balance sheet. As of December 31, we had $1.3 billion in cash and equivalents, deposits and investments. Additionally, as we enter the new year, we received $100 million upfront payment in early January in connection with our global license agreement with Novartis for certain CAR-T therapies targeting DLL3. Thus, we believe we have sufficient capital to fund our operating and capital expenditures through the end of 2025.

總而言之，我們的支出仍處於正軌，我們繼續保持強勁的資產負債表。截至 12 月 31 日，我們擁有 13 億美元的現金及等價物、存款和投資。此外，隨著進入新的一年，我們在 1 月初收到了 1 億美元的預付款，涉及我們與諾華就某些針對 DLL3 的 CAR-T 療法的全球許可協議。因此，我們相信我們有足夠的資本來為 2025 年底前的營運和資本支出提供資金。

Thank you. I now pass it back to Ying for closing remarks.

謝謝。現在我將其傳回給Ying以供結束語。

Thank you, Lori. 2023 was an impressive year for Legend. CARVYKTI has proven to be the fastest launched CAR-T therapy. The achievements of our global teams have set us up for great success in 2024, and we're poised to provide more therapy to even more patients around the world. I want to thank each of our 1,900 employees for their commitment and dedication to Legend.

謝謝你，洛瑞。 2023 年對 Legend 來說是令人印象深刻的一年。 CARVYKTI 已被證明是推出最快的 CAR-T 療法。我們全球團隊的成就為我們在 2024 年取得巨大成功奠定了基礎，我們準備為世界各地更多的患者提供更多的治療。我要感謝我們 1,900 名員工中的每一位對 Legend 的承諾和奉獻。

And with that, we'd like to take your questions. Operator, we're ready for the first question.

因此，我們願意回答您的問題。接線員，我們準備好回答第一個問題了。

(Operator Instructions) Our first question comes from Jessica Fye with JPMorgan.

（操作員說明）我們的第一個問題來自摩根大通的 Jessica Fye。

Question on supply, and I appreciate the color and prepared remarks. I know you put the year-end '25 target out there for, I think, 10,000 doses. You have a year-end 2024 target you could share? And if not, I guess, what's the right way to think about the, for example, the manufacturing step-ups you're going to ask the FDA to grant this year? Thank you.

關於供應的問題，我很欣賞顏色和準備好的備註。我知道您設定的 25 年底目標是 10,000 劑。有 2024 年底目標可以分享嗎？如果不是，我想，考慮今年您將要求 FDA 批准的生產升級等問題的正確方法是什麼？謝謝。

Jess, this is Ying. Thank you for the question about manufacturing. So I'll take that one. We did mention in the beginning of last year that our goal is to provide a combined global supply of 10,000 doses per year when we exit 2025. Beyond that, we're not providing any guidance on 2020 for manufacturing scale up.

傑西，這是英。感謝您提出有關製造的問題。所以我會接受那個。我們在去年初確實提到過，我們的目標是在 2025 年結束時每年提供 10,000 劑疫苗的全球總供應量。除此之外，我們沒有提供任何有關 2020 年生產規模擴大的指導。

But I can tell you that, just if you look at last year, we applied for FDA approval for 2 capacity increases in our site in Raritan, New Jersey and we did successfully achieve both approvals from FDA. This year, our plan is the same. That is we are planning additional 2 capacity increases that we plan to request FDA. So that's the same cadence as last year. That's the plan for 2024.

但我可以告訴你，只要你看看去年，我們就新澤西州拉里坦工廠的兩次產能增加申請了 FDA 批准，並且我們確實成功地獲得了 FDA 的兩項批准。今年，我們的計劃是一樣的。也就是說，我們計劃向 F​​DA 要求額外增加 2 項產能。這與去年的節奏相同。這是2024年的計畫。

Our next question comes from Jonathan Miller with Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Jonathan Miller。

I'd like to ask about your early pipeline both beyond DLL3 and that (inaudible), what can investors look forward to? And even if you're not specifying targets, can you give us a little bit of color about whether your choices are likely to be familiar to folks, they'll be familiar targets or these are new places to go looking for CAR? And then separately, do you have any plans to get into the autoimmune space like so many of your peers?

我想問一下你們早期的 DLL3 之外的管道（聽不清楚），投資者可以期待什麼？即使您沒有指定目標，您能否給我們一些訊息，說明您的選擇是否可能為人們所熟悉，他們是否會成為熟悉的目標，或者這些是尋找 CAR 的新地方？另外，您是否有像許多同行一樣進入自體免疫領域的計劃？

Thanks, Jonathan. This is (inaudible) the question. Yes. So on the target front, some of our pipeline targets are (inaudible). I probably can provide some high-level thinking about where we are heading towards through our internal pipeline. We have a few priorities. First is really try to build multiple myeloma franchise, especially for patients who are post CARVYKTI treatment. The net space, we are targeting -- some of the known target as well as novel target currently under research and development, where you see a fairly diverse platform with (inaudible) approach.

謝謝，喬納森。這就是（聽不清楚）問題。是的。因此，在目標方面，我們的一些管道目標是（聽不清楚）。我可能可以提供一些關於我們透過內部管道走向何方的高層次思考。我們有幾個優先事項。首先是真正嘗試建立多發性骨髓瘤專營權，特別是對於接受 CARVYKTI 治療後的患者。我們的目標是網路空間——一些已知的目標以及目前正在研究和開發的新穎目標，您可以在其中看到一個相當多樣化的平台（聽不清楚）。

Second priority we have is really focusing on the autoimmune disease indication. We see this as an emerging area with great opportunities. In this space, I think the differentiated approach is critical. Our internal focus at this point, primary on the allogeneic approach, and we also -- some type of programs (inaudible) space, but really focusing on the differentiation -- focusing the value those to patient approach can bring to the patient, bring to the treatment and setting.

我們的第二要務是真正關注自體免疫疾病的適應症。我們認為這是一個充滿機會的新興領域。在這個領域，我認為差異化的方法至關重要。在這一點上，我們的內部重點主要是同種異體方法，我們也——某種類型的程序（聽不清）空間，但真正關注的是差異化——關注那些對患者方法可以給患者帶來的價值，給患者帶來的價值。治療和設置。

We also have some investment in solid tumor space, where we are just focusing on some of the key hurdles associated with disease state, disease pathology. For example, (inaudible) commonly associated with solid tumor disease indication, which is the major limitation of the duration from the current (inaudible). So there, we are investing on the key technological innovation to address solid tumor target (inaudible) and how to generate the by standard cytotoxicity effect and, therefore, being able to extend the TFS, the benefit of retreatment. So that's probably will be just a high level sum. Thank you for the question.

我們也在實體腫瘤領域進行了一些投資，我們只是專注於與疾病狀態、疾病病理學相關的一些關鍵障礙。例如，（聽不清楚）通常與實體瘤疾病適應症相關，這是目前（聽不清楚）持續時間的主要限制。因此，我們正在投資關鍵技術創新，以解決實體腫瘤標靶（聽不清楚）以及如何產生標準細胞毒性效應，從而能夠延長 TFS（再治療的好處）。所以這可能只是一個高水準的總和。感謝你的提問。

And then one follow-up, if I may. I noticed your burn here at about $103 million as a quarter. It looks like you're not at a runway guidance to end of '25, seems like you're not guiding for a lot of improvement in burn rate or any improvement in revenue is offset by corresponding increases in spend. Is that a fair way to think about it?

如果可以的話，然後是一個後續行動。我注意到你一個季度的燒錢額約為 1.03 億美元。看起來你並沒有達到 25 年底的預期，似乎你沒有指導燃燒率的大幅提高，或者收入的任何改善都會被相應的支出增加所抵消。這是一個公平的思考方式嗎？

That's correct. If you take a look, the -- being conservative (inaudible) from way through the end of 2025. It's really going to be dependent upon our pipeline and how our pipeline advances. But we do believe as it stands today, we're comfortable with our cash balance, will bridge the profitability for the BCMA program.

這是正確的。如果你看一下，從 2025 年底開始，我們將保持保守（聽不清楚）。這實際上取決於我們的管道以及管道的進展。但我們確實相信，按照目前的情況，我們對現金餘額感到滿意，這將彌補 BCMA 計劃的盈利能力。

Our next question comes from Ziyi Chen with Goldman Sachs.

