Legend Biotech Corp (LEGN) 2023 Q3 法說會逐字稿

Good day, ladies and gentlemen. Thank you for standing by. Welcome to Legend Biotech Reports Third Quarter 2023 Financial Results Conference Call. (Operator Instructions). 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. You may begin.

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2023年第三季財務業績電話會議。 （操作員說明）。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。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 third quarter 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 will be joined by Guowei Fang, Chief Scientific Officer; and Steve Gavel, Head of Commercial Development for the U.S. and Europe.

早安，我是傳奇生物投資者關係和公共關係主管楊潔希。感謝您今天參加我們的電話會議，回顧我們 2023 年第三季的業績。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)。在準備好發言後，我們將開始問答環節。首席科學官方國偉也將加入我們；以及美國和歐洲商業發展主管 Steve Gavel。

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. I will now turn the call over to Ying.

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。我現在將電話轉給Ying。

Good morning, and thank you for joining us today to discuss the third quarter financial and corporate accomplishments of Legend Biotech. We are pleased with the progress we have made over the last quarter to advance our portfolio and pipeline of innovative therapies that are focused on addressing the serious and intractable disease patients face.

早安，感謝您今天加入我們討論傳奇生物第三季度的財務和企業成就。我們對上個季度在推進我們的創新療法組合和管道方面取得的進展感到高興，這些療法專注於解決患者面臨的嚴重和難治性疾病。

Last week, we announced that we have entered into an exclusive global licensing agreement with Novartis, which grants Novartis the rights to develop, manufacture and commercialize LB2102 and other potential CAR-T therapies, selectively targeting DLL3.

上週，我們宣布與諾華簽訂了全球獨家授權協議，該協議授予諾華開發、製造和商業化 LB2102 和其他潛在 CAR-T 療法的權利，選擇性地針對 DLL3。

LB2102 is an investigational autologous chimeric antigen receptor T cell therapy for the treatment of adult patients with extensive stage small cell lung cancer. As part of this agreement, we will receive an upfront payment of $100 million and are eligible to receive up to $1.01 billion in milestone payments as well as tiered royalties on net sales.

LB2102是一種在研自體嵌合抗原受體T細胞療法，用於治療患有廣泛期小細胞肺癌的成年患者。作為該協議的一部分，我們將收到 1 億美元的預付款，並有資格獲得高達 10.1 億美元的里程碑付款以及淨銷售額的分級特許權使用費。

We will also be reimbursed for development costs for the ongoing Phase I clinical trial, which will evaluate the safety and efficacy in patients with small cell lung cancer and patients with large cell neuroendocrine carcinoma, and to determine the recommended dose for Phase II study.

我們還將報銷正在進行的一期臨床試驗的開發費用，該試驗將評估小細胞肺癌患者和大細胞神經內分泌癌患者的安全性和有效性，並確定二期研究的建議劑量。

We're excited by this transaction, and we look forward to seeing how this therapy performs in the clinic. CARVYKTI, or cilta-cel continues to drive our revenue and direct our priorities. We have worked tirelessly to bring CARVYKTI to patients who are eligible for treatment and our efforts are reflected in the total net sales of $152 million in third quarter, bringing total net sales for 2023 to $341 million so far this year.

我們對這筆交易感到興奮，我們期待看到這種療法在臨床上的表現。 CARVYKTI 或 cilta-cel 繼續推動我們的收入成長並指導我們的優先事項。我們不懈努力，將 CARVYKTI 帶給有資格接受治療的患者，我們的努力體現在第三季 1.52 億美元的總淨銷售額中，使 2023 年迄今為止的總淨銷售額達到 3.41 億美元。

Our third quarter performance was driven by ongoing market launches, expanding market share and capacity improvements as well as the commercial launch of CARVYKTI in Germany, which contributed to quarter-over-quarter ex U.S. growth of 300%. In the U.S., we have experienced growth of 23% quarter-over-quarter. We remain steadfast in our goal to make CARVYKTI available and accessible to patients worldwide, and we look forward to sharing highlights of that journey with you today.

我們第三季業績的推動因素包括持續的市場推出、市場份額的擴大和產能的提高，以及 CARVYKTI 在德國的商業推出，這推動了除美國以外的季度環比增長 300%。在美國，我們的季度環比成長了 23%。我們始終堅定不移地致力於讓全球患者都能使用 CARVYKTI，我們期待今天與您分享這趟旅程的亮點。

We have progressively met strong demand for CARVYKTI in collaboration with Janssen. First, Janssen has scaled the in-house production of lentivirus at its factories in Switzerland and has another factory in the Netherlands under construction to complement and support LV supply, which should be online by 2025.

我們與楊森合作，逐步滿足了對 CARVYKTI 的強勁需求。首先，楊森在瑞士工廠擴大了慢病毒的內部生產，並在荷蘭建造了另一家工廠，以補充和支持慢病毒供應，預計將於 2025 年投產。

LV expansion is crucial because it is often the rate-limiting factor in any CAR-T manufacturing and growing LV supply is an important front in our ramp-up. Second, we're still on track with our preplanned capacity increase at our Raritan site and production from our CDMO is supporting that expansion next year.

LV 擴張至關重要，因為它通常是任何 CAR-T 製造的速率限制因素，而不斷增長的 LV 供應是我們產能提升的重要陣線。其次，我們仍按計劃實現力登工廠的產能成長， CDMO 的生產將支持明年的擴張。

Third, the first of our state-of-the-art manufacturing facilities in Ghent has received a license from the Federal Agency for Medicines and Health Products in Belgium. This was an important hurdle to clear. And once the investigation of medicinal product dossier is approved by local authorities we will begin manufacturing cilta-cel at Ghent for clinical use by end of this year. The Ghent facility will be an important part of the CARVYKTI supply chain network.

第三，我們在根特的第一個最先進的生產設施已獲得比利時聯邦藥品和保健品管理局的許可。這是一個需要清除的重要障礙。一旦藥品檔案調查獲得地方當局批准，我們將於今年年底開始在根特生產 cilta-cel 供臨床使用。根特工廠將成為 CARVYKTI 供應鏈網路的重要組成部分。

We're committed to bring CARVYKTI to more patients who are eligible for this important therapy. Our manufacturing ramp-up supports commercial delivery as well as our ongoing CARTITUDE development program with Janssen. Of the 5 clinical trials evaluating cilta-cel, 3 are ongoing and CARTITUDE-6, our Phase III study for frontline patients enrolled its first patient. The activation of 1 of our Ghent facilities will enable us to continue the commercial ramp we began in the U.S. while onboarding new clinical patients.

我們致力於將 CARVYKTI 帶給更多有資格接受這項重要療法的患者。我們的產能提升支援商業交付以及我們與楊森正在進行的 CARTITUDE 開發計劃。在評估 cilta-cel 的 5 項臨床試驗中，有 3 項正在進行中，我們針對第一線患者的 III 期研究 CARTITUDE-6 招募了第一位患者。我們根特一處設施的啟動將使我們能夠繼續在美國開始的商業擴張，同時吸收新的臨床患者。

In addition to making capacity enhancements, we work with roughly 60 certified treatment centers across the U.S. and are expanding access to CARVYKTI in select European countries, including Germany. Our teams are working hard on multiple fronts to bring this efficacious onetime treatment to patients in need. We are pleased to share that since trials began in 2018, we have treated more than 2,000 people with cilta-cel.

除了增強能力外，我們還與美國約 60 個經過認證的治療中心合作，並正在擴大包括德國在內的部分歐洲國家對 CARVYKTI 的使用範圍。我們的團隊正在多個方面努力工作，為有需要的患者提供這種有效的一次性治療。我們很高興地告訴大家，自 2018 年開始試驗以來，我們已經用 cilta-cel 治療了 2,000 多人。

Our pipeline is also robust, and we're exploring the potential of cell therapies in both hematologic malignancies and solid tumors. The funds from our transaction with Novartis will primarily be used to develop other promising pipeline assets such as our allogeneic cell therapies. The armoring used in LG2102 (sic) [LB2102] can also be deployed in other pipeline programs if validated in the clinic. We continue to explore innovation in our pipeline and are excited about their progression. Now I want to turn it to Lori.

我們的產品線也很強大，我們正在探索細胞療法在血液惡性腫瘤和實體腫瘤中的潛力。我們與諾華交易的資金將主要用於開發其他有前途的管道資產，例如我們的異體細胞療法。如果經過臨床驗證，LG2102（原文如此）[LB2102] 中使用的鎧裝也可以部署在其他管道項目中。我們繼續探索管道中的創新，並對它們的進展感到興奮。現在我想把它交給洛瑞。

Thank you, Ying, and good morning, everyone. As Ying mentioned, we are very pleased with our performance of our commercial product CARVYKTI this quarter, which generated approximately $152 million in total sales, an increase of 30% over the previous quarter, driven by ongoing market launches, expanding market share and capacity improvements. That performance also represents 176% year-over-year increase. As a reminder, we share equally in all profits and losses of CARVYKTI ex China with our partner, Janssen.

