Iovance Biotherapeutics Inc (IOVA) 2024 Q1 法說會逐字稿

Welcome to the Iovance Biotherapeutics conference call to discuss first-quarter 2024 results and recent corporate updates. My name is Livia, and I'll be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Iovance Biotherapeutics 電話會議，討論 2024 年第一季業績和最近的公司動態。我叫 Livia，我將擔任您今天通話的接線生。（操作員說明）請注意，本次會議正在錄製中。

I will now hand the conference call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.

我現在將電話會議交給 Iovance 投資者關係和企業傳播部高級副總裁 Sara Pellegrino。薩拉，你可以開始了。

Thank you, operator. Good afternoon and thank you for joining this conference call and webcast to discuss our first-quarter 2024 results and recent corporate update.

謝謝你，接線生。下午好，感謝您參加本次電話會議和網路廣播，討論我們 2024 年第一季的業績和最近的公司動態。

Dr. Fred Vogt, our Interim President and Chief Executive Officer, will provide an introduction and summarize key updates on our US commercial launch of Amtagvi and our pipeline program. Jim Ziegler, EVP Commercial, will highlight our initial insights for the US commercial launch of Amtagvi in advanced melanoma. Dr. Igor Bilinsky, COO, will highlight commercial manufacturing and capacity expansion plans.

我們的臨時總裁兼執行長 Fred Vogt 博士將介紹並總結我們在美國商業推出 Amtagvi 和我們的管道計劃的關鍵更新。商業執行副總裁 Jim Ziegler 將重點介紹我們對 Amtagvi 在美國商業上市治療晚期黑色素瘤的初步見解。首席營運長 Igor Bilinsky 博士將重點介紹商業製造和產能擴張計劃。

Jean-Marc Bellemin, CFO will review our financial results. And Dr. Friedrich Finckenstein, Chief Medical Officer, will review key pipeline update including upcoming clinical data presentations at ASCO and new next-generation approaches. Dr. Brian Gastman, Executive Vice President, Medical Affairs; and Dr. Raj Puri, Executive Vice President, Regulatory Strategy, are also on the call and available for the Q&A session.

財務長 Jean-Marc Bellemin 將審查我們的財務表現。首席醫療官 Friedrich Finckenstein 博士將審查關鍵的產品線更新，包括即將在 ASCO 上發布的臨床數據和新的下一代方法。Brian Gastman 博士，醫療事務執行副總裁；監管策略執行副總裁 Raj Puri 博士也將參加電話會議並參加問答環節。

Earlier this afternoon, we issued a press release that can be found on our corporate website at iovance.com. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaboration, cash position and expense guidance, and future updates.

今天下午早些時候，我們發布了一份新聞稿，您可以在我們的公司網站 iovance.com 上找到該新聞稿。在我們開始之前，我想提醒大家，本次電話會議期間發表的聲明將包括有關Iovance 的目標、業務重點、業務計劃和交易、收入、商業活動、臨床試驗和結果、監管批准和互動的前瞻性聲明，計劃和策略、研究和臨床前活動、我們技術的潛在未來應用、製造能力、監管反饋和指導、付款人互動、許可和協作、現金狀況和費用指導以及未來更新。

Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements.

前瞻性陳述受到許多風險和不確定性的影響，其中許多風險和不確定性超出了我們的控制範圍，包括我們在 SEC 文件中不時描述的風險和不確定性。我們的結果可能與今天電話會議期間預測的結果有重大差異。我們不承擔公開更新任何前瞻性聲明的義務。

With that, I will turn the call over to Fred.

這樣，我會將電話轉給弗雷德。

Thank you, Sara, and good afternoon, everyone. I'm pleased to host our first-quarter 2024 results conference call.

謝謝薩拉，大家下午好。我很高興主持我們 2024 年第一季業績電話會議。

This has been a decisive year for Iovance following our first FDA approval and strong start to the US launch of Amtagvi for patients with advanced melanoma. We expect the positive momentum at Iovance will continue to build throughout 2024 as we ramp up the US launch and execute across our broad clinical pipeline.

繼我們首次獲得 FDA 批准以及在美國推出治療晚期黑色素瘤患者的 Amtagvi 後，今年對 Iovance 來說是決定性的一年。我們預計，隨著我們加強在美國的上市力度並在廣泛的臨床管道中執行，Iovance 的積極勢頭將在 2024 年繼續增強。

To begin, we are very pleased that the high initial demand for Amtagvi continues to accelerate. Demand has increased month over month since approval and expected to grow further throughout the year. As of today, more than 100 patients are already enrolled for Amtagvi therapy and most are expected to be ready for infusion across the second and early third quarters of 2024. In addition, more than 60 additional patients have been identified at ATCs and are expected to enroll soon.

首先，我們非常高興地看到對 Amtagvi 的高初始需求持續加速。自批准以來，需求逐月增加，預計全年將進一步成長。截至目前，已有 100 多名患者登記接受 Amtagvi 治療，預計大多數患者將在 2024 年第二季和第三季初準備好接受輸注。此外，ATC 還確定了另外 60 多名患者，預計很快就會入組。

As existing and new ATCs continue to build experience, we expect patient enrollments to steadily increase throughout the year, supporting our expectations for sustained growth. As we anticipated, interest is very high on ATCs and they are demonstrating that they have the training, infrastructure, and capabilities to treat patients with the Amtagvi, which Jim will further highlight. We remain on track to have 50 total ATCs by the end of this month. We also set a new goal of at least 70 ATCs by the end of this year, representing the largest ever number of ATCs for a cell therapy launch.

隨著現有和新的 ATC 不斷累積經驗，我們預計全年病患入院人數將穩定增加，支持我們對持續成長的預期。正如我們預期的那樣，人們對 ATC 的興趣非常濃厚，他們正在證明自己擁有使用 Amtagvi 治療患者的培訓、基礎設施和能力，Jim 將進一步強調這一點。到本月底，我們仍有望擁有 50 個 ATC。我們還設定了今年年底至少 70 個 ATC 的新目標，這是細胞療法推出以來 ATC 數量最多的一次。

We are pleased to see positive reimbursement trends, which is a key indicator for success and adoption. Positive reimbursement decisions are supported by our clinical data and the recent addition of Amtagvi as the preferred second line or subsequent therapy in the National Comprehensive Cancer Network or NCCN guidelines. The time to treatment will accelerate as ATC has established a solid foundation for broad market access and reimbursement which will add to momentum. Jim will describe this in more detail.

我們很高興看到積極的報銷趨勢，這是成功和採用的關鍵指標。我們的臨床數據以及最近在國家綜合癌症網絡或 NCCN 指南中將 Amtagvi 添加為首選二線或後續治療方法都支持積極的報銷決定。隨著 ATC 為廣泛的市場准入和報銷奠定了堅實的基礎，治療時間將會加快，這將增加動力。吉姆將更詳細地描述這一點。

In terms of commercial manufacturing, we have two FDA approved manufacturing sites and sufficient capacity to meet near-term demand at launch setting a new bar for cell therapy launches. Our commercial manufacturing experience is very positive and is consistent with our prior clinical experience. We have successfully manufactured and delivered Amtagvi within our target turnaround time of 34 days. ATC has observed sufficient availability of manufacturing slots and reported positive experience in the scheduling process, which is critical for broader utilization. We expect to have ample capacity to meet the anticipated ramp up in demand this year.

在商業生產方面，我們擁有兩個 FDA 批准的生產基地，並且有足夠的能力滿足近期的上市需求，為細胞療法的上市樹立了新的標準。我們的商業製造經驗非常積極，並且與我們先前的臨床經驗一致。我們已在 34 天的目標週轉時間內成功製造並交付了 Amtagvi。ATC 觀察到製造時段有足夠的可用性，並報告了調度過程中的正面經驗，這對於更廣泛的利用至關重要。我們預計將有足夠的產能來滿足今年預期的需求成長。

Finally, long-term expansions are underway to more than double our currently built capacity for future growth. In addition to the US launch, we are working to enter new markets that can more than double the total addressable advanced melanoma patient population for Amtagvi. Regulatory submissions remain on track this year in the EU, UK, and Canada where we have the potential to begin driving significant additional revenue by the end of 2025.

最後，我們正在進行長期擴張，以使我們目前的產能增加一倍以上，以實現未來的成長。除了在美國上市之外，我們還致力於進入新市場，使 Amtagvi 可尋址的晚期黑色素瘤患者總數增加一倍以上。今年，歐盟、英國和加拿大的監管提交工作仍在順利進行，我們有可能在 2025 年底前開始在這些地區帶來大量額外收入。

We also continue to advance and expand our robust and exciting pipeline, including two registrational programs as well as new next-generation approaches that Friedrich will highlight on this call. As a fully integrated company is executing the US launch and developing a broad pipeline, Iovance is well positioned to remain a global leader in innovating, developing, and delivering TIL Cell Therapy for patients with cancer.