我們的下一個問題來自高盛的子怡陳。

And for the upcoming ODAC meeting on Friday, so could you share a bit more about the cutoff day for those data to potentially share with the committee? And also for the OS data for the ASH Trade Group who was shared in 2023 ASH which showed a very strong OS benefit compared to (inaudible) group. So will they discuss including ASH Trade Group as well, so which group would like to be more important per your previous communication with the regulators. And also we're trying to understand about your initial thoughts on the European countries launches. So any incremental updates on the launch and any preliminary strategy on that?

對於即將於週五召開的 ODAC 會議，您能否分享更多有關可能與委員會共享這些數據的截止日期的資訊？還有 ASH Trade Group 的作業系統數據，該數據在 2023 年 ASH 中共享，與（聽不清楚）群組相比，該數據顯示出非常強大的作業系統優勢。他們也會討論包括 ASH Trade Group 在內的問題，因此根據您先前與監管機構的溝通，哪個團體希望更重要。我們也試圖了解您對歐洲國家發布的初步想法。那麼關於發布的任何增量更新以及任何初步策略嗎？

This is Ying. I'll take your first question around ODAC. So at this point, I can tell you, we submitted 3 data cuts to the FDA and also EMA on overall survival because we were told by the FDA that the focus of the upcoming ODAC on March 15 will be overall survival. So as you mentioned, the first data cut was submitted in the BLA in June of last year, and that was part of the first pre-specified interim analysis with the data cut on November 1, 2022.

這是瑩。我將回答您關於 ODAC 的第一個問題。所以此時，我可以告訴你，我們向 FDA 和 EMA 提交了 3 個關於總體生存率的數據削減，因為 FDA 告訴我們，即將於 3 月 15 日舉行的 ODAC 的重點將是總體生存率。正如您所提到的，第一次資料削減已於去年 6 月在 BLA 中提交，這是 2022 年 11 月 1 日資料削減的第一個預先指定的中期分析的一部分。

And then as part of the day 120 safety update we submitted to the FDA in October of last year, we put in another update on survival from CARTITUDE-4. That was with a data cut of April of last year. And then most recently, on January 7, we submitted the latest survival data from CARTITUDE 4 with a data cut of December 13 of 2023.

然後，作為我們去年 10 月向 FDA 提交的第 120 天安全更新的一部分，我們添加了 CARTITUDE-4 的另一項生存更新。這是去年四月的數據下調的結果。最近，也就是 1 月 7 日，我們提交了 CARTITUDE 4 的最新存活數據，數據截止日期為 2023 年 12 月 13 日。

So those are the 3 different overall survival analysis we provided to the FDA and those are 3 data cuts that will be discussed on Friday by ODAC as well. In terms of ITT versus (inaudible), I can tell you that all our data analysis on the survival benefit was provided on the basis of intention to treat ITT and that is the all-cost mortality analysis, which is the most conservative scenario here.

這些是我們向 FDA 提供的 3 種不同的總體生存分析，這些是 3 種數據削減，ODAC 也將於週五討論。就 ITT 與（聽不清楚）而言，我可以告訴您，我們所有關於生存獲益的數據分析都是基於治療 ITT 的意圖，即全成本死亡率分析，這是這裡最保守的情況。

We do not plan to submit to the agency the data of survival on the basis of (inaudible). So I hope that answers your question about ODAC. And then I'll ask my colleague, Steve to comment on the European launch given the most recent CHMP opinion?

我們不打算向該機構提交基於（聽不清楚）的生存數據。我希望這能解答您關於 ODAC 的問題。然後我會請我的同事 Steve 根據 CHMP 的最新意見對歐洲的發布發表評論？

Yes. Thanks, Ying. A couple of things just to remind the listeners that our partner is responsible for CARVYKTI's launch planning outside the United States and with the exception of China. As far as Europe goes, as Ying mentioned, and maybe, I don't think he did mention. We are currently in Germany with CARVYKTI as well as Austria, and Austria came on board in December of last year.

是的。謝謝，瑩。有幾件事只是為了提醒聽眾，我們的合作夥伴負責 CARVYKTI 在美國以外（中國除外）的發布計劃。至於歐洲，正如應提到的，也許，我認為他沒有提到。我們目前在德國和奧地利與 CARVYKTI 合作，奧地利於去年 12 月加入。

The intention -- and this is through our partner. I know our partners in active negotiations currently around our new CARTITUDE-4 data. So in terms of guiding, in terms of the country launch planning, we don't have anything yet to guide because I know this is a pretty fluid environment right now with the agencies in Europe and our partners. So unfortunately, I can't guide you at this point in time.

這個意圖——這是透過我們的合作夥伴來實現的。我知道我們的合作夥伴目前正在圍繞我們的新 CARTITUDE-4 數據進行積極談判。因此，就指導而言，就國家推出計劃而言，我們還沒有任何指導，因為我知道目前歐洲機構和我們的合作夥伴的環境相當不穩定。不幸的是，我目前無法為您提供指導。

Our next question comes from Yaron Werber with TD Cowen.

我們的下一個問題來自 Yaron Werber 和 TD Cowen。

This is Jenna on for Yaron. I kind of wanted to ask about parkinsonism, which has seen more CARVYKTI than other CAR-Ts. What do you think CARVYKTI produces parkinsonism. And also, we spoke to (inaudible) that you can have pretty irreversible effects. So do you think that this is going to deter using earlier line setting, especially if competing CAR-T's don't show this?

這是亞倫的珍娜。我有點想問一下帕金森症，與其他 CAR-T 相比，CARVYKTI 的情況更多。您認為 CARVYKTI 會產生帕金森氏症嗎？而且，我們（聽不清楚）說，你可能會產生相當不可逆轉的影響。那麼您認為這會阻止使用早期的線路設置，特別是如果競爭的 CAR-T 沒有顯示這一點的話？

Jenna, this is Ying. I'll take your question on parkinsonism. Well, first of all, if you look at the data, that's both in clinical trials and also from the FDA AER's database, this phenomenon of parkinsonism is not unique on CARVYKTI. In fact, it was reported from patients who are taking on Yescarta, Kymriah and also ABECMA. And so far, as of end of last year, we could see about 7 cases reported in the FDA database from the U.S. patients. So that's the number. That's actually the fact.

珍娜，這是英。我會回答你關於帕金森氏症的問題。嗯，首先，如果你看一下數據，無論是臨床試驗中的數據還是 FDA AER 資料庫中的數據，這種帕金森氏症現象並不是 CARVYKTI 所獨有的。事實上，正在服用 Yescarta、Kymriah 和 ABECMA 的患者報告了這一情況。到目前為止，截至去年底，FDA 資料庫中我們可以看到大約 7 個來自美國患者的病例。這就是數字。這其實就是事實。

With regard to why you are seeing this kind of delayed parkinsonism, I would say there's a couple of hypotheses out there. For example, it could be because of the T-cell trafficking into the CNS or in the brain when the patient has a leaky blood-brain barrier after years of therapy or if the patient already had pre-existing neurology situations such as neuropathy. So that could be one of the hypothesis.

關於為什麼你會看到這種遲發性帕金森氏症，我想說有幾個假設。例如，當患者經過多年治療後出現血腦障壁滲漏時，或者患者已經患有神經病變等神經病學情況時，可能是由於 T 細胞流入中樞神經系統或大腦中。所以這可能是假設之一。

Although at this point, I don't think there's any solid clinical evidence to show which is the root cause of parkinsonism. Regarding your question on parkinsonism in the earlier lines. As we reported at ASCO, given the risk mitigation strategy we implemented following the 6 cases reported from CARTITUDE-1, we were able to show that the incidence of parkinsonism was going down from about 6% in CARTITUDE-1 to about 0.5% in CARTITUDE-4. And that was the grade 1 case we reported at ASCO.

儘管目前，我認為沒有任何可靠的臨床證據可以證明帕金森氏症的根本原因是什麼。關於您在前面幾行中關於帕金森症的問題。正如我們在ASCO 上報告的那樣，考慮到我們在CARTITUDE-1 報告的6 例病例後實施的風險緩解策略，我們能夠證明帕金森氏症的發生率從CARTITUDE-1 中的約6% 下降到CARTITUDE 中的約0.5% -4。這是我們在 ASCO 報告的 1 級病例。

So we believe that if you look at the earlier line patient population because of the risk mitigation and also potentially because of the patient baseline difference, we think that is entirely manageable phenomenon here. Thank you.

