Galapagos NV (GLPG) 2024 Q4 法說會逐字稿

Good day and thank you for standing by. Welcome to the Galapagos full-year 2024 financial results and business update conference call. (Operator Instructions)

您好，感謝您的支持。歡迎參加加拉巴哥 2024 年全年財務業績和業務更新電話會議。（操作員指示）

Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Sri Ramaswami. Please go ahead.

請注意，今天的會議正在錄音。現在我想將會議交給今天的第一位演講者 Sri Ramaswami。請繼續。

Thank you, operator. Good afternoon to all of you who are on the call from Europe, and good morning to all of you in the United States. Thank you all for joining us for Galapagos' full-year 2024 financial results and business update conference call. Last night, we issued a press release outlining these results. The press release, along with today's webcast presentation can be found on the Galapagos website.

謝謝您，接線生。歐洲來電的各位下午好，美國的各位早安。感謝大家參加加拉巴哥 2024 年全年財務表現及業務更新電話會議。昨晚，我們發布了一份新聞稿概述了這些結果。新聞稿以及今天的網路廣播演示可以在加拉巴哥網站上找到。

Before we begin, I would like to remind everyone that we will be making forward-looking statements on the call. These forward-looking statements include remarks concerning future developments of our company and our pipeline and possible changes in the industry and the competitive environment.

在我們開始之前，我想提醒大家，我們將在電話會議上做出前瞻性的陳述。這些前瞻性陳述包括有關我們公司和我們的產品線的未來發展以及行業和競爭環境可能發生的變化的評論。

Actual results may differ materially from those indicated by these statements and are accurate only as of the date of this recording February 13, 2025. Galapagos is not under any obligation to update statements regarding the future or to conform to these statements in relation to actual results unless required by law.

實際結果可能與這些聲明所示的結果有重大差異，並且僅在 2025 年 2 月 13 日記錄之日準確。除非法律要求，否則加拉巴哥沒有義務更新有關未來的聲明或根據實際結果遵守這些聲明。

Joining us on today's call from Galapagos' senior management team are Dr. Paul Stoffels, Chair and Chief Executive Officer; and Thad Huston, Chief Operating and Chief Financial Officer.

參加今天電話會議的加拉巴哥高階管理團隊包括董事長兼執行長 Paul Stoffels 博士；以及營運長兼財務長 Thad Huston。

With that introduction, let me now turn the call over to Dr. Stoffels. Paul?

介紹完畢，現在請容許我將電話轉給 Stoffels 博士。保羅？

Thank you, Sri, and thank you all for joining us today. 2024 was a productive and transformative year for Galapagos in which we made significant progress streamlining our business operations and advancing our leadership in cell therapy in oncology. One of our key accomplishments last year was the progress we made advancing GLPG5101, our flagship CD19 CAR-T clinical development program in multiple heart to treat NHL indications.

謝謝你，Sri，也謝謝大家今天加入我們。 2024 年對加拉巴哥來說是富有成效和變革的一年，我們在簡化業務運作和提昇在腫瘤細胞治療領域的領導地位方面取得了重大進展。我們去年取得的一項重要成就是推進 GLPG5101 的進展，GLPG5101 是我們的旗艦 CD19 CAR-T 臨床開發項目，用於治療多種心臟 NHL 適應症。

We were particularly pleased to receive FDA's IND clearance to begin clinical studies in the US. And with the compelling new results from the ATLANTA study we presented at the American Society of Hematology Annual Meeting in December.

我們非常高興獲得 FDA 的 IND 批准，可以在美國開始臨床研究。我們在 12 月的美國血液學會年會上展示了 ATLANTA 研究的令人信服的新結果。

I will discuss those results in greater detail later on this call. Throughout 2024, we focused on building our leadership position in cell therapy, where we executed a number of key partnerships and collaborations in support of those goals with companies such as Lonza on our decentralized platform, Thermo Fisher for the development of an ultrarapid PCR sterility test together with MyDiagnostics and Axelos part of Blood Centers of America to broaden our DMU network in the US.

我將在稍後的電話會議中更詳細地討論這些結果。在整個 2024 年，我們專注於打造我們在細胞治療領域的領導地位，為了實現這些目標，我們與 Lonza 等公司在我們的去中心化平台上建立了一系列重要的合作夥伴關係和合作關係，與 Thermo Fisher 合作開發超快速 PCR 無菌測試，並與 MyDiagnostics 和美國血液中心的 Axelos 部門合作，擴大我們在美國的網絡。

Separately, in 2024, we also signed an agreement with Adaptimmune for TCR T-cell therapy in solid tumors. Finally, we completed the transfer of the [Icelica] business to Alfasigma, which provided us with savings of approximately EUR200 million and for which we remain eligible for royalties on European sales. Based on this strong foundation, we are continuing to evolve our strategy for building Galapagos as a global leader in cell therapy.

另外，2024年，我們也與Adaptimmune簽署了針對實體腫瘤的TCR T細胞療法協議。最後，我們完成了將 [Icelica] 業務轉讓給 Alfasigma 的交易，這為我們節省了約 2 億歐元，並且我們仍然有資格獲得歐洲銷售的特許權使用費。基於這個堅實的基礎，我們正在不斷發展我們的策略，將加拉巴哥打造為細胞治療領域的全球領導者。

Toward that end, we are excited to start the new year with a focus on accelerating value creation by executing on our plan to separate into two publicly traded entities, Galapagos and SpinCo. SpinCo, a newly created Belgian company will invest to build a pipeline of innovative medicines through transformational transactions with Gilead as a partner. Galapagos will focus on accelerating global oncology leadership by addressing high unmet medical needs with a decentralized manufacturing platform and with full ownership of all other programs.

為此，我們很高興在新的一年專注於透過執行分拆為兩個上市公司（Galapagos 和 SpinCo）的計劃來加速價值創造。SpinCo 是一家新成立的比利時公司，將透過與吉利德合作的轉型交易來投資建立創新藥物管道。Galapagos 將專注於透過分散的製造平台和對所有其他項目的完全所有權來解決大量未滿足的醫療需求，從而加速全球腫瘤學領導地位。

As many of you know, in 2019, Galapagos entered into a 10-year global option license and collaboration agreement or OCA with Gilead. Since that time, Gilead, Galapagos and the biotech industry as a whole have all evolved.

眾所周知，2019 年，加拉巴哥與吉利德簽訂了為期 10 年的全球選擇權許可和合作協議（OCA）。自那時起，吉利德、加拉巴哥和整個生物技術產業都得到了發展。

Post separation, SpinCo will assume the OCA agreement with Gilead. Galapagos will be able to focus on executing its strategy for accelerated growth and sustainable value creation as a leader in the development and innovative manufacturing of cell therapies in hematological and solid tumors, further supporting our mission to bring transformational medicines to patients across the world.

分離後，SpinCo 將承擔與吉利德的 OCA 協議。加拉巴哥將能夠專注於執行其加速成長和永續價值創造策略，成為血液和實體腫瘤細胞療法開發和創新製造領域的領導者，進一步支持我們為全球患者提供轉化藥物的使命。

As such, we will seek partners for our small molecule programs, including our TYK2 inhibitor, and we will discontinue future small molecule research. By separating into two entities, each company will have the flexibility to allocate resources, pursue tailored strategies and maximize opportunities for growth and impact. We are offering a win-win for our shareholders as we can create even more value as independent entities with unique strategies in our respective areas of expertise.

因此，我們將為我們的小分子計畫尋找合作夥伴，包括我們的 TYK2 抑制劑，並且我們將停止未來的小分子研究。透過分拆為兩個實體，每家公司將能夠靈活地分配資源、推行客製化策略並最大限度地實現成長和影響機會。我們為股東提供雙贏，因為我們可以作為獨立實體在各自的專業領域中憑藉獨特的策略創造更多價值。

Let us now turn to the new and exciting opportunities for Galapagos as we forge ahead with the development and delivery of life-changing cell therapies to address patient needs in oncology. This planned transaction allows Galapagos to focus on leadership in cell therapies based on the following strong fundamentals.

現在讓我們轉向加拉巴哥群島新的、令人興奮的機遇，我們將繼續開發和提供改變生活的細胞療法，以滿足腫瘤患者的需求。此次計畫中的交易使加拉巴哥能夠基於以下強勁基本面專注於細胞療法領域的領導地位。

Firstly, we are well capitalized to advance our portfolio and platform toward value-creating milestones. Importantly, the termination of the OLCA for Galapagos gives us the autonomy to fully invest in and partner our own assets and programs and to realize the rewards of our future achievements.