我們也繼續推動和擴大我們強大而令人興奮的管道，包括兩個註冊計劃以及弗里德里希將在本次電話會議上強調的新的下一代方法。作為一家全面整合的公司，Iovance 正在美國進行上市並開發廣泛的產品線，因此 Iovance 處於有利地位，能夠在為癌症患者創新、開發和提供 TIL 細胞療法方面保持全球領先地位。

I'll now hand over to Jim, our Executive Vice President of Commercial who will speak in more detail about our launch metrics.

現在我將把工作交給我們的商務執行副總裁 Jim，他將更詳細地介紹我們的發布指標。

Thank you, Fred. We are excited about the potential for Amtagvi to transform the treatment paradigm in advanced melanoma. My objectives today are to highlight initial US launch metrics, which are supported by robust demand among ATCs and patients as well as progress with payers.

謝謝你，弗雷德。我們對 Amtagvi 改變晚期黑色素瘤治療模式的潛力感到興奮。我今天的目標是強調美國的初始啟動指標，這些指標得到了 ATC 和患者的強勁需求以及付款人的進展的支持。

ATCs are the key driver of demand and patient enrollments for Amtagvi. Launching with 30 ATCs was a testament to the significant unmet need in advanced melanoma and each center's high level of commitment to offer Amtagvi for their patients. Today, there are more than 40 ATCs and we remain on track to meet our goal of 50 total ATCs by the end of May. Due to increasing interest by hospitals that offer Amtagvi, we are now targeting at least 70 total ATCs by the end of the year.

ATC 是 Amtagvi 需求和患者註冊的主要驅動力。30 個 ATC 的啟動證明了晚期黑色素瘤的重大未滿足需求，以及每個中心為患者提供 Amtagvi 的高度承諾。目前，ATC 總數已超過 40 個，我們仍有望在 5 月底前實現 ATC 總數達到 50 個的目標。由於提供 Amtagvi 的醫院越來越感興趣，我們現在的目標是到今年年底至少擁有 70 個 ATC。

As Fred mentioned earlier, ATCs have enrolled more than 100 patients for Amtagvi treatment. A patient enrollment is defined as an Amtagvi treatment decision by the provider and patient. The patient enrollment is followed by commercial payer, prior authorization and a scheduled tumor procurement for manufacturing. Based on the patient journey timeline Amtagvi infusion for currently enrolled patients would likely occur across the second quarter and early third quarter.

正如 Fred 之前提到的，ATC 已招募了 100 多名患者接受 Amtagvi 治療。病患登記被定義為提供者和病患共同做出的 Amtagvi 治療決定。病患登記之後是商業付款、事先授權和預定的腫瘤採購用於製造。根據患者旅程時間表，目前入組患者的 Amtagvi 輸注可能會在第二季和第三季初進行。

In addition, existing ATCs are screening an increasing number of patients for treatment eligibility. With more than 60 patients currently in screening today, we expect a high conversion of additional patients to Amtagvi patient enrollment in the near-term for potential infusion in the third quarter. We are observing month over month growth and we anticipate sustained growth throughout the year as the number of ATCs expand and there is broader utilization of Amtagvi.

此外，現有的 ATC 正在對越來越多的患者進行治療資格篩檢。目前有超過 60 名患者正在接受篩檢，我們預計近期將有大量患者轉入 Amtagvi 患者登記，以便在第三季度進行可能的輸注。我們正在觀察逐月的成長，隨著 ATC 數量的增加以及 Amtagvi 的使用範圍的擴大，我們預計全年將持續成長。

In the short time since approval, favorable reimbursement trends and medical coverage policies have set us up for success and broad access for patients. Early launch data indicates that more than 75% of patients enrolled for Amtagvi are commercially insured which aligns with our expectations.

在獲得批准後的短時間內，有利的報銷趨勢和醫療保險政策為我們取得了成功並為患者提供了廣泛的服務。早期發布數據表明，超過 75% 的參加 Amtagvi 的患者擁有商業保險，這與我們的預期相符。

Thus far payers responsible for more than 200 million lives have approved at least one patient for Amtagvi treatment and notably 13 payers responsible for approximately 90 million covered lives have already published medical coverage policies that are consistent with label, clinical trials and the recently updated NCCN guidelines. We expect the remaining payers to issue similar favorable medical coverage policies and that timelines for financial clearance will accelerate as more payers, issue coverage policies.

迄今為止，負責超過2 億生命的付款人已批准至少一名患者接受Amtagvi 治療，尤其是負責約9,000 萬受保生命的13 個付款人已經發布了與標籤、臨床試驗和最近更新的NCCN 指南一致的醫療保險單。我們預計剩餘的付款人將發布類似的優惠醫療保險政策，並且隨著更多的付款人發布保險政策，財務清算的時間表將會加快。

In summary, we are extremely pleased with the early launch progress, and we expect steady growth as ATCs gain treatment experience, our ATC network expands and community referrals increase over time. I look forward to providing future updates on these important ATC reimbursement and performance metrics.

總之，我們對早期啟動進展感到非常滿意，隨著 ATC 獲得治療經驗、我們的 ATC 網路擴大以及社區轉診量的增加，我們預計會穩定成長。我期待著提供這些重要的 ATC 報銷和績效指標的最新更新。

I would like to acknowledge the very talented cross functional teamwork at Iovance. I'm even more pleased in the deep partnerships our team has established with ATCs. Collectively, our goal is to broaden and accelerate patient access to Amtagvi.

我要感謝 Iovance 非常有才華的跨職能團隊合作。更令我高興的是我們的團隊與 ATC 建立了深厚的合作關係。總的來說，我們的目標是擴大並加快患者獲得 Amtagvi 的機會。

I will now pass the call to Igor Bilinsky, our Chief Operating Officer, to highlight our manufacturing progress.

現在，我將致電我們的營運長伊戈爾·比林斯基 (Igor Bilinsky)，強調我們的製造進度。

Thank you, Jim. Today, I'd like to highlight our current manufacturing capabilities, experience with the Amtagvi US launch, as well as our capacity expansion plans to support significant further growth in demand that we anticipate in the US from geographic expansion and from our exciting clinical pipeline.

謝謝你，吉姆。今天，我想重點介紹一下我們目前的製造能力、Amtagvi 在美國上市的經驗，以及我們的產能擴張計劃，以支持我們預計美國因地域擴張和令人興奮的臨床管道而帶來的需求的進一步大幅增長。

Manufacturing is a core competency for us at Iovance and we built our own manufacturing facility, Iovance Cell Therapy Center or ICTC in Philadelphia. ICTC is one of the largest cell therapy manufacturing facilities in the world and the only one specifically designed for TIL manufacturing.

製造是我們 Iovance 的核心競爭力，我們在費城建立了自己的製造工廠，Iovance 細胞治療中心或 ICTC。ICTC 是世界上最大的細胞療法製造工廠之一，也是唯一專門為 TIL 製造而設計的工廠。

ICTC is now FDA approved for commercial manufacturing of Amtagvi for the US market and continues to serve patients in our clinical trials in melanoma, lung cancer and other indications in the US, Europe, Australia and other geographies. ICTC has been responsible for most of the commercial and tagging manufacturing volume to date.

ICTC 現已獲得 FDA 批准，可以在美國市場商業化生產 Amtagvi，並繼續為美國、歐洲、澳洲和其他地區的黑色素瘤、肺癌和其他適應症的臨床試驗中的患者提供服務。迄今為止，ICTC 負責大部分商業和標籤製造量。

In addition to ICTC, the FDA approved our contract manufacturer site for commercial manufacturing of Amtagvi. Having two approved facilities provides us with additional flexibility and capacity for both commercial and clinical patients.

除了 ICTC 之外，FDA 還批准了我們的合約製造商工廠用於 Amtagvi 的商業生產。擁有兩個經批准的設施為我們為商業和臨床患者提供了額外的靈活性和能力。

Overall, we believe that our manufacturing capabilities and capacity are setting a new bar for cell therapy launches and we're strategically planning ahead for anticipated demand in future. Turning to our early experience with commercial launch, we're executing as planned. The commercial manufacturing experience to date is consistent with prior clinical experience.