謝謝你，Ying，大家早安。正如應提到的，我們對本季商業產品CARVYKTI 的表現感到非常滿意，在持續的市場推出、擴大的市場份額和產能提升的推動下，該產品的總銷售額約為1.52 億美元，比上一季度成長30% 。這一業績也較去年同期成長 176%。謹此提醒，我們與我們的合作夥伴楊森公司平等分享 CARVYKTI 中國以外的所有利潤和損失。

Starting with cash and cash equivalents, time deposits and short-term investments of $1.4 billion, this will fund our planned operating and capital expenditures into 2025. Starting with revenue. Total revenues for the third quarter were $96 million, consisting of $75.9 million in collaboration revenue from the sale of CARVYKTI and $20.1 million in license revenue for the achievement of a milestone during the quarter as outlined in the global development plan under the Janssen Agreement for cilta-cel.

從 14 億美元的現金和現金等價物、定期存款和短期投資開始，這將為我們計劃到 2025 年的營運和資本支出提供資金。從收入開始。第三季總收入為 9,600 萬美元，其中包括出售 CARVYKTI 帶來的 7,590 萬美元合作收入和 2,010 萬美元的許可收入，用於在本季度實現 cilta 楊森協議下的全球發展計劃中概述的里程碑。 - cel。

Net loss for the 3 months ended September 30, 2023, was $62.2 million or a loss of $0.17 per share compared to a net loss of $85 million or $0.26 loss per share for the same period last year. For the 9 months ending September 30, 2023, net loss was $373.4 million or a loss of $1.07 per share compared to a net loss of $310.5 million or a loss of $0.99 per share for the 9 months ended September 30, 2022.

截至 2023 年 9 月 30 日的三個月淨虧損為 6,220 萬美元，即每股虧損 0.17 美元，而去年同期淨虧損為 8,500 萬美元，即每股虧損 0.26 美元。截至2023年9月30日的9個月，淨虧損為3.734億美元，或每股虧損1.07美元，而截至2022年9月30日的9個月，淨虧損為3.105億美元，或每股虧損0.99美元。

Moving on to expenses. Collaboration cost of revenue for the third quarter 2023 was $43.5 million compared to $25.5 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 年第三季的合作收入成本為 4,350 萬美元，去年同期為 2,550 萬美元。這些是聯想的合作銷售成本部分，與楊森協議下的合作收入以及支持製造能力擴張的支出有關。

Research and development expenses for the third quarter 2023 were $95.9 million compared to $104.5 million for the same period last year. The decrease of $8.7 million for the 3 months ended September 30, 2023, compared to the 3 months ended September 30, 2022, was due to timing of expenses incurred in connection with the master technology transfer manufacturing and clinical service agreement for BCMA CAR-T product with Janssen and Novartis Pharmaceuticals Corporation.

2023 年第三季的研發費用為 9,590 萬美元，去年同期為 1.045 億美元。截至2023年9月30日止三個月較截至2022年9月30日止三個月減少870萬美元，原因是與BCMA CAR-T主技術轉移製造和臨床服務協議相關的費用發生時間安排楊森和諾華製藥公司的產品。

Administrative expenses for 3 months ended September 30, 2023, were $28.1 million compared to $23.2 million for the same period last year. The increase of $4.9 million year-over-year is primarily due to the expansion of administrative functions to facilitate continuous business growth and continued investment in building Legend Biotech's global information technology infrastructure.

截至 2023 年 9 月 30 日的三個月管理費用為 2,810 萬美元，去年同期為 2,320 萬美元。年比增加490萬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 the 3 months ended September 30, 2023, was $21.1 million compared to $18.9 million for the same period last year. The increase of $2 million year-over-year due to costs associated with the commercialization of CARVYKTI.

截至 2023 年 9 月 30 日的三個月的銷售和分銷費用為 2,110 萬美元，而去年同期為 1,890 萬美元。由於 CARVYKTI 商業化相關成本，年增 200 萬美元。

To wrap up, our spending remains on track, and we continue to maintain a strong balance sheet. As of September 30, we had $1.4 billion in cash and equivalents, deposits and investments, which Legend Biotech believes will fund operating and capital expenditures into 2025. Thank you. I will now pass it back to Ying for closing remarks.

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 9 月 30 日，我們擁有 14 億美元的現金及等價物、存款和投資，傳奇生物相信這些資金將為 2025 年的營運和資本支出提供資金。謝謝。我現在將其傳回給Ying以供結束語。

Thank you, Lori. 2023 continues to be another remarkable year for Legend Biotech, and we look forward to closing out the year strong in the fourth quarter. We have made considerable strides in enhancing our manufacturing capabilities and lowering our out of spec rate.

謝謝你，洛瑞。 2023年對傳奇生物來說仍然是另一個非凡的一年，我們期待在第四季度以強勁的表現結束這一年。我們在提高製造能力和降低不合格率方面取得了長足的進步。

We're proud to be a fully integrated cell therapy company focused on both hematologic, malignancies and solid tumors.

我們很自豪能夠成為一家專注於血液學、惡性腫瘤和實體腫瘤的完全整合的細胞治療公司。

Looking forward, we'll continue to invest in our manufacturing capacity as we work to deliver CARVYKTI to patients expeditiously and responsibly. We'll also continue to expand our pipeline. At Legend Biotech, we strive to deliver long-term value to our shareholders and are encouraged by these developments. Thank you for joining us today. We'll now open the call up for questions.

展望未來，我們將繼續投資於我們的生產能力，努力快速、負責任地向患者提供 CARVYKTI。我們也將繼續擴大我們的管道。在傳奇生物，我們努力為股東創造長期價值，並對這些發展感到鼓舞。感謝您今天加入我們。我們現在將開始提問。

(Operator Instructions) Our first question is coming from the line of Gena Wang with Barclays.

（操作員說明）我們的第一個問題來自巴克萊銀行的 Gena Wang。

Also congrats on the great quarter. So maybe I have 2 questions. One is regarding I think this morning, we saw the news, the Bristol's ABECMA now they will require AdCom and a PDUFA got pushed out. And maybe based on that news, what is your interaction with the FDA so far? And are you also anticipating an AdCom?

也恭喜這個偉大的季度。所以也許我有兩個問題。一是關於我想今天早上，我們看到了新聞，布里斯託的 ABECMA 現在他們將要求 AdCom 和 PDUFA 被推出。也許根據該消息，到目前為止您與 FDA 的互動是怎樣的？您是否也期待 AdCom 的到來？

And second question is regarding the competitive landscape. In terms of the efficacy profile, we will see some update at ASH? What is your thoughts regarding staying competitive. And the other related question is a commercial strategy in the outpatient setting?

第二個問題是關於競爭格局。在功效方面，我們會在 ASH 上看到一些更新嗎？您對於保持競爭力有何想法？另一個相關問題是門診環境的商業策略？

Gena, thanks for the questions. So I'll take the first one first, which is regarding the AdCom that will be hosted by FDA ODAC for our competition. So I can tell you that given our interactions with the FDA so far on our CAR-T filing, clearly, the agency plays an emphasis on the OS benefit, overall survival benefit. And typically, the agency standard is that you have to demonstrate a significant PFS benefit with an overall encouraging trend in survival. So without disclosing anything further, I can tell you Gena that on August 4 when we received the filing acceptance for CARTITUDE-4 by the agency, we were advised that FDA was not planning to hold an AdCom or advisory committee to discuss this supplement. That was as of August.

吉娜，謝謝你的提問。因此，我將首先討論第一個問題，即關於將由 FDA ODAC 主辦的 AdCom 競賽。所以我可以告訴你，鑑於我們迄今為止在 CAR-T 申請上與 FDA 的互動，很明顯，該機構非常重視 OS 效益和整體生存效益。通常，機構標準是您必須展示顯著的 PFS 益處以及整體上令人鼓舞的生存趨勢。因此，在不透露任何進一步資訊的情況下，我可以告訴Gena，8 月4 日，當我們收到該機構對CARTITUDE-4 的備案接受時，我們被告知FDA 不打算召開AdCom 或諮詢委員會來討論該補充劑。那是截至八月的情況。

Secondly, I'm also very pleased to tell you that as part of our so-called 4-month safety update, we did submit to the FDA additional data, and again, we are seeing a stronger trend of overall survival since the last update when the data was presented at ASCO. So that's what I will say about the overall survival from CARTITUDE-4, and we remain very confident on the profile for CARVYKTI.