因此，我們認為，如果您考慮早期的患者群體，因為風險緩解，也可能因為患者基線差異，我們認為這是完全可以控制的現象。謝謝。

Our next question comes from Kelly Shi with Jefferies.

我們的下一個問題來自 Jefferies 的 Kelly Shi。

This is Dave on for Kelly Shi. Congrats on the progress. I have a couple of questions. One is as the multiple BCMA agents are available now, have you received any feedback from physician on how does they position CARVYKTI versus other treatment? Also on sales, when do you expect to provide sales guidance? And although you mentioned J&J will be responsible for outside U.S. Any color on when should we expect to record the first revenue in other countries in EU and Japan?

我是凱莉·施 (Kelly Shi) 的戴夫 (Dave)。祝賀取得的進展。我有一些問題。一是由於現在有多種 BCMA 藥物可供使用，您是否曾收到醫生關於他們如何定位 CARVYKTI 與其他治療的回饋？另外關於銷售，預計什麼時候提供銷售指導？儘管您提到強生將負責美國以外的業務，但我們何時應該預計在歐盟和日本等其他國家實現第一筆收入？

Why don't I take the last question around sales. So the -- as far as the EU in Japan, I mentioned that we're already in Austria and Germany. And unfortunately, because the negotiations being ongoing, we can't comment on what country may be up next in Europe. And that includes Japan for that matter.

我為什麼不回答關於銷售的最後一個問題。因此，就日本的歐盟而言，我提到我們已經在奧地利和德國了。不幸的是，由於談判正在進行中，我們無法評論歐洲下一個可能是哪個國家。這其中也包括日本。

I think your other question had to do with selection of CARVYKTI in terms of patient type. What we're seeing, obviously, right now within the U.S. and in Europe in the fifth line plus setting here in the States, I mean, as Ying mentioned in his opening remarks, we're running about an 80% market share in sites where we are basically competing against ABECMA. So I think that speaks volumes in terms of preference in terms of positions. And it's in all risk categories, whether be standard risk or high risk.

我認為您的另一個問題與根據患者類型選擇 CARVYKTI 有關。顯然，我們目前在美國和歐洲的第五條線以及美國這裡看到的情況，我的意思是，正如 Ying 在開場白中提到的那樣，我們在網站上佔有大約 80% 的市場份額我們基本上是在與ABECMA 競爭。所以我認為這對於立場的偏好很重要。它屬於所有風險類別，無論是標準風險還是高風險。

I think where you see some other product use around bispecific uses when potentially CARVYKTI may not be available or if a physician wants to bridge to a CAR-T therapy, you're seeing some uptick for sure in the bispecific space, I think that has -- in terms of market erosion, where you're seeing it at least in the research that we're doing is you're seeing the market erosion occurring with ABECMA when a bispecific is used in front of a CAR-T therapy as opposed to (inaudible).

我認為，當你看到一些圍繞雙特異性用途的其他產品使用時，可能無法使用CARVYKTI，或者如果醫生想要過渡到CAR-T 療法，你肯定會看到雙特異性領域的一些上升，我認為這已經- 就市場侵蝕而言，至少在我們正在進行的研究中，您會看到當雙特異性藥物用於 CAR-T 療法之前時，ABECMA 會發生市場侵蝕，而不是到（聽不清）。

I'll take your first question. I think it was on the label update. So I'll provide an answer into our respects. Number one is that you're all aware that in late last year, we did receive an official label update. That includes a 2-year minimum follow-up of the CARTITUDE-1 in late line multiple myeloma. And with that, FDA also included label update on AML and also MDS, so I want to provide a little bit of clarification on this.

我來回答你的第一個問題。我認為這是標籤更新。因此，我將提供一個答案以表達我們的敬意。第一，你們都知道，去年年底，我們確實收到了官方標籤更新。其中包括 CARTITUDE-1 在晚期多發性骨髓瘤的至少 2 年追蹤。除此之外，FDA 也更新了 AML 和 MDS 的標籤，所以我想對此進行一些澄清。

So if you look at the total of 97 patients from CARTITUDE-1, we saw 9 patients with 10 cases. If you look at the cumulative rate of AML/MDS, it's roughly 10%. But recall, this trial was started back in 2019. So essentially, in the last 5 years, the cumulative rate of AML/MDS is roughly 10%.

因此，如果您查看 CARTITUDE-1 中總共 97 名患者，我們看到了 9 名患者，10 例。如果你看看 AML/MDS 的累積發生率，大約是 10%。但請記住，這項試驗早在 2019 年就開始了。因此，從本質上講，在過去 5 年中，AML/MDS 的累積發生率約為 10%。

Now there's a paper that was published in ASH December of last year which looked at insurance claim database over 1,000 patients who were triple exposed, which means these patients have been treated with triple classes, including one drug from IMiD class, one drug from protease inhibitor and then one drug from CD38 antibody. So if you look at that patient population, even without any treatment, the background rate of developing MDS or AML is roughly 3% each year.

現在有一篇去年12月發表在ASH上的論文，研究了超過1000名三重暴露患者的保險理賠資料庫，這意味著這些患者接受了三重類別的治療，其中一種藥物來自IMiD類別，一種藥物來自蛋白酶抑制劑然後是一種來自CD38抗體的藥物。因此，如果你觀察一下患者群體，即使沒有任何治療，每年患有 MDS 或 AML 的背景率也大約是 3%。

Therefore, if you look at the data from CARTITUDE-1, we don't believe that is actually higher than the background rate. And we already got the label update on AML and MDS. Now regarding the second one, as you guys all saw from the public communication from the FDA. All 6 brands of CAR-T therapies will receive a label update on T-cell lymphoma. And FDA believes this is a class effect. So everyone will get similar or the same language. And right now, we and J&J are in discussion with the FDA about the exact language of label update.

因此，如果您查看 CARTITUDE-1 的數據，我們認為該數據實際上並不高於背景率。我們已經獲得了 AML 和 MDS 的標籤更新。現在關於第二個問題，正如你們從 FDA 的公開溝通中所看到的。所有 6 個品牌的 CAR-T 療法都將獲得 T 細胞淋巴瘤的標籤更新。 FDA 認為這是一種階級效應。所以每個人都會得到相似或相同的語言。目前，我們和強生正在與 FDA 討論標籤更新的確切語言。

Suffice to say that given the '23 cases reported from the FDA and also denominated is over 27,000 patients who were treated with those different than some clinical trial patients. It is a small and rare risk and we think we'll get the label update in the near future. You also have a question about feedback from physicians on how they think about CARVYKTI versus other novel therapies.

可以說，鑑於 FDA 報告的 23 例病例，還有超過 27,000 名患者接受了與某些臨床試驗患者不同的治療。這是一個小而罕見的風險，我們認為我們將在不久的將來獲得標籤更新。您也想了解醫生對 CARVYKTI 與其他新型療法的看法的回饋。

We have been in touch with our physicians and (inaudible). And at this point, we have not seen any prescription behavior that's changed based on the either T-cell lymphoma or AML/MDS label change. And if you look at efficacy, physicians continue to believe that CARVYKTI provides best-in-class efficacy with nearly 3 years PFS in late line. And then also, again, if you saw the results from CARTITUDE-4 compared to standard of care such as DPD or (inaudible) dexamethasone. We saw a 74% risk reduction in progression of that. And you will see on Friday how CARVYKTI has helped those patients in survival as well.

我們一直與我們的醫生保持聯繫（聽不清楚）。目前，我們還沒有看到任何處方行為因 T 細胞淋巴瘤或 AML/MDS 標籤變化而改變。如果您專注於療效，醫生仍然相信 CARVYKTI 提供一流的療效，晚期無惡化存活期 (PFS) 近 3 年。另外，如果您看到 CARTITUDE-4 與 DPD 或（聽不清楚）地塞米松等標準護理相比的結果。我們發現這種情況的進展風險降低了 74%。週五您將看到 CARVYKTI 如何幫助這些患者生存。

So at this point, I think it's still positioned as best-in-class efficacy with the one-time injection convenience. That is how physicians view CARVYKTI.