總體而言，我們相信我們的製造能力和產能正在為細胞療法的推出樹立新的標準，我們正在針對未來的預期需求進行策略規劃。談到我們早期商業發布的經驗，我們正在按計劃執行。迄今為止的商業製造經驗與先前的臨床經驗一致。

Turnaround time has been on target with initial launch expectations of approximately 34 days from receipt of tumor tissue to return shipment of Amtagvi to the ATC, which is then followed by lymphodepletion and infusion. We are confident in our capacity to meet the current and projected demands of the US launch in our clinical trials, as well as to support Iovance's planned future growth.

週轉時間已達到目標，最初的上市預期從收到腫瘤組織到將 Amtagvi 返回到 ATC，然後進行淋巴清除和輸注，大約需要 34 天。我們有信心有能力滿足美國臨床試驗的當前和預計需求，並支持 Iovance 計劃的未來成長。

ICTC as built today has the capacity to provide TIL therapies for more than 2,000 patients per year. A competent manufacturing team is important in biotech and cell therapy in particular. Right now, we are staffed appropriately for launch, and we are continuing to add headcounts to meet the demand for commercial Amtagvi as well as for our clinical trials.

目前建成的 ICTC 每年有能力為 2,000 多名患者提供 TIL 治療。一個有能力的製造團隊在生物技術和細胞治療領域尤其重要。目前，我們已配備了適當的啟動人員，並且我們正在繼續增加人員數量，以滿足商業 Amtagvi 以及臨床試驗的需求。

To fulfill our staffing needs, the ICTC Philadelphia location provides access to talent with cell therapy and gene therapy experience at other companies in the region, as well as the next generation of talent through the local schools and resources. In preparation for increasing commercial demand in the US and additional geographies and in support of our advancing clinical pipeline, further capacity expansion is now underway at ICTC and is expected to be completed in a few years.

為了滿足我們的人員需求，ICTC 費城辦事處為該地區其他公司提供具有細胞療法和基因療法經驗的人才，並透過當地學校和資源提供下一代人才。為了滿足美國和其他地區不斷增長的商業需求並支持我們不斷推進的臨床產品線，ICTC 正在進行進一步的產能擴張，預計將在幾年內完成。

Building out the existing shelf space of the facility is expected to enable ICTC to supply TIL therapies for more than 5,000 patients annually. Longer term, our vision is to supply TIL for over 10,000 patients annually from the ICTC accounts. We have an option to construct another building of the ICTC campus and plan to drive additional efficiencies by incorporating increased automation in our manufacturing process.

擴建該設施的現有貨架空間預計將使 ICTC 每年能夠為 5,000 多名患者提供 TIL 療法。從長遠來看，我們的願景是每年透過 ICTC 帳戶為 10,000 多名患者提供 TIL。我們可以選擇在 ICTC 園區建造另一棟大樓，並計劃透過在製造過程中提高自動化程度來提高效率。

In summary, our team is excited to provide Amtagvi and our investigational TIL therapies for patients with cancer. We are laser focused on the quality of the manufacturing process in the spirit of doing everything right first time at every step from incoming receipt of tumor sample, through manufacturing and product release, to outbound shipment of Amtagvi, to the commercial ATCs and investigational tools to clinical trial sites.

總之，我們的團隊很高興為癌症患者提供 Amtagvi 和我們的研究性 TIL 療法。我們高度關注製造過程的質量，本著從接收腫瘤樣本到製造和產品放行，到 Amtagvi 的出境運輸，到商業 ATC 和研究工具，每一步都第一次把每件事都做好的精神，臨床試驗地點。

I'm available to answer additional questions during the Q&A. And I will now hand the call over to Jean-Marc, our Chief Financial Officer.

我可以在問答期間回答其他問題。我現在將把電話轉交給我們的財務長讓-馬克。

Thank you, Igor. Today, I will review our current cash position as well as our results for the quarter ended on March 31, 2024. I will also highlight our 2024 outlook.

謝謝你，伊戈爾。今天，我將回顧我們目前的現金狀況以及截至 2024 年 3 月 31 日的季度業績。我也會強調我們的 2024 年展望。

As of March 31, 2024, Iovance had cash, cash equivalents, investments, and restricted cash of approximately $362.6 million. The current cash position and anticipated revenue from Amtagvi and Proleukin are expected to be sufficient to fund current and planned operation well into the second half of 2025.

截至 2024 年 3 月 31 日，Iovance 擁有現金、現金等價物、投資和限制性現金約 3.626 億美元。Amtagvi 和 Proleukin 目前的現金狀況和預期收入預計將足以為 2025 年下半年當前和計劃的運營提供資金。

Shifting to our first quarter financial results. Net loss for the first quarter ended March 31, 2024, was $113 million or $0.42 per share, compared to a net loss of $107.4 million or $0.50 per share for the first quarter ended March 31, 2023. The net loss for the first quarter of 2024 includes amortization of intangible assets acquired as part of the Proleukin transaction.

轉向我們第一季的財務表現。截至2024年3月31日的第一季淨虧損為1.13億美元，即每股0.42美元，而截至2023年3月31日的第一季淨虧損為1.074億美元，即每股0.50美元。2024 年第一季的淨虧損包括作為 Proleukin 交易一部分而收購的無形資產的攤銷。

Revenue for the first quarter ended March 31, 2024, was $715,000 and comprised of sales of Proleukin in licensed market outside of the US. Cost of sales for the first quarter ended March 31, 2024, was $7.3 million primarily related to inventoriable cost associated with sales of Proleukin and non-cash amortization expense for the acquired intangible asset for developed technology. There was no revenue or cost of sales in the first quarter ended March 31, 2023.

截至 2024 年 3 月 31 日的第一季營收為 71.5 萬美元，包括 Proleukin 在美國以外授權市場的銷售額。截至 2024 年 3 月 31 日的第一季銷售成本為 730 萬美元，主要與 Proleukin 銷售相關的庫存成本以及為開發技術而收購的無形資產的非現金攤銷費用有關。截至 2023 年 3 月 31 日的第一季沒有收入或銷售成本。

Research and development expenses were $79.8 million for the first quarter ended March 31, 2024, a decrease of $2.9 million compared to $82.7 million for the same period ended March 31, 2023. The decrease was primarily attributable to the transition to commercial Amtagvi remanufacturing in the most recent quarter, partially offset by increased cost associated with the purchase of raw materials, clinical trials driven primarily by the Phase 3 TILVANCE-301 clinical trial and the planned EU regulatory submissions for lifileucel.

截至2024年3月31日止第一季的研發費用為7,980萬美元，較截至2023年3月31日止同期的8,270萬美元減少290萬美元。這一下降主要歸因於最近一個季度向商業 Amtagvi 再製造的過渡，但部分被與採購原材料、主要由 3 期 TILVANCE-301 臨床試驗驅動的臨床試驗和計劃的歐盟監管提交相關的成本增加所抵消對於lifileucel。

Selling, general and administrative expenses were $31.4 million for the first quarter ended March 31, 2024, an increase of $3.3 million compared to $28.1 million for the same period ended March 31, 2023. The increase was primarily attributable to increases in headcount and related costs, including stock-based compensation to support the growth in their whole business and related corporate infrastructure as well as cost incurred to support the commercialization of Amtagvi and Proleukin, partially offset by a decrease in legal costs.

截至2024年3月31日的第一季度，銷售、一般及管理費用為3,140萬美元，較截至2023年3月31日的同期的2,810萬美元增加了330萬美元。這一增長主要歸因於員工人數和相關成本的增加，包括支持整個業務和相關企業基礎設施增長的股票薪酬以及支持 Amtagvi 和 Proleukin 商業化所產生的成本，但部分被法律費用。

Regarding our outlook for this year, we continue to guide towards full year 2024 cash burn in the range of $320 million to $340 million, excluding onetime expenses, and we'll continue to leverage opportunities to optimize spending. The US launch of Amtagvi, as well as the sales of Proleukin used in conjunction with the Amtagvi treatment regimen, are expected to drive significant revenue in the second half of 2024 and into 2025 and beyond.

關於今年的展望，我們繼續指導 2024 年全年現金消耗在 3.2 億至 3.4 億美元之間，不包括一次性費用，我們將繼續利用機會優化支出。Amtagvi 在美國的上市，以及與 Amtagvi 治療方案結合使用的 Proleukin 的銷售，預計將在 2024 年下半年、2025 年及以後帶來可觀的收入。

As a reminder, revenue recognition for Amtagvi occurs upon infusion, like other cell therapies, so we expect to begin recognizing and reporting significant revenue in the second quarter of this year. For additional information, please see this afternoon's press release and our Form 10-Q to be filed later today.

提醒一下，與其他細胞療法一樣，Amtagvi 的收入確認是在輸注時確認的，因此我們預計將在今年第二季開始確認並報告重大收入。如需了解更多信息，請參閱今天下午的新聞稿以及我們將於今天晚些時候提交的 10-Q 表格。

I will now hand the call to Friedrich, our Chief Medical Officer to discuss our clinical pipeline.