其次，我也很高興地告訴大家，作為我們所謂的 4 個月安全更新的一部分，我們確實向 FDA 提交了額外的數據，而且，自上次更新以來，我們再次看到整體生存趨勢更強當資料在ASCO 上公佈時。這就是我要說的關於 CARTITUDE-4 的整體存活率，我們對 CARVYKTI 的概況仍然非常有信心。

Secondly, on ASH and competition, I'm not to comment into any competitive data, but we stand behind the safety and efficacy of CARVYKTI, which been dosed by more than 2,000 patients already since we started the program, and that includes patients with dose in the commercial setting after FDA approval last year and also patients who were dosed in various CAR-T programs and also CAR-T program in China. So we are very, very happy to see the very deep, consistent, durable response in every setting of multiple myeloma, we have tested so far. With the commercial strategy, I'll ask my colleague, Steve to comment. Steve?

其次，關於 ASH 和競爭，我不會評論任何競爭數據，但我們支持 CARVYKTI 的安全性和有效性，自我們啟動該計劃以來，已經有 2,000 多名患者服用了該藥物，其中包括接受劑量的患者去年FDA 批准後，在商業環境中以及在各種CAR-T 項目和中國CAR-T 項目中接受給藥的患者中。因此，我們非常非常高興地看到迄今為止我們已經測試過的每一種多發性骨髓瘤的治療效果都非常深入、一致、持久。至於商業策略，我會請我的同事史蒂夫發表評論。史蒂夫？

Yes. Thanks, Ying. Thanks, Gena. I think your question had to do around outpatient and maybe I could just give you an update on what's happening in that particular area. We were holding constant at about 30% share in terms of inpatient versus outpatient. We're also forecasting as we enter in earlier lines with the CARTITUDE-4 launch next year is to exit. We hope to exit next year, I would assume maybe even doubling that. It's really predicated on bringing on board our sites and obviously, getting our consistent supply into market. But right now, from a share perspective, that's how our claims data is measuring up.

是的。謝謝，瑩。謝謝，吉娜。我認為你的問題與門診有關，也許我可以向你提供該特定領域正在發生的最新情況。就住院患者與門診患者而言，我們的份額維持在 30% 左右。我們也預測，隨著明年 CARTITUDE-4 發射的早期進展，我們將退出。我們希望明年退出，我想甚至可能會翻倍。這實際上是基於將我們的網站引入我們的網站，並且顯然是將我們的穩定供應推向市場。但現在，從股票的角度來看，這就是我們的索賠數據的衡量標準。

And our next question coming from the line of Jessica Fye with JPM Chase.

我們的下一個問題來自摩根大通的 Jessica Fye。

On the heels of the Novartis licensing, can you talk about what the next wave of targets Legend is interested in pursuing might be?

在獲得諾華許可之後，您能否談談傳奇有興趣追求的下一波目標可能是什麼？

Thanks, Jessica. This is Guowei. So we have extensive internal pipeline, both in our targets as well as in the allogeneic cell therapy front. In our target space, we continue to focus on blood cancer building better momentum franchise at the same time also expand into the solid tumor indications.

謝謝，傑西卡。這是國偉。因此，我們在我們的目標以及同種異體細胞治療領域擁有廣泛的內部管道。在我們的目標領域，我們繼續專注於血癌，建立更好的勢頭特許經營權，同時也擴展到實體腫瘤適應症。

In allogeneic space, we have several different platforms, and we have deep investments in gamma-delta T allogeneic platform in the past several years, one of our compound is R&D tested in the community setting, and we are waiting to collect clinical response profile and expand the allogeneic platform as well. Currently, the allogeneic platform is primarily focused on the blood cancer indication.

在同種異體領域，我們有幾個不同的平台，過去幾年我們對γ-δ T同種異體平台進行了深度投資，我們的一種化合物在社區環境中進行了研發測試，我們正在等待收集臨床反應概況和結果也擴大了同種異體平台。目前，同種異體平台主要專注於血癌適應症。

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

我們的下一個問題來自 Jefferies 的 Kelly Shi。

Congrats on the great progress. How should we think about the Q-over-Q growth of CARVYKTI into Q4, considering J&J and Legend manufacturing capacity increase and also the level of demand in the mainline settings as TALVEY experienced a great launch. And also, how do you estimate the seasonality impact from holidays and also I have a follow-up.

祝賀取得的巨大進步。考慮到強生和 Legend 製造能力的增加以及 TALVEY 經歷了一次偉大的推出後主線環境的需求水平，我們應該如何看待 CARVYKTI 進入第四季度的環比增長。另外，您如何估計假期對季節性的影響，我也有後續行動。

Thank you. Kelly, this is Lori. I'm going to give you just overview quarter-over-quarter, and then I'll turn it over to Steve. As you look out going into Q4, as we've talked about before, we are doing a step up. We have gotten that approved. But as we've indicated before, you won't really see the impact of that until Q1 of 2024. And as a reminder, we've also signaled that in Q4, we will be doing some comparability runs as we're getting some of our additional nodes for manufacturing capacity up and running for 2024 to help support these second-line launch. So with that, if you look at Q4, we're not giving specific guidance, but you're not going to see significant growth quarter-over-quarter because of both of those activities. And with that, Steve, I'll turn it over to you.

謝謝。凱莉，這是洛瑞。我將向您簡要介紹季度情況，然後將其交給史蒂夫。當你展望第四季時，正如我們之前討論過的，我們正在採取進一步措施。我們已經獲得批准。但正如我們之前指出的，要到 2024 年第一季度，您才能真正看到其影響。作為提醒，我們還表示，在第四季度，我們將進行一些可比性運行，因為我們得到了一些結果我們將在2024 年啟動並運行額外的製造能力節點，以幫助支援這些二線產品的推出。因此，如果你看看第四季度，我們不會給出具體的指導，但由於這兩項活動，你不會看到季度環比的顯著增長。史蒂夫，我就把它交給你了。

Yes. Kelly, it's Steve. I think your second one was to do with the tech launch. So what we're seeing in market research that we're running is where you see market share coming out of market in terms of CAR-T therapies has been that from ABECMA as opposed to cilta-cel. We're seeing still a robust demand in later line settings. And I think you're going to see that continue in market with the bispecifics, where if you see erosion in terms of share erosion, I see it coming from ABECMA at least that's been the latest data we've seen in our search.

是的。凱利，我是史蒂夫。我認為你的第二個與技術發布有關。因此，我們在正在進行的市場研究中看到，CAR-T 療法的市場份額來自 ABECMA，而不是 cilta-cel。我們看到後期生產線設置的需求仍然強勁。我認為你會看到雙特異性藥物市場繼續出現這種情況，如果你看到份額侵蝕的侵蝕，我認為它至少來自 ABECMA，這是我們在搜尋中看到的最新數據。

Terrific. And also regarding the initiation of CARTITUDE-6 trial in the frontline transplant-eligible patient population. Could you actually share -- should we expect the U.S. enrollment to start in near term? And even majority of the enrollment come from Europe, do you consider impact on the enrollment pace compared to CARTITUDE-5 trial?

了不起。還有關於在符合移植資格的第一線患者族群中啟動 CARTITUDE-6 試驗。您是否真的可以分享一下—我們是否應該期望美國的招生在近期內開始？即使大多數註冊來自歐洲，您是否考慮與 CARTITUDE-5 試驗相比對註冊速度的影響？

Thanks, Kelly. So we're very pleased to announce that the first patient has been enrolled last month in Spain. So we officially have kicked off the initiation of CARTITUDE-6 and we are going to initiate enrollment in the U.S. also very soon. At this point, I can tell you that we will promise to enroll a certain percentage of U.S.-based patients because we have to submit the data to the agency later to make sure that we have a representative U.S. patient population in the overall patients. Although probably the majority of patients will be enrolled ex U.S. for CARTITUDE-6.

謝謝，凱利。因此，我們非常高興地宣布，第一位患者已於上個月在西班牙入組。因此，我們正式啟動了 CARTITUDE-6，我們也將很快在美國啟動註冊。此時，我可以告訴你，我們會承諾招募一定比例的美國患者，因為我們稍後必須向該機構提交數據，以確保我們在整體患者中擁有代表性的美國患者群體。儘管可能大多數患者將在美國境外參加 CARTITUDE-6。

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

我們的下一個問題來自摩根士丹利的 Vikram Purohit。

We had 2. First, assuming you were to obtain approval for CARVYKTI for the expanded label based on the CARTITUDE-4 data by next April. Could you just walk us through your latest thinking on what you expect the ramp to look like in earlier line use in 2024 onwards.

我們有 2. 首先，假設您將在明年 4 月之前根據 CARTITUDE-4 數據獲得 CARVYKTI 擴展標籤的批准。您能否向我們介紹一下您對 2024 年以後早期線路使用中坡道的期望的最新想法。

And then secondly, back to the topic of competition. So Bristol-Myers in 270 have mentioned that they're making a bigger commercial push for ABECMA that includes site expansion to broaden out apheresis therapy. I wanted to see if you've noticed any competitive impact at this point from those efforts. And if you and J&J feel the need to increase your marketing and promotional spend, behind CARVYKTI in response to the efforts from Bristol-Myers and 2Seventy?

