Iovance Biotherapeutics Inc (IOVA) 2023 Q2 法說會逐字稿

Welcome to the Iovance Biotherapeutics Second Quarter 2023 Financial Results and Corporate Updates Conference Call. My name is Shannon and I will be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded.

歡迎參加 Iovance Biotherapeutics 2023 年第二季度財務業績和公司動態電話會議。我叫香農，我將擔任您今天通話的接線員。 （操作員說明）請注意，本次會議正在錄製中。

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

我現在將把電話轉給 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 us. Speaking on today's call, we have Dr. Fred Vogt, our Interim President and Chief Executive Officer; Dr. Igor Bilinsky, our Chief Operating Officer; Jim Ziegler, our Executive Vice President, Commercial; Dr. Friedrich Finckenstein, our Chief Medical Officer; and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Brian Gastman, Executive Vice President, Medical Affairs; and Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine, are available for the Q&A session.

謝謝你，接線員。下午好，感謝您加入我們。我們的臨時總裁兼首席執行官 Fred Vogt 博士在今天的電話會議上發言。 Igor Bilinsky 博士，我們的首席運營官； Jim Ziegler，我們的商務執行副總裁；我們的首席醫療官 Friedrich Finckenstein 博士；以及我們的首席財務官 Jean-Marc Bellemin。 Brian Gastman 博士，醫療事務執行副總裁；我們的監管戰略和轉化醫學執行副總裁 Raj Puri 博士也出席了問答環節。

This afternoon, we issued a press release that can be found on our corporate website at iovance.com, which includes the financial results for the 3 and 6 months ended on June 30, 2023, as well as recent corporate updates.

今天下午，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，其中包括截至2023 年6 月30 日的3 個月和6 個月的財務業績以及最近的公司更新。

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, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaborations, cash position and expense guidance and future updates. 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.

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、預商業活動、臨床試驗和結果、監管互動、計劃和戰略、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、許可和合作、現金狀況和費用指導以及未來更新。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存在重大差異。我們不承擔公開更新任何前瞻性陳述的義務。

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 am pleased to highlight several important milestones arrive in during the second quarter of 2023 and more recently. Our biologics license application, or BLA, for our lead TIL therapy, lifileucel, in advanced melanoma was accepted by the U.S. Food and Drug Administration, or FDA, for a 6-month priority review and granted a PDUFA date of November 25, 2023. In the acceptance letter, the FDA also informed us that they do not intend to host an advisory committee meeting and that no major review issues were identified. Lifileucel, if approved, will be the first cell therapy for the treatment of melanoma in addition to the first individualized onetime T cell therapy for solid tumor cancer.

謝謝薩拉，大家下午好。我很高興強調 2023 年第二季度及最近實現的幾個重要里程碑。我們針對晚期黑色素瘤的主要TIL 療法lifileucel 的生物製劑許可申請(BLA) 已被美國食品和藥物管理局(FDA) 接受，進行為期6 個月的優先審查，並授予PDUFA 日期為2023 年11 月25日。在接受函中，FDA 還告知我們，他們不打算主辦諮詢委員會會議，也沒有發現重大審查問題。 Lifileucel 如果獲得批准，將成為第一個治療黑色素瘤的細胞療法，以及第一個針對實體瘤的個體化一次性 T 細胞療法。

During the priority review process, we have continued to collaborate with the FDA as they review this [nuclease] treatment for advanced melanoma patients with limited options. We remain confident in our prospects for approval, given the unmet medical need, our strong clinical data and our positive interactions with -- feedback from the FDA. As we approach our PDUFA date, we are building capacity and staffing our Iovance Cell Therapy Center, or ICTC, to supply our projected demand for lifileucel at launch. In addition, our field teams are proceeding as planned with onboarding and site readiness activities for our authorized treatment centers, or ATCs, to treat the first lifileucel patient as soon as possible upon approval.