我現在將致電我們的首席醫療官弗里德里希，討論我們的臨床管道。

Thank you, Jean-Marc. I am pleased to speak today about our key clinical pipeline highlights in solid tumors, which as you all know, represent more than 90% of all diagnosed cancers in the US.

謝謝你，讓-馬克。我今天很高興談論我們在實體腫瘤方面的關鍵臨床管線亮點，眾所周知，實體腫瘤占美國所有診斷癌症的 90% 以上。

One of our key priorities is expanding the label for Amtagvi to address the need of patients with advanced melanoma in the frontline treatment setting. Our registrational Phase 3 trial, TILVANCE-301, is well underway and on track to support accelerated and full approvals of Amtagvi in combination with pembrolizumab in frontline advanced melanoma as well as regular approval of Amtagvi in post anti-PD-1 melanoma.

我們的首要任務之一是擴大 Amtagvi 的標籤，以滿足第一線治療中晚期黑色素瘤患者的需求。我們的註冊 3 期試驗 TILVANCE-301 正在順利進行，並有望支持 Amtagvi 與 pembrolizumab 聯合治療一線晚期黑色素瘤的加速和全面批准，以及 Amtagvi 在抗 PD-1 後黑色素瘤治療中的定期批准。

Global site activation and patient enrollment continue with strong momentum in the US, Europe, Australia, Canada, and additional countries. Our frontline advanced melanoma strategy is supported by Cohort 1A in our IOV-COM-202 trial in solid tumors and previously published data on TIL therapy in the pre-immune checkpoint inhibitor era.

全球站點啟動和患者登記在美國、歐洲、澳洲、加拿大和其他國家繼續保持強勁勢頭。我們的第一線先進黑色素瘤策略得到了 IOV-COM-202 實體瘤試驗中的隊列 1A 以及先前發布的前免疫檢查點抑制劑時代 TIL 治療數據的支持。

We look forward to an oral presentation of updated clinical data from Cohort 1A, which continue to strongly support our frontline development plans at the American Society of Clinical Oncology or ASCO Annual Meeting on May 31, 2024.

我們期待在 2024 年 5 月 31 日舉行的美國臨床腫瘤學會或 ASCO 年會上口頭介紹 1A 組的最新臨床數據，這些數據將繼續有力支持我們的一線開發計劃。

Shifting to our program in non-small cell lung cancer, we reported positive updates for our single arm registrational Phase 2 trial, IOV-LUN-202 in post anti-PD-1 non-small cell lung cancer. We resumed enrollment for new patients within a very short time after the US FDA lifted our partial clinical trial hold in the first quarter.

轉向我們的非小細胞肺癌項目，我們報告了 PD-1 後非小細胞肺癌的單臂註冊 2 期試驗 IOV-LUN-202 的積極更新。在美國 FDA 第一季取消部分臨床試驗後，我們在很短的時間內恢復了新患者的入組。

IOV-LUN-202 includes clinical sites in the US, Canada, and Europe with plans to include additional regions with strong track record for enrollment in lung cancer studies over the next few months. Enrollment has restarted with high demand, which is driven by encouraging data and further augmented by excitement from the approval of Amtagvi. We expect the registrational cohorts to be fully enrolled in 2025.

IOV-LUN-202 包括美國、加拿大和歐洲的臨床中心，並計劃在未來幾個月內將肺癌研究入組記錄良好的其他地區納入其中。受令人鼓舞的數據推動，並因 Amtagvi 獲得批准而進一步興奮，報名已重新啟動，需求旺盛。我們預計註冊隊列將於 2025 年全部註冊。

Current data from IOV-LUN-202 and the FDA interactions regarding our regulatory pathway continue to be positive and support our confidence in the opportunity for TIL cell therapy in lung cancer. The FDA has provided positive regulatory feedback on the proposed potency matrix for lifileucel in non-small cell lung cancer during a recent Type D meeting and as previously announced that the design of the single-arm IOV-LUN-202 trial may be acceptable for approval of lifileucel in post-anti-PD-1 non-small cell lung cancer.

IOV-LUN-202 的當前數據和 FDA 關於我們的監管途徑的相互作用繼續是積極的，並支持我們對肺癌 TIL 細胞治療機會的信心。FDA 在最近的 D 型會議上對 lifileucel 在非小細胞肺癌中的擬議效力矩陣提供了積極的監管反饋，並且正如之前宣布的那樣，單臂 IOV-LUN-202 試驗的設計可能可以接受批准lifileucel在抗PD-1 後非小細胞肺癌中的作用。

In other tumor types, we are starting a Phase 2 trial of lifileucel in post-anti-PD-1 endometrial cancer, which is a significant opportunity for TIL cell therapy. Our Phase 2 trial will include patients with advanced endometrial cancer, who progress after platinum-based chemotherapy and anti-PD-1 therapy, regardless of mismatch repair status of the tumor. Our rationale is supported by the TIL mechanism of action, which may benefit both patient populations, as well as preclinical and manufacturing success data that we plan to report later this year.

在其他腫瘤類型中，我們正在啟動 lifileucel 治療 PD-1 後子宮內膜癌的 2 期試驗，這是 TIL 細胞療法的一個重要機會。我們的 2 期試驗將包括晚期子宮內膜癌患者，無論腫瘤的錯配修復狀態如何，這些患者在鉑類化療和抗 PD-1 治療後出現進展。我們的理由得到了 TIL 作用機制的支持，該機制可能使患者群體受益，以及我們計劃在今年稍後報告的臨床前和生產成功數據。

There is a significant unmet medical need and no currently approved treatment options for the vast majority of patients with endometrial cancer in the post-anti-PD-1 treatment setting. Given this unmet medical need and the enthusiasm we've received from gynecological oncologists, we expect to enroll quickly and we look forward to seeing first data soon.

對於接受抗 PD-1 治療後的絕大多數子宮內膜癌患者來說，存在顯著的未滿足的醫療需求，目前沒有批准的治療方案。鑑於這種未滿足的醫療需求以及我們從婦科腫瘤學家那裡得到的熱情，我們預計會迅速註冊，並期待很快看到第一批數據。

As the leader in TIL cell therapy, Iovance is at the forefront of next generation approaches that have the potential to address unmet need for patients and solidify our long-term leadership in the space. We reached an important milestone for our genetically modified TIL cell therapy, IOV-4001, in the first-in-human GM1-201 trial in previously treated advanced melanoma or non-small cell lung cancer patients.

作為 TIL 細胞療法的領導者，Iovance 處於下一代方法的前沿，這些方法有潛力解決患者未滿足的需求，並鞏固我們在該領域的長期領導地位。在針對先前接受過治療的晚期黑色素瘤或非小細胞肺癌患者的首次人體 GM1-201 試驗中，我們的基因改造 TIL 細胞療法 IOV-4001 達到了一個重要的里程碑。

The Phase 1 safety portion concluded successfully and we are progressing into the multicenter Phase 2 efficacy stage of the trial. IOV-4001 utilizes the TALEN technology license from Cellectis to inactivate PD-1 during the TIL manufacturing process. We also have options to continue to develop other investigational gene edited TIL cell therapies with multiple knockout targets to potentially improve efficacy.

第一階段安全部分成功結束，我們正進入多中心第二階段療效試驗階段。IOV-4001 利用 Cellectis 的 TALEN 技術許可在 TIL 製造過程中滅活 PD-1。我們也可以選擇繼續開發其他具有多個敲除標靶的研究性基因編輯 TIL 細胞療法，以潛在提高療效。

We are also making great strides to advance additional next-generation programs towards the clinic. In the third quarter of 2024, we plan to submit an investigational new drug application or IND for a Phase 1/2 clinical trial of IOV-3001, a modified interleukin-2 or IL-2 fusion protein. At ASCO 2024, a poster will highlight preclinical data that supports the potential for improved safety with robust defector T cell expansion with IOV-3001.

我們也正在向臨床推進更多下一代計畫方面取得了長足進步。2024年第三季度，我們計劃提交IOV-3001（一種修飾的白細胞介素2或IL-2融合蛋白）的1/2期臨床試驗的研究性新藥申請或IND。在 ASCO 2024 上，一張海報將重點介紹臨床前數據，這些數據支持使用 IOV-3001 進行強大的叛逃 T 細胞擴增來提高安全性的潛力。

Lastly, on today's call, we are introducing IOV-5001, a new next-generation program. IOV-5001 is a genetically engineered TIL cell therapy with inducible and tethered IL-12. The addition of IL-12 has augmented TIL antitumor activity in vitro. IOV-5001 also builds on the improved efficacy of a prior generation IL-12 TIL therapy that was observed in a clinical trial at the National Cancer Institute or NCI.