因此，在這一點上，我認為它仍然被定位為同類最佳的功效和一次性注射的便利性。這就是醫生對 CARVYKTI 的看法。

Our next question comes from Leonid Timashev with RBC Capital Markets.

我們的下一個問題來自加拿大皇家銀行資本市場的 Leonid Timashev。

I also wanted to ask on the ODAC. And I guess, specifically, how you're thinking about competitive implications coming out of that mean? I guess with regards to the drug you're going to be sharing the committee with, do you think any setbacks for them are going to be a positive for you? Is there less market splitting potentially less competition? Or do you think if they succeed, that's going to be helpful, given that they can drive greater awareness. And I guess, is there any risk of the CAR-T space broadly being painted with the same brush depending on what the competitor present?

我也想問一下關於ODAC的問題。我想，具體來說，您如何考慮這種方式所帶來的競爭影響？我想關於你將與委員會分享的藥物，你認為他們遇到的任何挫折會對你產生正面的影響嗎？市場分裂是否會減少，競爭也會減少？或者你認為如果他們成功了，那將會有幫助，因為他們可以提高人們的意識。我想，根據競爭對手的表現，CAR-T 領域是否存在被廣泛使用相同刷子的風險？

Thanks, Leo, for the question. So I think if you look at the federal registered publication, you will see even though it's the same roster of ODAC, but it's actually 2 different panels. On the morning of March 15, ODAC will discuss the application from us on the second line indication for CARVYKTI. And then in the afternoon, same ODAC roster of KOLs and experts will discuss the application from competition in the third-line application.

謝謝裡奧提出這個問題。因此，我認為如果您查看聯邦註冊出版物，您會發現儘管它是相同的 ODAC 名冊，但實際上是 2 個不同的小組。 3月15日上午，ODAC將討論我們關於CARVYKTI二線適應症的申請。然後下午，同樣由 ODAC 名冊上的 KOL 和專家將討論三線應用競爭中的應用。

So I think it is a separate panel. It's not necessarily a panel on a CAR-T class. And I believe each application will be discussed and also debated by the (inaudible) and on its merit. So I can't comment on our competition application of data, but we firmly believe that CARVYKTI provides overwhelming benefit or in the PFS and also overall survival endpoints here. So that's what we can say about this.

所以我認為這是一個單獨的面板。它不一定是 CAR-T 類的小組。我相信每個申請都將根據其優點進行討論和辯論（聽不清楚）。因此，我無法評論我們的競賽數據應用，但我們堅信 CARVYKTI 在 PFS 以及整體生存終點方面提供了壓倒性的優勢。這就是我們對此可以說的。

And if you look at CAR-T as a class in general, in late-line multiple myeloma clearly, the class of therapy has provided a new option for patients who have treated -- who have been treated and also failed all major classes, including an IMiD, a protease inhibitor and also a CD38 antibody.

如果你將 CAR-T 視為一個總體類別，那麼在晚期多發性骨髓瘤中，這種療法顯然為已經接受治療但未通過所有主要類別的患者提供了新的選擇，包括IMiD、蛋白酶抑製劑和CD38 抗體。

At that point, these patients really did not have much choice besides the BCMA directed agents. So we firmly believe that there is a very important place for BCMA-directed CAR-T in the treatment of multiple myeloma here.

那時，除了 BCMA 定向藥物外，這些患者確實沒有太多選擇。所以我們堅信BCMA導向的CAR-T在多發性骨髓瘤的治療上有著非常重要的地位。

Our next question comes from Vikram Purohit with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Vikram Purohit。

We had two, one on the pipeline and one on commercialization. So on the pipeline, for the CARTITUDE-2 study, we were just curious what your latest thoughts were on timing for data from cohorts E&F. And then on commercialization, you mentioned that around 30% of patients are administered CARVYKTI in the outpatient setting. How high do you think that could go kind of in the near to midterm and what do you think facilitates greater use in the outpatient setting if you think that's a number that can move up significantly in the near term?

我們有兩個項目，一個正在籌備中，另一個正在商業化。因此，在 CARTITUDE-2 研究的籌備過程中，我們只是好奇您對 E&F 隊列資料的時間安排有何最新想法。關於商業化，您提到大約 30% 的患者在門診接受 CARVYKTI 治療。您認為在近期到中期這個數字會達到多高？如果您認為這個數字在短期內可能會大幅上升，那麼您認為什麼可以促進門診環境中更多的使用？

So I'll take the first question on CARTITUDE-2 cohort E&F question and then my colleague Steve will probably answer on the second. So on CARTITUDE-2 cohort E&F, as a reminder, we enrolled a total of roughly 60 patients in cohort E&F, and these are newly diagnosed multiple myeloma patients. So we're not providing any guidance. But at this point, I think the earliest timing when we can report data probably will be towards the end of this year. And as you know, Vikram, we always report data at major medical conferences. So that's what we can say about timing for cohort E&F. Steve?

因此，我將回答關於 CARTITUDE-2 隊列 E&F 問題的第一個問題，然後我的同事 Steve 可能會回答第二個問題。因此，在 CARTITUDE-2 E&F 群組中，提醒一下，我們在 E&F 群組中總共招募了大約 60 名患者，這些患者都是新診斷的多發性骨髓瘤患者。所以我們不提供任何指導。但就目前而言，我認為我們最早可以報告數據的時間可能是在今年年底。如你所知，維克拉姆，我們總是在重要的醫學會議上報告數據。這就是我們可以說的關於隊列 E&F 的時間安排。史蒂夫？

Thanks, Ying. Yes, the outpatient metric is an important metric, especially as we stand into earlier lines with much larger patient populations. So to the question about what's causing the increase. I mean there's a number of things that are driving outpatient use in the United States.

謝謝，瑩。是的，門診指標是一個重要的指標，特別是當我們處於較早的隊列中，患者群體要大得多時。那麼，關於導致增加的原因的問題。我的意思是，有很多因素推動了美國門診的使用。

One, as I mentioned, just around volume itself. Our sites are recognizing the fact that they need to look at other options other than admitting all these CAR-T patients into their hospitals. In terms of what are we assuming? I mean, like you said, we are at a 30 share today, roughly thereabout. I think we could easily double that. I think the issue of rate limit around the doubling of the outpatient metric would be largely on our ability to get product into market.

正如我所提到的，其中之一就是圍繞音量本身。我們的網站認識到，除了讓所有這些 CAR-T 患者入院之外，他們還需要考慮其他選擇。我們假設什麼？我的意思是，就像你說的，我們今天的股價是 30 股，大約是這個數字。我認為我們可以輕鬆地將其翻倍。我認為門診量加倍的速率限制問題很大程度上取決於我們將產品推向市場的能力。

We're very clear with our sites or sites that have been with us since the very beginning. They have much higher outpatient uses or rates in 30%. As new sites come on board, and we're hoping to get pushing to around 100 this year, if I just need to have patient reps, quite frankly, to ensure that what they're seeing in the global setting from a safety perspective, it's consistent with that of the label. So it's really right now just a matter of getting product into the hands of physicians and allowing them to use this drug to get comfortable with it and then also put the necessary infrastructure that they need to put in place for outpatient use.

我們對我們的網站或從一開始就一直在我們身邊的網站非常清楚。他們的門診使用率或比率要高得多，達到 30%。隨著新網站的加入，我們希望今年能增加到 100 個左右，如果我只需要有耐心的代表，坦白說，以確保他們從安全角度在全球環境中看到的內容，與標籤一致。因此，現在的問題實際上只是將產品交到醫生手中，讓他們能夠適應這種藥物，然後建立供門診使用所需的必要基礎設施。

Our next question comes from Kostas Biliouris with BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 Kostas Biliouris。

Congrats on the progress. A couple of questions from us. So the first one is around the 10,000 slots by year-end 2025, which is great to see again. I'm wondering how should we be thinking beyond 2026. Is there any saturation of the slots you can produce or you can potentially even double this 10,000 slots that you are guiding in the future if there is enough supply?