在優先審查過程中，我們繼續與 FDA 合作，他們正在審查這種針對選擇有限的晚期黑色素瘤患者的[核酸酶]治療方法。考慮到未滿足的醫療需求、我們強大的臨床數據以及我們與 FDA 反饋的積極互動，我們對獲得批准的前景仍然充滿信心。隨著 PDUFA 日期的臨近，我們正在為 Iovance 細胞治療中心 (ICTC) 進行能力建設和人員配備，以滿足我們對 lifileucel 上市時的預計需求。此外，我們的現場團隊正在按計劃為我們的授權治療中心 (ATC) 開展入職和現場準備活動，以便在獲得批准後儘快治療第一位 lifileucel 患者。

I would also like to highlight that we are now a commercial stage company after closing our transaction to acquire Proleukin, an IL-2 product used as part of the TIL therapy regimen, in May. We are integrating Proleukin into our organization as we prepare to launch lifileucel so that we can offer 2 important parts of the TIL regimen. As noted in today's press release, we recognized some revenue for the first time from Proleukin sales and expect to realize more significant revenue with the launch of lifileucel. Owning Proleukin also provides us with full control of the IL-2 supply chain and logistics surrounding TIL therapy, and we expect lower clinical trial expenses and future cost of goods for lifileucel.

我還想強調的是，在 5 月份完成收購 Proleukin（一種用作 TIL 治療方案一部分的 IL-2 產品）的交易後，我們現在是一家商業階段公司。在準備推出 lifileucel 時，我們正在將 Proleukin 整合到我們的組織中，以便我們可以提供 TIL 方案的兩個重要部分。正如今天的新聞稿中所指出的，我們首次從 Proleukin 銷售中確認了一些收入，並預計隨著 lifileucel 的推出，將實現更可觀的收入。擁有 Proleukin 還使我們能夠完全控制 IL-2 供應鍊和圍繞 TIL 治療的物流，我們預計 lifileucel 的臨床試驗費用和未來商品成本會降低。

Beyond our regulatory and commercial readiness activities for lifileucel, our robust TIL therapy pipeline includes 7 active clinical trials with the potential to strengthen and broaden our mission to be the global leader in innovating, developing and delivering TIL therapies for people with cancer across multiple solid tumors.

除了我們針對lifileucel 的監管和商業準備活動之外，我們強大的TIL 治療產品線還包括7 項活躍的臨床試驗，這些試驗有可能加強和擴大我們的使命，即成為為多種實體瘤患者創新、開發和提供TIL 療法的全球領導者。

In frontline melanoma, our confirmatory trial, TILVANCE-301, has begun randomizing patients and remains poised to be well underway upon a potential approval of lifileucel later this year. We have also made significant progress across our trials in non-small cell lung cancer, NSCLC. We recently announced positive clinical and regulatory updates related to IOV-LUN-202, our registrational single-arm Phase II trial in post-anti-PD-1 lung cancer. At the upcoming World Congress on Lung Cancer, or WCLC, in Singapore, we look forward to presenting detailed data from Cohort 3A of our IOV-COM-202 trial in anti-PD-1-naive lung cancer. The Cohort 3A data supports our strategy in upcoming trial in frontline lung cancer. This trial in frontline lung cancer can also potentially serve as a confirmatory trial to support an accelerated approval based on the IOV-LUN-202 trial.

在一線黑色素瘤中，我們的驗證性試驗 TILVANCE-301 已開始對患者進行隨機分組，並準備在今年晚些時候 lifileucel 可能獲得批准後順利進行。我們在非小細胞肺癌（NSCLC）試驗中也取得了重大進展。我們最近宣布了與 IOV-LUN-202 相關的積極臨床和監管更新，IOV-LUN-202 是我們針對 PD-1 後肺癌的註冊單臂 II 期試驗。在即將於新加坡舉行的世界肺癌大會 (WCLC) 上，我們期待展示我們的 IOV-COM-202 抗 PD-1 初治肺癌試驗第 3A 組的詳細數據。隊列 3A 數據支持我們即將進行的一線肺癌試驗的策略。這項針對一線肺癌的試驗也有可能作為一項驗證性試驗，以支持基於 IOV-LUN-202 試驗的加速批准。

As we prepare to launch lifileucel, Iovance now has almost 600 employees with experience in developing and commercializing oncology and cell and gene therapy products. I look forward to addressing your questions later during this call and will now ask Igor to present our manufacturing updates.