最後，在今天的電話會議上，我們將介紹 IOV-5001，一個新的下一代計畫。IOV-5001 是一種基因工程 TIL 細胞療法，具有誘導型和束縛性 IL-12。添加 IL-12 增強了 TIL 的體外抗腫瘤活性。IOV-5001 也建立在美國國家癌症研究所 (NCI) 的臨床試驗中觀察到的上一代 IL-12 TIL 療法的改善療效的基礎上。

IOV-5001 is currently in IND enabling studies. We plan to discuss IOV-5001 with the FDA at an INTERACT meeting in the third quarter of 2024 and anticipate an IND submission in early 2025. I'm happy to address questions about these programs and additional trials during the Q&A session.

IOV-5001 目前正在進行 IND 啟用研究。我們計劃在 2024 年第三季的 INTERACT 會議上與 FDA 討論 IOV-5001，並預計在 2025 年初提交 IND。我很高興在問答環節中解答有關這些計劃和其他試驗的問題。

I'll now turn the call over to the operator to begin the question-and-answer session.

我現在將把電話轉給接線員以開始問答環節。

(Operator Instructions) Michael Yee, Jefferies.

（操作員說明）Michael Yee，Jefferies。

We have maybe a two-part question. You gave some really great metrics around the indications of interest in the enrollment numbers. Can you maybe just describe sort of the journey of time from enrolling and then getting reimbursed and then I think sort of the 34 days to then inbound to get treated?

我們的問題可能分為兩部分。您針對註冊人數的興趣指標提供了一些非常好的指標。您能否描述一下從註冊到獲得報銷，然後我認為是 34 天到入境接受治療的時間歷程？

I'm just trying to think about how many of the 100 people who've enrolled are likely to get treated in this quarter and thinking about the consensus number and then thinking about how many of those would get treated in the third quarter? Maybe just talk a little bit about the journey and how you think about those 100 patients getting treated? Thank you.

我只是想想想，在本季度註冊的 100 名患者中有多少人可能會得到治療，並考慮共識數字，然後考慮其中有多少人會在第三季度得到治療？也許只是談談這段旅程以及您對這 100 名接受治療的患者有何看法？謝謝。

Yes, I can give you a little color on that. So the patients right now that are being enrolled right now could be, in theory, treated in the second quarter or, so when I say treated I mean infused revenue recognized in the second quarter or early in the third quarter.

是的，我可以給你一點顏色。因此，理論上，現在正在登記的患者可以在第二季度接受治療，或者，所以當我說治療時，我指的是第二季或第三季初確認的注入收入。

That's because as we mentioned it takes some time to do the financial clearance of the patients that come in and then they get resected and then there is a target right now which we're meeting of 34 days from the time we start manufacturing all the way through to completing the quality control testing and then the patient is lymphodepleted and infused after that. It's a little different than the clinical trial.

這是因為正如我們所提到的，需要一些時間來對進來的患者進行財務清算，然後對他們進行切除，然後我們現在有一個目標，即從我們開始生產之日起 34 天的目標直到完成品質控制測試，然後對患者進行淋巴清除並輸注。這與臨床試驗略有不同。

The clinical trial will move faster because the patients who are on bridging therapy, in many cases now they are on bridging therapy and we have to do it this way with the commercial product.

臨床試驗將進展得更快，因為正在接受橋接治療的患者，在許多情況下他們現在正在接受橋接治療，我們必須對商業產品這樣做。

So just to be clear, patients have been treated in April and then some of those patients, as you are going through it, would be treated in May and June as part of those 100?

需要明確的是，患者已在 4 月接受治療，然後其中一些患者（正如您正在經歷的那樣）將作為這 100 名患者的一部分在 5 月和 6 月接受治療？

Correct. And July and so on.

正確的。還有七月等等。

Okay. Got it. Thank you.

好的。知道了。謝謝。

Andrea Tan, Goldman Sachs.

安德里亞·譚，高盛。

Maybe a follow-up there. Just wondering if you're able to provide some numbers around those comments. Just of the 100 plus that have been enrolled, how many specifically have had their tumor resected thus far and how many have received an infusion?

也許會有後續行動。只是想知道您是否能夠提供有關這些評論的一些數字。僅在已登記的 100 多名患者中，到目前為止，具體有多少人已經切除了腫瘤，有多少人接受了輸液？

We can't give you the detail, otherwise you would actually have revenues at that point, but what we can tell you is that right now many of those patients have resected. We're moving through the process with them. I want to stress the importance of the patients that enrolled. Some of them will be infused.

我們無法向您提供詳細信息，否則您那時實際上會有收入，但我們可以告訴您的是，現在許多患者已經進行了切除。我們正在與他們一起完成整個過程。我想強調入組患者的重要性。其中一些將被注入。

Obviously, over that large time period that we just mentioned with Mike's question. We also have a few dropouts in OS stuff like that to account for as well. So it's very difficult for us to predict all that stuff. When we finally report revenues, we'll be able to say a little bit more about how that actually played out in the transition from enrolled numbers to revenues.

顯然，在我們剛剛提到的麥克問題中的很長一段時間內。我們還需要考慮一些作業系統方面的問題。所以我們很難預測所有這些事情。當我們最終報告收入時，我們將能夠更多地說明從註冊人數到收入的轉變過程中實際發生的情況。

Got it. And the nature of the dropout, if you're able to share a little bit more there?

知道了。輟學的本質是什麼，可以分享一下嗎？

Most of the time, the dropouts are caused by patient health issues and sadly some of the patients pass away while waiting for therapy and we've actually had that happen. It's an unfortunate consequence of the disease stage these patients are in.

大多數時候，輟學是由患者的健康問題引起的，遺憾的是，有些患者在等待治療時去世，我們實際上已經發生過這種情況。這是這些患者所處疾病階段的不幸後果。

That's usually what the issue is, the patient declines in health and is put on hospice or is test on the way before Amtagvi can be fully manufactured and tested for them. That's the driver of dropout rate for us.

這通常就是問題所在，患者的健康狀況惡化並被送往臨終關懷中心，或在 Amtagvi 完全生產和測試之前接受測試。這就是我們輟學率的驅動因素。

Okay. Thank you.

好的。謝謝。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Fred, just maybe you could provide any some more granularity around the 100 plus patients that have enrolled for TIL therapy, if you could what percentage actually have insurance in place and then the number of ATCs that have actually resected patients? Thank you.

Fred，也許您可以提供有關 100 多名已登記接受 TIL 治療的患者的更多詳細信息，如果您可以的話，實際擁有保險的百分比是多少，然後是實際切除患者的 ATC 數量？謝謝。

Hi, Peter, it's Jim Ziegler here. Virtually all of the 100 plus patients have insurance or have cash, so that's not been an issue right now. And by definition enrolled patient basically means there's the treatment decision followed soon thereby commercial payer prior authorization and the scheduled surgery.

嗨，彼得，我是吉姆·齊格勒。事實上，這 100 多名患者都有保險或有現金，所以現在這不是問題。根據定義，登記的患者基本上意味著很快就會做出治療決定，從而獲得商業付款人的事先授權和預定的手術。

Got you. Thank you. And then the ATCs that have actually resected a patient number?

明白你了。謝謝。那麼實際切除病人的ATC有多少呢？

Yes, we can't tell you exactly that, Peter, right now, but it's a substantial number. Let's call it that. It's increasing daily or at least weekly, and it's getting up to the point where hopefully all or almost all of them will have resected a patient in the not-too-distant future.

是的，彼得，我們現在還不能確切地告訴你這一點，但這是一個很大的數字。我們就這麼稱呼它吧。它每天或至少每週都在增加，並且已經達到了希望所有或幾乎所有的人都能在不遠的將來切除患者的程度。

Thank you. Just final question, you mentioned about cash, what percentage of patients are paying in cash?

謝謝。最後一個問題，您提到了現金，有多少比例的患者用現金付款？

We haven't disclosed that.

我們還沒有透露這一點。

Okay. Thank you so much.

好的。太感謝了。

It's a low number.

這是一個很低的數字。

Tyler Van Buren, TD Cowen.

泰勒·範布倫，TD·考恩。

Congrats on the progress. Shockingly, I have another question regarding the launch. Just regarding the dropouts for enrolled patients that you mentioned, can you discuss what the attrition rate for enrolled patients has looked like so far based upon the dropouts and or manufacturing success? And then, how that attrition rate might differ for patients that are in screening as we think about the 60 patients you mentioned?

