Legend Biotech Corp (LEGN) 2024 Q1 法說會逐字稿

Good day, ladies and gentlemen. Thank you for standing by. Welcome to Legend Biotech First Quarter 2024 Financial Results Conference Call.

美好的一天，女士們先生們。謝謝你的支持。歡迎參加傳奇生物2024年第一季財務業績電話會議。

(Operator Instructions)

（操作員說明）

Please note that today's conference may be recorded. I will now hand the conference over to your speaker host, Jessie Yeung, Head of Investor Relations and Public Relations. Please go ahead.

請注意，今天的會議可能會被錄音。我現在將會議交給演講主持人投資者關係和公共關係主管 Jessie Yeung。請繼續。

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 first quarter 2024 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.

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 2024 年第一季的業績。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)。

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.

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. Thank you.

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。謝謝。

Hello, everyone, and welcome to our first quarter earnings call. I am pleased that you could join us. As many of you on this call know, 2024 has been an eventful year for us. Obviously, our major news was the approval of CARVYKTI by the FDA and European Commission for second-line relapsed or refractory multiple myeloma. These approvals have the potential to change the treatment paradigm for tens of thousands of patients in the United States and Europe. The feedback from key opinion leaders, oncologists, advocates, patients and caregivers has been tremendous.

大家好，歡迎參加我們的第一季財報電話會議。我很高興你能加入我們。正如本次電話會議中的許多人所知，2024 年對我們來說是不平凡的一年。顯然，我們的重大新聞是 FDA 和歐盟委員會批准 CARVYKTI 用於二線復發或難治性多發性骨髓瘤。這些批准有可能改變美國和歐洲數萬名患者的治療模式。來自關鍵意見領袖、腫瘤學家、倡議者、患者和照護者的回饋非常巨大。

On March 15, we received international media attention when the FDA's Oncologic Drug Advisory Committee, or ODAC, meeting raised awareness about multiple myeloma and the positive benefit-risk profile of CARVYKTI.

3 月 15 日，FDA 腫瘤藥物諮詢委員會 (ODAC) 召開會議，提高了人們對多發性骨髓瘤和 CARVYKTI 積極獲益風險概況的認識，引起了國際媒體的關注。

ODAC's unanimous 11 to 0 recommendation in favor of CARVYKTI was independent and objective validation of its value proposition. We also added another noteworthy approval to our growing list. The Brazilian health regulatory agency has approved CARVYKTI for second-line multiple myeloma.

ODAC 以 11 比 0 的比例一致推薦 CARVYKTI，這是對其價值主張的獨立客觀驗證。我們還在不斷增長的清單中添加了另一個值得注意的批准。巴西衛生監管機構已批准 CARVYKTI 用於二線多發性骨髓瘤。

I am pleased to report that CARVYKTI is now available by prescription in Brazil. Our patient-facing colleagues and those who work in manufacturing are energized and eager to share our transformative therapy with more patients around the world.

我很高興地報告，CARVYKTI 現已在巴西透過處方取得。我們面向患者的同事和製造業工作人員充滿活力，渴望與世界各地更多的患者分享我們的變革性療法。

As you will see on our addressable market slide, our second-line indication translates to an addressable patient population of 80,000 across 3 major markets.

正如您將在我們的可尋址市場幻燈片中看到的，我們的二線適應症意味著 3 個主要市場的可尋址患者群體為 80,000 名。

Turning to financial development. CARVYKTI net trade sales for the first quarter were $157 million, which is a 100% increase year-over-year. Sequentially, net sales decreased by $2 million from $159 million in the fourth quarter of last year. This was a result of phasing due to the timing of orders and when they were delivered and built for as well as manufacturing testing needed for the upcoming expansion.

轉向金融發展。 CARVYKTI第一季淨貿易銷售額為1.57億美元，年增100%。隨後，淨銷售額比去年第四季的 1.59 億美元減少了 200 萬美元。這是由於訂單時間、交付和建造時間以及即將到來的擴張所需的製造測試而導致的分階段結果。

Importantly, there was growth in patient demand and obviously, that was before the recent second-line approvals. So we do anticipate continued growth for CARVYKTI, particularly in the second half of the year as we continue to add more swaps and expand our capacity. Right now, there's no higher priority in the company than making more supply available to the market and reducing the van-to-van time.

重要的是，患者需求有所增長，而且顯然這是在最近的二線藥物批准之前。因此，我們確實預期 CARVYKTI 會持續成長，特別是在今年下半年，因為我們將繼續增加更多掉期並擴大產能。目前，公司最優先考慮的事情莫過於向市場提供更多供應並減少貨車之間的時間。

We're working to expand production from every angle. We're continually increasing production at our Raritan, New Jersey facility, where we have doubled sale processing capacity since the beginning of 2023. We're laser-focused on completing physical expansion of our Raritan site this year. We plan to double CARVYKTI capacity by the end of 2024 compared to the end of 2023.

我們正在努力從各個角度擴大生產。我們不斷提高新澤西州 Raritan 工廠的產量，自 2023 年初以來，我們的銷售處理能力已增加了一倍。我們計劃在 2024 年底前將 CARVYKTI 產能比 2023 年底增加一倍。

Our production capacity will be augmented later in the year when our Obelisc facility in Ghent, Belgium is approved for commercial production. Clinical production already started back in January. With the second-line FDA approval, the specifications for manufacturing CARVYKTI were widened, which should give us greater yield going forward.

今年晚些時候，當我們位於比利時根特的 Obelisc 工廠獲準進行商業生產時，我們的生產能力將會增強。臨床生產早在一月就已經開始。隨著二線 FDA 的批准，生產 CARVYKTI 的規格得到擴大，這應該會為我們帶來更高的產量。

Finally, Legend and J&J expanded a previous agreement with Novartis to perform commercial manufacturing for CARVYKTI through the end of 2029. The increases to our production capacity will help ensure we meet our target of annualized capacity of 10,000 patient slots by the end of 2025.

最後，傳奇和強生擴大了先前與諾華的協議，在 2029 年底之前進行 CARVYKTI 的商業生產。

Our cash balance now stands at $1.3 billion, which we believe provides us the resources needed to increase production and gives us financial runway into 2026 when we expect to begin to achieve an operating profit. In other developments, we continue to bring more hospitals online as authorized treatment centers. We have now a total of 72 U.S. hospitals certified to treat CARVYKTI patients.

我們的現金餘額目前為 13 億美元，我們相信這為我們提供了增加產量所需的資源，並為我們提供了到 2026 年預計開始實現營業利潤的財務跑道。在其他方面，我們繼續將更多醫院作為授權治療中心上線。目前，美國共有 72 家醫院獲得了治療 CARVYKTI 患者的認證。

So our reach in the community is growing in parallel with the increase in eligible patients. Outpatient treatment comprises approximately 1/3 of our volume and remains an important differentiator for us. Due to the longer onset of CRS for CARVYKTI patients, this side effect can potentially be managed in the outpatient setting, which allows those hospital beds to be utilized for other patients who need them.

因此，隨著符合條件的患者數量的增加，我們在社區中的影響力也不斷擴大。門診治療約占我們治療量的 1/3，並且仍然是我們的重要差異化因素。由於 CARVYKTI 患者的 CRS 發病時間較長，這種副作用可能在門診環境中得到控制，使這些醫院病床可用於其他需要的患者。

Finally, since our last earnings call in March, we published our first ESG report. Not only does it summarize our achievements as a responsible corporate citizen, the report provides a great overview of the company and transparency into how we conduct our business.

最後，自 3 月上次財報電話會議以來，我們發布了第一份 ESG 報告。該報告不僅總結了我們作為負責任的企業公民所取得的成就，還提供了對公司的全面概述以及我們開展業務的透明度。

To sum up, so far in 2024, we have achieved our significant regulatory goals and are working to execute with excellence to meet the growing demand for CARVYKTI.

總而言之，2024 年迄今為止，我們已經實現了重要的監管目標，並正在努力卓越執行，以滿足對 CARVYKTI 不斷增長的需求。

Now I would like to turn the call over to Lori to walk you through the financials for the first quarter. Lori?

現在我想將電話轉給洛里，讓您了解第一季的財務狀況。洛瑞？

Thank you, Ying. And good morning, everyone. As Ying mentioned, we generated approximately $157 million in total net sales for CARVYKTI during the first quarter, an increase of 118% year-over-year. Sequential growth was roughly flat due to the timing of orders and when they were delivered and billed for as well as manufacturing, testing needed for the upcoming expansions. As a reminder, we show equally in all profits and losses for CARVYKTI ex China with our partner, Janssen.

謝謝你，瑩。大家早安。正如應提到的，我們第一季 CARVYKTI 的總淨銷售額約為 1.57 億美元，年增 118%。由於訂單時間、交付和計費時間以及即將到來的擴張所需的製造和測試，連續成長大致相當。提醒一下，我們與我們的合作夥伴楊森在中國以外的 CARVYKTI 的所有利潤和虧損中均等。

Turning to revenue. Total revenues for the first quarter were $94 million, consisting of $78.5 million of collaboration revenue from the sale of CARVYKTI and license revenue of $12.2 million from the recognition of deferred revenue in connection with our agreement with Novartis to develop, manufacture and commercialize LB2102 and other potential CAR-T therapies selectively targeting DL3.

轉向收入。第一季總收入為 9,400 萬美元，其中包括來自銷售 CARVYKTI 的 7,850 萬美元合作收入和來自與諾華就開發、製造和商業化 LB2102 及其他藥物的協議確認遞延收入的 1,220 萬美元授權收入。性標靶DL3 的潛在CAR-T 療法。

Net loss for the quarter ended March 31, 2024, was $59.8 million or a loss of $0.16 per share compared to a net loss of $112.1 million or a loss of $0.34 per share for the same period last year.

截至 2024 年 3 月 31 日的季度淨虧損為 5,980 萬美元，即每股虧損 0.16 美元，而去年同期淨虧損為 1.121 億美元，即每股虧損 0.34 美元。

Moving on to expenses. Collaboration cost of revenue for the first quarter of 2024 was $49.1 million compared to $35.6 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 expansions.

繼續討論支出。 2024 年第一季的合作收入成本為 4,910 萬美元，去年同期為 3,560 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。

Additionally, cost of license and other revenue for the first quarter of 2024 was $5.6 million compared to no cost of license and other revenue for the first quarter of 2023. These costs are in connection with our agreement with Novartis to develop, manufacture and commercialize LB2102 and other potential CAR-T therapies selectively targeting DL3.

此外，2024 年第一季的授權和其他收入成本為 560 萬美元，而 2023 年第一季沒有授權和其他收入成本。選擇性標靶DL3 的潛在CAR-T 療法。

Research and development expenses for the first quarter 2024 were $101 million compared to $84.9 million for the same period last year. The increase of $16.1 million for the 3 months ended March 31, 2024, compared to 3 months ended March 31, 2023, was due to primarily to research and development activities in cilta-cel, including higher patient enrollment for Phase III clinical trials and continued investment as well in our solid tumor programs, which includes 2 IND approvals that advanced into Phase I development.