其次，回到競爭的議題。因此，百時美施貴寶 (Bristol-Myers) 在 270 中提到，他們正在對 ABECMA 進行更大的商業推動，其中包括擴大站點以擴大單採療法。我想看看您是否注意到這些努力對競爭產生了任何影響。如果您和強生覺得有必要增加您的行銷和促銷支出，支援 CARVYKTI 以回應百時美施貴寶和 2Seventy 的努力？

It's Steve. So let me try to take them. I think the second part of your question had to do with site expansion also promotional spend. We'll continue to expand sites over time. We'll exit this year, we think, right around 70 sites and will see our site expansion is predicated on delivering in our manufacturing capacity increasing. So we are targeting by the end of next year to be exiting at about between 90 to 100. So that hopefully answers your question around site expansion.

是史蒂夫。所以讓我嘗試接受它們。我認為你問題的第二部分與網站擴展和促銷支出有關。隨著時間的推移，我們將繼續擴大站點。我們認為，今年我們將退出大約 70 個工廠，我們的工廠擴張取決於我們製造能力的增加。因此，我們的目標是到明年年底退出數量約為 90 到 100 個。因此，這有望回答您有關網站擴展的問題。

And as I remember, as I continue to state there, this is more than just site expansion. All these sites are not created equal in terms of the numbers of patients that they treat. Our philosophy is continue to increase our site expansion to ensure that we can accommodate the demand within those sites.

我記得，正如我繼續指出的那樣，這不僅僅是網站擴展。所有這些站點在其治療的患者數量方面並不相同。我們的理念是繼續擴大我們的站點，以確保我們能夠滿足這些站點內的需求。

I think your second question had to do with CARTITUDE-4 or can somebody help me here...

我認為你的第二個問題與 CARTITUDE-4 有關，或者有人可以幫助我嗎？

The ramp.

坡道。

The ramp. Yes. So thanks. So how we're planning the CARTITUDE-4 ramp in terms of the forecast perspective, we were initially and we continue to assume a very quick ramp-up, especially in the high-risk population in second line plus. In some of the research that we filled in post ASCO, once we release the CARTITUDE-4 data, we're also seeing high demand also in the standard risk population. So generally speaking, again, we're very excited, as you can imagine, in launching CARTITUDE-4 for our patients. But we see it much broader than we were initially thinking beyond the high-risk group.

坡道。是的。那謝謝啦。因此，從預測的角度來看，我們如何規劃 CARTITUDE-4 的提升，我們最初並且繼續假設一個非常快速的提升，特別是在二線以上的高風險群中。在我們在 ASCO 後填寫的一些研究中，一旦我們發布了 CARTITUDE-4 數據，我們也發現標準風險族群的需求也很高。所以總的來說，正如你可以想像的那樣，我們對為我們的患者推出 CARTITUDE-4 感到非常興奮。但我們看到的範圍比我們最初想像的要廣泛得多，超出了高風險群體的範圍。

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

Congrats on the quarter. I wanted to stick with the competition discussion for just a little bit. We've been hearing that there's actually been capacity constraints in the CAR-T space as a whole was actually BCMA and CD19-directed CAR-Ts competing for beds and infusion capacity. I guess, is this something that you're seeing as you're continuing to launch CARVYKTI? Do you expect any dynamic to lift or continue?

恭喜本季。我想繼續討論一下比賽。我們聽說整個 CAR-T 領域實際上存在容量限制，實際上是 BCMA 和 CD19 定向 CAR-T 爭奪床位和輸液容量。我想，這是您在繼續推出 CARVYKTI 時所看到的嗎？您預計任何動力會提升或持續嗎？

It's Steve. I'll take that again. I think that's a very, very good point. So that's why it's so important, this is why you're seeing a large percentage now of sites moving to hospital outpatient for cilta-cel. So yes, so to your point, it's a very valid point that you cannot continue to treat CAR-T therapies as just a single inpatient mortality. We knew that leading into launch. And it was the reason why we were continuing to monitor how the market was moving to outpatient to increase capacity to your point.

是史蒂夫。我會再接受一次。我認為這是一個非常非常好的觀點。這就是為什麼它如此重要，這就是為什麼你現在看到很大比例的 cilta-cel 站點轉移到醫院門診。所以，是的，所以就你的觀點而言，你不能繼續將 CAR-T 療法視為單一的住院患者死亡率，這是一個非常有效的觀點。我們在發布之前就知道這一點。這就是為什麼我們繼續監控市場如何轉向門診以增加容量以達到您的目的的原因。

So you address capacity in essence, 2 ways, right? So you continue to monitor to see how the market is moving in the outpatient setting, and as I stated earlier, running at about 3 out of 10 patients now being treated that way, and we see that continuing to grow significantly over time. So that's the first piece of that of solving that issue.

所以你本質上可以透過兩種方式來解決容量問題，對吧？因此，您將繼續監測門診市場的發展情況，正如我之前所說，目前大約有十分之三的患者正在接受這種治療，而且我們看到隨著時間的推移，這種情況繼續顯著增長。這是解決該問題的第一步。

And then the second way you resolve that is by increasing sites themselves, and we'll continue to do that as well. So it's a combination of a number of different moving parts. So we'll see how the market is moving in the outpatient setting. And then we'll also continue to add more and more sites to accommodate, to your point, the patient volume to ensure that we have enough -- or the sites have enough volume to pull through the volume of patients for our indication.

解決這個問題的第二種方法是增加網站本身，我們也將繼續這樣做。所以它是許多不同運動部件的組合。因此，我們將看看門診市場的走勢如何。然後我們還將繼續添加越來越多的站點來容納患者數量，以確保我們有足夠的患者量，或者站點有足夠的容量來容納我們適應症的患者量。

And Leonid, this is Ying. Maybe I want to add that. If you look at the number of transplants that are performed in the setting of myeloma, it's about 9,000 transplants, that's performed every year in the United States market. So we think at this point, at least for multiple myeloma, we're not approaching that limit in terms of hospital beds yet. As you know, if you look at our supply into the market, right, we're nowhere near that 9,000 number yet. Thank you.

列昂尼德，這是英。也許我想補充一點。如果你看一下在骨髓瘤背景下進行的移植手術的數量，你會發現美國市場每年進行的移植手術數量約為 9,000 例。因此，我們認為目前，至少對於多發性骨髓瘤，我們在醫院床位方面尚未接近這項限制。如您所知，如果您看看我們的市場供應量，您會發現我們還遠遠沒有達到 9,000 個數字。謝謝。

And our next question 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. I just have 2. The first one, can you give us a little bit of a sense, we're hearing that not now, but potentially later on, recess slots might become more of a bottleneck as you're ramping up capacity. I don't know if you can give us a little bit of a sense of how much capacity there is now? And what can you do to enhance it?

偉大的。我只有 2 個。第一個，你能給我們一點感覺嗎？我們聽說現在不是，但以後可能，當你增加容量時，休息槽可能會成為一個瓶頸。不知道您能否為我們介紹一下現在的容量有多少？你可以做什麼來增強它？

And then secondly, it looks like the facility in Europe, in Belgium has now got approved on a local basis, and you're noting that you need to wait for investigational medicinal products approval in local authorities. Is that not centralized to the EMA? Or is it sort of different, done differently in Europe? And I just reaffirm that you're not foreseeing any sort of limitation and how many slots you're going to have in that plant in Europe?

其次，看起來歐洲、比利時的設施現在已經在當地獲得了批准，您注意到您需要等待當地當局對研究性藥品的批准。這不是集中到 EMA 了嗎？還是歐洲的做法有所不同？我只是重申，您沒有預見到任何形式的限制，以及您在歐洲的工廠將有多少個槽位？

This is Steve again. Why don't I take a crack at the apheresis question. The apheresis question really varies by site. I know we've been having a number of conversations with our sites as we work collaboratively to onboard them and certify them. So the apheresis question really is being upfront addressed by our sites because what they are doing is forecasting what the volume looks like for them, whether it be for obviously the CARTITUDE-1 launch, which they have a pretty good idea, obviously, by now. But more importantly, CARTITUDE-4.

這又是史蒂夫。我為什麼不嘗試單採術問題？單採術問題確實因地點而異。我知道，在我們合作加入並認證網站的過程中，我們已經與我們的網站進行了多次對話。因此，我們的網站確實預先解決了單採問題，因為他們正在做的是預測他們的數量，無論是顯然是為了 CARTITUDE-1 的發射，顯然，他們現在已經有了一個很好的主意。但更重要的是，CARTITUDE-4。

So as I keep mentioning, we are addressing this in a number of different ways, this question around capacity. And right now, like I said, the number that I was guiding earlier in terms of roughly90 to 100 that I gave earlier in terms of number of sites, is in response to a number of these capacity questions to ensure that the marketplace has enough aggregate capacity to pull this indication through. Ying, do you want to take the second question?