首先，我們擁有充足的資本來推動我們的產品組合和平台邁向創造價值的里程碑。重要的是，加拉巴哥群島 OLCA 的終止使我們有自主權充分投資和合作我們自己的資產和項目，並實現我們未來成就的回報。

We remain focused on providing broader and faster access to cell therapies with our innovative decentralized manufacturing approach and our goal of seven days vein-to-vein time. Not only does this bring logistical and cost benefits, but by providing patients with fit cells, we believe we are improving efficacy and safety and offering a solution for many more patients, especially those patients with a very short life expectancy.

我們將繼續致力於透過創新的分散製造方法和七天靜脈到靜脈時間的目標，提供更廣泛、更快速的細胞療法。這不僅帶來了後勤和成本效益，而且透過為患者提供合適的細胞，我們相信我們正在提高療效和安全性，並為更多患者，特別是那些預期壽命很短的患者提供解決方案。

We are advancing our cell therapies currently in clinical development, which we believe have potential to be best-in-class through the delivery of fresh and fit cells. In addition to our six European clinical sites in the Netherlands and Belgium, we are expanding the ATLANTA clinical trial in the US, where we are engaging with leading cancer centers in Boston.

我們正在推進目前處於臨床開發階段的細胞療法，我們相信透過提供新鮮和健康的細胞，我們的療法有可能成為一流的。除了位於荷蘭和比利時的六個歐洲臨床站點外，我們還在美國擴大亞特蘭大臨床試驗，並與波士頓領先的癌症中心合作。

Our aim is to start pivotal studies in 2026 to support our ongoing clinical trials and to ensure pivotal readiness we are expanding our decentralized manufacturing network in the US and Europe, giving patients direct access to our therapies and limiting logistical constraints.

我們的目標是在 2026 年開始關鍵研究，以支持我們正在進行的臨床試驗，並確保關鍵準備就緒，我們正在擴大我們在美國和歐洲的分散製造網絡，讓患者直接獲得我們的治療並限制物流限制。

We are also building global partnerships with hospital networks and health care organizations to increase access significantly. All of this is being done in a highly cost-effective way that takes advantage of our automated, closed sterile production system with limited manual work and is designed to improve access and reduce the cost of goods significantly.

我們也正在與醫院網路和醫療保健組織建立全球合作夥伴關係，以大幅提高醫療服務可近性。所有這些都是以極具成本效益的方式進行的，利用我們的自動化、封閉的無菌生產系統，減少手動操作，旨在改善獲取途徑並顯著降低商品成本。

We will also look to partner our platform with cell therapy companies, leveraging our unique manufacturing platform and network for broader access, for example, as we did with Adaptimmune in solid tumors. To support sustainable value creation, we are building a pipeline of next-generation cell therapies that have the potential to address some of the limitations of current therapies by taking advantage of combination, targeting and armoring to best treat a range of hematological and solid tumors.

我們還將尋求與細胞治療公司合作，利用我們獨特的製造平台和網路實現更廣泛的應用，例如，我們與 Adaptimmune 在實體瘤領域合作。為了支持可持續的價值創造，我們正在建立下一代細胞療法管道，該管道有可能透過利用組合、靶向和裝甲來解決當前療法的一些局限性，從而最好地治療一系列血液學和實體腫瘤。

Most importantly, our ambition in cell therapy and the [plant] separation are designed to benefit the patients we serve by both accelerating and expanding our ability to bring new medicines to market. Our decentralized manufacturing was designed to overcome the limitations of current cell therapy manufacturing, which is centralized and bears higher cost burdens with longer production and delivery times and delivering cryopreserved cells

最重要的是，我們在細胞療法和[植物]分離方面的雄心壯志旨在透過加速和擴大我們將新藥推向市場的能力使我們服務的患者受益。我們的分散式生產旨在克服當前細胞療法生產的局限性，目前細胞療法生產是集中式的，成本負擔更高，生產和交付時間更長，並且需要交付冷凍保存的細胞

A seven-day vein-to-vein time is designed to provide fresh fit cells, which we believe enhance the therapeutic profile by producing highly potent cells that are less exhausted, less toxic and persist longer. We currently have six operational and approved manufacturing sites in several European countries and are actively expanding in Europe and the US with Landmark Bio in Boston operational for ATLANTA.

為期七天的靜脈輸注時間旨在提供新鮮的健康細胞，我們相信，透過產生消耗較少、毒性較小且持續時間較長的高效細胞，可以增強治療效果。我們目前在幾個歐洲國家擁有六個已投入營運並獲批的生產基地，並且正在積極拓展歐洲和美國市場，位於波士頓的 Landmark Bio 正在為亞特蘭大市場營運。

We believe the advantages of our Cocoon process make it ideal for near point-of-care manufacturing, given its close system, lean design, user-friendly interface, data monitoring capabilities, automation and scalability. We have a long-term strategic collaboration with Lonza for the supply of cocoons and cassettes. We truly are excited by the opportunity ahead for Galapagos to lead in cell therapy drug development, and this decentralized manufacturing platform is core to that strategy.

我們相信，由於 Cocoon 製程具有封閉的系統、精益的設計、用戶友好的介面、數據監控功能、自動化和可擴展性等優勢，因此非常適合近點護理製造。我們與 Lonza 建立了長期戰略合作關係，供應蠶繭和蠶盒。我們真的為加拉巴哥在細胞治療藥物開發領域處於領先地位的機會感到興奮，而這個分散的製造平台是該策略的核心。

Moving forward, Galapagos will focus on unlocking the broad reaching potential of this decentralized cell therapy manufacturing platform as we advance a robust cell therapy pipeline. In line with our goal to be a more focused and streamlined organization, we are implementing a strategic development approach CD19 CAR-T portfolio by prioritizing resources on GLPG5101, our most advanced assets cleared for clinical development by the FDA and the European regulatory authority and with the fastest part to market.

展望未來，加拉巴哥將致力於釋放這個分散式細胞治療製造平台的廣泛潛力，同時推動強大的細胞治療管道建設。為了實現成為更專注和精簡的組織的目標，我們正在實施 CD19 CAR-T 產品組合的策略發展方法，優先將資源投入到 GLPG5101 上，這是我們最先進的資產，已獲得 FDA 和歐洲監管機構的臨床開發批准，並且是上市速度最快的產品。

In order to fully realize that potential, we are accelerating and expanding the ATLANTA Phase I/II clinical study of GLPG5101 into additional aggressive lymphomas, such as Richter transformation and in chronic lymphocytic leukemia, where we believe we can drive the greatest impact for patients.

為了充分發揮這一潛力，我們正在加速和擴展亞特蘭大 I/II 期 GLPG5101 臨床研究，將其應用於其他侵襲性淋巴瘤，例如 Richter 轉化和慢性淋巴細胞白血病，我們相信我們可以在這些領域為患者帶來最大的影響。

Our plan is to move into pivotal studies in 2026 with an aim to have a first approval in 2028. As part of this focused strategy, we are deprioritizing activities related to GLPG5201, our second CD19 CAR-T candidate, pending the advancement of GLPG5101 in Richter transformation and chronic lymphocytic leukemia. In tandem, we are advancing the Phase I/II study of GLPG5301 in multiple myeloma while also strengthening our early-stage pipeline of next-generation multi-targeting armored cell therapies for hematological and solid tumors.

我們的計劃是在 2026 年進入關鍵研究階段，並力爭在 2028 年獲得首次批准。作為這項重點策略的一部分，我們正在降低與我們的第二個 CD19 CAR-T 候選藥物 GLPG5201 相關的活動的優先級，等待 GLPG5101 在 Richter 轉化和慢性淋巴細胞白血病方面的進展。同時，我們正在推進 GLPG5301 治療多發性骨髓瘤的 I/II 期研究，同時也在加強我們針對血液腫瘤和實體腫瘤的下一代多靶點裝甲細胞療法的早期研發管線。

To ensure long-term innovation and value creation, we expect to advance one of these preclinical assets into first in human clinical studies in 2025. Further reinforcing our commitment to delivering transformational therapies.

為了確保長期創新和價值創造，我們預計在 2025 年將其中一項臨床前資產推進到首次人體臨床研究。進一步加強我們提供轉化療法的承諾。

We are progressing uza-cel, a TCRT candidate for head and neck cancer through our partnership with Adaptimmune. We believe that the combination of fresh, fast and fit has the potential for transformative impact and we can see from the data recently presented at ASH, a promising safety and efficacy profile for GLPG5101 in patients with mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma and diffuse larege B-cell lymphoma.