2024 年第一季的研發費用為 1.01 億美元，而去年同期為 8,490 萬美元。與截至2023年3月31日的三個月相比，截至2024年3月31日的三個月增加了1,610萬美元，主要是由於cilta-cel的研發活動，包括III期臨床試驗的患者入組人數增加以及持續的以及對我們的實體瘤項目的投資，其中包括兩項 IND 批准，並已進入 I 期開發。

Administrative expenses for 3 months ended March 31, 2024, were $31.9 million compared to $22.2 million for the same period last year. The increase of $9.7 million year-over-year is primarily due to the expansion of administrative functions and infrastructure to increase manufacturing capacity. Selling and distribution expense for 3 months ending March 31, 2024, was $24.2 million compared to $18 million for the same period last year. The increase of $6.3 million year-over-year due to the costs associated with the commercialization of CARVYKTI, including the expansion of the sales force and second-line indication and launch preparations.

截至 2024 年 3 月 31 日的三個月管理費用為 3,190 萬美元，去年同期為 2,220 萬美元。年比增加 970 萬美元主要是由於擴大行政職能和基礎設施以提高製造能力。截至 2024 年 3 月 31 日的三個月銷售和分銷費用為 2,420 萬美元，而去年同期為 1,800 萬美元。年比增加 630 萬美元是由於與 CARVYKTI 商業化相關的成本，包括擴大銷售團隊以及二線適應症和上市準備。

To summarize, our spending remains on track, and we continue to maintain a strong balance sheet. As of March 31, we have $1.3 billion in cash and equivalence, deposits and investments. Additionally, we earned in April a milestone payment of $45 million in connection with the FDA's approval of CARVYKTI's label expansion to treat second-line multiple myeloma in accordance with the Janssen agreement. Thus, we believe we have sufficient capital to fund our operating and capital expenditures into 2026 when we expect to begin to achieve an operating profit. Thank you.

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 3 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，由於 FDA 根據楊森協議批准 CARVYKTI 標籤擴展以治療二線多發性骨髓瘤，我們在 4 月獲得了 4500 萬美元的里程碑付款。因此，我們相信我們有足夠的資本為 2026 年的營運和資本支出提供資金，屆時我們預計將開始實現營運利潤。謝謝。

I will now pass it back to Ying for closing remarks.

我現在將其傳回給Ying以供結束語。

Thank you, Lori. To sum up, 2024 has already been a monumental year for Legend with a string of regulatory successes. CARVYKTI continues to be the fastest launched CAR-T therapy and now we have new opportunities to serve even more patients. I want to thank each of our 1,900 employees for their commitment and dedication that will ensure patients who need CARVYKTI are able to access it.

謝謝你，洛瑞。綜上所述，2024 年對於聯想來說是具有里程碑意義的一年，並取得了一系列監管成功。 CARVYKTI 仍然是推出最快的 CAR-T 療法，現在我們有新的機會為更多患者提供服務。我要感謝我們 1,900 名員工中的每一位員工的承諾和奉獻，這將確保需要 CARVYKTI 的患者能夠獲得它。

And with that, we'd like to take your questions.

因此，我們願意回答您的問題。

(Operator Instructions)

（操作員說明）

Now our first question coming from the line of Jessica Fye with JPMorgan.

現在我們的第一個問題來自摩根大通的 Jessica Fye。

I have two, please, sort of related. First, I know 1Q was impacted by a number of non-revenue batches for comparability work. How should we think about the scale of that work in 2Q and beyond? And then second, when you talk about doubling capacity from the end of '23 to the end of '24, but I think you mentioned that the Obelisc commercial production was going to be kind of back-half weighted or back-end weighted. What does that mean for how we should think about revenue year-over-year in '24 relative to '23?

我有兩個，有點相關。首先，我知道第一季受到許多非收入批次的可比性工作的影響。我們該如何看待第二季及以後這項工作的規模？其次，當您談到從 23 年底到 24 年底將產能翻倍時，但我認為您提到 Obelisc 商業生產將採用後半加權或後端加權。這對我們如何看待 24 年相對於 23 年的年比收入意味著什麼？

I'm just trying to figure out kind of is it one-to-one on that doubling year-end from your end to your end of capacity? Or are there other factors we should think about when we're thinking about revenue this year?

我只是想弄清楚，從你的能力結束到你的能力結束，年底翻倍是一對一的嗎？或者說，當我們考慮今年的收入時，我們還應該考慮其他因素嗎？

This is Ying. I'll help answer those two. So first on the manufacturing investments, I would tell you that qualitatively in first quarter of this year, we did have a number of non-revenue-generating rounds. And that includes bringing up the CMO from Novartis and also bringing up a couple of other additional nodes, including our facilities in Ghent up for production, including clinical and then in the future also for commercial production.

這是瑩。我來幫忙解答這兩個問題首先，關於製造業投資，我想告訴大家，從品質上來說，今年第一季度，我們確實進行了許多非創收輪次投資。這包括從諾華建立 CMO，並建立其他幾個節點，包括我們在根特的設施進行生產，包括臨床，然後在未來也用於商業生產。

So I cannot disclose exactly the number of the non-revenue-generating rounds, but it is on a similar order of magnitude compared to, for example, clinical rounds. And we do expect that for the rest of the year, in the next 3 quarters, that number will come down. The reason is we are pretty much complete in terms of the work we're doing with Novartis.

因此，我無法準確透露非創收輪次的數量，但與臨床輪次相比，其數量級相似。我們確實預計，在今年剩餘時間裡，在接下來的三個季度，這個數字將會下降。原因是我們與諾華所做的工作基本上已經完成。

So we believe that Novartis is in a position to file IND very soon. And assuming the IND is cleared by the FDA, we expect Novartis to start clinical trial production in the third quarter and then followed by commercial production first quarter of next year.

因此我們相信諾華能夠很快提交 IND 申請。假設 IND 獲得 FDA 批准，我們預計諾華將在第三季開始臨床試驗生產，然後在明年第一季進行商業生產。

And then, of course, we also have 2 other facilities in Ghent. The first one, Phase I is called Obelisc, and Obelisc is already producing for CARTITUDE-6 as we speak, and we expect pending regulatory approval probably around late third quarter or early fourth quarter this year, fourth quarter this year, Obelisc will start commercial production.

當然，我們在根特還有另外 2 個工廠。第一個階段稱為Obelisc，就在我們說話的時候，Obelisc 已經在為CARTITUDE-6 生產，我們預計可能會在今年第三季末或第四季初左右獲得監管批准，今年第四季度，Obelisc將開始商業化生產。

And then followed by our much larger facility in Belgium called the Tech Lane. Tech Lane right now is on track to complete physical construction and validation by end of this year. So we expect that facility to start clinical trial production early next year, followed by commercial production in the second half of 2025. So that's kind of like the cadence.

接下來是我們位於比利時的更大的工廠，稱為 Tech Lane。 Tech Lane 目前預計在今年年底前完成實體建設和驗證。因此，我們預計工廠將於明年初開始臨床試驗生產，然後在 2025 年下半年進行商業生產。

And then to address your second question, as I just mentioned, Obelisc is expected to start commercial production late 3Q or early 4Q this year. So in general, I think we have said that we are looking at a roughly doubling of our capacity from 2023 to 2024. We don't provide guidance for the product sales. But I think the capacity expansion gives you a good idea of where the revenue would lie, consistent with our policy to have similar or same closure -- disclosure from J&J, which does not provide product-specific guidance, we cannot guide the product sales. But I think that doubling of expansion gives you confidence that where the revenue would be in terms of growth year-over-year.

然後回答你的第二個問題，正如我剛才提到的，Obelisc預計將在今年第三季末或第四季初開始商業生產。因此，總的來說，我認為我們已經說過，我們的目標是從 2023 年到 2024 年將產能增加一倍。但我認為產能擴張讓你很好地了解收入將在哪裡，這與我們的類似或相同關閉政策相一致——強生公司披露，它不提供特定產品的指導，我們無法指導產品銷售。但我認為，擴張一倍可以讓你對收入的年成長充滿信心。

Can I just clarify, when you say doubling of capacity, there's other factors as it relates to revenue, whether it's kind of like in-spec, out of spec, the amount going to clinical trials, the amount going to these comparability batches or what have you. So when you say doubling of capacity, is that just like total capacity inclusive of all these other things that may not generate revenue? Or is that commercial capacity?

我能否澄清一下，當你說產能翻倍時，還有其他與收入相關的因素，無論是符合規格、不符合規格、進入臨床試驗的數量、這些可比批次的數量還是什麼你。那麼，當你說產能翻倍時，這是否就像包含所有其他可能不會產生收入的因素在內的總產能一樣？或者說這就是商業能力？

That is correct. When we talk about capacity, that includes the number of total slots from all nodes of production. That includes clinical production, that includes non-revenue manufacturing investment rounds, that includes commercial production. And then when you think about commercial production, yes, of course, you have to make assumption of the in-spec success rate, right? I mean we're encouraged by the trend so far this year because given what we're seeing in Q1 and now in Q2, that continues to improve.

那是對的。當我們談論容量時，它包括所有生產節點的總槽數。這包括臨床生產，包括非收入製造投資輪次，包括商業生產。然後，當您考慮商業生產時，是的，當然，您必須假設符合規格的成功率，對吧？我的意思是，我們對今年迄今為止的趨勢感到鼓舞，因為考慮到我們在第一季和現在第二季所看到的情況，情況持續改善。

So then there's, of course, the net pricing. So audits will figure into the revenues. But when we talk about total capacity, we're talking about order capacity, order flux from different nodes, and that includes everything.

當然，還有淨定價。因此，審計將計入收入。但當我們談論總容量時，我們談論的是訂單容量、來自不同節點的訂單流量，這包括一切。

And our next question coming from the line of Gena Wang with Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

Maybe I'll just follow Jessica's questions. So should we still expect revenue growth in second quarter, '24 or should we wait into second half, '24 when Obelisc commercial production on board in 3Q, 4Q?

也許我會繼續回答潔西卡的問題。那麼，我們是否仍然應該預期第二季（24 年）的營收成長，還是應該等到下半年（24 年 Obelisc 在第三季、第四季開始商業生產時）？

And another related question is regarding CARTITUDE-5 and 6, now mainly 6, you still have maybe roughly 700 patients that need to be enrolled. Where do you expect these 700-patient enrollment mainly at? Would that be in New Jersey site? Or would that be in Belgium site?

另一個相關問題是關於 CARTITUDE-5 和 6，現在主要是 6，可能還有大約 700 名患者需要入組。您預計這 700 名患者主要在哪裡入組？那會在新澤西網站嗎？還是在比利時網站？

This is Lori. I'll take your first question on revenue. We do expect to see some growth in Q2. But as we've talked about, we expect pronounced growth in the second half of the year. As Ying mentioned, we have different factors coming into play in the second half of the year.