正如我一直提到的，我們正在以多種不同的方式解決這個問題，即圍繞容量的問題。現在，就像我說的，我之前指導的大約 90 到 100 個站點數量是為了回答其中一些容量問題，以確保市場有足夠的總量推動這一跡象的能力。瑩，你想回答第二個問題嗎？

I'll take the question about the European facility. So we did receive a GMP certificate issued by the local FAG, which is the counter part of FDA in Belgium. And that is sufficient for us to start the clinical production next month in the U.S. -- sorry, in Belgium. And then specifically on your question about U.S. FDA. So right now, our plan is to start clinical production by end of this year in Belgium for certain clinical trials. And then about mid or next year in 2024, we're planning to seek regulatory approval for our Obelisc, Ghent facility to start producing commercial CARVYKTI.

我將回答有關歐洲設施的問題。所以我們確實收到了當地FAG頒發的GMP證書，FAG是比利時FDA的對應機構。這足以讓我們下個月在美國（抱歉，在比利時）開始臨床生產。然後特別是關於你關於美國 FDA 的問題。所以現在，我們的計畫是今年年底在比利時開始臨床生產，進行某些臨床試驗。然後，大約在 2024 年年中或明年，我們計劃為根特方尖碑工廠尋求監管部門批准，開始生產商業 CARVYKTI。

Initially, we're planning to supply only the European market. So at this point, we will not need FDA approval. In the future, in the case where we do have excess capacity that we could use from the Ghent facilities, then we plan to come back and ask FDA approval.

最初，我們計劃僅供應歐洲市場。所以目前我們不需要 FDA 的批准。將來，如果我們確實有多餘的產能可以使用根特工廠的產能，那麼我們計劃回來請求 FDA 批准。

So you're right, in the case of commercial production for U.S. patients, we would need SBRA approval by the FDA. But right now, in the very near future, we're only designating the Ghent facilities for our European commercial demand and also clinical trial demand. But still, that does help our supply in the U.S. because, as you know, right now, we're only producing both clinical trial materials and commercial CARVYKTI from our New Jersey facility. So whenever we can divert some of the demand from European market and also clinical trials to Ghent, that will free up more slots from our Raritan, New Jersey facility. I hope that answers your question.

所以你是對的，如果要為美國患者進行商業生產，我們需要 FDA 的 SBRA 批准。但目前，在不久的將來，我們僅指定根特設施以滿足我們的歐洲商業需求和臨床試驗需求。但這仍然有助於我們在美國的供應，因為如您所知，目前我們僅在新澤西工廠生產臨床試驗材料和商業 CARVYKTI。因此，只要我們能夠將歐洲市場和臨床試驗的部分需求轉移到根特，就會從我們新澤西州力登工廠騰出更多的空位。我希望這能回答你的問題。

And our next question coming from the line of Linhai Zhao from Goldman Sachs.

我們的下一個問題來自高盛的趙林海。

Two quick questions on the financials. The first one is as we are still enrolling for CARTITUDE-5 and now starting to enroll for CARTITUDE-6 and R&D expenses remained flat well over a quarter. How should we see the R&D spending in fourth quarter and in 2024? And the second question is it seems that the gross profit margin slightly decreased quarter-over-quarter. And can you share with us any color on potential gross profit margin improvement in the near term?

關於財務的兩個簡單問題。第一個是我們仍在註冊 CARTITUDE-5，現在開始註冊 CARTITUDE-6，研發費用在四分之一以上保持持平。我們該如何看待第四季和2024年的研發支出？第二個問題是，毛利率似乎較上季略有下降。您能否與我們分享有關近期毛利率潛在改善的任何資訊？

This is Lori. In regards to the R&D spend, I think you'll see a consistent quarter-over-quarter. I mean the activities itself have been pretty consistent with our investment in front lines for the CARVYKTI program as well as our pipeline. So we continue going into 2024, we expect to see continual spend consistent with our historic.

這是洛瑞。關於研發支出，我認為您會看到季度環比保持一致。我的意思是，這些活動本身與我們對 CARVYKTI 項目以及我們的管道的前線投資非常一致。因此，進入 2024 年，我們預計支出將持續與歷史水準一致。

I'm sorry, can you repeat the second question?

抱歉，您能重複第二個問題嗎？

Yes, sure. The second question is about the gross profit margin. When do we expect to see a further increase on the profit margin?

是的，當然。第二個問題是關於毛利率。我們預計什麼時候利潤率會進一步增加？

So from a gross margin perspective, we have been seeing improvements from a product perspective. As a reminder, for gross margins, we have the product gross margin in there as well as the OpEx related to facility investments. So that's why it's hard for you to see the continual improvement in gross margin because as we've talked about, we continue to expand our capacity with manufacturing, so we continue to have expenses hitting in that gross margin line.

因此，從毛利率的角度來看，我們從產品的角度看到了改善。提醒一下，對於毛利率，我們有產品毛利率以及與設施投資相關的營運支出。因此，這就是為什麼您很難看到毛利率持續改善，因為正如我們所討論的，我們繼續擴大製造能力，因此我們的費用繼續觸及毛利率線。

But as our volumes have increased and as we've made also some process improvements, our margins are improving from a product perspective, but we don't give specific guidance on those actual percentages.

但隨著我們產量的增加以及我們也進行了一些流程改進，從產品角度來看，我們的利潤率正在提高，但我們沒有對這些實際百分比給予具體指導。

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

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

I'm going to ask about DLL3 actually in entree to solid tumors more broadly. Can you walk us through the dose levels for the DLL3 Phase I versus CARVYKTI? And maybe talk a little bit about how that relates to your expectations for dosing in solid tumors more broadly? And I have a follow-up.

我要問的是 DLL3 實際上在更廣泛的實體瘤中的作用。您能否向我們介紹一下 DLL3 I 期與 CARVYKTI 的劑量等級？也許可以談談這與您對更廣泛的實體瘤劑量的期望有何關係？我有一個後續行動。

Hi, Jonathan, thanks for the question. This is Steve. So if you look at our disclosure on clinicaltrials.gov, you will see that we're planning to test 4 different doses, ranging from 0.3 million cells per kilogram body weight up until 1 million to 2 million cells per kilogram body weight. So this is a weight-based dosing plan. And because this is a solid tumor, and we foresee that you may need a little bit bigger dose than in the hematologic cancers.

你好，喬納森，謝謝你的提問。這是史蒂夫。因此，如果您查看我們在 ClinicalTrials.gov 上披露的內容，您會發現我們計劃測試 4 種不同的劑量，範圍從每公斤體重 30 萬個細胞到每公斤體重 100 萬至 200 萬個細胞。所以這是一個基於體重的劑量計劃。因為這是一種實體腫瘤，我們預期您可能需要比血液癌更大的劑量。

So if you look at our prior dose-ranging finding trials for the hematology such as multiple myeloma indication, this is a little bit higher starting dose given that we probably need a larger amount of T cells. But on the other hand, we did put an armor namely the dominant negative TGFBeta armor to help expansion and penetration into the tumor setting. So that is the dose we're looking at for DLL3 in Phase I.

因此，如果您查看我們先前針對血液學（例如多發性骨髓瘤適應症）的劑量範圍發現試驗，您會發現，考慮到我們可能需要更大量的 T 細胞，起始劑量稍高一些。但另一方面，我們確實放置了一個盔甲，即顯性負TGFBeta盔甲，以幫助擴張和滲透到腫瘤環境中。這就是我們在第一階段尋找 DLL3 的劑量。

And then on the CARTITUDE-4 label. Can you remind us how big an impact that will have on out of spec rate when -- assuming it does get approved. And should we expect that out of spec rate change to happen immediately on approval? Or will there be a ramp period or some sort of recertification for that?

然後是 CARTITUDE-4 標籤。您能否提醒我們，假設它確實獲得批准，這將對超標率產生多大的影響。我們是否應該期望在批准後立即發生不符合規範的利率變動？或者是否會有一個過渡期或某種形式的重新認證？

Sure. So part of our sBLA filing submitted to the FDA, we ask the agency to widen the release back based on the clinical data from the Phase III randomized controlled trial in second line beyond population, because we provide a significant amount of so-called sensitivity analysis to the agency, trying to correlate the release back with the clinical outcomes, such as PFS and survival.