祝賀取得的進展。我們有幾個問題。所以第一個是到 2025 年底大約有 10,000 個名額，很高興再次看到這個情況。我想知道我們應該如何思考 2026 年之後的情況。您可以生產的老虎機數量是否會飽和，或者如果供應充足，您甚至有可能將未來指導的 10,000 個老虎機數量增加一倍？

And the second question is on CARTITUDE-4 data. If I recall correctly, last year, you showed that during the briefing phase, the CARVYKTI arm had more events than the standard of care arm, although both arms were under standard of care. I recall that there was not really any characteristic between the speculations that could explain this difference, I'm wondering if there is any update on this front.

第二個問題是關於 CARTITUDE-4 資料的。如果我沒記錯的話，去年，您表明在簡報階段，CARVYKTI 組的事件比標準護理組多，儘管兩個組都處於標準護理之下。我記得這些猜測之間並沒有任何特徵可以解釋這種差異，我想知道這方面是否有任何更新。

I'll take your question. So on the first one regarding the 10,000 slots by end of 2025. Obviously, we and our partner, J&J have plans to extend beyond that 10,000 capacity because we do see that there will be a quite significant demand once the drug is approved in the second line and beyond. So I would say we cannot provide any specific guidance on which year. But I can tell you given the roughly $1 billion CapEx program we are conducting now, we think with certain incremental investments, we can actually get to a larger number in the near future after 2026.

我來回答你的問題。因此，第一個關於2025 年底前10,000 個槽位的問題。顯然，我們和我們的合作夥伴強生(J&J) 計劃擴大超過10,000 個槽位的容量，因為我們確實看到，一旦該藥物在第二個階段獲得批准，就會有相當大的需求線以上。所以我想說我們無法就哪一年提供任何具體指導。但我可以告訴你，鑑於我們現在正在進行的大約 10 億美元的資本支出計劃，我們認為透過一定的增量投資，我們實際上可以在 2026 年之後的不久的將來達到更大的數字。

Now of course, there is a limit of what we can do with this current round of CapEx. So -- we and our partner already are thinking about the next step. In fact, a decision could potentially be made this year in 2024, whether we need to conduct another round of CapEx or not? It all depends on, obviously, regulatory approvals and also the market assessment based on the feedback from physicians.

當然，現在我們可以利用這一輪資本支出做的事情是有限的。因此，我們和我們的合作夥伴已經在考慮下一步。事實上，今年2024年可能會做出決定，是否需要進行另一輪資本支出？顯然，這一切都取決於監管部門的批准以及基於醫生回饋的市場評估。

So we do surveys of physicians from time to time based on latest clinical data and also the competitive landscape and you guys can stay tuned on our CapEx plan here. On your second question on the initial imbalance of PFS events in the first couple of months when both arms of the CARTITUDE-4 patients are receiving exactly the same, either bridging therapy on the CARVYKTI arm or the Standard of Care in (inaudible).

因此，我們會根據最新的臨床數據和競爭格局，不時對醫生進行調查，大家可以在這裡關注我們的資本支出計畫。關於你的第二個問題，即頭幾個月內PFS 事件的初始不平衡，當時CARTITUDE-4 患者的雙臂接受完全相同的治療，無論是CARVYKTI 臂的橋接治療還是（聽不清楚）的標準護理。

We and our partner have tried exhaustively to look at all the subgroup analysis and also baseline characteristics. And in fact, Kostas, I can assure you that, that was a question from regulators because we did have the (inaudible) meeting in February when EMA conducted that committee to look at CARTITUDE-4 data. And that was a key question.

我們和我們的合作夥伴已竭盡全力查看所有亞組分析和基線特徵。事實上，Kostas，我可以向你保證，這是監管機構提出的問題，因為我們確實在 2 月份召開了（聽不清楚）會議，當時 EMA 領導該委員會查看 CARTITUDE-4 數據。這是一個關鍵問題。

So I can tell you that after the exhaustive analysis, the only thing we found was that there's a slight imbalance on the dose density for a couple of Standard of Care regimens, including some dose difference in (inaudible) and then some dose difference in (inaudible). And you guys will see that on the briefing book. I think I believe that will be published on Wednesday. So that's the only difference we could have seen.

所以我可以告訴你，經過詳盡的分析後，我們唯一發現的是幾個標準護理方案的劑量密度存在輕微不平衡，包括（聽不清楚）中的一些劑量差異，以及（聽不見）。你們會在簡報上看到這一點。我想我相信它將在周三發布。所以這是我們能看到的唯一區別。

Now does that difference in dose intensity of (inaudible) account for the imbalance in the first couple of months. Unfortunately, the post-hoc analysis, it's difficult to conclude that. But that's pretty much the only thing we could find out. And that is also why after looking at all the data as you see Kostas, we did receive a very clean label from CHMP recommendation, right?

現在，劑量強度的差異（聽不清楚）是否可以解釋前幾個月的不平衡。不幸的是，事後分析，很難得出這樣的結論。但這幾乎是我們唯一能找到的東西。這也是為什麼在查看 Kostas 的所有數據後，我們確實收到了 CHMP 推薦的非常乾淨的標籤，對吧？

If you look at the document, you said that CARVYKTI is recommended for second-line treatment of multiple myeloma after patient has received 1 line of treatment. That includes an IMiD and also protease inhibitor and also the patients are refracted to Revlimid. That's exactly the enrollment criteria for CARTITUDE-4, and that's a clean label we got from Europe. So that hopefully gives you a hint. Thank you.

如果你看文檔，你說CARVYKTI在病人接受1線治療後推薦用於多發性骨髓瘤的二線治療。其中包括 IMiD 和蛋白酶抑制劑，且患者無法使用來那度胺 (Revlimid)。這正是 CARTITUDE-4 的註冊標準，也是我們從歐洲獲得的清潔標籤。希望這能給你一個提示。謝謝。

Our next question comes from Ash Verma with UBS.

我們的下一個問題來自瑞銀集團的 Ash Verma。

So in terms of the belt to get to 10,000 annual doses exiting 2025, by our math, you'll need a slot expansion of roughly 30% every 6 months to get to those pools. Does that align with your thinking and then how much of the 10,000 doses are you expecting Europe to contribute? So that's one. And then secondly, can you comment on the European price in the long run? Would it trend more towards where U.S. pricing is? Or is there any different dynamic at play there?

因此，就到 2025 年退出每年 10,000 劑的劑量帶而言，根據我們的計算，您需要每 6 個月擴大約 30% 的時間段才能到達這些池。這符合您的想法嗎？您預計歐洲將貢獻 10,000 劑疫苗中的多少？這就是其中之一。其次，您能否對歐洲的長期價格發表評論？它會更傾向於美國的定價嗎？或是有什麼不同的動力在運作嗎？

Yes. Maybe I'll take the last question first and then I'll turn to Ying to talk some of the manufacturing questions you had. Yes. In terms of the European pricing, you're going to see some guidance coming out shortly related to Germany pricing dose. We expect to see that by the end of the month, possibly going into the early part of April. So stay tuned on that. Ying, you want to talk about the manufacturing question?

是的。也許我會先回答最後一個問題，然後我會轉向 Ying 談談您遇到的一些製造問題。是的。就歐洲定價而言，您很快就會看到一些與德國定價劑量相關的指導。我們預計到本月底，可能會持續到四月初。所以請繼續關注。 Ying，您想談談製造問題嗎？

Yes. So Ash, let me talk about how we plan to get to that 10,000 number by end of 2025. So first of all, we have 3 internal notes, right? In Raritan, like I mentioned earlier in this call, we already got 2 increases in capacity last year and we're planning something similar this year. And we'll continue to do that in the year of 2025 as well, so that's part of that. But beyond that, we and J&J are doing actually the physical expansion of the Raritan side.

是的。 Ash，讓我談談我們計劃如何在 2025 年底之前達到 10,000 個數字。首先，我們有 3 個內部說明，對吧？在力登，正如我之前在本次電話會議中提到的，去年我們已經增加了兩次產能，今年我們也計劃進行類似的事情。我們也將在 2025 年繼續這樣做，所以這是其中的一部分。但除此之外，我們和強生其實正在對力登方面進行實體擴張。

So essentially, after this physical construction is done this year in 2024. We are doubling our effective area of manufacturing in the Raritan side. So that will also figure into the capacity increase in the year of 2025 because once the physical construction is done this year, we'll spend months installing the equipment, training the staff and then get all the suites validated on the current GMP standard. So that's an important part of the Raritan increase, right?