這是洛瑞。我將回答你關於收入的第一個問題。我們確實預計第二季會出現一些成長。但正如我們所討論的，我們預計今年下半年將顯著成長。正如我們應該提到的，下半年我們有不同的因素在發揮作用。

With the Raritan ramp, we expect a second capacity ramp coming on there. Obelisc facility is the largest driver with that coming online in order to do some commercial production. And then we do have a CMO that we anticipate clinical production can shift there that will free up some commercial capacity at Raritan.

隨著力登產能的提升，我們預期第二個產能提升也會隨之而來。 Obelisc 設施是最大的推動者，其上線目的是進行一些商業生產。然後我們確實有一個 CMO，我們預計臨床生產可以轉移到那裡，這將釋放 Raritan 的一些商業能力。

So in addition to that, as we start to get these additional nodes that come online, we will have some multiple country launches we anticipate in the back half of the year. And as you know, with the complexity of cell therapy, some of the -- achieving those sales will depend upon how those launches go. And you've seen in prior launches, we tend to get a lot of the acute patients first. So we want to be conservative, but we do anticipate a more pronounced growth in the second half of the year.

因此，除此之外，當我們開始讓這些額外的節點上線時，我們預計將在今年下半年在多個國家推出。如您所知，由於細胞療法的複雜性，實現這些銷售將取決於這些產品的上市進展。您在先前的發布中已經看到，我們往往會先接待許多急性患者。因此，我們希望保持保守，但我們確實預計下半年會有更明顯的成長。

Ying, do you want to take the CARTITUDE-5 and CARTITUDE-6 question?

Ying，你想回答 CARTITUDE-5 和 CARTITUDE-6 問題嗎？

Yes, Gena. So on CARTITUDE-5, we have completed all international enrollment already for CARTITUDE-5 and that's actually above our preplanned number. Right now, we're just enrolling additional U.S.-based patients, so that we satisfy the minimum of the U.S. patient representation by the FDA. So by now, we have manufactured a significant portion of CARTITUDE-5 patients.

是的，吉娜。因此，在 CARTITUDE-5 上，我們已經完成了 CARTITUDE-5 的所有國際註冊，這實際上超出了我們預先計劃的數量。目前，我們正在招募更多美國患者，以便滿足 FDA 規定的美國患者代表的最低要求。所以到目前為止，我們已經製造了很大一部分 CARTITUDE-5 患者。

Now on CARTITUDE-6, since we opened the enrollment in October last year, right now, it's enrolling really fast. It's actually faster than our plan. So in terms of where we're manufactured for those trials, I can tell you that, right now, Raritan, New Jersey is the main site for CARTITUDE-5 manufacturing. For CARTITUDE-6, right now actually, again, our first facility called Obelisc is the main site for that trial now, and will shift to other sources. But we're trying to really save the Raritan facility for commercial production for the rest of 2024. So that's where we're manufacturing for CARTITUDE-5 and CARTITUDE-6 for now.

現在CARTITUDE-6，自從我們去年10月份開始招生以來，現在招生速度非常快。實際上比我們的計劃要快。因此，就我們用於這些試驗的製造地點而言，我可以告訴您，目前新澤西州 Raritan 是 CARTITUDE-5 製造的主要地點。對於 CARTITUDE-6，現在實際上，我們的第一個名為 Obelisc 的設施現在是該試驗的主要地點，並將轉移到其他來源。但我們正努力在 2024 年剩餘時間內真正保留 Raritan 工廠用於商業生產。

And our next question coming from the line of Kelly Shi with Jefferies.

我們的下一個問題來自凱莉·施 (Kelly Shi) 與杰弗里斯 (Jefferies) 的對話。

Congrats on achieving a great milestone in early approval. So for the launch in the U.S., could you talk about back to the current launch activities? Have you started treating patients in second to fourth line? And do you see a switch from lifeline? And I also have a follow-up.

恭喜您在早期批准方面實現了一個偉大的里程碑。那麼對於在美國的發布，您能談談目前的發布活動嗎？您是否已開始治療二線至四線患者？您是否看到生命線發生了轉變？我還有一個後續行動。

Yes, why don't I take that question. This is Steve Gavel. I think the question had to do with part of for the status of it and patients and so forth and so on. One of the things I do want to just piggyback a little bit to Lori's response earlier concerning the second half component of this year, even though the product was approved in earlier lines in April, there's just a natural lag in the market, especially with a CARTITUDE-4 launch where we are looking for getting patients referred into our institutions.

是的，我為什麼不回答這個問題。這是史蒂夫·蓋維爾。我認為這個問題與它的現狀和病人等等有關。我確實想藉用 Lori 早些時候關於今年下半年的回應的一件事，儘管該產品在 4 月份的早期產品線中獲得了批准，但市場存在自然滯後，尤其是在CARTITUDE-4 啟動，我們正在尋找將患者轉介到我們的機構。

So I think this is some of the key differences with the CARTITUDE-1 launch versus 4, that there will be a natural lag in it just because of the referral piece of this. Now also to Lori's point, there are a number of patients that meet the eligibility criteria today in our hospitals that are moving very quickly through the approval processes and so forth.

所以我認為這是 CARTITUDE-1 與 4 的一些關鍵區別，僅僅因為其中的建議部分，它就會出現自然的延遲。現在，洛里也指出，今天我們醫院中有許多符合資格標準的患者，他們正在快速完成審批流程等。

So again, we continue to do very quickly in terms of patient identification and apheresis, but I did want to caution you all that it's just a natural phenomenon of referrals and manufacturing and ultimately to revenue recognition. That's why we're basing our assumption on a really strong second half.

再說一遍，我們在患者識別和血漿分離術方面繼續做得非常快，但我確實想提醒大家，這只是轉診和製造以及最終收入確認的自然現象。這就是為什麼我們將我們的假設建立在下半場非常強勁的基礎上。

And also to reach the goal of 10,000 doses by year-end for 2025, would you need to consider the sign up for additional CDMO contract? Also what percentage of the patients would be needed to treat in all patient settings to reach 10,000 doses go if we're assuming like on the hospital side, there's also capacity constraints?

另外，為了在 2025 年底實現 10,000 劑疫苗的目標，您是否需要考慮簽署額外的 CDMO 合約？另外，如果我們假設醫院方面也存在容量限制，那麼在所有病患環境中需要接受多少百分比的病患才能達到 10,000 劑劑量？

So Kelly, let me take the first half of the question, and then I'll ask Steve to talk about the outpatient administration of CARVYKTI. So when we look at the goal of reaching 10,000 annualized dose capacity by end of 2025, we believe that with existing nodes are 4 nodes, right, that includes our own site in Raritan, New Jersey, our 2 sites in Ghent, Obelisc and Tech Lane, plus on Novartis site here, that should be pretty much give us the reach to that number.

凱利，讓我回答問題的前半部分，然後我將請史蒂夫談談 CARVYKTI 的門診管理。因此，當我們考慮到2025 年底達到年化劑量能力10,000 劑的目標時，我們認為現有節點是4 個節點，對吧，其中包括我們在新澤西州Raritan 的站點、我們在根特、Obelisc 和Tech的2 個站點Lane，再加上諾華網站，這應該足以讓我們達到這個數字。

Of course, we're continuing to evaluate the CDMO of other companies that could potentially give us a boost as well. So stay tuned on that front. And then I'll ask Steve to talk about the outpatient illustration of CARVYKTI.

當然，我們正在繼續評估其他公司的 CDMO，這也可能為我們帶來推動。所以請繼續關注這方面。然後我會請 Steve 談談 CARVYKTI 的門診插圖。

So you're hearing at the top, talking about roughly about 1/3 of all patients now being treated in the outpatient setting. That's grown quite a bit. I mean that's to give you a comparator versus other CAR-Ts in the market that we compete with is they're right around 15%. So I think the question was what -- from an outpatient perspective, what would we need to see in order to achieve the target doses that you referenced earlier.

所以你聽到的是高層正在談論目前在門診接受治療的大約 1/3 的患者。這已經長大不少了我的意思是，這是為了給你一個與我們競爭的市場上其他 CAR-T 的比較，它們的準確率約為 15%。所以我認為問題是——從門診患者的角度來看，我們需要看到什麼才能達到您之前提到的目標劑量。

We expect by the end of 2025 to be at least double to where we are today. And it's reflected in the growth in the outpatient sector that we are seeing today. So we are relatively confident that we are going to be there. I think the one wrinkle and you're seeing now, a number of our sites investigating this today is the partnerships that they are going to be and they're currently embarking with other outpatient players, whether it be in the community setting, I'm talking about pure community retail setting.

我們預計到 2025 年底，數量將至少是目前的兩倍。這反映在我們今天看到的門診部門的成長中。所以我們相對有信心我們會在那裡。我認為你現在看到的一個問題是，我們今天調查這一問題的許多網站是他們將要建立的合作夥伴關係，他們目前正在與其他門診參與者建立合作夥伴關係，無論是在社區環境中，我'我說的是純粹的社區零售環境。

And actually, if you haven't seen a good example of that is back in 2022, HCA Healthcare announced a partnership with McKesson, which is U.S. Oncology. And I know that they are very interested in leveraging outside of their own hospitals to bring these therapies out to as many patients that are eligible to receive them.

事實上，如果您還沒有看到一個很好的例子，那麼早在 2022 年，HCA Healthcare 就宣布與 McKesson（美國腫瘤學公司）建立合作關係。我知道他們非常有興趣在自己的醫院之外利用這些療法，將這些療法帶給盡可能多有資格接受這些療法的患者。

So you'll see the definition of outpatient will change quite a bit over the next couple of years, not just hospital outpatient, but in the next few years, you will start to see community administration of our program.

因此，您將看到門診患者的定義在未來幾年內將發生很大變化，不僅僅是醫院門診患者，而且在接下來的幾年中，您將開始看到我們專案的社區管理。

Our next question coming from the line of Jon Miller with Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Jon Miller。

This is Umer filling in for Jon. Ying, I don't have any single question on CARVYKTI today. And instead, I want to focus on a very important area in CAR-T space, which I don't think has come up in Legend conversations. So you have this triple-targeted CAR-T ongoing in China since March 22. I think it's wrapping up now. That's CD19, CD20, CD22 on autologous. And separately, you have this LUCAR-G39P, which is the dual targeting CD19, CD20 ALLO that I think you just started Phase I, both are these in China. My question is, shouldn't those trials have been an autoimmune and/or is that a plan that you're intending to do near term?

這是烏默（Umer）接替喬恩（Jon）。 Ying，我今天對 CARVYKTI 沒有任何問題。相反，我想專注於 CAR-T 領域的一個非常重要的領域，我認為這個領域在 Legend 對話中沒有出現。因此，自 3 月 22 日以來，這種三靶點 CAR-T 療法一直在中國進行。那是自體的 CD19、CD20、CD22。另外，還有這個 LUCAR-G39P，這是雙標靶 CD19、CD20 ALLO，我認為你們剛開始第一階段，兩者都是在中國。我的問題是，這些試驗不應該是一種自體免疫試驗和/或這是您近期打算進行的計劃嗎？

I will ask our CSO, Dr. Guowei Fang, to answer your question.