祝賀取得的進展。令人震驚的是，我還有一個關於發射的問題。就您所提及的登記病患的退出率而言，您能否根據退出率和/或生產成功情況討論迄今為止登記病患的流失率？然後，當我們考慮您提到的 60 名患者時，對於正在篩檢的患者來說，流失率可能會有何不同？

Yes. Right now, Tyler, it's in line with our expectations. There's been a few dropouts as well as manufacturing aspects, not many and based on our experience we feel like it's playing out the way we had expected. We're only going to get better at this.

是的。現在，泰勒，這符合我們的預期。在製造方面也有一些退出，但不是很多，根據我們的經驗，我們覺得它正在按照我們預期的方式進行。我們只會在這方面做得更好。

The patients that are dropping out sometimes were the ones waiting for Amtagvi therapy and obviously that will be less of an issue as we go forward with the launch here. So I can't give you any quantitative numbers on that right now. Obviously, it's very early for this, but it's in line with what we anticipated and we're able to handle.

有時退出的患者是等待 Amtagvi 治療的患者，顯然，隨著我們在這裡推出該療法，這將不再是一個問題。所以我現在無法給你任何定量的數字。顯然，現在還為時過早，但它符合我們的預期並且我們能夠處理。

Yanan Zhu, Wells Fargo Securities.

朱亞楠，富國銀行證券。

Thanks for taking our questions and congrats on the progress. Just wondering, for dropouts, Fred, could you comment on whether we could look at maybe perhaps clinical trials experience and historically to get a sense of what might be the percentage of patients who couldn't wait for the duration of the manufacturing and perhaps also insurance approval in this case period? And then wondering about how evenly are the, more than 100 enrolled patients are distributed across the 40-plus centers?

感謝您提出我們的問題並祝賀我們的進展。只是想知道，對於輟學者，弗雷德，您能否評論一下我們是否可以看看也許是臨床試驗經驗和歷史記錄，以了解等不及生產持續時間的患者的百分比，也許還可以在這種情況下保險核准嗎？然後想知道 100 多名入組患者分佈在 40 多個中心的分佈如何？

And lastly, I think I heard a comment Jim made about month-over-month growth are still expected going forward in the number of enrolled patients. Just want to make sure, I get the get the right. And, could that, if that's correct, could the increase, other than driven by obviously increased ATCs, could that still be driven in part by increased number of patients from the already enrolled started ATCs? Thanks.

最後，我想我聽到了吉姆關於入組患者數量預計仍將逐月增長的評論。只是想確保我得到了正確的答案。而且，如果這是正確的，那麼除了由 ATC 明顯增加推動之外，這種增長是否仍可能部分由已登記啟動的 ATC 中患者數量的增加推動？謝謝。

Hey, Yanan, the comparison between the dropout rate in the clinical trial and commercial is a little bit different. In a clinical trial we don't have the financial clearance issues, we don't have any of that kind of thing and the patients are basically being raised through the therapy.

嘿，Yanan，臨床試驗和商業中的退出率比較有點不同。在臨床試驗中，我們不存在財務清算問題，我們沒有任何此類問題，患者基本上是透過治療來養育的。

As you know, we had a very advanced patient population in the trial late line and they were not being bridged and nothing was being done. They had to -- we couldn't do that because of the trial. So it's a very different experience than treating a patient now, where we do have the financial clearance too. It takes a little bit of time to resolve, but we've been making progress on that. Obviously, it's going quite well right now for us.

如您所知，我們在試驗後期有一群非常晚期的患者群體，他們沒有被橋接，也沒有採取任何措施。他們必須這樣做——由於審判，我們不能這樣做。因此，這與現在治療患者的經驗非常不同，我們也確實擁有財務許可。解決這個問題需要一點時間，但我們一直在這方面取得進展。顯然，我們現在進展順利。

But also, we're bridging in many cases, we're bridging those patients, and those patients are not necessarily as far along in the treatment journey as they were in the clinical trial. So I don't think you compare dropout between the two. I don't think it's a very good comparison at all.

而且，在許多情況下，我們正在為這些患者架起橋樑，而這些患者在治療過程中不一定會像在臨床試驗中那樣走得那麼遠。所以我不認為你會比較兩者之間的輟學。我認為這根本不是一個很好的比較。

Your second question was how many patients can wait for treatment. I don't really have a good estimate for you right now on that. That's something we'll have to see. But as the launch goes, I think we we'll have some indication of what number of patients really currently because we'll see the dropout rate and we'll understand that.

你的第二個問題是有多少患者可以等待治療。我現在對此還沒有一個好的估計。這是我們必須要看到的。但隨著發布的進行，我認為我們將得到一些關於當前實際患者數量的信息，因為我們將看到退出率，我們會理解這一點。

And finally, regarding month-over-month growth like Jim mentioned, it could be driven just by the number of patients. So we have centers. Right now that are enrolling at high capacity and many of the analysts are out there calling those centers and getting information from them and you know all about that. And they're saying things like right now we're enrolling X a month and six months from now we'll be enrolling X plus five a month or X plus three a month or whatever it is. So we expect that to be the case across many of our centers even without the addition of ATCs we expect the number of patients to go up.

最後，關於吉姆提到的逐月增長，它可能只是由患者數量驅動。所以我們有中心。現在正在大量報名，許多分析師都在打電話給這些中心並從他們那裡獲取信息，你知道這一切。他們說現在我們每個月招收 X 名學生，六個月後我們將每月招收 X 名加上 5 名學生，或每月招收 X 名加上 3 名學生，或其他什麼。因此，我們預計我們的許多中心都會出現這種情況，即使不增加 ATC，我們預計患者數量也會增加。

Those are great color. Could you, sorry, touch on the second point about how evenly are the currently enrolled patients distributed across the centers?

這些顏色很棒。抱歉，您能否談談第二點，即目前入組的患者在各中心的分佈如何？

We missed that one. Jim, you want to get that one?

我們錯過了那個。吉姆，你想買那個嗎？

Sure, I can take that. Hi, Yanan, it's Jim here. Like other cell therapy launches and in fact oncology launches, most launches don't have even distribution of adoption across the centers. And what we will expect over time is all centers will gain experience and increase utilization within each of the centers, but it is not normally distributed for any of the other launches out there.

當然，我可以接受。嗨，亞南，我是吉姆。與其他細胞療法的發布以及事實上的腫瘤學發布一樣，大多數發佈在各個中心的採用分佈並不均勻。隨著時間的推移，我們預計所有中心都將獲得經驗並提高每個中心的利用率，但它通常不會分佈於任何其他發布的中心。

Very helpful. Thank you.

很有幫助。謝謝。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Can you comment on, if there's any anecdotal feedback on the experience with IL-2 so far and how often that would come up as a potential reason not to pursue a treatment with Amtagvi? And then can you also comment on the profile of the average patient in process right now?

您能否評論一下迄今為止使用 IL-2 的經驗是否有任何軼事反饋，以及這些反饋是否會成為不接受 Amtagvi 治療的潛在原因？那麼您能否評論一下目前正在接受治療的普通患者的情況？

I think you mentioned there have been patient deaths in this waiting period. Are you getting a lot later-line patients or are you getting some earlier-line patients too? Thanks.

我想你提到在等待期間有患者死亡。您是否接待了許多後期排隊的患者，還是也接待了一些早期排隊的患者？謝謝。

Hi, this is Brian Gastman, I'm happy to answer that. We have not seen really any pushback for use of IL-2 and in fact some of the cell therapists who are getting involved in this beyond the medical oncologist who start with the patients have actually commented how IL-2 is not a rate-limiting issue for them and even mentioned to me personally how it's self-limiting reversible toxicities. That is absolutely not been an issue.

你好，我是布萊恩·加斯特曼，我很高興回答這個問題。我們還沒有看到任何使用 IL-2 的阻力，事實上，除了從患者入手的腫瘤內科醫師之外，一些參與這一領域的細胞治療師實際上已經評論過 IL-2 並不是一個速率限制問題對他們來說，甚至親自向我提到它是如何自限性可逆毒性的。這絕對不是問題。

And I would add that one thing that we've noted was our education to this authorized treatment centers has paid off. The patient selection overall has been pretty good, if I have to say for myself, not knowing what we would have expected.

我想補充一點，我們注意到的一件事是我們對這個授權治療中心的教育已經得到了回報。如果我必須為自己說的話，整體而言，患者的選擇非常好，不知道我們會期望什麼。

The actual drop-off because of progression is rather low. What happens is it's rare enough that it raises an eyebrow, but it's not a very common event at all. It's just something that's happened at least once. But it's definitely no more maybe even less than what we were expecting.