因此，從本質上講，在今年 2024 年實體建設完成後，我們將把 Raritan 方面的有效製造面積擴大一倍。因此，這也將計入 2025 年的產能成長，因為一旦今年的實體施工完成，我們將花費數月時間安裝設備、培訓員工，然後根據當前 GMP 標準對所有套件進行驗證。所以這是力登成長的一個重要部分，對吧？

And then let's talk about the 2 other notes in Belgium. So the first one is called Obelisc, which is a stand-alone building released. That started clinical batch production in January. And our plan is to bring that site to commercial production for European demand by end of this year. So towards the end of this year, we'll have another commercial note at Ghent. And then the much larger facility called Tech Lane, which is roughly 240,000 square foot by design.

然後我們來談談比利時的另外兩個注意事項。所以第一個叫Obelisc，是發布的獨立建築。一月開始臨床批量生產。我們的計劃是在今年年底前將工廠投入商業生產，以滿足歐洲的需求。因此，到今年年底，我們將在根特發布另一份商業票據。然後是更大的設施，稱為 Tech Lane，設計面積約為 240,000 平方英尺。

The physical construction will be done by end of this year. So our plan is to bring that Tech Lane facility to clinical production early next year. And again, in the second half of 2025, that Tech Lane facility will enter into commercial production mode. So those are the 3 internal nodes. And those are very important cornerstone strategies, how we can get to that 10,000.

實體建設將於今年底完成。因此，我們的計劃是明年初將 Tech Lane 設施投入臨床生產。 2025 年下半年，Tech Lane 工廠將再次進入商業生產模式。這就是 3 個內部節點。這些都是非常重要的基石策略，我們如何才能達到那 10,000 個。

Now beyond that, you guys all know, we executed a 3-way agreement with Novartis last year. It was for 3-year clinical supply. Right now, we're expecting Novartis to file for IND potentially first half of this year. Now that pending the FDA approval of the IND, Novartis will start to produce clinical trial material for us. So that external CMO strategy is also an important pillar of our strategy to get to that 10,000. So all this combined by end of 2025, we're on track at this point to get to that $10,000 annual capacity.

除此之外，你們都知道，我們去年與諾華簽署了一項三方協議。用於 3 年臨床供應。目前，我們預計諾華可能會在今年上半年提交 IND 申請。現在等待 FDA 批准 IND，諾華將開始為我們生產臨床試驗材料。因此，外部 CMO 策略也是我們實現 10,000 家策略的重要支柱。因此，到 2025 年底，所有這些加在一起，我們目前預計將達到 10,000 美元的年產能。

And last, I think, Ash, you asked about the revenue split. Obviously, it's way too early for us to comment because right now, whatever revenue we generate for CARVYKTI from Europe, it's all really by allocation because there's only so much capacity we could allocate to Europe.

最後，我想，阿什，你問到了所得分配的問題。顯然，我們現在發表評論還為時過早，因為現在，無論我們從歐洲為 CARVYKTI 創造什麼收入，這實際上都是透過分配來實現的，因為我們可以分配給歐洲的產能有限。

But in the future, once we have enough capacity to satisfy demand from both the U.S. and European demand, then if you look at some of the prior CAR-T revenue split, it's usually roughly maybe 50-50, slightly favoring the U.S. and then the ex-U.S., especially European revenue is just shy of 50%. So we think that should be the same dynamic for BCMA CAR-T myeloma.

但在未來，一旦我們有足夠的能力來滿足美國和歐洲的需求，那麼如果你看看之前的一些 CAR-T 收入分配，通常大約是 50-50，稍微有利於美國，然後美國以外地區，尤其是歐洲地區的收入略低於50%。因此，我們認為 BCMA CAR-T 骨髓瘤的動態應該相同。

Our next question comes from Edward Tenthoff with Piper Sandler.

我們的下一個問題來自愛德華·滕托夫和派珀·桑德勒。

And I appreciate all the good color and the update today. Congrats on the progress. So my question really has to do with kind of second line plus utilization. How do you envision physicians prioritizing patients assuming label expansion? Do you think that will see CARVYKTI use move earlier line as evidenced by the kind of superior results that you saw from CARTITUDE-4. Is it really going to be up to the sites, how they're allocating CARVYKTI? Any color on your early thoughts on that would be appreciated.

我很欣賞今天所有的好顏色和更新。祝賀取得的進展。所以我的問題確實與第二行加上使用率有關。您如何看待假設標籤擴展時醫生優先考慮患者的情況？您是否認為 CARVYKTI 會使用提前移動線，正如您從 CARTITUDE-4 中看到的那種卓越結果所證明的那樣。這真的取決於網站如何分配 CARVYKTI 嗎？如果您對此有任何早期想法，我們將不勝感激。

Yes. Why don't I take that since we just have some data readout specific to that question. So if you step back and look at the myeloma population segmented by standard risk versus high risk. That's how we do it. And if you assume that of that high-risk population, they represent about 25% of the total, and that's pretty consistent across all lines of therapy.

是的。為什麼我不接受這個，因為我們只有一些特定於該問題的數據讀數。因此，如果您退後一步，請看看按標準風險與高風險劃分的骨髓瘤族群。我們就是這樣做的。如果你假設高風險族群中，他們約佔總數的 25%，而且這在所有治療方案中都相當一致。

What our data is showing, and we ran some research right after last year's ASCO when we released this data and we actually just re ran it recently. And it's been fairly consistent. So based upon the results that Ying shared earlier in terms of our CARTITUDE-4 data, we're seeing, for sure, that 20% to 25% high-risk group moving over or physician is going very quickly with CAR-T therapy (inaudible) and second line.

我們的數據顯示了什麼，我們在去年 ASCO 會議之後發布這些數據時進行了一些研究，實際上我們最近剛剛重新運行了它。而且一直都相當一致。因此，根據 Ying 先前分享的 CARTITUDE-4 數據結果，我們可以肯定地看到，20% 到 25% 的高風險群體或醫生正在快速接受 CAR-T 療法（聽不清楚）和第二行。

And then we're also seeing -- and this was a bit of a change, which was a positive change for patients is, yes, with even within the standard risk population, physicians have said that they see them moving forward with CARVYKTI in standard risk in second line plus population as well. So that's quite exciting. Now that -- as you know, that's quite a sizable patient population for us. But that data, like I said, is fairly fresh now. We just had that readout here in the first quarter.

然後我們也看到——這是一個小小的變化，這對患者來說是一個積極的變化，是的，即使在標準風險人群中，醫生也表示他們看到他們在標準風險人群中繼續使用CARVYKTI二線及人群的風險也是如此。所以這非常令人興奮。如您所知，這對我們來說是一個相當大的患者群體。但正如我所說，這些數據現在還相當新鮮。我們剛剛在第一季獲得了該數據。

I guess the last maybe tidbit of information, this real quickly is does the new dynamic that this launch represents is the referral dynamic, especially in the standard risk group, so as opposed to our CARTITUDE-1 launch, which was pretty much most of those (inaudible) plus patients were already within our hospitals through our partner and our partners fully staff trained up and ready to go.

我想最後一個消息可能是，這次發布所代表的新動態是推薦動態，特別是在標準風險組中，所以與我們的 CARTITUDE-1 發布相反，後者幾乎是其中的大部分（聽不清）加上患者已經通過我們的合作夥伴進入我們的醫院，我們的合作夥伴的工作人員經過全面培訓並準備就緒。

They'll be pushing from a referral front in the outpatient setting where most of the standard risk patients are today to refer those patients that are CAR-T eligible to our site. So that's the only, I would say, added wrinkle to the second line plus indication is really this active engagement in terms of referral from the outpatient clinics into our hospital.

他們將從門診轉診前沿推動將那些符合 CAR-T 資格的患者轉診到我們的網站，目前大多數標準風險患者都在門診轉診。因此，我想說，這是第二條線的唯一補充，加上指示實際上是從門診診所轉診到我們醫院方面的積極參與。

Our next question comes from Justin Zelin with BTIG.