我請我們的CSO方國偉博士來回答你的問題。

This is an important question. And our disease-focused area, both oncology and autoimmune diseases, for both assets we have plans to develop those in autoimmune disease indication as well, and it's in process.

這是一個重要的問題。我們的重點疾病領域是腫瘤學和自體免疫疾病，對於這兩種資產，我們也計劃開發針對自體免疫疾病適應症的資產，並且正在進行中。

And when would that start, Ying? And would it be a U.S. trial? I think that's the other very important question, obviously.

那什麼時候開始呢，英？這會在美國進行審判嗎？顯然，我認為這是另一個非常重要的問題。

Currently, our U-1 is in the process of initiating the autoimmune IT study in China across multiple disease indications. For the U.S. autoimmune diseases asset, our current strategy is focusing on the auto-generic approach given some of the key challenges associated with the target treatment options. So for example, the requirement of lympho-depletion and the requirement of manufactured at the individual patient level, high cost, et cetera. We have assets in the process of initiating the U.S. IND [enabling] study. We will get those additional information in the future.

目前，我們的U-1正在中國啟動針對多種疾病適應症的自體免疫IT研究。對於美國自體免疫疾病資產，考慮到與目標治療方案相關的一些關鍵挑戰，我們目前的策略重點是自體仿製藥方法。例如，淋巴清除的要求以及在個別患者層級製造的要求、高成本等等。我們正在啟動美國 IND [授權] 研究的過程中擁有資產。我們將來會得到這些額外的資訊。

Sorry, one last one. If I may just clarify, in that ALLO trial for U.S., I'm assuming that's your CD19, CD20 dual targeting. Is it safe to assume that you would not need the full site loading, the preconditioning for autoimmune?

抱歉，最後一張。我可以澄清一下，在美國的 ALLO 試驗中，我假設這是您的 CD19、CD20 雙重目標。可以安全地假設您不需要完整的網站載入、自體免疫的預處理嗎？

That's an open question. And I think we will make a decision based on the clinical data we are collecting. In terms of targeting mechanisms, we have -- we think that autoimmune disease, I'll cover a very broad spectrum of different diseases, and we want to have options and choice for patients.

這是一個懸而未決的問題。我認為我們將根據我們收集的臨床數據做出決定。在標靶機制方面，我們認為自體免疫疾病，我將涵蓋非常廣泛的不同疾病，我們希望為患者提供選擇和選擇。

In terms of targeting mechanism, CD19, CD20 certainly validate the type of mechanism. I think plasma also play a major component in BCMA-driven disease pathology. So we are also considering the BCMA as additional type of opportunities.

在標靶機制方面，CD19、CD20無疑驗證了這種機制的類型。我認為血漿在 BCMA 驅動的疾病病理學中也發揮著重要作用。因此，我們也將 BCMA 視為其他類型的機會。

And Umer, I know you had a question about the disclosure and also moving to U.S. IND. So I will just add that, you see that we already initiated the triple specific CD19, CD20 program, and it will probably start dosing for autoimmune by end of this year. So based on that clinical data, we will make the decision when and how to move assets into the U.S. IND process.

Umer，我知道您對披露以及轉向美國 IND 有疑問。所以我想補充一點，你看我們已經啟動了三重特異性 CD19、CD20 計劃，並且可能會在今年年底開始針對自身免疫用藥。因此，根據這些臨床數據，我們將決定何時以及如何將資產轉移到美國 IND 流程。

And of course, like Dr. Fang just mentioned, we are very interested in whether we can either bypass or lower the dose intensity for fluid lympho-depletion regimen. That is one goal of our IIT trials in China. So is also the trial we're conducting for the dual-targeting ALLO CD19, CD20 [come directly] program.

當然，就像方博士剛才提到的，我們非常感興趣的是我們是否可以繞過或降低液體淋巴清除方案的劑量強度。這是我們在中國開展個人所得稅試點的目標之一。我們正在進行的雙標靶 ALLO CD19、CD20 [直接來] 計劃的試驗也是如此。

Sounds great. So it sounds like you could have some autoimmune data next year. Is that a reasonable conclusion from all of this?

聽起來很棒。所以聽起來明年你可能會得到一些自體免疫數據。從這一切得出的結論合理嗎？

Without officially guiding, yes, that's a possibility.

如果沒有官方指導，是的，這是有可能的。

And our next question is coming from the line of Yaron Werber with TD Cowen.

我們的下一個問題來自 Yaron Werber 和 TD Cowen。

Great. Let me maybe just follow Umer's last question and then I have a question on CARVYKTI. Can you just discuss a little bit the concept of autologous with the triple CD19, CD20 and CD22 versus with ALLO, it looks like you're doing dual targeting. Can you just help us understand kind of your thoughts, why not do triple in both? And then I have a follow-up on CARVYKTI.

偉大的。也許讓我繼續回答 Umer 的最後一個問題，然後我有一個關於 CARVYKTI 的問題。您能否稍微討論一下使用三重 CD19、CD20 和 CD22 與 ALLO 進行自體同源的概念，看起來您正在做雙重靶向。您能否幫助我們了解您的想法，為什麼不將兩者都做三倍呢？然後我對 CARVYKTI 進行了跟進。

So for tumor targeting, it's the design principle is to drive the deep response by targeting multiple B-cell biomarkers. And so for that, we are currently initiating the IIT study and the clinical data. For the ALLO, we are going to have different targeting mechanism. And based on the IIT study, we will have additional insight in terms of which disease we should target among different autoimmune indications.

因此，對於腫瘤靶向，其設計原則是透過靶向多個 B 細胞生物標記來驅動深度反應。為此，我們目前正在啟動 IIT 研究和臨床數據。對於 ALLO，我們將有不同的目標機制。基於 IIT 研究，我們將進一步了解在不同的自體免疫適應症中我們應該針對哪種疾病。

Okay. With the dual, but you'll keep that as a dual 19, 20 only because you don't need to drive deeper responses. Is that the thinking? Or you just need to reset the immune system?

好的。使用雙通道，但您將其保留為雙通道 19、20，只是因為您不需要驅動更深的響應。是這樣的想法嗎？還是你只需要重置免疫系統？

Yes. So we are talking to both CD19 and CD20 as well as with different assets, talking to CD19 and BCMA from a different aspect.

是的。所以我們正在談論 CD19 和 CD20 以及不同的資產，從不同的方面談論 CD19 和 BCMA。

Okay. Got it. Okay. Maybe just to move back. I have a quick question on CARVYKTI. Can you give us a little bit of a sense now that second-line is approved, is the auto specs now different pretty much and easier across the board? Or is the FDA still keeping a certain bar sort of on fourth line onwards and a different bar in the second line?

好的。知道了。好的。也許只是為了搬回來。我有一個關於 CARVYKTI 的簡單問題。既然二線產品已獲得批准，您能否給我們一些了解，汽車規格現在是否有很大不同，並且全面變得更容易？或者 FDA 是否仍然在第四行開始保留某個欄，並在第二行保留一個不同的欄？

This is Ying. I'll answer your question. So the answer is that when we received FDA approval on April 5 for second-line, we did receive 1 label with 1 spec. So as of today, right, if we treat any patient on label, the release spec is the same for second-line patients versus a fifth line and beyond. And also, by the way, it is a wider release spec.

這是瑩。我來回答你的問題。所以答案是，當我們在 4 月 5 日收到 FDA 批准二線藥物時，我們確實收到了 1 個帶有 1 個規格的標籤。因此，從今天開始，如果我們治療任何標籤上的患者，二線患者與五線及以上患者的釋放規格是相同的。而且，順便說一句，它是一個更廣泛的發行規範。

So I know it's early days, but based on the data from the full month of March production, which we test in April, so far, we're seeing encouraging trends in OS so far based on either probably wider release spec approved by the FDA and also potentially once we start to see more second-line patients rolling in, the natural evolution of better baseline for those patients.

所以我知道現在還為時過早，但根據我們在4 月份測試的3 月份全月生產數據，到目前為止，我們看到操作系統的令人鼓舞的趨勢，基於FDA 批准的可能更廣泛的發布規範而且，一旦我們開始看到更多的二線患者湧入，這些患者的基線就會自然演變。

And those release spec, how do they compare with ABECMA and maybe TECARTUS as far as you can tell?

就您所知，這些發布規格與 ABECMA 甚至 TECARTUS 相比如何？

Without disclosing the number, I can tell you that based on latest data we have on out of spec, I think our success rate is approaching that of our competition at this point. Of course, like I said, it's very early days, we have only March production data, we have only a little bit partial of the April production data.

在不透露具體數字的情況下，我可以告訴您，根據我們掌握的超出規格的最新數據，我認為我們的成功率目前已接近我們的競爭對手。當然，就像我說的，現在還為時過早，我們只有三月的生產數據，我們只有四月生產數據的一小部分。

Okay. And maybe just final, I think you talked about 100 ATC target for the year. What's the gating kind of rate to open all of those? Is it capacity? Or are there other factors as well?

好的。也許只是最後，我想您談到了今年 100 架 ATC 的目標。打開所有這些的門檻是多少？是容量嗎？或是有其他因素嗎？

Yes. No, it's Steve Gavel. I mean, the gating element is really the site certification process. One thing to take note and I've talked about this on previous calls, is as we add more and more sites, you don't see nearly the volume that you see in our initial -- our Phase I site. So -- but we will continue to certify sites and our tenants to get between 90 to 100 this year. The key metric, just so you know what we look at is because there's so much outpatient now, administration in our facilities on a per site basis, we're seeing much more throughput per site versus what you would see, for example, with ABECMA. So I just want to make sure we're kind of viewing this the same way.

是的。不，我是史蒂夫蓋維爾。我的意思是，門控元素實際上是網站認證過程。需要注意的一件事是，我在之前的電話中談到過這一點，即隨著我們添加越來越多的站點，您幾乎看不到在我們最初的第一階段站點中看到的數量。所以，但我們將繼續對場地和租戶進行認證，今年將達到 90 到 100 個。關鍵指標，讓您知道我們關注的是什麼，因為現在有這麼多門診病人，我們的設施中每個站點的管理，我們看到每個站點的吞吐量比您看到的要高得多，例如，使用ABECMA 。所以我只是想確保我們以同樣的方式看待這個問題。

And our next question coming from the line of Ziyi Chen with Goldman Sachs.

我們的下一個問題來自高盛的陳子儀。

Just 2 questions. One is on the EU launch. Well, I think the U.S. has been down quarter-over-quarter, but you have been increased to 23%, which is still growing nicely. So could you share a bit more color on the Europe pricing? And also, how is the reimbursement coverage in your countries? And also, any updates on the commercial launch in U.K. and in Japan?