我們正在透過與 Adaptimmune 的合作，推進頭頸癌 TCRT 候選藥物 uza-cel 的研發。我們相信，新鮮、快速和合適的組合具有產生變革性影響的潛力，我們可以從最近在 ASH 上公佈的數據中看到，GLPG5101 對套細胞淋巴瘤、邊緣區淋巴瘤、濾泡性淋巴瘤和瀰漫性大 B 細胞淋巴瘤患者俱有良好的安全性和有效性。

As of April 25, 2024, data cutoff, 49 patients received CD19 CAR-T cell therapy infusion, and safety results were available for 45 patients and efficacy was available for 42 patients. As you can see, we achieved high overall response and complete response rates. Here, we show 100% of patients with refractory relapsed mantle cell lymphoma, 95% of patients with refractory relapsed follicular lymphoma and marginal zone lymphoma and 54% of patients with refractory relapsed and diffuse large B-cell lymphoma achieved a complete response.

截至 2024 年 4 月 25 日數據截止，49 名患者接受了 CD19 CAR-T 細胞療法輸注，其中 45 名患者的安全性結果可獲得，42 名患者的療效結果可獲得。如您所見，我們實現了較高的整體回應率和完全回應率。在這裡，我們顯示 100% 的難治性複發性套細胞淋巴瘤患者、95% 的難治性複發性濾泡性淋巴瘤和邊緣區淋巴瘤患者以及 54% 的難治性復發性和瀰漫性大 B 細胞淋巴瘤患者獲得了完全緩解。

At dose level two, the complete response rate was 71% and the overall response rate, 86% for diffuse large B-cell lymphoma. Of evaluable patients achieving complete response, 80% were minimal ideal disease negative and remained in complete response at the time of data cutoff. And we are seeing very reassuring safety data with low levels of ICANNs. This translates to less patients in need of intensive care, less time in hospital and more time at home with family. Not only are we seeing strong data around the response rates, but we are also seeing that those response rates are durable.

在劑量二下，瀰漫大B細胞淋巴瘤的完全緩解率為71%，整體緩解率為86%。在達到完全緩解的可評估患者中，80％達到最低理想疾病陰性，並且在數據截止時仍處於完全緩解狀態。我們看到 ICANN 的安全數據非常令人放心，而且安全水平較低。這意味著需要重症監護的患者減少、住院時間減少，而有更多的時間在家陪伴家人。我們不僅看到了有關回應率的強勁數據，而且我們還看到這些回應率是持久的。

Across Phase I, Phase II, 32 of 37 or 86% of responding patients had an ongoing response at the time of last assessment or end of study. Of the 15 minimal residual disease evaluable patients with a complete response, 12 patients or 80% achieved mineral residual disease negativity and remained in complete response and data cutoff. The median study follow-up was 3.3 months for follicular lymphoma and diffuse large B-cell lymphoma with a range of 0.9 to 21.2 months and 4.4 months for mantle cell lymphoma with a range of 1 to 24.4 months.

在第 I 階段和第 II 階段，37 名有反應的患者中有 32 名（即 86%）在最後一次評估或研究結束時持續有反應。在 15 名具有完全緩解的可評估微小殘留疾病患者中，12 名患者（80%）實現了礦物質殘留疾病陰性並保持完全緩解和數據截止。濾泡性淋巴瘤和瀰漫性大 B 細胞淋巴瘤的中位研究追蹤時間為 3.3 個月（範圍為 0.9 至 21.2 個月），套細胞淋巴瘤的中位研究追蹤時間為 4.4 個月（範圍為 1 至 24.4 個月）。

GLPG5101 showed an encouraging safety profile with the majority of higher than or equal to grade 3 events being hematological, 96% of patients, 47 or 49 received an infusion with fresh CD19 CAR-T cell therapy, of which 91.5%, 43 out of 47 achieved a vein-to-vein time of seven days, eliminating the need for bridging therapy.

GLPG5101 顯示出令人鼓舞的安全性，其中大多數高於或等於 3 級的事件都是血液學事件，96% 的患者（47 或 49 名）接受了新鮮的 CD19 CAR-T 細胞療法輸注，其中 91.5%（47 名中的 43 名）實現了七天的靜脈到靜脈時間，無需進行橋接治療。

Of note, strong and consistent vivo CAR-T expansion levels and products consisting of stem-like early memory phenotype T cells were observed in all doses tested. The summary of these data underscore our enthusiasm for going all in on GLPG5101, a flagship CD19 program. Our new strategy positions us to build on the clinical success we have seen thus far.

值得注意的是，在所有測試劑量中都觀察到強烈且一致的體內 CAR-T 擴增水平和由幹細胞樣早期記憶表型 T 細胞組成的產物。這些數據的總結強調了我們對全力投入旗艦 CD19 項目 GLPG5101 的熱情。我們的新策略使我們能夠在迄今為止的臨床成功的基礎上再接再厲。

Turning now to our small molecule programs in immunology where our most advanced candidate is our TYK2 inhibitor GLPG3667. Preclinical and first in human clinical data showed GLPG3667 to be a selective and potent inhibitor of TYK2, resulting in near complete inhibition of type 1 interferon signaling for a 24-hour cycle, which is supportive of once daily administration. We intentionally selected SLE and DM as our first indications because type 1 interferon plays a key role in both diseases.

現在談談我們的免疫學小分子項目，其中我們最先進的候選藥物是 TYK2 抑制劑 GLPG3667。臨床前和首次人體臨床數據顯示，GLPG3667 是一種選擇性強效的 TYK2 抑制劑，可在 24 小時內幾乎完全抑制 1 型乾擾素訊號傳導，支持每日一次給藥。我們特意選擇 SLE 和 DM 作為我們的首要適應症，因為 1 型乾擾素在這兩種疾病中都起著關鍵作用。

Our Phase II program offers an attractive partnership opportunity. I'm pleased to report that we recently completed screening in the SLE Phase III enabling clinical study ahead of schedule and anticipate top line results for GLPG3667 in SLE and DM in the first half of 2026.

我們的第二階段計劃提供了一個有吸引力的合作機會。我很高興地報告，我們最近提前完成了 SLE III 期臨床研究的篩選，並預計 2026 年上半年 GLPG3667 在 SLE 和 DM 領域的頂級結果。

Beyond SLE and DM, TYK2 inhibition offers potential in several other autoimmune indications, further expanding its market opportunity. A bold new strategy is focused on advancing our cell therapy leadership. As such, we are seeking to partner a promising small molecule portfolio, which was built on more than 20 years of research and where we have identified more than five programs in both oncology and immunology.

除了 SLE 和 DM，TYK2 抑制在其他幾種自體免疫適應症中也具有潛力，進一步擴大了其市場機會。一項大膽的新策略致力於提升我們的細胞治療領導地位。因此，我們正在尋求與一個有前景的小分子產品組合合作，該產品組合建立在 20 多年的研究基礎之上，我們已經在腫瘤學和免疫學領域確定了五個以上的項目。

The continued unmet medical need in a number of immune-mediated diseases offers a significant market opportunity and should make our programs an attractive opportunity for companies already operating in immunology. As you can see on this slide, we have an exciting year ahead with the potential to achieve a number of value-driving catalysts.

許多免疫介導疾病中持續存在的未滿足的醫療需求提供了巨大的市場機會，並且應該使我們的計畫成為對已經從事免疫學業務的公司有吸引力的機會。正如您在這張投影片上看到的，我們迎來了激動人心的一年，並有可能實現許多價值驅動催化劑。

Moving ahead with our focus on cell therapy, patient recruitment is ongoing in Europe with leading cancer centers in Boston to be activating following US FDA IND application clearance of 5101. We continue to build out our immune network and are focused on building the infrastructure and attracting talent to support the start of registrational studies with GLPG5101 in 2026 as well as our planned global expansion.

隨著我們繼續專注於細胞療法，我們正在歐洲進行患者招募，波士頓領先的癌症中心將在美國 FDA IND 申請 5101 批准後啟動招募工作。我們將繼續建立我們的免疫網絡，並專注於建立基礎設施和吸引人才，以支持 2026 年啟動 GLPG5101 的註冊研究以及我們計劃中的全球擴張。

Our aim is to complete the Phase III enabling studies with our TYK2 inhibitor in SLE and DM while seeking partnerships. We progress our early-stage next-generation cell therapy pipeline in hematological and solid tumors, including uza-cel.

我們的目標是完成 TYK2 抑制劑在 SLE 和 DM 治療中的 III 期臨床研究，同時尋求合作。我們正在推進血液學和實體瘤領域的早期下一代細胞治療管道，包括 uza-cel。

With that overview, let me turn the call over to my colleague, Thad Huston, for an overview of the exciting transaction we recently announced and for a review of our full year 2024 financials. Thad?