當然。因此，在我們提交給 FDA 的 sBLA 文件的一部分中，我們要求該機構根據二線以外人群的 III 期隨機對照試驗的臨床數據擴大發布範圍，因為我們提供了大量所謂的敏感性分析向該機構報告，試圖將釋放與臨床結果（例如PFS 和存活率）關聯起來。

So based on that data, we and our partner at J&J are very confident that we should be able to receive a wider release back. And if we do receive such a wider release back from the agency then eventually, we hope that the auto spec rate can decrease by additional 5 to 10 percentage points from where it is today. That is our expectation of course. We have to wait until we see the label and also the FDA approve the release back next April when the PDUFA date hits. But that is our hope.

因此，根據這些數據，我們和強生的合作夥伴非常有信心，我們應該能夠獲得更廣泛的釋放。如果我們最終確實從該機構收到瞭如此廣泛的發布，那麼我們希望汽車規格率能夠比目前的水平再下降 5 到 10 個百分點。這當然是我們的期望。我們必須等到明年 4 月 PDUFA 日期到來時看到標籤，並且 FDA 批准發布。但這是我們的希望。

And to the second part of your question, let's say, if we do receive a label and a wide release back today, it is going to take a little bit of time because once we start to roll out the second line in the market, and then we start to see more uptake. You will gradually see that lower OS will take place in the manufacturing process.

對於你問題的第二部分，假設我們今天確實收到了一個標籤並廣泛發布，這將需要一點時間，因為一旦我們開始在市場上推出第二條線，然後我們開始看到更多的採用。您將逐漸看到較低的作業系統將在製造過程中發生。

Just to clarify what you just said there, when you say you take a little time to see that out-of-spec benefits come through, is that because you're only going to see that out-of-spec benefit in the second line plus patients? Is it not going to also apply to manufacturing in later lines?

只是為了澄清您剛才所說的內容，當您說您需要一點時間才能看到超出規格的好處時，是因為您只會在第二行中看到超出規格的好處加上病人？難道它不會也適用於以後的生產線嗎？

You raised a very good question, Jonathan. Unfortunately, I don't have an answer to you because we would have wait and see what the agency gives us. It's possible that we'll get a uniform release back from both the first indication and the second indication, but it's also possible that the agency decides to give us 2 sets of release backs, which happened before. I'm sure you're aware to one of the CD19 CAR-T's in the market.

你提出了一個非常好的問題，喬納森。不幸的是，我沒有給你答案，因為我們會等著看該機構給我們什麼。我們有可能從第一個指示和第二個指示中獲得統一的釋放，但也有可能該機構決定給我們兩組釋放，這之前發生過。我相信您知道市場上的一種 CD19 CAR-T。

So at this point, I actually don't know the answer, but it's a very good question. We'll have to wait and see what the FDA says.

所以在這一點上，我實際上不知道答案，但這是一個非常好的問題。我們必須等待，看看 FDA 會說什麼。

And our next question coming from the line of Ash Verma from UBS.

我們的下一個問題來自瑞銀集團的 Ash Verma。

I have 2. So just in terms of your partnership with Novartis, could that eventually allow you to use their T-Charge program to further lower the CARVYKTI end-to-end time. And then second one, just wanted to see where you are on the CARTITUDE-2 study with the Cohort E and F, I just wanted to get an idea. Is that something that we could see at the ASH abstracts late breaker tomorrow? Or is this more for ASCO next year?

我有 2。因此，就您與諾華的合作而言，最終是否可以讓您使用他們的 T-Charge 計劃來進一步縮短 CARVYKTI 端到端時間。然後第二個，只是想看看你在 CARTITUDE-2 研究中 E 組和 F 組的情況，我只是想知道一個想法。我們可以在明天的 ASH 摘要晚會中看到這一點嗎？還是明年 ASCO 會更關注這個？

So for the T-Charge platform, it's a unique manufacturing platform developed by Novartis, and this is only applied for LB2102. Internally, we are also developing local manufacturing process, and we are going to move internal development manufacturing process into other cell therapy product in the future.

所以對於T-Charge平台來說，它是諾華開發的一個獨特的製造平台，而且這只適用於LB2102。在內部，我們也在開發本地製造工藝，未來我們將把內部開發製造工藝轉移到其他細胞治療產品中。

Ash, this is Ying. I'll take the second part of your question, which has to do with the CARTITUDE-2 Cohort E and F. So I can tell you that at this point, we have completed enrollment for both quality to Cohort E and F in the newly diagnosed patient cohort. But we're not going to release data at this moment because, as you know, typically in the frontline setting, the PFS is relatively long. So we believe it will be more informative when we present data with a longer follow-up. So you should stay tuned when we present Cohort E and F in the future.

阿修，這是瑛。我將回答你問題的第二部分，這與 CARTITUDE-2 隊列 E 和 F 有關。所以我可以告訴你，此時，我們已經完成了新的隊列 E 和 F 的品質註冊。確診患者隊列。但我們目前不打算發布數據，因為如您所知，通常在前線環境中，PFS 相對較長。因此，我們相信，當我們提供更長的後續數據時，它會提供更多資訊。因此，當我們將來介紹 E 組和 F 組時，請您繼續關注。

Our next question coming from Konstantinos Biliouris from BMO Capital Markets.

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

Hello, everyone, and congrats on the quarter. One question from us on the clinical ongoing trials. Can you comment on whether the enrollment in CARTITUDE-5 is completed, and given that the CARTITUDE-6 trial is slightly larger than CARTITUDE-5, should we expect any impact from this increase on the commercial slots or these 2 are somewhat independent now with the clinical manufacturing support from Novartis and the Ghent sites.

大家好，恭喜本季。我們就正在進行的臨床試驗提出一個問題。您能否評論一下CARTITUDE-5 的註冊是否已完成，並且考慮到CARTITUDE-6 試驗比CARTITUDE-5 稍大，我們是否應該預期這種增加對商業時段的影響，或者這兩個現在在某種程度上是獨立的來自諾華和根特工廠的臨床生產支援。

Thank you, Konsta, for your questions. So on CARTITUDE-5, we're very much on track to complete the ex U.S. enrollment of CARTITUDE-5 back-end of this year. And now we're looking at potentially over-enrolling CARTITUDE-5 in the U.S. because as I mentioned previously in this call, we would like to have a very representative U.S. patient population in the overall patients enrolled in CARTITUDE-5.

謝謝康斯塔提出的問題。因此，在 CARTITUDE-5 上，我們非常有希望今年能完成 CARTITUDE-5 後端在美國的註冊工作。現在，我們正在考慮在美國過度招募CARTITUDE-5 的可能性，因為正如我之前在本次電話會議中提到的，我們希望在CARTITUDE-5 招募的患者總數中擁有非常具有代表性的美國患者群體。

So we're going to probably extend the U.S. enrollment by about 1 quarter into the first quarter of next year. But at this point, I can tell you that we're very pleased with the enrollment status. Like I said, we're pretty much down for the ex U.S. portion for CARTITUDE-5 by end of this year. So everything is going according to plan, but we do want to over-enroll up in the U.S. given the demand from patients and also given the fact that we'd like to have a higher percentage of U.S. patients in this trial.

因此，我們可能會將美國的招生時間延長約一個季度，直到明年第一季。但此時，我可以告訴您，我們對註冊狀態非常滿意。正如我所說，到今年年底，我們對 CARTITUDE-5 的前美國部分的預期非常樂觀。因此，一切都按計劃進行，但考慮到患者的需求，以及我們希望在這項試驗中擁有更高比例的美國患者，我們確實希望在美國超額入組。

On CARTITUDE-6, we just started our first patient last month in Spain, and it will probably take us about a couple of years while to enroll. So regarding to the production, we likely will utilize our Ghent facility that's coming online next month to start production of CARTITUDE-6. We could also use additional capacity from our CDMO to satisfy that demand for CARTITUDE-6 production. That is our current plan now.

在 CARTITUDE-6 上，我們上個月剛在西班牙開始治療第一位患者，我們可能需要大約幾年的時間才能註冊。因此，在生產方面，我們可能會利用下個月上線的根特工廠開始生產 CARTITUDE-6。我們也可以利用 CDMO 的額外產能來滿足 CARTITUDE-6 生產的需求。這就是我們目前的計劃。

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。

Congrats on the strong quarter. So can you give us an update on the out-of-spec rate for CARVYKTI today, just how things have been trending. And second, just on pipeline strategy. Will you look to continue to seek partnerships for your pipeline assets in the future? Or could you internally develop them and bring them forward?

恭喜季度表現強勁。那麼您能否向我們介紹一下今天 CARVYKTI 不合格率的最新情況，以及事情的發展趨勢。其次，就管道策略而言。您未來是否會繼續為您的管道資產尋求合作夥伴關係？或者你可以在內部開發它們並推進它們嗎？

So Justin, I'll talk about the out-of-spec rate question. We're very pleased where things have been trending in the last 6 months or so. Our out-of-spec rate has been decreasing and also stabilizing. And it's been consistently in the teens range. And right now, it does stand below the 18% on label out-of-spec rate. Thanks to the very much hard work from the Legend team and J&J team in the New Jersey facility.