由於進展而導致的實際下降相當低。這種情況非常罕見，足以引起人們的注意，但它根本不是一個很常見的事件。這只是至少發生過一次的事情。但它絕對不會比我們的預期更多甚至更少。

And one follow-up if I can, just on the, you said about 60 patients are in screening right now. What would be kind of common reasons that a patient would fail that screen to not pursue treatment?

如果可以的話，我會進行一次跟進，您說目前約有 60 名患者正在接受篩檢。患者未通過篩檢而不繼續治療的常見原因有哪些？

Well, they have to go through the financial clearance. They may not be eligible. They may not be on label effectively. They may not have melanoma in some cases. There can be all sorts of things that can disqualify patients with normal medical screening of patients for prescription.

好吧，他們必須透過財務清算。他們可能沒有資格。它們可能沒有有效地標記在標籤上。在某些情況下，他們可能沒有黑色素瘤。有各種各樣的因素可能會導致患者失去對患者進行正常醫療篩檢以獲得處方的資格。

Yes. Just like the enrolled patients that we currently have, we expect a high conversion because these treating physicians understand the unmet need and are choosing in as much as possible the right patients balancing the unmet need.

是的。就像我們目前登記的患者一樣，我們預計會有很高的轉換率，因為這些治療醫生了解未滿足的需求，並盡可能選擇合適的患者來平衡未滿足的需求。

Great. Thanks for taking our questions. Congrats on the progress.

偉大的。感謝您回答我們的問題。祝賀取得的進展。

Asthika Goonewardene, Truist.

Asthika Goonewardene，真理主義者。

Thanks for taking my questions and also my congrats on the quarter here and the update. I know this question variations of this have been asked, but let me try it this way. Of the 100 patients who have been enrolled, can you tell us how many have been resected so far?

感謝您提出我的問題，並對本季和更新表示祝賀。我知道這個問題已經被問過，但讓我嘗試一下這種方式。在已入組的 100 名患者中，您能告訴我們到目前為止有多少人已被切除嗎？

Not yet, Asthika, but there is a very large number that have been resected, I can tell you that.

還沒有，Asthika，但我可以告訴你，有很大一部分已經被切除。

Got it. Okay. And then, Fred, when talking about getting financial clearance, can you give us some sort of an idea from enrollment, how many days does it take on average to get financial clearance? I understand it's very early in the launch, but so far what are you seeing?

知道了。好的。然後，Fred，在談到獲得財務清算時，您能否從註冊時給我們一些想法，平均需要多少天才能獲得財務清算？我知道現在還處於發布初期，但到目前為止您看到了什麼？

It is very early in the launch, and it's very consistent with what we seeing with other cell therapy launches. Prior authorizations take about three days and single case agreements vary. It ranges anywhere between two to six weeks with an average of three to four.

目前還處於發布的早期階段，與我們在其他細胞療法發布中看到的情況非常一致。事先授權大約需要三天時間，並且單一案例協議有所不同。時間範圍為兩到六週，平均為三到四週。

Got it. Okay. And then lastly, about how many on average vials of IL-2 do you anticipate being used per patient? I know it could be up to 18, but what are you seeing so far in the patients that have been dosed?

知道了。好的。最後，您預期每位患者平均會使用多少瓶 IL-2？我知道可能會達到 18 例，但到目前為止，您在已接受給藥的患者中看到了什麼？

I don't have anything new to add there, except that I can say in the trial was six -- the average was for the median bar I think whatever it was 16 and I would expect something similar in real practice, but I don't think I would want to quote a stat to you right now. It's close to 18, though, per patient and that's the way it should be.

我沒有什麼新的東西要補充，除了我可以說在試驗中是6——平均數是中位數，我認為無論它是16，我期望在實際實踐中會出現類似的情況，但我不這樣做我想我現在不想向您引用統計數據。不過，每個病人的數量接近 18 個，這也是應該的。

Got it. Thanks, guys. Thanks for taking the questions.

知道了。多謝你們。感謝您提出問題。

Joe Catanzaro, Piper Sandler.

喬·卡坦扎羅，派珀·桑德勒。

Hey, guys, appreciate you taking my questions here. Maybe similarly some sort of same question in a different vein as we think about the cadence and rate of the 100 patients ultimately being fused. At the end of February, you said there were about 20 patients in progress, we're now about two months past that, I guess. So can you say or give any sort of additional comments on how many of those 20 patients were ultimately infused?

嘿，夥計們，感謝您在這裡回答我的問題。當我們思考 100 名患者最終融合的節奏和比率時，也許會以不同的方式提出相同的問題。2 月底，您說大約有 20 名患者正在接受治療，我想現在已經過去兩個月了。那麼，您能否對這 20 名患者中有多少人最終接受了輸液發表評論？

And then my second question is on the early sort of experience or feedback you're seeing on the use of bridging therapy, are physicians using that and then stopping once they receive Amtagvi and ready to go? Are they sort of receiving the cell shipment and sort of continuing bridging therapy for a prolonged period of time if the patient is benefiting and tolerating that? Thanks.

然後我的第二個問題是關於您在使用橋接療法方面看到的早期經驗或回饋，醫生是否使用該療法，然後在接受 Amtagvi 並準備好後停止？如果患者受益並且能夠耐受的話，他們是否會接受細胞運輸和長期持續的橋接治療？謝謝。

Yeah, Joe, I can take the first part and then I'll have Brian answer the second part. Of the 20 patients back then, that number obviously has become more than 160 today and I can't tell you exactly how many of those 20 moved through. I really don't know, but I would think the vast majority of them move through to actual -- at least be in the treatment process, I'm not sure if they've all been infused. We don't have that information just yet.

是的，喬，我可以回答第一部分，然後我會讓布萊恩回答第二部分。在當時的 20 名患者中，這個數字在今天顯然已超過 160 名，我無法告訴你這 20 名患者中有多少人通過了治療。我真的不知道，但我認為絕大多數都進入了實際狀態——至少在治療過程中，我不確定他們是否都已被注入。我們還沒有這些資訊。

But importantly, what we reported is 10 and 20 on February 28 is now more than 100 and more than 160. So you can see the upswing there is pretty significant. Brian, can you talk a little bit about the bridging?

但重要的是，我們2月28日報道的是10個和20個，現在已經超過100個和160多個。所以你可以看到那裡的上升非常顯著。Brian，可以談談橋接嗎？

Yeah. I think it's important to note that we don't have clear line of sight on every patient. The way they get entered into our system, there's a certain level of assumption that the physician has a background in treating the patient.

是的。我認為重要的是要注意我們並沒有對每個患者都有清晰的視線。當他們進入我們的系統時，我們會在一定程度上假設醫生具有治療患者的背景。

Where we get the information is when a peer-to-peer or our response (technical difficulties) and when that happens, we get good, we really get good engagement with the sites, the physicians treating the patients. We offer them, obviously, scientific exchange when needed. And that's where we found out about maybe bridging patients.

我們獲得資訊的地方是當點對點或我們的回應（技術困難）時，當這種情況發生時，我們會變得很好，我們確實與網站、治療患者的醫生有良好的互動。顯然，我們在需要時為他們提供科學交流。這就是我們發現可能為患者架起橋樑的地方。

Interestingly, sometimes the bridging therapy is literally done not because the patient is progressing or can't make it to the therapy. But sometimes, the patients themselves want to sort of dictate when the therapy is being given. So bridging therapy really affords a lot of latitude for these physicians. But how often it's actually being used, we probably won't know until some real-world evidence comes out.

有趣的是，有時橋接治療實際上並不是因為患者正在進展或無法接受治療而完成。但有時，患者會自己想決定何時進行治療。因此，橋接療法確實為這些醫生提供了巨大的自由度。但它實際使用的頻率如何，我們可能不會知道，直到一些現實世界的證據出來。

Okay. Great. That's all really helpful. Thanks for taking my question.

好的。偉大的。這一切都非常有幫助。感謝您提出我的問題。

Reni Benjamin, JMP Securities.

雷尼·本傑明，JMP 證券。

I'm kind of curious about whether there's the potential for a backlog at the manufacturing site and how you might handle that. With the number of patients and surgeries that are happening, how do samples kind of wait, I guess, before they're getting processed? How many samples can you handle in a month? That'd be my first question.

我有點好奇製造現場是否有可能積壓訂單以及如何處理。我想，考慮到患者數量和正在進行的手術數量，樣本在處理之前是如何等待的？你們一個月可以處理多少樣品？這是我的第一個問題。

And then second, just switching gears to the Type D meeting you had for non-small cell lung cancer, it looks like you got positive feedback on a proposed potency matrix. And I thought we were kind of all done with discussions regarding potency matrix. So I'd love to get some ideas to what's happening there.