只有 2 個問題。其中之一是關於歐盟的啟動。嗯，我認為美國逐季下降，但已經增加到 23%，仍然成長良好。那麼您能否分享更多有關歐洲定價的資訊？另外，你們國家的報銷範圍如何？另外，在英國和日本的商業發布有什麼最新消息嗎？

And a small financial question is really regarding the DLL3 partnerships. So we understand that upfront payment. You just recognize about USD 12 million in the first quarter out of the $100 million upfront payment. So is that the specific accounting timing for that? So it's going to be spread out over the next few quarters?

一個小的財務問題確實與 DLL3 合作關係有關。所以我們理解預付款。您僅在第一季確認了 1 億美元預付款中的約 1,200 萬美元。這是具體的會計時間嗎？那麼它會分散在接下來的幾個季度嗎？

And secondly, there is a cost of license related in connection to that. So could you help -- helping us to understand a bit more about where does this cost coming from?

其次，存在與此相關的許可成本。那麼你能幫忙——幫助我們更了解這筆成本從何而來嗎？

Yes. We'll try to unpack this -- a lot of things from that. I want to take the first European question. So I think folks on the line are aware a good partner is responsible for ex U.S. promotional activity, specifically in Europe. I can't tell if you're aware of this already, if you're into a partner in Germany, Austria, in both CARTITUDE-1 and 4.

是的。我們將嘗試解開這個問題——從中得到很多東西。我想回答第一個歐洲問題。因此，我認為線路中的人們都知道一個好的合作夥伴負責美國以外的促銷活動，特別是在歐洲。我不知道你是否已經意識到這一點，如果你在德國、奧地利的 CARTITUDE-1 和 4 領域都有合作夥伴。

The other thing to take note from a global allocation, even though we are in those countries, the majority of the global slot allocation is coming into the United States. I think you had a question around pricing. Pricing has not been disclosed as of yet in Europe. So we can't unfortunately provide information around that until it becomes publicly disclosed. I'm trying to think of the other European questions that were out there. Let's see here. On the pricing and reimbursement piece.

全球分配中需要注意的另一件事是，即使我們位於這些國家，但全球老虎機分配的大部分都進入了美國。我認為您對定價有疑問。歐洲的定價尚未公佈。因此，不幸的是，在公開披露之前，我們無法提供相關資訊。我正在嘗試思考其他歐洲問題。我們來看看這裡。關於定價和報銷部分。

Again, we aren't commenting yet -- we have received approvals, obviously, in Japan, but we have yet to launch there. And again, I'm going to defer to my partner on that one because they have not disclosed their intention on timing there nor as far as in the U.K. as well.

再說一次，我們還沒有發表評論——顯然，我們已經在日本獲得了批准，但我們還沒有在那裡推出。再說一次，我將在這一問題上聽從我的合作夥伴的意見，因為他們還沒有透露他們在那裡或英國的時間安排。

Lori, you can get the next one.

洛瑞，你可以拿下一張。

So for DL3, as you guys saw on the -- how we recognize that in the P&L, there's actually 3 different locations of what we're recognizing there and then on our balance sheet. As you guys remember, and we disclosed, we received $100 million upfront payment. However, we have to defer the recognition of that $100 million over time for the activities that we're performing -- that we're obligated to perform as part of the collaboration agreement.

因此，對於 DL3，正如你們在我們如何認識損益表中看到的那樣，實際上我們在資產負債表上認識到了 3 個不同的位置。正如你們所記得的，我們透露，我們收到了 1 億美元的預付款。然而，隨著時間的推移，我們必須推遲承認我們正在進行的活動的 1 億美元——作為合作協議的一部分，我們有義務履行這些活動。

So to your question of how will that spread out, yes, that will spread out over various quarters in the future as we continue to do our activities that we're obligated to perform for that study. Now we do have a passthrough. There are certain material costs that we will passthrough those costs to our collaboration partner.

因此，對於您提出的問題，這將如何傳播，是的，隨著我們繼續進行我們有義務為該研究開展的活動，這將在未來的各個季度傳播。現在我們確實有了一個passthrough。我們會將某些材料成本轉嫁給我們的合作夥伴。

So we recognize that as other income. So that is actually separated out. And then the cost of the license is the actual -- what triggers that revenue recognition is the cost that we've incurred based upon those obligations that we have to perform. So that's the actual cost that we're incurring for the clinical study.

所以我們將其視為其他收入。所以這實際上是分開的。然後許可證的成本是實際的－觸發收入確認的是我們根據我們必須履行的義務而產生的成本。這就是我們臨床研究所產生的實際成本。

And our next question coming from the line of 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部的 Leonid Timashev。

Wanted to maybe talk -- ask on sort of the cadence of data that we should expect for the rest of the year. And specifically, I'm curious on cohorts E and F, when we might see that data? What level of follow-up and what sort of efficacy measures we should be focusing on? And then really to that I guess what in your mind is the PFS benchmark that we should be looking for there and for CARTITUDE-5 as a whole?

也許想談談——詢問我們今年剩餘時間應該預期的數據節奏。具體來說，我對 E 組和 F 組很好奇，我們什麼時候可以看到這些數據？我們應該關注什麼程度的追蹤以及什麼樣的有效性措施？然後，我想您認為我們應該在那裡尋找以及整個 CARTITUDE-5 的 PFS 基準是什麼？

This is Ying. So first, maybe I can just give you a quick review of ASCO. We expect to present some data from one cohort, Cohort D. These are the patients who did not achieve optimal response to the standard care regimen in the front-line. And then for Cohort E and F, we enrolled and dosed a total of roughly 60 patients in newly diagnosed multiple myeloma.

這是瑩。首先，也許我可以給您快速回顧一下 ASCO。我們希望提供一組（D 組）的一些數據。然後，對於 E 組和 F 組，我們招募了大約 60 名新診斷的多發性骨髓瘤患者並進行了給藥。

So right now, we're expecting to release and publish the data at a major medical meeting towards the end of the year. So that's roughly the timing for cohorts E and F. And in terms of the level of follow-up, I think you should expect to see a year of follow-up or maybe even longer than that.

因此，現在，我們預計將在年底前的重要醫學會議上發布和公佈這些數據。因此，這大致就是 E 組和 F 組的時間安排。

If you talk about the PFS benchmark, so for CARTITUDE-5, as you know, the standard of care regimen we use here is RVD or Revlimid, Velcade and dexamethasone. If you look at the registration study for that regimen online, the median PFS is about 34, 35 months. And that is the benchmark we're looking at to beat, right? I just want to remind you that this is a superiority trial.

如果您談論 PFS 基準，那麼對於 CARTITUDE-5，如您所知，我們在這裡使用的護理方案標準是 RVD 或 Revlimid、Velcade 和地塞米松。如果您在線上查看該方案的註冊研究，您會發現中位 PFS 約為 34、35 個月。這就是我們想要超越的基準，對吧？我只是想提醒你，這是一場優勢試驗。

And then for CARTITUDE-6, I think you got the answer from the PERSEUS trial that was presented at ASH last year, that is a DRVD regimen in combination of stem cell transplant. So there, you're looking at the 4-year PFS rate of 84%, and that's the benchmark we're looking at, right?

然後對於 CARTITUDE-6，我想您從去年 ASH 上展示的 PERSEUS 試驗中得到了答案，那就是 DRVD 方案結合幹細胞移植。那麼，您看到的是 84% 的 4 年 PFS 率，這就是我們正在考慮的基準，對嗎？

Again, we are looking at a superiority in PFS as a primary endpoint. Now given the recent ODAC vote, we will be engaging with the agency to talk about potential of using MRD as an endpoint to accelerate the approval time line. So if you look at CARTITUDE-5, MRD negativity is already a secondary endpoint.

我們再次將 PFS 的優越性視為主要終點。鑑於最近的 ODAC 投票，我們將與該機構合作討論使用 MRD 作為端點來加快審批時間的潛力。因此，如果您查看 CARTITUDE-5，MRD 陰性已經是次要終點。

And then for CARTITUDE-6, if you look at our clinicaltrials.gov, actually, the co-prime endpoint is PFS and MRD negativity. So we will follow all the patients through MRD negativity. And at the same time, we plan to engage the FDA and the EMA to talk about the potential of using MRD as endpoint as well.

然後，對於 CARTITUDE-6，如果您查看我們的 ClinicalTrials.gov，實際上，共同主要終點是 PFS 和 MRD 陰性。因此，我們將追蹤所有 MRD 陰性的患者。同時，我們計劃與 FDA 和 EMA 合作討論使用 MRD 作為終點的潛力。

And our next question coming from the line of Vikram Purohit from Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Vikram Purohit。

We just had 2 on CARVYKTI. The first on the topic of future disclosures, Ying and team, do you anticipate providing kind of a split of patients by line of therapy or any directional sense of how kind of patients used in the quarter has trended between earlier line versus later lines in the coming quarters of performance data?

我們剛剛在 CARVYKTI 上吃了 2 個。第一個關於未來披露的主題，Ying 和團隊，您是否預計按治療線提供患者的分類，或者對本季度使用的患者類型在早期線與後期線之間的趨勢有任何方向性的了解？個季度的業績數據？

And then secondly, I know you don't provide long-term guidance, but looking at a couple of years out, how do you expect the CARVYKTI sales base to kind of trend U.S. versus EMA?

其次，我知道您沒有提供長期指導，但展望幾年後，您預計 CARVYKTI 銷售基礎在美國與 EMA 的趨勢如何？

It's an important metric because it's your question around looking at line of therapy use. It's an important question. It's a very difficult question to track from. So just because of the available data that's in the public domain right now around that.

這是一個重要的指標，因為這是一個圍繞治療方案的問題。這是一個重要的問題。這是一個非常難以追蹤的問題。所以只是因為現在公共領域有可用的數據。

So let me give you away how we're thinking about this. So we're assuming in a year -- year plus time, about 70% of our product use is going to be an earlier line of therapies, early-line treatments, I should say. And that's going to increase over time. It's because the market is so large and obviously, there's high demand to use this in patients that are doing quite well but we will not be, per se, teasing that out by line of therapy, not because we don't want to, but like I said, you get that data through different sources.

那麼讓我告訴你我們是如何考慮這個問題的。因此，我們假設在一年多的時間裡，我們大約 70% 的產品使用將是早期療法，我應該說是早期療法。隨著時間的推移，這種情況還會增加。這是因為市場如此之大，顯然，對於狀況良好的患者來說，使用這種藥物的需求很高，但我們本身不會透過治療來解決這個問題，不是因為我們不想這樣做，而是因為就像我說的，你可以透過不同的來源取得這些數據。

One of the big sources is claims data, but the source information is a bit choppy. So to answer your question directly, we will not be disclosing that by line. Ying, there's a second follow-up.

索賠數據是重要來源之一，但來源資訊有點不穩定。因此，為了直接回答您的問題，我們不會逐行透露這一點。英，還有第二個後續。

Yes. So Vikram, on your second question, I mean, again, we're not in a position to provide guidance for CARVYKTI. But as you know, typically, when you launch a new indication, it takes about 3 years to get to that peak sales.