我們的下一個問題來自 BTIG 的 Justin Zelin。

Congrats on the progress. So Ying, I wanted to ask if you could give us an update on the out-of-spec rate that you're seeing and your confidence on the FDA's widening of the out-of-spec window with the most recent submission.

祝賀取得的進展。 Ying，我想問您是否可以向我們提供您所看到的不合格率的最新信息，以及您對 FDA 在最近提交的文件中擴大不合格窗口的信心。

Justin, thanks for the question. So I think what I can say is that in the last 9 months or 3 quarters or so, the out spec rate has been quite stable, like we mentioned, it's in the teens range. So at this point, we are seeing a very stable trend of OS. And the next leg up would be pending the FDA approval, we hope we'll get a wider release spec and then we hope to have another significant reduction in the out spec rate.

賈斯汀，謝謝你的提問。所以我想我可以說的是，在過去 9 個月或 3 個季度左右的時間裡，超出規格率一直相當穩定，就像我們提到的那樣，它在十幾歲的範圍內。所以在這一點上，我們看到作業系統的趨勢非常穩定。下一步將等待 FDA 的批准，我們希望能夠獲得更廣泛的發布規格，然後我們希望再次大幅降低規格外率。

Now regarding the FDA approval. So as you know, Justin, we did submit it in the supplemental (inaudible) in June of last year asking us the FDA to widen our release spec based on the clinical data we received from CARTITUDE-4 data. So we provided a wealth of what I call the sensitivity analysis by correlating the release spec with the clinical outcome.

現在關於FDA的批准。如你所知，賈斯汀，我們確實在去年 6 月的補充文件（聽不清楚）中提交了它，要求 FDA 根據我們從 CARTITUDE-4 數據收到的臨床數據擴大我們的發布規範。因此，我們透過將發布規範與臨床結果相關聯，提供了大量我所說的敏感度分析。

At this point, we are still confident that we should be able to receive the wider spec but we don't comment on detailed interaction with the agency. You're going to have to wait and see when we receive the FDA approval, then we'll let you guys know what kind of the regulatory action the agency has taken.

目前，我們仍然相信我們應該能夠收到更廣泛的規範，但我們不會就與該機構的詳細互動發表評論。你們必須等著看我們何時獲得 FDA 的批准，然後我們會讓你們知道該機構採取了什麼樣的監管行動。

Our next question comes from Mitchell Kapoor with H.C. Wainwright.

我們的下一個問題來自米切爾·卡普爾 (Mitchell Kapoor) 和 H.C.溫賴特。

I have 2. The first one is kind of on the strategy of moving into earlier lines, knowing that you'll undoubtedly treat patients who would have otherwise been treated in the later line setting, can you kind of help us contextualize the true additional expansion opportunity of moving into earlier lines?

我有 2。第一個是關於進入較早生產線的策略，知道您無疑會治療本來會在較晚生產線設置中接受治療的患者，您能否幫助我們將真正的額外擴展背景化有機會進入較早的生產線嗎？

And then the second is on the strategy of the sales force messaging, assuming a new approval in the earlier line setting, with new accounts, do you expect to ask the physician to potentially put patients on CARVYKTI in later lines first and then move to earlier lines? Or would you initially ask them to begin their patients in earlier line setting?

第二個是關於銷售人員訊息傳遞的策略，假設在較早的線路設定中獲得新的批准，並且有新的帳戶，您是否希望要求醫生可能首先將患者放在較晚的線路中使用CARVYKTI，然後再轉移到較早的線路路線？或者您最初會要求他們在較早的線路設定中開始為患者提供服務嗎？

Yes, this is Steve. Thanks for that question. That's a good one. So we will be -- obviously, we'll be in launch mode with CARTITUDE-4. So we will be messaging hard. Obviously, the new indication, the second line plus nature of it in all the patients that meet the eligibility criteria. So we will be really from a messaging perspective, really dominating our message here on CARTITUDE-4 and second-line plus.

是的，這是史蒂夫。謝謝你提出這個問題。這是一件好事。所以我們將會——顯然，我們將進入 CARTITUDE-4 的啟動模式。所以我們會努力傳達訊息。顯然，新的適應症、二線藥物及其性質適用於所有符合資格標準的患者。因此，我們將真正從訊息傳遞的角度來看，真正主導我們在 CARTITUDE-4 和二線 plus 上的消息。

As far as the eligible patient population, I could actually give you some numbers here that may help you and these are folks who -- patients -- these are global numbers that meet the eligibility criteria, not necessarily a treated population, but at least the patients that are eligible. This may help with some of your math, your modeling. So in the frontline setting, this is a global number.

至於符合條件的患者群體，我實際上可以在這裡給你一些可能對你有幫助的數字，這些人是患者，這些是符合資格標準的全球數字，不一定是接受治療的群體，但至少是符合有條件的患者。這可能會對你的一些數學和建模有所幫助。所以在前線環境中，這是一個全球數字。

We foresee about 22,000 patient opportunity globally CARTITUDE-4, there's about a tripling of that moving to 60,000. (inaudible) around the same number, 20,000 to 28,000. So hopefully, that will give you some perspective in terms of incremental impact as we go into earlier lines.

我們預計 CARTITUDE-4 全球將有約 22,000 個患者機會，這一數字將增加三倍，達到 60,000 個。 （聽不清楚）大約相同的數字，20,000 到 28,000。因此，希望當我們進入前面的內容時，這會給您帶來增量影響方面的一些看法。

Our next question comes from George Farmer with Scotiabank.

我們的下一個問題來自豐業銀行的喬治法默。

You guys mentioned 80% market share of CARVYKTI in multiple myeloma versus ABECMA. Can you comment on what's driving that decision for physicians to use ABECMA even in the first place? And do you think that can improve? And then second question, maybe I missed this. Are you still guiding for profitability in 2026?

你們提到 CARVYKTI 與 ABECMA 相比，在多發性骨髓瘤的市佔率為 80%。您能否評論一下是什麼促使醫師決定使用 ABECMA？您認為這可以改進嗎？然後是第二個問題，也許我錯過了這個。您還在指導2026年的獲利能力嗎？

This is Steve again. We had a little mechanical difficulty on hearing. Could you repeat that first question? I think you added -- the question was related to ABECMA and ABECMA use.

這又是史蒂夫。我們的聽力有一點機械困難。你能重複第一個問題嗎？我想你補充說——這個問題與 ABECMA 和 ABECMA 的使用有關。

Yes. So you guys said you had like 80% market share, right? And just like wondering what's driving that decision to even use ABECMA, do you think, and over CARVYKTI? And can you improve upon that? And then the second question had to do with profitability in 2026. Is that still a message you guys are communicating?

是的。你們說你們擁有大約 80% 的市場份額，對嗎？就像想知道是什麼促使您決定使用 ABECMA，而不是 CARVYKTI？你能對此進行改進嗎？第二個問題與 2026 年的獲利能力有關。你們仍然在傳達這樣的訊息嗎？

Sure. I'll take the first one. Sorry guys, we were having some WiFi problems, they got all right here. Can you guys hear me okay on your end?

當然。我就拿第一個。抱歉，大家，我們遇到了一些 WiFi 問題，他們在這裡一切都好。你們聽得到我的聲音嗎？

Yes.

是的。

Okay, good. Okay. I think the first question had to do with, once again, ABECMA use and why you are going to bother using ABECMA. I think what's happening here, and this is the research now speaking is there's still a large number of patients in this second line setting that we just, quite frankly, can't satisfy yet. So therefore, thankfully, there's another CAR-T therapy available. and you're seeing ABECMA used in that setting. It's quite -- it's that simple.

好的。好的。我認為第一個問題再次與 ABECMA 的使用以及為什麼您要費心使用 ABECMA 有關。我認為這裡發生的事情，這就是現在的研究，仍然有大量患者處於二線治療中，坦白說，我們還無法滿足。因此，值得慶幸的是，還有另一種 CAR-T 療法可用。您會看到 ABECMA 在該設定中使用。就這麼簡單。

The other thing to think about, and we -- in the United States, we don't have marrying territories or commercial map, so to speak. We're not all in identical centers. So in some centers where ABECMA is, obviously, they're the only CAR-T in town, they're going to get ABECMA but that doesn't happen very frequently. So that is the other area where you might see some ABECMA use just in terms of the commercial footprint being a bit different than us. Lori, do you want to talk about process?