有了上述概述，請允許我將電話轉給我的同事 Thad Huston，請他概述我們最近宣布的令人興奮的交易，並回顧我們 2024 年全年的財務狀況。薩德？

Thanks, Paul. We remain very excited by the opportunities we can create by separating Galapagos into two entities. Paul has reviewed the benefits for Galapagos as an independent company that can now fully own its programs and platform. But now let's look at how we plan to create value from SpinCo. Over the past few years, there have been significant advances in science, technology and clinical development of new medicines.

謝謝，保羅。我們對將加拉巴哥群島一分為二所能創造的機會感到非常興奮。保羅回顧了加拉巴哥作為一家獨立公司所獲得的益處，該公司現在可以完全擁有自己的程式和平台。但現在讓我們看看我們計劃如何從 SpinCo 創造價值。過去幾年，科學技術和新藥臨床開發取得了重大進展。

Unfortunately, the capital markets have been tight over this time period, leaving many companies struggling for financing. For companies with capital to deploy, such as SpinCo, we believe this creates multiple opportunities to build value. Here, you can see the initial actions that are planned for setting up SpinCo for success. We expect to complete the separation around midyear for SpinCo and to prepare for listing on Euronext and NASDAQ.

不幸的是，這段時間資本市場一直很緊俏，導致許多公司融資困難。對於 SpinCo 等擁有資本可部署的公司，我們相信這創造了創造價值的多重機會。在這裡，您可以看到為成功建立 SpinCo 而計劃採取的初步行動。我們預計 SpinCo 的分離將在年中左右完成，並為在泛歐交易所和納斯達克上市做準備。

In the coming months, during the separation, SpinCo will appoint a seasoned executive team and independent non-executive Directors with proven track records in biotech company building and strategic transaction execution.

在接下來的幾個月中，在分離期間，SpinCo 將任命一支經驗豐富的執行團隊和獨立非執行董事，他們在生物技術公司建立和策略交易執行方面擁有良好的業績記錄。

A prospectus will be made publicly available at least one month prior to the spin-off. -- and all Galapagos shareholders are to receive SpinCo shares on a pro rata basis proportional to their ownership of Glapicos shares.

招股說明書將在分拆前至少一個月公開發布。 ——所有 Galapagos 股東都將按照其持有的 Glapicos 股份比例獲得 SpinCo 股份。

Turning now to our financial results. For our full year 2024 financial results, our total revenues are EUR276 million, which includes EUR35 million of supply revenues related to Jyseleca and EUR241 million in collaboration revenues. Research and development expenses were EUR335 million, which is a 39% increase year-over-year driven by our expansion of oncology CAR T.

現在來談談我們的財務結果。就我們 2024 年全年財務表現而言，我們的總收入為 2.76 億歐元，其中包括與 Jyseleca 相關的 3,500 萬歐元供應收入和 2.41 億歐元合作收入。研發費用為 3.35 億歐元，較去年同期成長 39%，這得益於我們擴大腫瘤 CAR T 業務。

G&A and sales and marketing expenses were flat at EUR134 million. We had a net profit for the year of EUR74 million, driven by EUR185 million from fair value adjustments, currency exchange and interest income as well as the net profit from discontinuing operations, which includes a gain of EUR53 million on the sale of the Jyseleca business to Alfasigma.

一般行政費用及銷售和行銷費用持平於 1.34 億歐元。我們全年淨利潤為 7,400 萬歐元，其中 1.85 億歐元來自公允價值調整、貨幣兌換和利息收入，以及終止經營的淨利潤，其中包括將 Jyseleca 業務出售給 Alfasigma 的 5,300 萬歐元收益。

Now looking at our balance sheet. We ended 2024 with approximately EUR3.3 billion in cash. Our cash burn for 2024 was EUR374 million, excluding business development or cash burn was EUR293 million, which is within our guidance range of EUR280 million to EUR320 million.

現在來看看我們的資產負債表。截至 2024 年，我們的現金餘額約為 33 億歐元。我們 2024 年的現金消耗為 3.74 億歐元，不包括業務發展或現金消耗為 2.93 億歐元，這在我們的 2.8 億歐元至 3.2 億歐元的指導範圍內。

Upon separation, Galapagos will be capitalized with approximately EUR500 million in cash which is expected to provide runway to 2028 as our normalized cash burn is projected to be in the range of EUR175 million to EUR225 million. SpinCo is expected upon separation to be capitalized with approximately EUR2.45 billion. Following the separation, Galapagos will be focused on accelerating the development of our flagship CD19 CAR-T program through our innovative decentralized manufacturing platform.

分離後，加拉巴哥將獲得約 5 億歐元現金，預計可為 2028 年的營運提供支持，因為我們的正常現金消耗預計在 1.75 億歐元至 2.25 億歐元之間。預計 SpinCo 分離後的資本將達到約 24.5 億歐元。分離之後，Galapagos 將專注於透過我們創新的分散製造平台加速我們旗艦 CD19 CAR-T 專案的開發。

Our aim is to start pivotal studies in 2026, aiming for a first approval in 2028. We will continue to develop next-gen cell therapy programs in hematological and solid tumors. We plan to initiate clinical development of a novel CAR-T candidate in 2025. We will also develop a worldwide decentralized manufacturing network for the delivery of our cell therapy.

我們的目標是在 2026 年開始關鍵研究，並爭取在 2028 年獲得首次批准。我們將繼續開發血液腫瘤和實體腫瘤的下一代細胞治療方案。我們計劃於 2025 年啟動新型 CAR-T 候選藥物的臨床開發。我們還將建立一個全球分散的製造網絡來提供我們的細胞療法。

Importantly, we will have the autonomy to partner our decentralized manufacturing platform and network as well as our differentiated cell therapy pipeline. With this focused strategy, we are also implementing a significant restructuring to realign our footprint and to reduce our cash burn.

重要的是，我們將擁有自主權來合作我們的分散製造平台和網路以及我們的差異化細胞治療管道。透過這項重點策略，我們也實施了重大重組，以重新調整我們的業務範圍並減少現金消耗。

Turning to the opportunities we have by creating SpinCo where we are equally excited by its potential to create value by focusing on building a pipeline of innovative medicines through transformational transactions. We are forming SpinCo with sufficient resources to pursue high-quality assets, fund development and to invest in its portfolio.

談到我們透過創造 SpinCo 所獲得的機遇，我們同樣對其透過專注於透過轉型交易建立創新藥物管道而創造價值的潛力感到興奮。我們正在組成 SpinCo，擁有足夠的資源來追求優質資產、資助開發並投資其投資組合。

If Gilead decides to opt in to SpinCo programs under the OCA, then SpinCo will be able to leverage Gilead's strong expertise and late-stage development and commercial capabilities in key therapeutic areas. The SpinCo Board will have a majority of independent directors and will be led by an experienced executive leadership team.

如果吉利德決定加入 OCA 下的 SpinCo 計劃，那麼 SpinCo 將能夠利用吉利德在關鍵治療領域的強大專業知識和後期開發及商業能力。SpinCo 董事會將由大多數獨立董事組成，並由經驗豐富的執行領導團隊領導。

Importantly, Gilead has committed to negotiating in good faith amendments to the OCA on a transaction-by-transaction basis to achieve positive value for SpinCo and all of its shareholders. We have an exciting year ahead as we advance our clinical programs and early-stage pipeline of next-generation cell therapies in a number of important cancer indications and with the launch of our newly created SpinCo.

重要的是，吉利德已承諾以誠信的態度逐筆交易協商修改 OCA，從而為 SpinCo 及其所有股東實現積極的價值。隨著我們推動多種重要癌症適應症的臨床計畫和下一代細胞療法的早期研發管線，並推出我們新成立的 SpinCo，我們迎來了令人興奮的一年。

Throughout the coming year, we expect to achieve a number of value-creating milestones that will further our commitment to transforming patient outcomes through life-changing science and innovation. Thank you once again for your time today and for your continued interest and support of our mission.

在未來的一年裡，我們期望實現一系列創造價值的里程碑，這將進一步推動我們致力於透過改變生活的科學和創新來改變患者的結果。再次感謝您今天抽出時間以及對我們使命的持續關注和支持。

Operator, we are now ready to open the call for questions.

接線員，我們現在可以開始回答問題了。

(Operator Instructions) Xian Deng, UBS.

（操作員指示）瑞銀 (UBS) 的 Xian Deng。

And this is regarding to 5101 and also 5201. Thank you very much for the very useful data review for 5101 and make sense of why you want to expand that. But just wondering, given you're also deprioritizing 5201. Just wondering if you could remind us what's the difference between the two CD19 contract for those two CAR-Ts. I'm just wondering why are you -- if you could maybe elaborate a bit more why you are deprioritizing 5201?