是的。 Vikram，關於你的第二個問題，我的意思是，我們無法為 CARVYKTI 提供指導。但如您所知，通常情況下，當您推出新適應症時，大約需要 3 年才能達到銷售高峰。

And as of now, we are not changing the projection that CARVYKTI will peak at $5 billion plus. And by the way, that is really on stipulation that we'll have a healthy market share in second line for which we already have received official approval from both FDA in the U.S. and EMA in Europe. So we feel confident about the growth potential for CARVYKTI in the second line in the next few years.

截至目前，我們不會改變 CARVYKTI 的峰值將達到 50 億美元以上的預測。順便說一句，這實際上是基於我們將在二線產品中擁有健康的市場份額，我們已經獲得了美國 FDA 和歐洲 EMA 的正式批准。所以我們對CARVYKTI未來幾年二線的成長潛力充滿信心。

And our next question coming from the line Kostas Biliouris from BMO Capital Markets.

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

One question from us on the guidance around the 10,000 slot production by year-end 2025. Can you maybe provide some color around the number of FDA approvals on manufacturing copies in case you will need to be able to manufacture this launch by year-end 2025?

我們有一個關於到 2025 年底前生產 10,000 個老虎機的指導問題。

So let me just give you a little bit more details about how we think about all the different nodes, right? So obviously, right now, the only commercial production site is Raritan, New Jersey facility. And we are implementing an FDA-approved increase as of now.

那麼，讓我為您提供更多關於我們如何看待所有不同節點的細節，對嗎？顯然，目前唯一的商業生產基地是新澤西州力登工廠。目前我們正在實施 FDA 批准的增加措施。

And then we expect to have another increase towards the second half of the year. So that's what we're doing with Raritan. And then, meanwhile, we and our partner, Johnson & Johnson, are conducting a physical expansion of the Raritan facility. So that progression should complete by end of this year. So over the course of next year, we are going to validate the equipment and then bring all the fees up to the GMP facility standards.

然後我們預計下半年會再次增加。這就是我們與力登所做的事情。同時，我們和我們的合作夥伴強生公司正在對力登工廠進行實體擴建。因此，這項進展應在今年底完成。因此，在明年，我們將驗證設備，然後將所有費用提高到 GMP 設施標準。

So sometime next year, towards the second half, we expect that doubling of the manufacturing area in Raritan to start to contribute to additional capacity. So that's what we're doing for Raritan.

因此，明年下半年的某個時候，我們預計力登的製造面積將翻一番，從而開始增加產能。這就是我們為 Raritan 所做的事情。

And then for the 2 facilities in Ghent, the first one, Obelisc right now is already manufacturing for clinical trial. And I just said in the call that towards probably late 3Q or early 4Q, we expect that facility to receive the regulatory approval for commercial production. The much larger Tech Lane facility in Ghent, right now, we're on track to complete all the validation work by end of this year. So that we expect clinical trial production to start early next year in 2025. And in the second half of next year, that facility will also come online pending regulatory approval for commercial production.

對於根特的 2 個工廠，Obelisc 目前已經開始生產用於臨床試驗的第一個工廠。我剛剛在電話中表示，我們預計該工廠將在第三季末或第四季初獲得商業生產的監管批准。目前，位於根特的 Tech Lane 工廠規模要大得多，我們預計在今年年底前完成所有驗證工作。因此，我們預計臨床試驗生產將於明年初 2025 年開始。

And then we talked about Novartis as CMO. Again, we expect the commercial production to start early next year. So if you look at those 4 nodes, right, we're adding 3 additional for commercial production starting second half of this year and then throughout 2025. That's how we can achieve the 10,000 dose capacity by end of next year, all these 4 nodes together.

然後我們談論了諾華公司的首席行銷長。我們再次預計商業生產將於明年初開始。因此，如果你看一下這4 個節點，對吧，我們將從今年下半年開始，然後在整個2025 年額外增加3 個用於商業生產。 ，所有這4 個節點一起。

And I can tell you that without disclosing all the technical details, if we track as of last Friday, we're on track to achieve that 10,000 total capacity by end of next year, given where we are in Raritan, where we are in the Ghent facilities and where we are with Novartis.

我可以告訴你，在不透露所有技術細節的情況下，如果我們截至上週五進行跟踪，我們預計在明年年底前實現 10,000 輛總產能，考慮到我們在 Raritan 的處境，我們在根特設施以及我們與諾華的合作地點。

And our next question coming from the line of George Farmer with Scotiabank.

我們的下一個問題來自豐業銀行的喬治法默。

Ying, can you comment a little bit about how this wider release-back approval translates -- may translate into top line sales? Number one. Number two, also recognizing that CARVYKTI is moving into second-line primarily, at least in the relapsed/refractory fourth-line plus, can you talk a little bit about dynamics between how CARVYKTI is being positioned against bispecifics? It looked like that there was a bit of a surprise number from J&J when they reported.

Ying，您能否評論一下這種更廣泛的回滾批准如何轉化為頂線銷售？第一。第二，也認識到 CARVYKTI 正在主要進入二線，至少在復發/難治性四線加上，您能談談 CARVYKTI 如何針對雙特異性藥物進行定位之間的動態嗎？看起來強生公司在報告時給的數字有點令人驚訝。

And then also finally, can you go into a little bit more detail on how you get to your cash you should -- you spend out to 2026?

最後，您能否更詳細地介紹一下您如何獲得應有的現金——您在 2026 年之前的支出？

I'll take the first question and then ask Steve and Lori to provide answers for the second and third one. So on a wider release spec granted by the FDA in April, I think what we have said previously is that based on our modeling and also the data from CARTITUDE clinical program, we believe this widened spec should result in additionally 5 to 10 percentage points lower OS compared to before the wider release spec was approved by the FDA.

我將回答第一個問題，然後請史蒂夫和洛里回答第二個問題和第三個問題。因此，根據FDA 在4 月批准的更廣泛的發布規範，我認為我們之前所說的是，根據我們的模型以及CARTITUDE 臨床計劃的數據，我們認為這一擴大的規範應該會導致另外5 到10 個百分點的降低與 FDA 批准更廣泛的發布規範之前相比，作業系統。

So right now, like I said, it's still very early days. But based on what we are seeing so far, the OS is already coming down by roughly 5% last month. So that is very encouraging, and we're going to have to have a little bit longer follow-up data to provide you with better confidence about where exactly the OS will be. But so far, things are trending very positively. Steve?

所以現在，就像我說的，還為時過早。但根據我們迄今為止所看到的情況，作業系統上個月已經下降了大約 5%。因此，這是非常令人鼓舞的，我們將需要更長一點的後續數據，以便讓您對作業系統的具體位置更有信心。但到目前為止，事情的發展趨勢非常積極。史蒂夫？

Yes. So why don't I take the question around how we're positioning the assets specifically for the CARTITUDE-4 launch in second line and then I'll get into a little bit around later lines in bispecifics. So it is our #1 promotional focus to launch CARTITUDE-4 in the second line plus setting. There's clearly a clear differential there versus standard of care, and it's going to be basically a single-minded focus for my team.

是的。那麼，我為什麼不圍繞我們如何專門為第二行中的 CARTITUDE-4 發布定位資產來回答這個問題，然後我將在雙特異性的後續行中進行一些討論。因此，在二線以上環境中推出 CARTITUDE-4 是我們的第一大促銷重點。與護理標準相比，這顯然存在明顯的差異，這基本上將成為我的團隊的一心一意的焦點。

The other thing, though, in terms of the bispecific question because it's the appropriate one, in later lines of therapy, you heard Ying in the opening talk about [speed]. One of the things that is clearly apparent to us, and Ying mentioned, I think, a Janssen surprise number bispecific.

然而，另一件事是，就雙特異性問題而言，因為它是適當的問題，在後來的治療中，你聽到英在開場談論[速度]。其中一件事對我們來說是顯而易見的，我認為，Ying 提到了楊森令人驚訝的雙特異性數字。

What's happening there, and this is honestly something that we could foresee coming, is that one of the things that's a key focus for us, you heard Ying talking about it is not only generate more slots in the market but get faster into the market.

那裡正在發生的事情，老實說，這是我們可以預見的事情，這是我們重點關注的事情之一，你聽到Ying 談到它不僅在市場上產生更多的機會，而且更快地進入市場。

And that's extremely important in later-line disease, where patients are progressing very rapidly. So that's where you saw the growth happening with the bispecifics as teclistamab hit the market and then was followed by [Tal].

這對於晚期疾病極為重要，因為患者的進展非常迅速。因此，當 teclistamab 進入市場時，您會看到雙特異性藥物的成長，然後是 [Tal]。

One of the things I do want to point out to is something we talk to our partner quite a bit about is as now Tal has entered into the market in fifth line plus in the U.S., what you're starting to see is a shift in the dynamic in terms of what bispecific is used in front of one another.

我確實想指出的一件事是，我們與合作夥伴經常談論的事情是，現在 Tal 已進入美國五線以上市場，您開始看到的是轉變就雙特異性在彼此面前使用的動態而言。

What we're seeing, and it makes sense is with Tal coming on board now, you're seeing a shift where Tal is actually being used first in front of [Tec]. And the reason for that, and this is going out in research, this is a very effective bridging strategy to also get the cilta-cel.

我們所看到的是，隨著 Tal 現在加入，你會看到一個轉變，Tal 實際上首先在 [Tec] 之前使用。原因正在研究中，這是一種非常有效的橋接策略，也可以獲得 cilta-cel。

So in the past, with Tal not being around, obviously, the market had no other option but to use teclistamab if they needed it to bring a patient. The challenge there is you're also targeting the same BCMA target. We know there's efficacy there. But by using [Tau] instead, you're obviously targeting a different target.

因此，在過去，由於 Tal 不在身邊，顯然，如果市場需要使用 teclistamab 來輸送患者，他們別無選擇，只能使用 teclistamab。挑戰在於您也針對相同的 BCMA 目標。我們知道那裡有功效。但透過使用 [Tau] 來代替，你顯然瞄準了不同的目標。

So they want to preserve the BCMA target to get the CARVYKTI. So maybe it's a little bit more than you had asked for, but I did want to just point that out to you that even though in this case, Tau might be used with some of these quicker progressing patients, we anticipate them to get to sell at a later point in time. Lori?

所以他們想保留 BCMA 目標來獲得 CARVYKTI。所以也許這比你要求的要多一點，但我確實想向你指出，即使在這種情況下，Tau 可能會用於一些進展較快的患者，但我們預計他們會出售在稍後的時間點。洛瑞？

I'll take the question on cash and the runway into 2026. As you guys know, we ended Q1 with $1.3 billion in cash. If we take a look over the next 2 to 3 years, that will be adequate cash to bridge us until we get to profitability from the BCMA program. But what I do want to say is that doesn't prohibit us from potentially looking at additional couple of raises. And that's really going to be dependent upon pipeline advancement. If there's something that we want to do on a business development perspective, and also if there's a certain level of working capital that we want to maintain, so yes, we do see us having adequate cash to get to profitability, but there are other factors that will come into play if we decide that we do on the raise of additional capital.