賈斯汀，我將討論不合格率問題。我們對過去 6 個月左右的發展趨勢感到非常高興。我們的不合格率一直在下降並且趨於穩定。而且一直都在青少年範圍內。目前，它確實低於標籤上 18% 的不合格率。感謝新澤西工廠的傳奇團隊和強生團隊的辛勤工作。

We have tried very hard to refine our manufacturing product by looking at various reasons for OS and also improving our OS on various work streams. So that's where we are. I don't think we're very much different from the competition's out-of-spec rate at this point. So I think we're seeing a very encouraging trend. And like I mentioned, we do expect this to continue to go down, especially after FDA approved the second line indication.

我們非常努力地透過研究作業系統的各種原因來改進我們的製造產品，並在各種工作流程上改進我們的作業系統。這就是我們現在的情況。我認為目前我們與競爭對手的不合格率沒有太大不同。所以我認為我們看到了一個非常令人鼓舞的趨勢。正如我所提到的，我們確實預計這一數字將繼續下降，特別是在 FDA 批准二線適應症之後。

On the pipeline, the BD question, I'm going to refer that to our colleague, Guowei.

關於 BD 的問題，我將把這個問題轉給我們的同事郭偉。

Thanks for the question. In terms of pipeline development strategy, we are open to both internal development as well as seeking out the collaboration partnership. Our goal of pipeline development is to accelerate the development time line and maximize the value for each individual assets so that we can bring differentiated and potentially transformative therapy to patients sooner.

謝謝你的提問。在管道開發策略上，我們既開放內部開發，也尋求合作夥伴。我們管道開發的目標是加快開發時間並最大化每個資產的價值，以便我們能夠更快地為患者帶來差異化和潛在變革性的治療。

In this particular case for LB2102, we see a unique synergy between ourself and Novartis. We have a unique product design, a unique construct sequence and unique armor mechanism to facilitate the immune cell infiltration and overcome immune suppression in the tumor market environment, whereas Novartis has its unique manufacturing process, which is particularly important for a disease of small cell lung cancer. As you know that disease progresses very fast and a faster manufacture process would add value to the product profile. So in this case, we see the synergy.

在 LB2102 的這個特殊案例中，我們看到了我們自己和諾華之間獨特的協同作用。我們有獨特的產品設計、獨特的建造序列和獨特的裝甲機制，以促進免疫細胞浸潤，克服腫瘤市場環境中的免疫抑制，而諾華有其獨特的製造工藝，這對於小細胞肺部疾病尤為重要癌症。如您所知，疾病進展非常快，更快的製造過程將為產品檔案增加價值。所以在這種情況下，我們看到了協同作用。

And then in the future, we will continue to evaluate asset by asset, and try to find synergy and realize the additional value where it's possible. At the same time, if we have asset, we can develop by ourselves. We will also do it in our facility.

未來，我們將繼續逐項評估資產，並努力尋找協同效應，盡可能實現附加價值。同時，如果我們有資產，我們就可以自己發展。我們也將在我們的工廠進行。

And our next question coming from the line of Mitchell Kapoor from H. C. Wainwright.

我們的下一個問題來自 H. C. Wainwright 的米切爾·卡普爾 (Mitchell Kapoor)。

I just wanted to ask a little bit more about the supply constraints. And if you could give kind of a quantitative sense of where we are in terms of meeting demand. I think at one point, there was a lot of supply exceeding demand in terms of -- I think there was about 15% being able to be met. Could you just talk about where we're at today? And if you can't give a quantitative number, could you just kind of help us understand the trend?

我只是想多問一些有關供應限制的問題。如果您能定量地了解我們在滿足需求方面的情況。我認為在某一時刻，大量的供應超過了需求——我認為大約有 15% 的供應能夠滿足。您能談談我們今天的情況嗎？如果你不能給出一個定量的數字，你能幫助我們了解這個趨勢嗎？

Mitch, thanks for the question. And I'm going to answer this one. So if you look at the reported revenue last quarter, which was $152 million and $140 million coming from the U.S. you sort of can guesstimate the number of patients we served in the commercial setting last quarter. I cannot give you exactly the percentage of demand. We are satisfying, but I can tell you starting from the beginning of the year, we always track our backlog in terms of patients waiting in the queue every month. And I can tell you from January until now, really essentially we're seeing exactly pretty much the same number of patients in the backlog in the queue.

米奇，謝謝你的提問。我要回答這個問題。因此，如果您查看上季報告的收入（來自美國的 1.52 億美元和 1.4 億美元），您可以猜測上季度我們在商業環境中服務的患者數量。我無法給你確切的需求百分比。我們很滿意，但我可以告訴你，從今年年初開始，我們總是根據每月排隊等候的患者來追蹤我們的積壓情況。我可以告訴你，從一月到現在，實際上我們看到隊列中積壓的患者數量幾乎相同。

So we're not seeing any difference in terms of demand for this product at this point. And we're working very hard to initiate robust and reliable supply. So we are going to continue to expand our supply. As you just heard from our colleagues on the call, we did receive the second FDA approval in the increase of our capacity recently. So we're continuing to ramp up given that approval. And then we're planning additional increases in capacity from our New Jersey facility next year as well.

因此，目前我們沒有看到對該產品的需求有任何差異。我們正在非常努力地啟動強大、可靠的供應。因此，我們將繼續擴大供應。正如您剛剛在電話會議上從我們的同事那裡聽到的那樣，我們最近確實獲得了 FDA 的第二次產能增加批准。因此，在獲得批准後，我們將繼續加強。然後我們也計劃明年進一步增加新澤西工廠的產能。

If you look at the number of patients, we think are within the so-called addressable market in the U.S., about 13,000 patients die every year, unfortunately, from multiple myeloma and probably around 8,000 to 9,000 patients are eligible for receiving CAR-T therapy. So at this point, given our supply, we think still we're nowhere near being able to supply all the demand for CARVYKTI at this point.

如果你看一下患者數量，我們認為在美國所謂的潛在市場內，不幸的是，每年約有 13,000 名患者死於多發性骨髓瘤，並且可能有大約 8,000 至 9,000 名患者有資格接受 CAR-T 療法。因此，在這一點上，考慮到我們的供應，我們認為我們目前還遠遠無法滿足 CARVYKTI 的所有需求。

Okay. And could you just kind of help us understand what the launch preparation is looking like for moving into earlier lines? Is it mainly just messaging changes with the sales force? Or what else can you tell us about how you're preparing for it, if approved?

好的。您能否幫助我們了解進入早期生產線的啟動準備工作是什麼樣的？主要是與銷售人員的訊息傳遞有變化嗎？或者如果獲得批准，您還能告訴我們您是如何準備的嗎？

Yes, Mitch, I'll take that one. It's Steve. So no, it's a bit different, right? So you're moving from a later line population that was largely -- these patients were largely in many of our major academic centers. In the earlier lines from the second-line population, this will be a very different type of launch where you're largely reliant on the referral.

是的，米奇，我想要那個。是史蒂夫。所以不，有點不同，對吧？因此，您是從後來的人群中轉移出來的，這些患者主要來自我們的許多主要學術中心。在二線人群的早期線路中，這將是一種非常不同的發布類型，您在很大程度上依賴推薦。

So what the U.S. team has been working very closely with our partner is working through the models in terms of how to appropriately reach that outpatient clinic to ensure that an appropriate referral is made to one of our cilta-cel centers. So it's a bit different. You'll see some increase in FDA expansion on behalf largely of our partner at Janssen because they play largely in that outpatient space.

因此，美國團隊一直與我們的合作夥伴密切合作，透過模型研究如何適當地到達門診診所，以確保適當轉診到我們的其中一個 cilta-cel 中心。所以有點不同。您將看到 FDA 的擴張有所增加，這主要是代表我們楊森的合作夥伴，因為他們主要在門診領域發揮作用。

From the U.S. Legend perspective, you'll see some increase as we increase sites, but our commercial footprint for Legend has been largely built around the inpatient setting as opposed to outpatient. I hope that answers your question.

從美國 Legend 的角度來看，隨著我們增加站點，您會看到一些增長，但我們 Legend 的商業足跡主要是圍繞住院環境而不是門診建立的。我希望這能回答你的問題。

And our next question coming from the line of Wilfred Yuen from Daiwa Capital Markets.

我們的下一個問題來自大和資本市場的 Wilfred Yuen。

Congrats on the results. Well, I just have a follow-up on the gross margin currently at 43%, 44% over the past 2 quarters. So you mentioned about expanding capacity. So what are the other driver on margin on the gross margin given we have multiple facility, both internal and external coming online as well as improving our spend rate. So what are the key moving parts actually? And how should we be thinking of the margin profile maybe even in the longer term as well.