這是關於 5101 和 5201 的。非常感謝您對 5101 提供的非常有用的數據審查，並解釋了您為什麼要擴展它。但只是好奇，鑑於您也降低了 5201 的優先順序。只是想知道您是否可以提醒我們這兩種 CAR-T 的兩份 CD19 合約之間有什麼區別。我只是想知道你為什麼——你是否可以更詳細地解釋為什麼要降低 5201 的優先順序？

Paul Stoffels here. Let me explain. We were running 5201 and 5101 in parallel for clinical trials in Phase I/II. And we saw excellent efficacy and safety for both of them. And we think and we believe very much that this is driven by fresh sells high-content memory cells, we do the job there to make that kind of outcome. But the main reason then is for us to simplify is that building a decentralized manufacturing network in the world for running two CD19 is quite steep.

這裡是保羅‧斯托弗爾斯 (Paul Stoffels)。讓我解釋一下。我們正在同時執行 5201 和 5101 進行 I/II 期臨床試驗。我們發現它們均具有出色的功效和安全性。我們認為並且我們非常相信這是由新鮮銷售的高容量儲存單元推動的，我們在那裡開展工作以實現這種結果。但我們要簡化的主要原因是，在世界範圍內建立一個分散的製造網路來運行兩個 CD19 是相當困難的。

And so by not duplicating the product transfer and validation about all the DMUs we are setting up, we could focus much more on accelerating our pipeline on our main assets. And so adding the CLL and Richter transformation to the 5101 will accelerated the two indications most likely to the market. And that's why reprioritizing the two indications on the 5101, we have already the agreement of the FDA on the Richter -- that's already done.

因此，透過不重複我們正在設定的所有 DMU 的產品轉移和驗證，我們可以更加專注於加速我們主要資產的管道。因此，將 CLL 和 Richter 變換添加到 5101 將加速這兩個最有可能進入市場的跡象。這就是為什麼要重新確定 5101 的兩個適應症的優先順序，我們已經就 Richter 獲得了 FDA 的同意——這已經完成了。

We are completing work on the CLL to also include that in the IND to that off as soon as possible in the US. So it is really accelerating by simplifying and really believing that the fresh cells do the job in making the difference in the CD19 space.

我們正在完成 CLL 的工作，以便將其納入 IND，並儘快在美國實現。因此，透過簡化並真正相信新鮮細胞能夠在 CD19 空間中發揮作用，它確實在加速。

Phil Nadeau, TD Cowen.

菲爾·納多 (Phil Nadeau)，TD Cowen。

Just a follow-up on the last one and then another question on the separation. Just in terms of 5101 versus 5201, were there any differences in terms of manufacturing process or characteristics between the two programs? That's the first question. And then second, in terms of the separation transaction, what is rate limiting at this point? Is it hiring of the management team? Or are there other logistical or legal steps that are really gaining.

這只是對上一個問題的後續回答，然後是關於分離的另一個問題。就 5101 與 5201 而言，這兩個程序在製造製程或特性方面是否有差異？這是第一個問題。其次，就分離交易而言，目前的速率限制是什麼？是聘請管理團隊嗎？或是否有其他真正有益的後勤或法律措施。

Jeevan Sheety, oncology. In answer to your first question, in terms of the issues regarding manufacturing, they are the same, the fundamentals of fresh cells in fresh product out, seven-day vein to vein, resulting in a superior product. The vectors are different. But however, the basis of our decision was made on the very significant and compelling data from 5101 and the issue regarding complexity. With regard to the second question, Thad.

Jeevan Sheety，腫瘤學。回答您的第一個問題，就製造問題而言，它們是相同的，基本原理都是將新鮮細胞放入新鮮產品中，經過七天的靜脈移植，最終生產出優質的產品。向量不同。但是，我們做出這項決定的基礎是來自 5101 的非常重要和令人信服的數據以及有關複雜性的問題。關於第二個問題，薩德。

Yes. Thad Huston here. I think clearly, we are in the process of a number of different elements related to the separation. Valeria could also add to that, including the hiring of a management team, and that process is underway. Obviously, there's a number of different legal steps as well.

是的。這裡是泰德·休斯頓。我認為很明顯，我們正處於與分離相關的許多不同要素的過程中。瓦萊麗亞還可以補充一些內容，包括聘請管理團隊，而這項流程正在進行中。顯然，還有許多不同的法律步驟。

This is Valeria. So I think as with any listing on Nasdaq and on Euronext we're preparing diligently for the listing, and that will be subject to the review of FSMA and SEC. And in addition, prior to the spin-off, the spin and the separation will be subject to the shareholders' approval at an extraordinary general meeting of shareholders that will take place at midyear with required approval being obtained, we can be listing a few days thereafter.

這是瓦萊麗亞。因此，我認為，與在納斯達克和泛歐交易所上市的任何公司一樣，我們正在為上市做認真的準備，這將接受 FSMA 和 SEC 的審查。此外，在分拆之前，分拆和分離還需要在年中召開的臨時股東大會上獲得股東批准，如果獲得必要的批准，我們可以在幾天後上市。

For the fact that the noncore Galapagos Board is working very hard to recruit seasoned CEO and several executives as well as an independent nonexecutive director team for the Board. So that is actually ongoing, and we plan to have several people on board by the time we spin.

事實上，非核心的加拉巴哥董事會正在努力為董事會招募經驗豐富的執行長和幾位高階主管以及一個獨立的非執行董事團隊。所以這實際上是持續進行的，我們計劃在旋轉時有幾個人加入。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

Maybe another one on 5201. Can you just help us understand, I guess, how far along you guys were on the IND filing process when you made the decision to prioritize 5101. And I guess, what gives you the most confidence that 5101 will look similar to the promising data you've generated from 5201 CLL and then secondly, just wondering if you could give us the latest update on the types of assets that the SpinCo may be looking for.

也許 5201 上還有另一個。我想，您能否幫助我們了解一下，當你們決定優先考慮 5101 時，你們的 IND 申請流程進行到了哪一步？我想，是什麼讓您最有信心 5101 看起來與您從 5201 CLL 產生的有希望的數據相似？其次，我只是想知道您是否可以向我們提供有關 SpinCo 可能正在尋找的資產類型的最新更新。

Yes. Why we are confident that the 5201, 5101 are pretty similar. We see similar efficacy safety activity, also the expansion if we the manufacturing and then the administration in the expansion, we see a very significant expansion happening in the patients similar to the 5101 with the 5201. So that's where we don't think the sector is doing the drive of the difference. The fact that we won't make the difference.

是的。為什麼我們確信 5201 和 5101 非常相似。我們看到了類似的功效安全性活動，如果我們在製造和管理方面進行擴展，我們會看到與 5101 和 5201 類似的患者出現了非常顯著的擴展。因此，我們認為該行業並沒有發揮差異化的作用。事實上我們不會做出任何改變。

We are comfortable that the way we make the cells is going to drive the difference. And the main reason to do this is to to, as I said earlier, is to align on a simplification of the immune network. We're going we are required by the authorities to do a validation doing equivalent studies between all of the immune sites in the world. If you do that, it's a cumbersome and very work-intensive process.

我們確信，我們製造細胞的方式將會帶來差異。這樣做的主要原因是為了，正如我之前所說，簡化免疫網絡。我們將按照當局的要求，對世界上所有的免疫點進行驗證和等效研究。如果這樣做，這將是一個繁瑣且非常耗費工作量的過程。

Running two processes next to each other in the same DMUs, means we have to double that and that would delay the overall progress of our company if we had to parallel process those at this moment in time in a significant way across the world.

在相同的決策單元 (DMU) 中同時運行兩個流程意味著我們必須將其翻倍，如果我們必須在全球範圍內以顯著的方式並行處理這兩個流程，那麼這將延遲我們公司的整體進度。

We are running in Europe to already in parallel, that is the 5101 and the 5301, the BCMA target in Europe, adding a third one to the network would be a very significant challenge to really bring that into pivotal studies as we want to start those next year. And that's why we concluded to offer optimization and efficiency, let's focus on one key CD19 than do the BCMA in early stage and learn whether it is a competitive product.

我們在歐洲已經同時運行 5101 和 5301，即歐洲的 BCMA 目標，在網路中添加第三個目標將是一個非常重大的挑戰，以便真正將其納入關鍵研究，因為我們希望明年開始這些研究。這就是為什麼我們決定提供最佳化和效率，讓我們專注於一個關鍵的 CD19，而不是在早期階段進行 BCMA，並了解它是否是一個有競爭力的產品。

But then third, also start focusing on our next generation assets, which are in progress and maybe John can talk a little bit more about that, just to highlight a few things about that because that's also important in our portfolio, why we make this prioritization. John?