在我們準備推出 lifileucel 時，Iovance 目前擁有近 600 名員工，他們在腫瘤學、細胞和基因治療產品的開發和商業化方面擁有豐富的經驗。我期待著稍後在本次電話會議中回答您的問題，現在將請伊戈爾介紹我們的製造最新情況。

Thank you, Fred. It has been a productive first half of the year at ICTC. We are preparing for the commercial launch of lifileucel and building the manufacturing organization to supply lifileucel to patients upon approval, while providing supplies for our clinical trials and supporting extended access. We are committed to operational excellence and have provided TIL therapy for more than 600 patients to date with a consistent manufacturing success rate of more than 90%. Our capacity and hiring plans remain on track to support our forecasted demand at launch.

謝謝你，弗雷德。 ICTC 今年上半年是富有成效的。我們正在準備 lifileucel 的商業推出，並建立生產組織，以便在獲得批准後向患者提供 lifileucel，同時為我們的臨床試驗提供用品並支持擴大使用範圍。我們致力於卓越運營，迄今為止已為 600 多名患者提供了 TIL 治療，生產成功率始終保持在 90% 以上。我們的產能和招聘計劃仍按計劃進行，以支持我們在推出時的預測需求。

The ICTC is expected to supply most of the commercial TIL therapies upon approval, with our contract manufacturers providing further flexibility to optimally balance capacity and patient demand. We look to establish TIL as the next paradigm shift in class of cancer therapy. And the ICTC is currently built to supply TIL products for more than 2,000 patients annually. Additional existing shelf space at ICTC can also be built out to ultimately supply TIL products for more than 5,000 patients annually from this facility. Longer term, our vision is to build capacity for more than 10,000 patients annually by adding new facilities as well as streamlining and automating manufacturing processes.

ICTC 預計將在獲得批准後提供大部分商業 TIL 療法，而我們的合同製造商將提供進一步的靈活性，以最佳地平衡產能和患者需求。我們希望將 TIL 確立為癌症治療類別的下一個範式轉變。 ICTC 目前建成每年為 2,000 多名患者提供 TIL 產品。 ICTC 還可以擴建現有的貨架空間，最終從該設施每年為 5,000 多名患者供應 TIL 產品。從長遠來看，我們的願景是通過增加新設施以及簡化和自動化製造流程，每年為超過 10,000 名患者提供治療能力。

Intellectual property or IP is also a critical component at Iovance that supports and protects our proprietary manufacturing processes and know-how. We currently own at least 60 granted or allowed U.S. and international patents, including Gen 2 patent rights that we expect to provide exclusivity into 2038. Extensive details on Iovance-owned IP is available on our corporate website and within our annual reports on Form 10-K.

知識產權或 IP 也是 Iovance 的一個關鍵組成部分，它支持和保護我們專有的製造工藝和專有技術。我們目前擁有至少60 項已授予或允許的美國和國際專利，包括我們預計將在2038 年提供排他性的第2 代專利權。有關Iovance 擁有的知識產權的詳細信息，請參閱我們的公司網站和表格10 的年度報告 - K.

I would now like to hand the call over to Jim Ziegler to highlight our commercial launch preparations. Jim?

我現在想將電話轉交給吉姆·齊格勒，重點介紹我們的商業發布準備工作。吉姆？

Thank you, Igor. At Iovance, we are pioneering TIL therapy with the potential to transform the practice of medicine in advanced melanoma and additional solid tumors. Our experienced commercial and cross-functional teams with deep cell therapy experience are building the foundation for a strong lifileucel launch while integrating Proleukin to offer as a supportive part of the TIL regimen.

謝謝你，伊戈爾。在 Iovance，我們正在開創 TIL 療法，有可能改變晚期黑色素瘤和其他實體瘤的醫學實踐。我們經驗豐富的商業和跨職能團隊擁有深厚的細胞治療經驗，正在為 lifileucel 的強大推出奠定基礎，同時整合 Proleukin 作為 TIL 療法的支持部分。

Commercial launch readiness is on track as we approach our 25 November PDUFA date. Today, I will highlight onboarding for our authorized treatment centers, or ATCs, private and public payer engagement and commercial operational readiness activities. First, we are well positioned to achieve our goal to onboard 40 ATCs within the first 90 days. We are actively working with ATCs to operationalize their TIL service line capabilities and to ensure multidisciplinary teams at each center are ready to administer the lifileucel treatment regimen upon FDA approval.