祝賀結果。嗯，我只是對過去兩個季度的毛利率進行了跟踪，目前為 43%，44%。所以你提到了擴大產能的問題。那麼，考慮到我們擁有多個設施，包括內部和外部設施，以及提高我們的支出率，毛利率的其他驅動因素是什麼。那麼關鍵的移動部件實際上是什麼？從長遠來看，我們應該如何考慮利潤狀況。

So just on the gross margin, again, as we talked about, there's 2 components in the gross margin. So from your perspective, when you look at quarter-over-quarter, it's a little bit hard for you to model it out. As I mentioned before, we continue to see improvement in the gross margin from a product perspective.

因此，就毛利率而言，正如我們所討論的，毛利率有兩個組成部分。因此，從您的角度來看，當您查看季度環比時，您很難對其進行建模。正如我之前提到的，從產品角度來看，我們繼續看到毛利率的改善。

Your gross margins are going to improve as your volumes go up, we've also have our out of spec that's gone down based upon also process improvements we've made at the plant. So we are seeing the steady progression of the improvement under the gross margins from a product perspective. But you're going to continually get noise in that number we report externally because we have to report the facilities expansion, the expense side of it that cannot be capitalized.

隨著產量的增加，您的毛利率將會提高，我們的不合格產品也根據我們在工廠進行的製程改進而下降。因此，從產品角度來看，我們看到毛利率正在穩定改善。但你會不斷地從我們對外報告的數字中聽到噪音，因為我們必須報告設施擴張，以及無法資本化的費用方面。

And as you know, we have expansion going on in (inaudible). We have expansion going on in Raritan, we have expansion going on in Belgium, and we also have expansion going on with our CMOs. So you're going to continue to see a lot of facilities expense related to those capital investments through the end of 2025. So it's going to create noise. Some quarters are going to be higher than others, just depending upon where we are with some of those capital projects.

如您所知，我們正在進行擴張（聽不清楚）。我們正在力登進行擴張，我們正在比利時進行擴張，我們也正在與 CMO 進行擴張。因此，到 2025 年底，您將繼續看到與這些資本投資相關的大量設施費用。因此，這會產生噪音。有些季度會高於其他季度，這取決於我們在其中一些資本項目上的進展。

But if there's something specific, if you want to talk and submit more question and we can always set up a call with you and try to go over a little bit more detail, but I can't give any granular numbers -- I can't disclose any granular numbers from a product perspective.

但是，如果有具體的事情，如果您想談談並提交更多問題，我們隨時可以與您通話並嘗試討論更多細節，但我無法給出任何具體數字 - 我可以'不要從產品角度披露任何具體數字。

And our next question coming from the line of Kelsey Goodwin with Guggenheim.

我們的下一個問題來自凱爾西·古德溫與古根漢的關係。

Congrats on the quarter. I guess 2 quick ones for me. I guess, first, do you have any updated view on how we should think about profitability for the joint venture, maybe kind of building on some of these past questions on gross margin. And then kind of following up on that, I guess, how should we think about the longer-term COGS for CARVYKTI kind of once these capital expenses are no longer included in those line items? And yes, maybe kind of what out of spec in manufacturing failure rate do you base in the assumption for longer-term COGS?

恭喜本季。我想對我來說有兩個快速的。我想，首先，您對我們應該如何考慮合資企業的盈利能力有什麼最新的看法，也許是建立在過去關於毛利率的一些問題的基礎上的。然後，我想，一旦這些資本支出不再包含在這些項目中，我們應該如何考慮 CARVYKTI 的長期銷貨成本？是的，也許您基於長期銷貨成本的假設，得出了哪些超出規格的製造故障率？

Kelsey. So profitability, the messaging is still consistent with what we signaled before. For the BCMA program, we're looking to have breakeven and profitability by the end of 2025. And from a company perspective, we're striving for profitability by 2026. And I always put a disclaimer in there. It will depend upon what happens with our pipeline development, what we look to do from a business development perspective. But based upon the trajectory of what we know now, that is what we've been signaling.

凱爾西。因此，獲利能力方面的訊息仍與我們先前發出的訊號一致。對於 BCMA 計劃，我們希望到 2025 年底實現收支平衡和盈利。從公司角度來看，我們力爭到 2026 年實現盈利。我總是在其中添加免責聲明。這將取決於我們的管道開發情況，以及我們從業務開發角度希望做什麼。但根據我們現在所知的軌跡，這就是我們一直在發出的信號。

From a longer-term COGS, as I mentioned earlier, you're going to continue to see noise in that COGS line, all the way through at the end of '25 going into 2026. We're not giving any guidance on our actual COGS. I would say for your modeling purposes, you could probably use what's been the standard in the industry. It would be a good proxy for you for your modeling.

從長期的銷貨成本來看，正如我之前提到的，你將繼續看到銷貨成本線中的噪音，一直到 25 年底到 2026 年。我們不會就我們的實際情況提供任何指導。貨成本。我想說，出於建模目的，您可能可以使用行業標準。這將是您建模的一個很好的代理。

Okay. Great. And maybe just one quick follow-up then on the profitability. I guess, to what extent is that breakeven profitability by 2025? How much is that reliant on hitting that 10,000 commercial doses by the end of the year?

好的。偉大的。也許只是對盈利能力的一個快速跟進。我猜想，到2025年，損益平衡的獲利能力會達到什麼程度？這對到年底達到 10,000 劑商業劑量的依賴程度有多大？

Kelsey, I hope you understand that we cannot really disclose our internal modeling. But what I can say is that if you look at the COGS for CAR-T as a general modality, the cost of goods is probably somewhat higher than the typical cost of goods of monoclonal antibodies.

凱爾西，我希望你理解我們不能真正透露我們的內部模型。但我可以說的是，如果你將 CAR-T 的 COGS 視為一般模式，那麼商品成本可能會比單株抗體的典型商品成本略高。

However, the SG&A in terms of selling and distribution costs, it will be much lower. You can tell that from our financials, right? While we almost quadrupling our sales for CARVYKTI this year versus last year, if you look at quarterly spend in sales and marketing, it's actually slightly lower than what we spent last year. So that gives a hint how we think about the profitability of CARVYKTI overall.

然而，就銷售和分銷成本而言，SG&A 會低得多。你可以從我們的財務狀況看出這一點，對嗎？雖然我們今年 CARVYKTI 的銷售額比去年幾乎翻了兩番，但如果你看看銷售和行銷方面的季度支出，你會發現它實際上略低於我們去年的支出。這暗示了我們如何看待 CARVYKTI 的整體獲利能力。

And our next question coming from the line of Sami Corwin with William Blair.

我們的下一個問題來自薩米·科爾文和威廉·布萊爾。

Given you plan on over enrolling CARTITUDE-5 now, will that delay when we should expect data from that trial? And then do you plan on providing any revenue guidance for CARVYKTI beginning of 2024.

鑑於您現在計劃超額招募 CARTITUDE-5，這會延遲我們預期該試驗數據的時間嗎？那麼您是否計劃在 2024 年初為 CARVYKTI 提供任何收入指導？

Thanks for the question, Sami. So on the first question, no, we don't expect any delay because like I mentioned, we are pretty much on track to close all the ex U.S. enrollment for CARTITUDE-5, which is the majority of the patients by end of this year. That's exactly according to our plan. And then we're only over-enrolling in the U.S. next quarter just to make sure that we have a representative percentage of U.S. patients in this trial. So at this point, we do not expect any delay in terms of readout of CARTITUDE-5.

謝謝你的提問，薩米。因此，關於第一個問題，不，我們預計不會有任何延遲，因為就像我提到的那樣，我們幾乎有望在今年年底前關閉CARTITUDE-5 的所有前美國註冊，這將是大多數患者的情況。這完全符合我們的計劃。然後我們下個季度才會在美國超額入組，以確保我們在這項試驗中擁有代表性的美國患者百分比。因此，目前我們預期 CARTITUDE-5 的讀出不會有任何延遲。

And then on product guidance, we're not really giving product guidance for the year of 2024 because our partner J&J has this policy of not providing product specific guidance. So unfortunately, we will not be in a position to provide you with the guidance for CARVYKTI sales.

然後在產品指導方面，我們並沒有真正提供 2024 年的產品指導，因為我們的合作夥伴強生（J&J）有不提供特定產品指導的政策。因此，遺憾的是，我們無法為您提供 CARVYKTI 銷售指導。

And at this time, we have no further questions in the queue. Ladies and gentlemen, this concludes today's conference call. Thank you all for your participation, and you may now disconnect.

目前，我們隊列中沒有其他問題了。女士們、先生們，今天的電話會議到此結束。感謝大家的參與，現在您可以斷開連線了。