但第三，也要開始關注我們正在進行的下一代資產，也許約翰可以多談談這一點，只是強調一些關於這一點的事情，因為這在我們的投資組合中也很重要，這就是為什麼我們要優先考慮這一點。約翰？

Thanks, Paul. My name is John Mellors. I'm the Head of cell therapy discovery and early development at Galapagos. And I'm pleased to let the audience know that we are working very hard around the clock to develop next-generation CAR-T cell therapies that include multi-targeting of cancer-associated antigens and arming to prevent suppression of CAR-T cells by the cancer microenvironment.

謝謝，保羅。我的名字是約翰‧梅勒斯。我是加拉巴哥細胞療法發現和早期開發的負責人。我很高興地告訴觀眾，我們正在日以繼夜地努力開發下一代 CAR-T 細胞療法，包括多標靶癌症相關抗原和武裝以防止癌症微環境對 CAR-T 細胞的抑制。

We have four main objectives in NHL, in myeloma, in lung cancer and in ovarian cancer. And our first product has been approved for clinical development and will enter proof-of-concept studies by the end of the year, and that's a multi-targeting CAR-T for NHL and ALL.

我們有四個主要目標，即非何杰金氏淋巴瘤、骨髓瘤、肺癌和卵巢癌。我們的首款產品已獲準進行臨床開發，並將於今年年底進入概念驗證研究，這是針對 NHL 和 ALL 的多靶點 CAR-T 療法。

For myeloma, we intend to target the space that follows BCMA targeting therapy. And for lung cancer, we are targeting a validated clinical target plus an additional target and for ovarian cancer two targets in combination.

對於骨髓瘤，我們打算針對 BCMA 標靶治療之後的空間。對於肺癌，我們針對的是經過驗證的臨床目標加上一個額外的目標；對於卵巢癌，我們則針對兩個目標的組合。

And let me just emphasize that each of these indications are high unmet medical needs and we believe we can have an impact and by impact, I mean, more frequent responses, deeper responses and longer duration of response with our arming and multi-targeting strategy.

我只想強調一下，這些適應症中的每一種都是未滿足的醫療需求，我們相信我們能夠產生影響，我的意思是，透過我們的武裝和多目標策略，我們可以實現更頻繁的反應、更深入的反應和更長的反應持續時間。

And just confirming here that the first asset is internally ready to get into clinical trials, and that is being prepared, as John was saying, before the year-end. So I think that's also one of the big objectives for the year is progressing the first asset of our next generation into the clinic.

這裡只是確認一下，第一項資產已在內部準備好進入臨床試驗，而且正如約翰所說，準備工作將在年底前完成。因此，我認為這也是今年的一大目標，即將我們下一代的第一項資產推向臨床。

Yes. Brian, let me take this, that here, of the SpinCo question. First of all, I want to say that we're really excited about the creation of SpinCo. SpinCo will clearly have more greater flexibility and access to acquire assets with significant potential without having the need to fit in the Galapagos strategy. So there's a lot more broad opportunities to do deals.

是的。布萊恩，讓我來回答關於 SpinCo 的問題。首先，我想說，我們對 SpinCo 的成立感到非常興奮。SpinCo 顯然將擁有更大的靈活性和獲取具有巨大潛力的資產的管道，而無需適應加拉巴哥策略。因此，有更多更廣泛的交易機會。

And of course, partnering with Gilead and working closely with them with well-capitalized organization they can really compete for the highest quality targets across the biotech space. And the types of assets, I think we're identifying or clearly to find a pipeline of innovative medicines that really have the potential to treat diseases with significant unmet need across any different types of indications with a focus on virology, immunology and oncology.

當然，透過與吉利德合作並與其資金雄厚的組織密切合作，他們可以真正在生物技術領域爭奪最高品質的目標。而對於資產類型，我認為我們正在識別或明確尋找一系列創新藥物，這些藥物真正有潛力治療任何不同類型適應症中存在重大未滿足需求的疾病，重點是病毒學、免疫學和腫瘤學。

Faisal Khurshid, Leerink Partners.

Faisal Khurshid，Leerink Partners。

I just want to ask, as you're kind of preparing for pivotal development on 5101. Can you talk a little bit about what the potential indication and kind of trial strategy looks like there. And then also as a potential approval could be a few years away now, what is the US-based manufacturing footprint look like? And what is your progress towards getting that into place?

我只是想問一下，因為您正在為 5101 的關鍵開發做準備。您能否稍微談談那裡的潛在適應症和試驗策略？而且由於潛在的批准可能還需要幾年時間，美國的製造業足跡是什麼樣的？您在實現這一目標方面取得了哪些進展？

Jeevan Shetty. Again, with regard to the indications that we have planned, you know that we've shared data at ASH regarding the ATLANTA study in the indications of mantle cell, mantle zone lymphoma as well as NHL. We intend to expand that into a number of other indications, Burkitt's lymphoma, in particular, primary CNS lymphoma as well as high-risk diffuse large B-cell lymphoma.

傑文·謝蒂。再次，關於我們計劃的適應症，您知道我們已經在 ASH 上分享了有關 ATLANTA 研究的數據，該研究針對的是套細胞、套區淋巴瘤以及 NHL 的適應症。我們打算將其擴展到其他一些適應症，特別是伯基特淋巴瘤、原發性中樞神經系統淋巴瘤以及高風險瀰漫大B細胞淋巴瘤。

So areas where the unmet need is significant and where the seven-day vein-to-vein time fresh cells in fresh product out has significant contributions to the outcome for patients we will be led by the data that we see in our Phase II. And clearly, we will communicate more comprehensively as the data emerges. But our tenants are really significant unmet need that benefit from our platform.

因此，在未滿足需求顯著的領域以及為期七天的靜脈對靜脈時間新鮮細胞輸入新鮮產品對患者結果有重大貢獻的領域，我們將以我們在第二階段看到的數據為指導。顯然，隨著數據的出現，我們將進行更全面的溝通。但我們的租戶確實有未滿足的重大需求，他們從我們的平台中受益。

And on the manufacturing side, we have obviously the decentralized manufacturing structure. So it's a model where, of course, we want to have validated sites like we have our initial site with Landmark Bio in the Boston area, so can cover the Boston area, major hospitals, which we're also partnering with.

在製造方面，我們顯然擁有分散的製造結構。所以這是一個模型，當然，我們希望擁有經過驗證的站點，就像我們在波士頓地區與 Landmark Bio 合作的初始站點一樣，這樣可以覆蓋波士頓地區和主要醫院，我們也與這些醫院合作。

But we're also looking to have regional sites in kind of high-density areas throughout the US, East Coast, West Coast, south and north of the US. And so trying to get the right coverage as we go adding sites by site. Like we said, Paul in his remarks, we had Blood Centers of America, for example, with the West Coast coverage as one site and continuing to add those over time.

但我們也希望在美國東岸、西岸、南部和北部等人口密集地區建立區域站點。因此，我們嘗試在逐一新增網站的過程中獲得正確的覆蓋範圍。就像我們保羅在演講中所說的那樣，我們有美國血液中心，例如，將西海岸作為一個站點進行覆蓋，並隨著時間的推移繼續添加這些站點。

To start with, first of all, we need to target where the high-density oncologists are in these very specialty areas. And then for commercial, will broaden out into other sites as we want to cover the whole of the US. But we, at this moment, all of our TMUs are focused on getting the maximum number of patients in the indications we are looking for. So there is like a two-step where complete the studies. These sites are ready for commercial when we can start, but we'll work further over the year to determine where other sites will be.

首先，我們需要瞄準這些專業領域中腫瘤學家密集的地方。然後對於商業來說，我們將擴展到其他站點，因為我們希望覆蓋整個美國。但目前，我們所有的 TMU 都致力於獲得盡可能多的符合我們所需適應症的患者。因此，完成研究需要兩個步驟。當我們開始的時候，這些站點已經準備好投入商業運營，但是我們將在未來一年進一步努力，以確定其他站點的位置。

Got it. And are the regulatory requirements different between having these manufacturing sites with the clinical trial as opposed to commercial use?

知道了。這些用於臨床試驗和商業用途的製造基地的監管要求是否不同？

Well, there are some additional requirements for pivotal, which we are preparing for, and we are comfortable that we are ready for that by next year when we start the clinical trials. Today, it's a very high standard. We have to meet, of course, because we provide biologicals and human cells.