隨著 11 月 25 日 PDUFA 日期的臨近，商業發布準備工作已步入正軌。今天，我將重點介紹我們授權治療中心（ATC）的入職、私人和公共付款人參與以及商業運營準備活動。首先，我們完全有能力實現在前 90 天內安裝 40 台 ATC 的目標。我們正在積極與 ATC 合作，實施他們的 TIL 服務線能力，並確保每個中心的多學科團隊準備好在 FDA 批准後實施 lifileucel 治療方案。

A significant number of ATCs are currently participating in the onboarding process and we believe they are excited about offering TIL therapy. This high level of enthusiasm at our ATCs is reflected by significant investments of time and resources to develop their TIL service line and to prepare for anticipated demand and capacity needs among advanced melanoma patients.

目前，大量 ATC 正在參與入職流程，我們相信他們對提供 TIL 療法感到興奮。我們的 ATC 投入了大量的時間和資源來開發他們的 TIL 服務線，並為晚期黑色素瘤患者的預期需求和能力需求做好準備，這反映了我們 ATC 的高度熱情。

Bed capacity, for example, is assessed during our onboarding process. Our targeted ATCs report sufficient inpatient hospital beds to accommodate and support lifileucel and other cell therapies. We are also piloting our IovanceCares enrollment, scheduling and chain of identity and chain of custody capabilities and training curriculum. We are encouraged as ATCs have provided positive feedback on our customer-centric IovanceCares' design and build.

例如，床位容量是在我們的入職流程中進行評估的。我們的目標 ATC 報告有足夠的住院病床來容納和支持 lifileucel 和其他細胞療法。我們還在試點 IovanceCares 註冊、調度、身份鍊和監管鏈功能以及培訓課程。我們深受鼓舞，因為 ATC 對我們以客戶為中心的 IovanceCares 設計和構建提供了積極的反饋。

Turning to market access. Our reimbursement strategies are on track to ensure timely and appropriate access for patients upon approval. Our market access team continues to engage the key national and regional payers who are responsible for approximately 90% of covered lives. Based on our payer interactions, we expect coverage consistent with label and similar to recent CAR-Ts. For Medicare patients, hospitals already have reimbursement established under DRG 018, which provides more appropriate payment immediately upon launch.

轉向市場准入。我們的報銷策略正在按計劃進行，以確保患者在獲得批准後及時、適當地獲得服務。我們的市場准入團隊繼續與負責約 90% 承保生活的主要國家和地區付款人合作。根據我們與付款人的互動，我們預計覆蓋範圍與標籤一致，並且與最近的 CAR-T 類似。對於 Medicare 患者，醫院已經根據 DRG 018 建立了報銷，該報銷一經推出就立即提供更合適的付款。

As we prepare for launch, I want to acknowledge our cross-functional teams who are committed to ensure patients can be treated at ATCs and have access to reimbursement for lifileucel upon approval.

在我們準備推出時，我要感謝我們的跨職能團隊，他們致力於確保患者能夠在 ATC 接受治療，並在獲得批准後獲得 lifileucel 的報銷。

I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight our clinical progress.

現在我將把電話轉給我們的首席醫療官弗里德里希·芬肯斯坦，以強調我們的臨床進展。

Thank you, Jim. Today, I would like to summarize recent updates with our TIL therapy pipeline and next-generation technologies. I'll begin with TILVANCE-301, our registrational trial for accelerated and full approval of lifileucel in combination with pembrolizumab in frontline advanced melanoma. TILVANCE-301 is also designed as confirmatory trial to support full approval of lifileucel in post-anti-PD-1 advanced melanoma.