我將討論有關現金和 2026 年前景的問題。如果我們展望未來 2 到 3 年，這將是足夠的現金來支撐我們，直到我們從 BCMA 計劃中實現盈利。但我想說的是，這並不妨礙我們考慮額外的幾次加薪。這實際上取決於管道的進展。如果我們想從業務發展的角度做某事，並且如果我們想維持一定水平的營運資金，那麼是的，我們確實看到我們有足夠的現金來實現盈利，但還有其他因素如果我們決定籌集額外資金，這一點就會發揮作用。

And our next question coming from the line of Justin Zelin with BTIG.

我們的下一個問題來自 BTIG 的 Justin Zelin。

Steve, can you talk about some of the factors that are constraining outpatient administration and just the dynamic that centers decide on whether to offer outpatient administration?

史蒂夫，您能談談限制門診管理的一些因素以及中心決定是否提供門診管理的動態嗎？

Yes, sure. Thanks for that question. There's a number of different factors. The challenge in later-line disease is the fact that you're dealing with a very difficult-to-treat patient to begin with, right? So I think just from a patient perspective, it's a challenge. However, as we see in our trends, we're saying almost 30% of the time, our facilities are working quite effectively to treat those very difficult-to-treat patients.

是的，當然。謝謝你提出這個問題。有許多不同的因素。後期疾病的挑戰在於，您一開始就面對的是一位非常難以治療的患者，對嗎？所以我認為僅從患者的角度來看，這是一個挑戰。然而，正如我們在趨勢中看到的那樣，我們說幾乎 30% 的時間裡，我們的設施在治療那些非常難以治療的患者方面非常有效。

What you're going to see, though, in an earlier line more mobile patient, out of many of these patients are often working is it becomes much easier for the sites. And that's what we are projecting as well, right? So from a patient selection, these are more mobile patients and some of the patient-related issues that the sites were challenged with, will get a bit easier for them.

不過，您將看到，在較早排隊的流動性更強的患者中，其中許多患者經常工作，這對於站點來說變得更加容易。這也是我們的計劃，對吧？因此，從患者選擇來看，這些是流動性更強的患者，網站面臨的一些與患者相關的問題對他們來說會變得更容易一些。

So that's the first thing. And the other thing that we keep an eye on is their intent to move forward. The question was asked earlier around capacity, right? So the sites recognize this, and they also want to use outpatient CAR-T administration as a strategy to reduce the amount of resources, to treat the numbers of patients that are eligible for this therapy.

這是第一件事。我們關注的另一件事是他們前進的意圖。之前問過關於容量的問題，對嗎？因此，這些網站認識到了這一點，他們也希望使用門診 CAR-T 給藥作為減少資源量的策略，以治療符合該療法資格的患者數量。

So just from a resource perspective, sites also look at this as a very effective strategy to do so. So we're very excited about this, and you've heard me talk about a little bit on the back end and one of the questions around outpatient, you will see with this program a very different type of migration to full outpatient use.

因此，僅從資源角度來看，網站也將其視為一種非常有效的策略。因此，我們對此感到非常興奮，並且您已經聽過我談論了一些後端問題以及有關門診的問題之一，您將透過該計劃看到一種完全不同類型的遷移到完全門診使用。

Our strategy, we've been very deliberate on how we went to market with this program. And I think I'm proud in terms of what's going on in the marketplace, in terms of introducing this into the hospitals, having the hospitals move into their outpatient clinics. And like I said, over time, our hospitals are looking at other third-party partners on how to take this even further out to the community, to ensure that these numbers that we talked about earlier 10,000 doses, et cetera, we can meet that potential. So it's a very exciting step.

我們的策略是，我們非常慎重地考慮如何將該計劃推向市場。我認為我對市場上正在發生的事情、將其引入醫院、讓醫院搬進門診診所感到自豪。就像我說的，隨著時間的推移，我們的醫院正在尋找其他第三方合作夥伴，研究如何將這一點進一步推廣到社區，以確保我們之前談到的10,000 劑劑量等數字，我們能夠滿足這一目標潛在的。所以這是非常令人興奮的一步。

Our next question coming from the line of 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 this like double the capacity by year end '24 versus '23, like what is the respective annualized dose goal for this, just to make sure we understand the apples-to-apple comparison to your year-end '25 goal of 10,000 doses capacity?

因此，就這一點而言，到 24 年底與 23 年底將容量翻倍，例如相應的年化劑量目標是多少，只是為了確保我們了解與 25 年底目標的逐個比較10,000劑容量？

And then second, I wanted to ask is PERSEUS quad regimen adoption in the first-line setting, eventually, do you think that these delays are -- shrinks the second-line pool of patient for CARVYKTI in the long run effectively? These patients can have several years of progression-free survival, which could arguably impact the downstream market opportunity for CARVYKTI.

其次，我想問的是 PERSEUS 四聯療法在一線治療中的採用，最終，您認為這些延遲從長遠來看是否有效地縮小了 CARVYKTI 的二線患者群體？這些患者可以有數年的無惡化存活期，這可能會影響 CARVYKTI 的下游市場機會。

Yes, Ash. So, let me help with your first question. So yes, by end of 2025, we have this goal of reaching 10,000 annualized dose capacity, right? But that is when we exit 2025. So I just want to remind you that when we go into 2025, right, we are not going to be at the 10,000 but then because of the introduction of additional sites into the commercial production mode, we'll be able to end the year in 2025 with that capacity and it doesn't stop there because we'll continue to maximize the capacity from each of those nodes I mentioned.

是的，阿什。那麼，讓我來幫忙解答你的第一個問題。所以，是的，到 2025 年底，我們的目標是達到年化劑量能力 10,000 劑，對吧？但這是我們退出 2025 年的時候。年底，我們將能夠擁有這樣的容量，而且它不會止步於此，因為我們將繼續最大限度地提高我提到的每個節點的容量。

So we believe that we'll be able to actually get to a much higher number than that 10,000 dose. Once we complete all the expansion from the additional nodes with the investment here. So it's going to be hard for me to give you any quantitative distribution among the 3 -- I mean, sorry, the 4 different nodes we mentioned. But I can tell you that Raritan, New Jersey remains our biggest facility and in the foreseeable future, Raritan will be the most productive site in terms of the total output, probably followed by our sites in Tech Lane, Belgium.

因此，我們相信我們實際上能夠獲得比 10,000 劑更高的劑量。一旦我們用這裡的投資完成了所有附加節點的擴展。因此，我很難為您提供這 3 個節點之間的任何定量分佈——我的意思是，抱歉，我們提到的 4 個不同節點。但我可以告訴您，新澤西州力登仍然是我們最大的工廠，在可預見的未來，力登將成為總產量最高的工廠，其次可能是我們位於比利時 Tech Lane 的工廠。

So that is how we think about the total peak capacity and then how we would plan to distribute the capacity among the different nodes. With regarding your second question, how DRVD getting into the front line would potentially affect the second-line opportunity, I'll ask Steve to answer.

這就是我們如何考慮總峰值容量，以及我們如何計劃在不同節點之間分配容量。關於你的第二個問題，DRVD進入一線會如何影響二線機會，我請史蒂夫回答。

Yes. So thanks for the question. So we -- just so you know, we've been -- we've modeled certain assumptions in terms of how -- in terms of eligible patient populations progressing on the quad. So I guess from an eligible patient population, has been accounted for in our forecast. And that forecast then we've obviously communicated that with the manufacturing counterpart. So I guess from my perspective, again, we've accounted for that and we kind of added it in our supply plan.

是的。謝謝你的提問。所以我們——正如你所知，我們已經——根據合格患者群體在四方進展方面的方式，對某些假設進行了建模。所以我猜想，我們的預測已經考慮到了符合條件的患者群體。我們顯然已經與製造業同行溝通了這項預測。所以我想從我的角度來看，我們已經考慮到了這一點，並將其添加到我們的供應計劃中。

And then, Ash, maybe I'll just add to Steve to answer that. Number one, you do have this 20%, 25% so-called patients with high-risk cytogenetics mutation, and those patients unfortunately do not respond well. So they'll relapse. And that is why we are releasing the data at ASCO for Cohort D.

然後，阿什，也許我會補充史蒂夫來回答這個問題。第一，確實有 20%、25% 所謂的高風險細胞遺傳學突變患者，但不幸的是，這些患者反應不佳。所以他們會復發。這就是為什麼我們在 ASCO 上發布 D 組資料的原因。

These patients do not achieve optimal or a complete response from DRVD. They need a second-line therapy, right? That is your early adoption market. And then obviously, we are conducting CARTITUDE-5 trial. If you look at clinicaltrials.gov disclosure, we expect the primary position in the year 2026.

這些患者沒有從 DRVD 中獲得最佳或完全緩解。他們需要二線治療，對吧？這就是您的早期採用市場。顯然，我們正在進行 CARTITUDE-5 試驗。如果您查看 ClinicalTrials.gov 的披露信息，我們預計 2026 年將佔據主要位置。

So hopefully, within a couple of years, we'll have first-line label. And then obviously, we are going to pivot from second line to frontline when that happens.

因此，希望在幾年內，我們將擁有一線品牌。顯然，當這種情況發生時，我們將從第二線轉向前線。

Our next question coming from the line of Sean McCutcheon with Raymond James.

我們的下一個問題來自肖恩·麥卡琴 (Sean McCutcheon) 和雷蒙德·詹姆斯 (Raymond James)。

Maybe to put a finer point on that MRD negativity at [FAM] outcome. What do you think are the implications here for, I guess, CARTITUDE-5, CARTITUDE-6 timelines? And do you suppose the official draft guidelines will come in, in time to be impactful there or a bit too late? And what's your view on what the details for that MRD negativity requirement could be in CARTITUDE-6 to 12-month sustained MRD-negative CR? Do you think that's likely to be the bar? Or do you think maybe an earlier landmark could be informed or acceptable?

也許可以更好地說明 [FAM] 結果中 MRD 的負面影響。我想，您認為這對 CARTITUDE-5、CARTITUDE-6 時間表有何影響？您認為官方指南草案會及時推出以產生影響還是有點太晚了？您對 CARTITUDE-6 至 12 個月持續 MRD 陰性 CR 中 MRD 陰性要求的細節有何看法？你認為這可能是酒吧嗎？或者您認為早期的里程碑是否可以被告知或接受？

And then just as a follow-on to that, what do you think is the impact on the competitive dynamic for your earlier competitors if they're able to utilize MRD in -- across different lines of therapy?

接下來，您認為如果您的早期競爭對手能夠在不同的治療領域利用 MRD，那麼您認為對他們的競爭動態有何影響？

So first of all, we have all along worked through the MRD endpoint, right? If you look at all the CAR-T program trials, everyone has MRD measurement in the trial built-in. Like I mentioned just on the call today, in CARTITUDE-6, we actually have already designed the trial with MRD negativity as a co-primary endpoint with all this in our mind.