嗯，對於關鍵問題還有一些額外的要求，我們正在為此做準備，我們相信，到明年開始臨床試驗時，我們已經準備好了。今天，這是一個非常高的標準。當然，我們必須開會，因為我們提供生物製劑和人體細胞。

And so we -- there is not much difference, but it all has to do in the end with also further automating the quality release testing and further demonstrating comparability and equivalents across the different sites. So as we go, we will strengthen that. But today, we already meet a fairly high level of requirement close to commercial.

因此我們 - 沒有太大的區別，但最終都與進一步自動化品質發布測試以及進一步展示不同站點之間的可比性和等效性有關。因此，隨著我們的前進，我們將加強這一點。但今天我們已經達到了相當高、接近商業化的要求。

(Operator Instructions) Judah Frommer, Morgan Stanley.

（操作員指示） Judah Frommer，摩根士丹利。

Just curious if you could share any indication of interest from potential external partners for manufacturing on the decentralized manufacturing units at this point? Or is that something that you haven't necessarily of conversations on yet?

我只是好奇，您是否可以分享一下目前潛在的外部合作夥伴對分散式製造單位製造的興趣？或者這是您還未必會談論的事情？

Yes, we have inbound questions from external partners to get on our platform. Of course, we are making sure that we are first build up ready to go with our clinical trials. But for example, the collaboration with Adaptimmune started on -- with the interest on our platform. We validated that TCRT, if you produce on our platform has a similar kind of features as when we do with the CAR-Ts for the hematological testing. And there progressing with Adaptimmune to NxStage and starting clinicals, I think, 18, 24 months from now.

是的，我們收到了來自外部合作夥伴關於如何進入我們平台的問題。當然，我們要確保先做好臨床試驗的準備。但例如，與 Adaptimmune 的合作始於對我們平台的興趣。我們驗證了，如果您在我們的平台上生產，TCRT 具有與我們用於血液學測試的 CAR-T 類似的功能。我認為 Adaptimmune 正在向 NxStage 邁進，並開始臨床研究，從現在起 18 到 24 個月後。

But that is one of the examples, but we have multiple objects which we are evaluating. And there are two things there for us. It's one we can partner on the platform, but we can also strategically partnering on co-development with partners and that would be our main interest is looking at people who are interested to have to where we can access where we can strategically partner on on the truck, on the cell therapy combined with the platform. So -- and our teams are very active in having those discussions.

但這只是其中一個例子，但我們正在評估多個物件。對我們來說有兩件事。我們可以在平台上進行合作，但我們也可以與合作夥伴在共同開發方面進行策略合作，而我們的主要興趣是尋找對我們可以在哪裡進行策略合作以及在卡車上、在結合平台的細胞療法上進行策略合作感興趣的人。所以——我們的團隊非常積極地進行這些討論。

And just wanted to add, in addition to this is the fact that as a cell therapy leader, we lead also hematology and oncology in these partnerships. For example, Adaptimmune is a head and neck indication solid tumor indication with significant unmet need and that is the form of the collaborations that we're having as well.

我想補充的是，除此之外，作為細胞療法的領導者，我們在這些合作中還在血液學和腫瘤學領域處於領先地位。例如，Adaptimmune 是一種頭頸部實體腫瘤適應症，具有重大未滿足的需求，這也是我們正在進行的合作形式。

Yes, I think it's really exciting for us to also look at this post separation and have the flexibility to partner with many different types of companies that have maybe manufacturing limitations or just capacity constraints or don't have the capital to potentially invest in having a unique differentiated platform that we have.

是的，我認為，對於我們來說，在分離之後能夠靈活地與許多不同類型的公司合作是非常令人興奮的，這些公司可能存在製造限製或產能限制，或者沒有資本來投資於我們擁有的獨特差異化平台。

And there's one particular region in the world, which is very underserved. And then that's Asia. And so there, we get requests from governments as well on CDMOs to partner on the platform to provide access in those regions. That's somewhat further off, but you see the fact that we have a scalable decentralize manufacturing capacity or capability with cocoons and good results, it is very attractive for other parts of the world, including those regions who don't have access and still have very high medical need in this space.

世界上有一個特定地區的服務嚴重不足。接下來是亞洲。因此，我們也收到了來自政府以及 CDMO 的請求，希望我們在平台上合作，為這些地區提供存取服務。這有點遙遠，但你看，我們擁有可擴展的分散製造能力或能力，具有良好的效果，這對世界其他地區非常有吸引力，包括那些無法獲得但在該領域仍有很高醫療需求的地區。

Jason Gerberry, Bank of America Securities.

美國銀行證券公司的 Jason Gerberry。

This is [Chi] on for Jason. I have a question on 5301. So based on the press release, it looks to me that you're taking a hard look at whether you will work on to advance 5301 further in development in multiple myeloma. Is it because of the competitive dynamics in the BCMA CAR-T space or complexity of setting up a DMD network for a second CAR-T or a bit of both? Maybe can you talk about the analysis that you're specifically looking at in the Phase I study on the PEPILIO study?

這是 Jason 的 [Chi]。我對 5301 有疑問。因此，根據新聞稿，在我看來，您正在認真考慮是否要進一步推進 5301 在多發性骨髓瘤領域的開發。是因為 BCMA CAR-T 領域的競爭動態，還是為第二個 CAR-T 設定 DMD 網路的複雜性，或者兩者兼具？您能否談談您在 PEPILIO 研究第一階段研究中特別關注的分析？

And what criteria you want to see 5301 meet in order for you to advance the asset in the pivotal trial? And if I may ask a quick follow-up on the indication pursuit plan for 5101, are you prioritizing one or two of the indications as you think about capital preservation in 2026 and beyond?

您希望 5301 符合哪些標準，以便您在關鍵試驗中推進該資產？如果我可以快速跟進 5101 的適應症追求計劃，那麼在考慮 2026 年及以後的資本保全時，您是否優先考慮其中的一兩個適應症？

Jeevan Shetty again. I'll take the first part of the question. With regard to the PAPILIO study, it is very clear what the competitive environment actually looks like with regard to the incumbents. So we know what parameters we need to beat or be equivalent to in both safety and efficacy. And so that is very clear.

又是 Jeevan Shetty。我來回答問題的第一部分。就 PAPILIO 的研究而言，我們可以很清楚地看到現有企業面臨的競爭環境究竟是什麼樣的。因此我們知道在安全性和功效方面我們需要超越或達到哪些參數。這是非常清楚的。

And really, our determination will be based on the benefit risk ratio and the -- and the safety and efficacy, in particular. I have to add that we are making very good progress with the PAPILIO study. Clearly, we're recruiting well, and we will share data at an upcoming hematology conference. The internal determination will be based on how competitive we are with the incumbent. But progress overall is good.

實際上，我們的決定將基於效益風險比以及—特別是安全性和有效性。我必須補充一點，我們在 PAPILIO 研究方面取得了非常好的進展。顯然，我們的招募工作進展順利，我們將在即將舉行的血液學會議上分享數據。內部決定將取決於我們與現任者的競爭力。但整體來說進展是好的。

Yes. With regard to the, we'll wait to determine for the BMUs there on where the first data are and the expansion of that and the expansion to other parts of the world. For 5101, you asked on the prioritization. What is remarkable is that with the KOLs we talk in the clinics, and they see this high unmet unmet medical need NHL indications. All of the indications we are listed, the majority of them are interested to all of the KOLs we work with today.

是的。關於這一點，我們將等待確定那裡的 BMUs 的第一批數據在哪裡，以及這些數據的擴展以及向世界其他地區的擴展。對於 5101，您詢問的是優先順序。值得注意的是，當我們在診所與 KOL 交談時，他們看到了 NHL 適應症中如此高的未滿足醫療需求。在我們列出的所有跡像中，大多數都引起了我們今天合作的所有 KOL 的興趣。

And that is -- that's where we don't prioritize at the moment, the indications. We give access to the to participate with the patients in these expansion cohorts, which we are making, and that gives us the insight later this year on what are -- what will you take as priorities going into the pivotal studies for registration.

這就是——這就是我們目前不優先考慮的跡象。我們允許患者參與我們正在進行的這些擴展隊列，這讓我們在今年稍後能夠了解在進行註冊的關鍵研究中您將把什麼作為優先事項。

But so far, these indications we list on the slide you have seen during the presentation, those are all open or one by one, they will all be open for inclusion. And there are specialty centers, but most of the people are interested in the majority of the ones we have there.

但到目前為止，我們在演示過程中看到的幻燈片上列出的這些跡像都是開放的，或者逐一開放，它們都將開放以供納入。那裡有專科中心，但大多數人只對我們那裡的大多數中心感興趣。

Sean McCutcheon, Raymond James.

肖恩麥卡琴、雷蒙德詹姆斯。

So for the 2020 cash runway guidance, can you speak to maybe what milestones programs and potentially further efficiency measures are contemplated within that guidance?