謝謝你，吉姆。今天，我想總結一下我們的 TIL 治療管道和下一代技術的最新進展。我將從 TILVANCE-301 開始，這是我們的註冊試驗，旨在加速和全面批准 lifileucel 與派姆單抗 (pembrolizumab) 聯合治療一線晚期黑色素瘤。 TILVANCE-301 還被設計為驗證性試驗，以支持 lifileucel 在抗 PD-1 後晚期黑色素瘤中的全面批准。

The first patient was randomized in the second quarter and TILVANCE-301 remains on track to be well underway at the time of a potential approval of lifileucel later this year. We also continue to activate global sites in key geographies with a large presence of melanoma patients and the potential for strong enrollment.

第一位患者在第二季度被隨機分配，TILVANCE-301 仍在順利進行中，屆時 lifileucel 可能會在今年晚些時候獲得批准。我們還繼續在擁有大量黑色素瘤患者且有大量入組潛力的關鍵地區激活全球站點。

In our small cell lung cancer, we have 6 cohorts across 3 Iovance studies to investigate multiple treatment regimens in various populations and stages of disease. This afternoon, I will highlight our IOV-LUN-202 registrational trial in post anti-PD-1 non-small cell lung cancer patients as well as the anti-PD-1-naive non-small cell lung cancer patient Cohort 3A in our IOV-COM-202 basket trial.

在我們的小細胞肺癌中，我們在 3 項 Iovance 研究中有 6 個隊列來研究不同人群和疾病階段的多種治療方案。今天下午，我將重點介紹我們在接受抗PD-1 治療後的非小細胞肺癌患者以及我們的3A 隊列中未接受過抗PD-1 治療的非小細胞肺癌患者的IOV-LUN-202 註冊試驗。 IOV-COM-202 籃子試用。

Last month, we reported regulatory and clinical updates for our registrational Phase II LUN-202 trials in post anti-PD-1 non-small cell lung cancer. At a type B pre-Phase III meeting, the FDA provided positive regulatory feedback at the design of the single-arm Phase II IOV-LUN-202 trial may be acceptable for approval of LN-145 TIL therapies in post-anti-PD-1 non-small cell lung cancer. Cohorts 1 and 2 include our registrational population of EGFR, ROS and/or ALK mutation negative patients who have progressed on or after chemotherapy and anti-PD-1 therapy.

上個月，我們報告了抗 PD-1 後非小細胞肺癌註冊 II 期 LUN-202 試驗的監管和臨床更新。在 B 型 III 期前會議上，FDA 就單臂 II 期 IOV-LUN-202 試驗的設計提供了積極的監管反饋，該試驗可能可以接受批准 LN-145 TIL 療法用於抗 PD 後治療。 1.非小細胞肺癌。第 1 組和第 2 組包括我們登記的 EGFR、ROS 和/或 ALK 突變陰性患者群體，這些患者在化療和抗 PD-1 治療期間或之後病情出現進展。

For patients with actionable genomic mutations other than EGFR, ROS or ALK, we will require at least 1 line of an FDA-approved targeted therapy as indicated. Based on the regulatory discussions, we completed a preliminary analysis of the registrational Cohorts 1 and 2 in the IOV-LUN-202 trial. We are very pleased with the initial ORR and durability from this analysis. Confirmed ORR by RECIST version 1.1 was 26.1%. All 6 responses were ongoing at the time of the data analysis, including 1 complete response and 5 partial responses. The median duration of response, or DOR, was not reached in the ongoing responses range from 1.4 plus to 9.7 plus months.

對於攜帶除 EGFR、ROS 或 ALK 之外的可操作基因組突變的患者，我們將需要至少 1 種經 FDA 批准的靶向治療。根據監管討論，我們完成了 IOV-LUN-202 試驗中註冊隊列 1 和 2 的初步分析。我們對此次分析的初始 ORR 和耐久性非常滿意。 RECIST 1.1 版確認的 ORR 為 26.1%。在數據分析時，所有 6 項答复均正在進行中，包括 1 項完整答復和 5 項部分答复。持續緩解時間範圍為 1.4 個月以上至 9.7 個月以上，但未達到中位緩解持續時間 (DOR)。

Looking ahead, we are amending the protocol to enroll a total of approximately 120 patients within Cohorts 1 and 2. Enrollment is already underway at more than 40 active clinical sites in the U.S., Canada and Europe. And we expect to fully enroll our registrational cohorts in the second half of 2024. Based on the FDA feedback, we plan to pursue accelerated approval based on the LUN-202 trial, a planned trial in frontline advanced non-small cell lung cancer, which we will discuss with FDA later this year, is designed to serve as the confirmatory trial.