首先，我們一直在研究 MRD 端點，對嗎？如果你看所有的 CAR-T 項目試驗，你會發現每個人的試驗中都內建了 MRD 測量。正如我今天在電話會議上提到的，在 CARTITUDE-6 中，我們實際上已經設計了以 MRD 陰性作為共同主要終點的試驗，並考慮到了這一切。

So if you look at ODAC recommendation, right, the ODAC voted to recommend a 12-month MRD negativity as a potential endpoint. Right now, we don't expect FDA to publish the official guidance documents, but we do plan to engage with the agency to talk about the endpoint for CARTITUDE-5 and 6. And for CARTITUDE-5, it probably would make a small difference because anyway, we expect the readout to be in 2026.

因此，如果您查看 ODAC 建議，您會發現 ODAC 投票建議將 12 個月的 MRD 陰性作為潛在終點。目前，我們預計 FDA 不會發布官方指導文件，但我們確實計劃與該機構合作討論 CARTITUDE-5 和 6 的終點。在2026 年公佈。

Now for a CARTITUDE-6, it could make a big difference because if you look at our disclosure on clinicaltrials.gov, primary completion is estimated at 2033. Now if FDA does agree upon the 12-month MRD negativity in combination, for example, with CR or any other endpoint as a potential endpoint for accelerated approval. Then we can make that much, much faster in terms of the process, right? Because if we can complete all the enrollments for CARTITUDE-6 by end of next year, which is end of '25 then if the 12-month MRD negativity is amenable at the endpoint, that means potentially by end of 2026, we could have that kind of read out, right? So it does help a lot for frontline trials.

現在，對於CARTITUDE-6，它可能會產生很大的影響，因為如果您查看我們在ClinicalTrials.gov 上的披露，預計初步完成時間為2033 年。 ，例如，將 CR 或任何其他終點作為加速批准的潛在終點。那我們就可以讓流程變得更快，對嗎？因為如果我們能夠在明年年底（即25 年底）之前完成CARTITUDE-6 的所有註冊，那麼如果12 個月的MRD 陰性在終點處是可以接受的，這意味著可能到2026 年底，我們可以做到這一點有點讀出來，對吧？所以它對於一線試驗確實有很大幫助。

Now if you look at competition, I mean, I think in second line based on our experience, it doesn't change too much, right? Because the median PFS for our control was about 12 months. So I wanted to complete the enrollment, the readout shouldn't take that much longer. So I don't think there's a huge difference if you look at the second line or third line. But for frontline, it does make a significant difference here.

現在，如果你看看競爭，我的意思是，我認為根據我們的經驗，在第二線，它不會改變太多，對嗎？因為我們對照的中位 PFS 約為 12 個月。所以我想完成註冊，讀出不應該花那麼長時間。所以我認為如果你看第二行或第三行，沒有很大的區別。但對於前線來說，這確實有很大的不同。

In terms of the bar, I don't think there is a quantitative bar here that the regulators have already determined at this point. But you can follow our disclosure from CARTITUDE-4, CARTITUDE-2, CARTITUDE-1 trial, right? In general, we achieved a very high MRD negativity rate. In fact, at ASH last year, we even published the data from CARTITUDE-1.

就門檻而言，我認為監管機構目前還沒有確定量化門檻。但你可以從 CARTITUDE-4、CARTITUDE-2、CARTITUDE-1 試驗中了解我們的揭露，對嗎？總的來說，我們取得了非常高的 MRD 陰性率。事實上，在去年的 ASH 上，我們甚至發布了 CARTITUDE-1 的數據。

If you look at patients who achieved 6, 12 months or even longer than 12 months MRD negativity in combination of CR, those patients tend to have a very good prognosis in terms of longer-term PFS and survival. So we do have data from the CARTITUDE program to show that if a patient can achieve complete response in combination with some sort of longer-term MRD negativity, that is a very good predictive marker for a long-term outcome here.

如果觀察 MRD 陰性與 CR 相結合達到 6、12 個月甚至超過 12 個月的患者，這些患者在長期 PFS 和存活方面往往具有非常好的預後。因此，我們確實有來自 CARTITUDE 計劃的數據表明，如果患者能夠實現完全緩解並結合某種長期 MRD 陰性，那麼這對於長期結果來說是一個非常好的預測標誌。

And our next question coming from the line of 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 two, the first one I wanted to ask a bit on the second-line launch and the payer discussions. Can you just talk about kind of the color of payer discussions in the second-line population? And how did those second-line reimbursement discussions compare to those that you have had previously for later-line reimbursement discussions?

我有兩個問題，第一個我想問一下有關二線推出和付款人討論的問題。您能談談二線人群中付款人討論的色彩嗎？這些二線報銷討論與您之前進行的後期報銷討論相比如何？

And then the second question is on COGS. Could you just talk about the trend in COGS, and any impacting factors or levers that could influence the COGS in the future?

第二個問題是關於銷貨成本。您能否談談COGS的趨勢，以及未來可能影響COGS的影響因素或槓桿？

It's Steve. Why don't I take the first question around payer and contrast CARTITUDE-4 versus 1? So it all comes down with these payer conversations around the value proposition associated with treatment-free interval, obviously the CARTITUDE-4 data is significant in terms of our PFS improvement.

是史蒂夫。為什麼我不回答有關付款人的第一個問題並將 CARTITUDE-4 與 1 進行對比？因此，這一切都取決於這些付款人圍繞與無治療間隔相關的價值主張的對話，顯然 CARTITUDE-4 數據對於我們的 PFS 改善而言非常重要。

Payers -- the net of this in an earlier-line setting, payers love a product like cilta-cel, in terms of the benefit that we are able to give not only from a financial perspective, but also from a patient perspective in terms of the patient-related metrics.

付款人－在早期的環境中，付款人喜歡像 cilta-cel 這樣的產品，因為我們不僅能夠從財務角度提供好處，而且還從病人角度提供好處與病人相關的指標。

So all systems are a go in terms of early-line approvals in terms of -- from a reimbursement perspective, we have had no issues at all. As a matter of fact, the payers, the privates in particular, are one of our biggest advocates out there.

因此，從報銷的角度來看，所有系統在早期審批方面都是可行的，我們根本沒有遇到任何問題。事實上，付款人，特別是私人，是我們最大的支持者之一。

I'll take the COGS actually. So as you move into the second line and the payer structure changes, to your question, where you're going to see that is in the gross-to-net adjustment. On the COGS line, the reason that you see variability, actually has to do with the manufacturing capacity investments that we're making.

其實我會選擇 COGS。因此，當您進入第二行並且付款人結構發生變化時，對於您的問題，您將在總淨值調整中看到這一點。在銷貨成本線上，您看到變化的原因實際上與我們正在進行的製造能力投資有關。

So you will continue to see the COGS variability as we start to bring these in, finalize the capital investments and bring these nodes online in '24 and actually '25. So you continue to see that noise, it's the revenue line and the gross to net where you'll see the impact for the second-line launch.

因此，當我們開始引入這些、最終確定資本投資並在 24 年甚至 25 年將這些節點上線時，您將繼續看到 COGS 的變化。因此，你會繼續看到這種噪音，這是收入線和淨毛利率，你會看到二線產品推出的影響。

So if I come back to that first point because it just occurred to me one more thing around the payers piece of this, it ties back into the issue around outpatient administration as well. I mean other than the treatment-free interval component of this, as you can imagine, private insurers love the fact of a now a CAR-T therapy that can be given by hospitals very safely in the outpatient setting just purely from a cost reduction as opposed to admitting these patients, keeping them in some time for weeks to reduce costs and continue to maintain these patients safely and then also benefit from that long-term, treatment-free interval is a very compelling story to private insurers.

因此，如果我回到第一點，因為我剛剛想到了有關付款人的另一件事，那麼它也與門診管理問題有關。我的意思是，除了其中的免治療間隔部分之外，正如您可以想像的那樣，私人保險公司喜歡現在的CAR-T 療法，醫院可以在門診環境中非常安全地提供這種療法，這純粹是為了降低成本：對於私人保險公司來說，反對收治這些患者，讓他們住院數週以降低成本，並繼續安全地維持這些患者，然後從長期的、免治療的間隔中受益，這是一個非常引人注目的故事。

Our next question coming from the line of Rick Bienkowski with Cantor Fitzgerald.

我們的下一個問題來自里克·比恩科斯基（Rick Bienkowski）和康托·菲茨杰拉德（Cantor Fitzgerald）。

For the CARVYKTI launch in Europe, could you comment on the number of certified treatment centers that are open in Germany and Austria? And how many are expected to be certified by the end of the year? And as a second question, Ying, I was hoping you could expand on the prepared comments around reducing the CARVYKTI van-to-van time. Could you talk about the work that's being done here and if there are any internal targets for how much this could be improved?

對於 CARVYKTI 在歐洲的推出，您能否評論一下在德國和奧地利開設的經過認證的治療中心的數量？預計到今年年底會有多少人獲得認證？作為第二個問題，Ying，我希望您能詳細闡述有關減少 CARVYKTI 車到車時間的準備意見。您能否談談這裡正在進行的工作以及是否有任何可以改進的內部目標？

Why don't I take the first question around Germany around sites? Unfortunately, I cannot get into the details around sites and the rollout plan in Germany. I know it's -- I can tell you this. It's very robust. And I could also tell you the fact that in any country, the site certification process is often somewhat lengthy. So I'm bringing that up because I know our partners are working very hard to bring more and more sites on board, but I can't unfortunately get into specifics around numbers of sites.

為什麼我不回答德國網站的第一個問題？不幸的是，我無法詳細了解德國的站點和推出計劃。我知道這是——我可以告訴你這一點。它非常堅固。我也可以告訴你一個事實，在任何國家，站點認證過程通常都比較漫長。所以我提出這個問題是因為我知道我們的合作夥伴正在非常努力地讓越來越多的網站加入進來，但遺憾的是我無法詳細說明網站數量。

Okay. So on the question about van-to-van, I can tell you that our goal is to get to a median of less than 4 weeks by the end of this year. And also, we have a new metric to measure, which is P90. That means 90% of all the sellback we shipped out will fall into the -- what we call apheresis to receipt to less than 5 weeks. So that is our goal by end of this year. That means average what we saw shorter and then pretty much all the patients will be able to receive that within 5 weeks. That is our goal here.

好的。因此，關於貨車到貨車的問題，我可以告訴你，我們的目標是到今年年底達到中位數不到 4 週。而且，我們還有一個新的衡量標準，那就是 P90。這意味著我們運出的所有回售產品中有 90% 將在不到 5 週的時間內完成，即我們所謂的「單採到收貨」。這就是我們今年底的目標。這意味著我們看到的平均時間會更短，然後幾乎所有患者都能夠在 5 週內收到該結果。這就是我們的目標。

I'm showing no further questions at this time. Ladies and gentlemen, this concludes today's teleconference. Thank you for your participation, and you may now disconnect.

我目前沒有提出任何進一步的問題。女士們、先生們，今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。