另一個需要考慮的是，我們——在美國，可以這麼說，我們沒有結婚領土或商業地圖。我們並不都在相同的中心。因此，顯然，在 ABECMA 所在的一些中心，他們是鎮上唯一的 CAR-T，他們將獲得 ABECMA，但這種情況並不經常發生。因此，這是您可能會看到一些 ABECMA 使用的另一個領域，只是商業足跡與我們略有不同。 Lori，你想談談流程嗎？

Sure. So the managing is still consistent with profitability in 2026. We've talked about bridging to profitability for the BCMA program. What's going to be critical there is our penetration into earlier lines of therapy and kind of our uptake on the revenues and continuing to drive our costs down. And then the other component of that is really, I talked about earlier, is our pipeline advancement. So by 2026, we are projecting that we can break even or be profitable from an overall company perspective.

當然。因此，管理仍然與 2026 年的盈利能力保持一致。我們已經討論了 BCMA 計劃的盈利能力。至關重要的是我們對早期治療方案的滲透以及我們對收入的吸收並繼續降低我們的成本。我之前談到過，其中的另一個組成部分實際上是我們的管道進步。因此，到 2026 年，我們預計從公司整體角度來看，我們可以實現收支平衡或獲利。

Our next question comes from Gena Wang with Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

Sorry, I dialed in late, so I apologize if those questions already been asked. So first question is regarding -- I think you mentioned that in the past, by the end of 2025, your capacity can reach 10,000 doses? And what would take for you to reach 20,000 to 25,000 doses? And how long would that take? And then second question is regarding ODAC, later this week. So maybe if you can share like what kind of data you submit to the FDA? And do you expect some discussion regarding the toxicity profile such as the neurotox?

抱歉，我遲到了，所以如果這些問題已經被問到，我深感抱歉。第一個問題是──我想你過去提到過，到2025年底，你們的產能可以達到10,000劑？需要什麼才能達到 20,000 到 25,000 劑劑量？那需要多長時間？第二個問題是關於 ODAC，將於本週稍後提出。那麼也許您可以分享一下您向 FDA 提交的資料類型嗎？您是否期望對毒性特徵（例如神經毒素）進行一些討論？

This is Ying. I'll take your questions. So on the first one, I think I have commented previously that with this current round of very extensive capital investment between us and our partner, J&J, we think we can go beyond that 10,000 and potentially goes to the numbers to put it. It will take some incremental investment, and it will take probably another couple of years to get there.

這是瑩。我會回答你的問題。因此，關於第一個問題，我想我之前已經評論過，透過我們和我們的合作夥伴強生公司之間本輪非常廣泛的資本投資，我們認為我們可以超越 10,000，並有可能用數字來表達。這需要一些增量投資，而且可能還需要幾年時間才能實現。

But at this point, I would rather not share any details around that. Just suffice to say that, yes, we'll go beyond 10,000 with this current round of CapEx and also potentially help from our external partners on (inaudible) side. So that's the answer for your question -- the first question.

但目前，我不想分享任何相關細節。我只想說，是的，我們本輪的資本支出將超過 10,000，並且還可能從我們的外部合作夥伴（聽不清楚）方面獲得幫助。這就是你的問題的答案——第一個問題。

And then the second one regarding ODAC, I can tell you that it's very clear from the PFA communication in writing and also verbal of that -- the focus of the ODAC will be discussed in the overall survival benefit CARVYKTI provides in this patient population valued in the CARTITUDE-4 study. And in the context of some early imbalance, which you have seen from the PFS curve, right? So that's really the focus of the ODAC here in terms of what they're focusing on.

然後是關於 ODAC 的第二個問題，我可以告訴您，從 PFA 的書面和口頭溝通中可以清楚地看出 - ODAC 的重點將討論 CARVYKTI 在這一患者群體中提供的總體生存獲益CARTITUDE-4研究。在一些早期失衡的背景下，您從 PFS 曲線中看到了這一點，對嗎？因此，這確實是 ODAC 的重點所在。

Now I'm sure it's a 4-hour ODAC session. And in any ODAC meeting, they always talk about the overall risk benefit. And that probably will touch upon also some of the adverse events, including CRS, neurotox, second primary malignancies. But like I mentioned, again, the survival is the focus -- the survival benefit is the focus not the SPM issue or the neurotox issue at this point based on what we heard from FDA. Thank you.

現在我確定這是一個 4 小時的 ODAC 會議。在任何 ODAC 會議上，他們總是談論整體風險收益。這也可能涉及一些不良事件，包括慢性鼻竇炎、神經毒素、第二原發惡性腫瘤。但正如我再次提到的，生存是焦點——根據我們從 FDA 聽到的情況，生存獲益是重點，而不是 SPM 問題或神經毒素問題。謝謝。

Our next question comes from Kelsey Goodwin with Guggenheim.

我們的下一個問題來自古根漢的凱爾西古德溫。

First, I guess, how should we think about the first quarter '24 sales given kind of the step up in the back half of '23 and likely not being fully recognized given the fourth quarter sales that we saw? And then secondly, on the AdCom. So given both are on the same day and crossover is obviously a main focus. Could you remind us the rationale for not allowing crossover in CARTITUDE-4? And do you think that, that might be a hang up for the FDA in any way?

首先，我想，考慮到 23 年下半年的成長，以及考慮到我們看到的第四季的銷售情況，我們應該如何看待 24 年第一季的銷售？其次，關於 AdCom。因此，考慮到兩者都在同一天，交叉顯然是一個主要焦點。您能否提醒我們 CARTITUDE-4 中不允許交叉的理由？您是否認為這對 FDA 來說可能是一個障礙？

So for quarter-over-quarter growth, we're not giving specific guidance, but I can tell you, we do anticipate quarter-over-quarter growth with more pronounced growth in the second half of the year with the anticipated launch into the second line setting. Ying, I don't know if you want to talk about crossover?

因此，對於季度環比增長，我們沒有給出具體的指導，但我可以告訴你，我們確實預計季度環比增長，下半年增長將更加明顯，預計進入第二季度線路設置。瑩，不知道你想不想聊跨界？

Sure. So thank you for the question, Kelsey. As you know, there is some difference between the 2 trials. And in the CARTITUDE-4 study, we did not allow crossover, which means we did not provide the patients who progressed on the Standard of Care to cross over to (inaudible).

當然。謝謝你的提問，凱爾西。如您所知，兩次試驗之間存在一些差異。在 CARTITUDE-4 研究中，我們不允許交叉，這意味著我們沒有為在護理標準上取得進展的患者提供交叉（聽不清楚）。

However, once the patient progresses on the Standard of Care, they can actually get any commercially available therapy, including the 2 commercially available CAR-T therapies and also the commercially available bispecifics. And also, they can enroll into clinical trials. So you will see some of the details on Wednesday when a briefing will come out, what those subsequent therapies those patients receive.

然而，一旦患者在護理標準上取得進展，他們實際上可以獲得任何市售療法，包括兩種市售 CAR-T 療法以及市售雙特異性藥物。而且，他們還可以參加臨床試驗。因此，您將在周三發布簡報時看到一些細節，這些患者將接受哪些後續治療。

But I can tell you, yes, there are patients who did receive CAR-T therapies after progression. So that's the fact. Now on the other hand, even though we didn't allow the crossover. But -- before we started enrolling patients, we actually had a very brief communication with both FDA and also EMA as global regulators to talk about the product of CARTITUDE-4 including the -- not allowing the crossover design. So at this point, I don't think that will be a big focus of debate here at ODAC.

但我可以告訴你，是的，確實有一些患者在疾病進展後接受了 CAR-T 治療。這就是事實。現在，另一方面，即使我們不允許交叉。但是，在我們開始招募患者之前，我們實際上與 FDA 和 EMA 作為全球監管機構進行了非常簡短的溝通，討論 CARTITUDE-4 的產品，包括不允許交叉設計。因此，我認為目前這不會成為 ODAC 爭論的焦點。

That's all the questions we have for today. Thank you for your participation. You may now disconnect. Everyone, have a great day.

這就是我們今天要問的所有問題。感謝您的參與。您現在可以斷開連線。大家，祝你有美好的一天。