其次，只需切換到您針對非小細胞肺癌舉行的 D 型會議，看起來您就提議的效力矩陣得到了積極的回饋。我想我們已經完成了關於效力矩陣的討論。所以我很想了解那裡發生的事情的一些想法。

Igor, are you able to comment on the manufacturing question?

伊戈爾，您能對製造問題發表評論嗎？

I can comment on that. So thanks for the question, it's Igor Bilinsky. So right now, as I mentioned, we have sufficient capacity at our manufacturing facility and contract manufacturer for launch.

我可以對此發表評論。謝謝你的提問，我是伊戈爾‧比林斯基。因此，正如我所提到的，現在我們的製造工廠和合約製造商有足夠的能力來推出。

So the capacity is sufficient to meet demand from the commercial on target patients as well as the clinical trial and we actually continue hiring additional staff because we anticipate demand to be growing into the remainder of '24 and beyond. So I think -- I hope that answers your question the capacity is right now certainly adequate for the demand we're seeing.

因此，容量足以滿足針對目標患者的商業以及臨床試驗的需求，我們實際上繼續僱用更多員工，因為我們預計需求將在 24 年剩餘時間及以後增長。所以我認為——我希望能回答你的問題，目前的容量肯定足以滿足我們所看到的需求。

And then on the Type D question, is Raj available? Raj, can you take that question? We may be a little, we may have a breakdown here, Reni, in the audio, I will take it for you.

然後關於 D 類問題，Raj 有空嗎？拉吉，你能回答這個問題嗎？我們可能有一點，我們這裡可能會出現故障，雷尼，在音頻中，我替你接。

We have to have regulatory meetings with the FDA for each indication for potency assays right now. Now ultimately, we may be able to take a platform approach. I'm sure you've seen Peter, Marks talking lately about platforms and this kind of thing. But as of today, what we're doing is we're going to the FDA with each of our indications and talking to them about the specifics of the potency assay for that indication and that's what we successfully did recently for non-small cell lung, which is a very important step in getting towards a BLA submission for non-small cell lung cancer with lifileucel.

我們現在必須就效力測定的每個適應症與 FDA 召開監管會議。現在最終，我們也許能夠採取平台方法。我相信你最近見過 Peter、Marks 談論平台和這類事情。但截至今天，我們正在做的是，我們將向FDA 報告我們的每項適應症，並與他們討論針對該適應症的效力測定的具體細節，這就是我們最近針對非小細胞肺成功所做的事情，這是向使用 lifileucel 提交非小細胞肺癌 BLA 的過程中邁出的非常重要的一步。

And as we think about timing, Fred, like can we at least assume that since you -- it took pretty a decent amount of time to get that discussion lead and for everyone to be on the same page. We say that that's kind of 80%, 90% there already with non-small cell lung cancer and so things should go by a lot quicker or are we kind of back to the drawing board with each indication?

弗雷德，當我們考慮時間安排時，我們至少可以假設，自從您以來，我們花了相當多的時間來引導討論並讓每個人都達成共識。我們說非小細胞肺癌的發生率已經達到了 80%、90%，所以事情應該進展得更快，或者我們是否會針對每種適應症重新回到繪圖板？

No, no, we're definitely not back to the drawing board. What we're doing now is we're doing it what we think is the right way. We're getting in front of the FDA at the right point in our clinical development program for non-small cell lung.

不，不，我們絕對不會回到繪圖板。我們現在正在做的是，我們正在以我們認為正確的方式去做。我們在非小細胞肺臨床開發計劃的正確時刻走在了 FDA 的前面。

You can see we're still enrolling for that study. We've got enough data now from enough patients that we can actually show them what we think is a viable potency matrix proposal with data from the actual pivotal patients, which is very important.

您可以看到我們仍在招募該研究。我們現在已經從足夠的患者那裡獲得了足夠的數據，我們實際上可以向他們展示我們認為可行的效力矩陣建議，以及來自實際關鍵患者的數據，這非常重要。

While we're early enough in the study to be able to make adjustments should they have questions or have things they want to change. As opposed to what we did the last time with melanoma, it was effectively do that all after the fact or largely after the fact if the study was already complete.

雖然我們在研究中處於足夠早的階段，如果他們有疑問或有想要改變的事情，我們能夠做出調整。與我們上次對黑色素瘤所做的事情相反，如果研究已經完成，那麼這實際上是在事後或大部分事後進行的。

So what we're doing now we think is the right way to develop polyclonal T cell therapies and this should actually accelerate and speed up our process, so that when we finish non-small cell lung, we go straight to a pre BLA meeting and straight to a submission.

因此，我們認為現在正在做的事情是開發多克隆 T 細胞療法的正確方法，這實際上應該加速我們的進程，以便當我們完成非小細胞肺治療時，我們可以直接參加 BLA 前會議，直接提交。

Great. Thanks for taking the questions.

偉大的。感謝您提出問題。

Ben Burnett, Stifel.

本·伯內特，斯蒂菲爾。

I was wondering if you could maybe just talk about the patient flow within the hospital. Are you seeing any bottlenecks popping up, like for example, are there any -- have there been any learnings that have needed to happen sort of efficiently coordinate with the surgeon or anything like that?

我想知道您是否可以談談醫院內的病人流動。您是否看到任何瓶頸，例如，是否有任何需要與外科醫生或類似人員進行有效協調的學習？

Yeah, actually, I would say the opposite. We've really seen a tremendous enthusiasm from the surgeon all the way through the cell therapists and the nurses that treat these patients. We've seen a hospital bend over backwards to find operator in time, space in the hospital.

是的，實際上，我會說相反的。我們確實看到了從外科醫生到細胞治療師和治療這些患者的護士的巨大熱情。我們已經看到一家醫院竭盡全力在醫院的時間和空間內尋找操作員。

We really haven't experienced any of the potential bottlenecking, even as we increase. Most of the things that we encounter are really just sort of small questions on details, but not the big issues like having a time or place to treat a patient.

即使我們在增加，我們確實沒有遇到任何潛在的瓶頸。我們遇到的大多數事情實際上只是一些細節上的小問題，而不是像有時間或地點治療病人這樣的大問題。

Okay. That's excellent. And if you could also just comment on just the quality of tumor sample coming in for manufacturing, I guess, how is like kind of the specifications around those tumor samples compared to like what you saw in clinical trials?

好的。那太好了。如果您也可以只評論用於製造的腫瘤樣本的質量，我想，與您在臨床試驗中看到的相比，這些腫瘤樣本的規格怎麼樣？

I can take that or Igor if you would like.

如果你願意的話，我可以接受，也可以接受伊戈爾。

I'd be happy to. Good question. So far, the experience has been very consistent with our clinical experience, including the quality and the size and the quality of the tumor samples for manufacturing.

我很樂意。好問題。到目前為止，這些經驗與我們的臨床經驗非常一致，包括用於製造的腫瘤樣本的品質、大小和品質。

Okay. Got it. Thank you.

好的。知道了。謝謝。

Thank you. And ladies and gentlemen, that's all the time we have for our Q&A session. I will now turn the call back over to Dr. Fred Vogt for any closing remarks.

謝謝。女士們先生們，這就是我們問答環節的全部時間。現在，我將把電話轉回給 Fred Vogt 博士，讓其發表結束語。

Thank you again for joining the Iovance Biotherapeutics' first-quarter 2024 financial results and corporate update conference call. As we've shared on this call, we are very pleased with the strength of the Amtagvi launch and excited to see accelerated growth throughout the rest of 2024.

再次感謝您參加 Iovance Biotherapeutics 2024 年第一季財務業績和公司更新電話會議。正如我們在本次電話會議上分享的那樣，我們對 Amtagvi 的推出感到非常滿意，並很高興看到 2024 年剩餘時間的加速成長。

Thank you to those in the patient, healthcare, and advocacy communities, our partners and our exceptional Iovance team. I would also like to thank our shareholders and covering analysts for their support. We look forward to presenting data at ASCO and lifileucel and frontline melanoma. And we'll host an analyst and investor event on May 31.

感謝患者、醫療保健和倡導社區的人們、我們的合作夥伴和我們出色的 Iovance 團隊。我還要感謝我們的股東和分析師的支持。我們期待在 ASCO 和 lifileucel 和前線黑色素瘤上展示數據。我們將於 5 月 31 日舉辦分析師和投資者活動。

Please feel free to reach out to our Investor Relations team for follow-up. Thank you.

請隨時聯絡我們的投資者關係團隊進行後續追蹤。謝謝。

Ladies and gentlemen, that does conclude our conference call for today. Thank you for your participation. You may now disconnect.

女士們先生們，我們今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。