那麼，對於 2020 年現金流指引，您能否談談該指引中考慮了哪些里程碑計畫以及潛在的進一步效率措施？

Yes, this is Thad here. Good question. So we look ahead, obviously, we're going through a pretty significant restructuring of the business that Paul mentioned as well, reducing our overall head count by about 40%, focusing in cell therapy, and we brought our burn rate down excluding business development from EUR293 million in 2024 to a range where we're saying of about [$175 million to $225 million] per year.

是的，我是薩德。好問題。因此，展望未來，顯然，正如 Paul 所提到的，我們正在進行一次相當重大的業務重組，將我們的總員工人數減少約 40%，專注於細胞療法，並且我們將不包括業務開發的燒錢率從 2024 年的 2.93 億歐元降至每年約 [1.75 億美元至 2.25 億美元] 的範圍。

We can certainly work towards the lower end of that range depending on some of the choices. We're initially investing to build out the DMU network that investment will kind of move down over time, but then we'll have the clinical investment that will pick up. And so that's why I would give kind of this range.

根據一些選擇，我們當然可以努力達到該範圍的下限。我們最初投資建立 DMU 網絡，隨著時間的推移，投資將逐漸減少，但隨後我們的臨床投資將會增加。這就是我給出這種範圍的原因。

We're saying the range is kind of taking us to 2028 because that's assuming midyear with approximately $500 million at separation. So we do see that we'll have runway there. We also have a number of milestones and key inflection points, obviously, going into pivotal in 2026. Obviously completing the pivotal studies for 5101. We'll also see the readout from 5301.

我們說這個範圍將持續到 2028 年，因為這是假設年中分離時的價值約為 5 億美元。所以我們確實看到那裡會有跑道。顯然，我們還有許多里程碑和關鍵轉折點，2026 年將進入關鍵階段。顯然完成了 5101 的關鍵研究。我們還將看到 5301 的讀數。

We'll have 5701, and as also mentioned, we'll have some of our internal next-generation platforms going into the clinic, and we anticipate that we'll have a multiple number of programs between now and 2028, the one to the clinic.

我們將有 5701 個項目，正如所提到的，我們將把一些內部的下一代平台投入到臨床中，我們預計從現在到 2028 年，我們將有多個項目投入臨床。

And in addition, we're also looking to do potentially partnership deals on the platform, and we see tremendous opportunity there. So there's a number of key milestones and a number of really exciting things that will help us get to that 2028 first launch, hopefully.

此外，我們還希望在該平台上達成潛在的合作協議，我們看到了巨大的機會。因此，有許多關鍵的里程碑和許多真正令人興奮的事情將幫助我們實現 2028 年的首次發射。

Jacob Mekhael, KBC Securities.

Jacob Mekhael，KBC 證券。

I just had one on the ATLANTA 1 study in the US. When do you expect to dose the first patient? And maybe can you please provide some insight behind this small delay there?

我剛參加了美國 ATLANTA 1 的研究。您預計什麼時候給第一位病人用藥？您能否提供一些關於這個短暫延遲的解釋？

Yes. Jeevan here again. Thank you very much for the question. In Europe, the patient recruitment is ongoing with the US, clearly with the FDA IND application secured and also the inclusion of the leading cancer centers in Boston being engaged. We're working really pretty hard towards enrolling the first patient into the study.

是的。Jeevan 又來了。非常感謝您的提問。在歐洲，病患招募工作正在美國進行，顯然已經獲得了 FDA IND 申請，也納入了波士頓領先的癌症中心的參與。我們正在非常努力地招募第一位患者參與這項研究。

We -- so we're very confident that we will be able to recruit the patient imminently. There are clearly some procedural and operational components in the final stages of starting the trial that we are working towards, but we're very confident that we will have our first patient very soon.

因此我們非常有信心能夠很快招募到病人。顯然，我們正在努力完成試驗開始的最後階段的一些程序和操作部分，但我們非常有信心很快就會迎來第一位患者。

(Operator Instructions) Sebastiaan van der Schoot, Van Lanschot Kempen.

（操作員說明）Sebastiaan van der Shoot、Van Lanschot Kempen。

I was hoping that you could expand on the differences between the decentralized and centralized manufacturing. But then from the standpoint of the regulator compared to previous CAR-T trials in the registrational setting, and do you expect any differences in terms of patient number or follow-up to demonstrate consistency between the different number of the DMUs?

我希望您能夠詳細說明分散製造和集中製造之間的差異。但從監管機構的角度來看，與註冊環境中先前的 CAR-T 試驗相比，您是否預期患者數量或追蹤方面會存在任何差異，以證明不同數量的 DMU 之間的一致性？

Well, I'll start with your last remark. We run comparative -- we run comparative and validation trials are on the different DMUs, we come with the same product out of that manufacturing site like large companies do, we do the same type of validation where large companies do that centrally in their sites. We do that across sites.

好吧，我就從你的最後一句話開始。我們進行比較——我們在不同的 DMU 上進行比較和驗證試驗，我們像大公司一樣從製造現場生產出相同的產品，我們進行與大公司在其站點集中進行的相同類型的驗證。我們在各個站點都這麼做。

And we follow the principle of split samples where we validate that across different DMUS and validate that all of these DMUs function the same. So we have to comply with the high standards of central manufacturing in order to deliver these CAR-T cells. And that's where we don't assume any different indications from different regions in the world. We go for -- we go for indication by indication, combining US and European patients.

我們遵循分割樣本的原則，在不同的 DMUS 中進行驗證，並驗證所有這些 DMU 的功能是否相同。因此，為了提供這些 CAR-T 細胞，我們必須遵守中央製造的高標準。這就是為什麼我們不會假設世界不同地區會有任何不同的跡象。我們根據美國和歐洲患者的情況進行針對性治療。

Yes, I'd just add, generally, though, I mean we have significant benefits for our decentralized manufacturing model. And that's where we think that, again, the regulatory pathway that Paul mentioned it has to be applied. But I think the delivery of fresh cells we obviously see this unique clinical benefit, but there's also a number of logistical benefits and cost benefits that we also see with our delivery and our model.

是的，我只是想補充一點，總的來說，我們的分散製造模式為我們帶來了顯著的好處。這就是我們認為必須應用保羅所提到的監管途徑的地方。但我認為，我們顯然看到了新鮮細胞輸送的獨特臨床益處，但我們的輸送和模式也帶來了許多物流益處和成本效益。

Okay. And if I may, just one more question regarding the deal terms of uza-cel. Can you remind us of those deal terms? And then you also mentioned that you are looking for similar partnerships in the future. Can you expand on that?

好的。如果可以的話，我再問一個關於 uza-cel 交易條款的問題。您能提醒我們這些交易條款嗎？然後您也提到您正在尋找未來類似的合作關係。能詳細闡述嗎？

Yes. So we did the uza-cel deal, where we essentially have an option agreement on uza-cel. We're doing head and neck cancer as an initial indication. It was, I believe, $100 million option at least initial payment, but we have the option to go up to three different indications, including ovarian and some others and where essentially we're testing the product on the Cocoon and the platform, and then where we could opt in and basically take over the commercialization and development rights.

是的。因此我們達成了 uza-cel 交易，實際上我們對 uza-cel 有一個期權協議。我們的初步適應症是頭頸癌。我相信，這至少是 1 億美元的首付款，但我們可以選擇三種不同的適應症，包括卵巢和其他一些適應症，基本上我們會在 Cocoon 和平台上測試產品，然後我們可以選擇加入並基本上接管商業化和開發權利。

There are no further questions for today. I would now like to hand the conference over to your speaker, Sri Ramaswami, for any closing remarks.

今天沒有其他問題了。現在，我想將會議交給發言人 Sri Ramaswami，請他做最後發言。

Again, thank you all for joining us today. The team will be in Boston presenting at the TD Cowen Healthcare Conference on Tuesday, March 4 at 1:50 PM Eastern Time. And the following week will be in Miami, participating at the Barclays Healthcare Conference. Please reach out if you're interested in connecting with us in person at these events. Have a wonderful day, and we look forward to seeing some of you in March.

再次感謝大家今天的參加。該團隊將於美國東部時間 3 月 4 日星期二下午 1:50 在波士頓參加 TD Cowen 醫療保健會議。接下來的一周將前往邁阿密參加巴克萊醫療保健會議。如果您有興趣在這些活動中親自與我們聯繫，請與我們聯繫。祝您有美好的一天，我們期待三月與您相見。

This concludes today's conference call. Thank you for participating. You may all disconnect. Have a nice day.

今天的電話會議到此結束。感謝您的參與。你們都可以斷開連線。祝你今天過得愉快。