展望未來，我們正在修改方案，在第 1 組和第 2 組中總共招募約 120 名患者。美國、加拿大和歐洲的 40 多個活躍臨床中心已經開始招募。我們預計將在 2024 年下半年全面招募我們的註冊隊列。根據 FDA 的反饋，我們計劃基於 LUN-202 試驗尋求加速批准，這是一項針對一線晚期非小細胞肺癌的計劃試驗，該試驗我們將在今年晚些時候與FDA 討論，旨在作為驗證性試驗。

Our strategy in frontline advanced non-small cell lung cancer is proceeding in parallel. We plan to report detailed data from Cohort 3A of the IOV-COM-202 trial at the upcoming World Conference on Lung Cancer. Cohort 3A is investigating our TIL therapy, LN-145 in combination with pembrolizumab in patients with advanced non-small cell lung cancer who are naive to ICI treatment. We reported positive top line results from Cohort 3A in a corporate update earlier this year. In the press release, confirmed ORR by RECIST 1.1 was 47%, 8 responders out of 17 patients, including 2 ongoing complete responses, or CRs.

我們在一線晚期非小細胞肺癌方面的戰略正在同步進行。我們計劃在即將召開的世界肺癌大會上報告 IOV-COM-202 試驗第 3A 組的詳細數據。第 3A 組正在研究我們的 TIL 療法 LN-145 與派姆單抗聯合治療未接受過 ICI 治療的晚期非小細胞肺癌患者。我們在今年早些時候的公司更新中報告了 3A 組的積極頂線業績。在新聞稿中，RECIST 1.1 確認的 ORR 為 47%，17 名患者中有 8 名有反應，其中包括 2 名正在進行的完全緩解 (CR)。

Responses were observed regardless of PD-01 status and safety was consistent with other studies of Iovance TIL therapies in combination with pembrolizumab. We have been very pleased by the response rate and durability of the response so far. In the distinct clinical subsets in Cohort 3A, ORR was 80% in 5 patients who were treatment-naive and 43% in 7 patients who have progressed after chemotherapy. ORR was 58.7% when combining the 12 patients in the treatment naive or post-chemo EGFR wild-type population. These results inform the design and target population of our planned frontline Phase III study.

無論 PD-01 狀態如何，都會觀察到緩解，並且安全性與 Iovance TIL 療法與 pembrolizumab 聯合使用的其他研究一致。迄今為止，我們對響應速度和響應的持久性感到非常滿意。在隊列 3A 的不同臨床亞組中，5 名未接受治療的患者的 ORR 為 80%，7 名化療後病情進展的患者的 ORR 為 43%。將 12 名未接受治療或化療後 EGFR 野生型人群的患者合併起來，ORR 為 58.7%。這些結果為我們計劃的一線 III 期研究的設計和目標人群提供了信息。

In addition, we were encouraged to observe 1 complete response among the 5 patients with EGFR mutation for the tumors and progression after prior treatment with TKI, who typically do not respond to pembrolizumab alone. At WCLC, we plan to report durability and additional Cohort 3A data in approximately the same number of patients. The initial results will be published in an abstract on August 16.Then an updated data analysis with additional duration of follow-up will be included in the overall presentation on September 11.

此外，我們鼓勵觀察 5 名 EGFR 突變患者中的 1 名患者在先前接受 TKI 治療後腫瘤和進展完全緩解，這些患者通常對單獨的派姆單抗沒有反應。在 WCLC，我們計劃報告大約相同數量的患者的耐久性和其他隊列 3A 數據。初步結果將於 8 月 16 日以摘要形式發布。然後，更新的數據分析和額外的隨訪時間將包含在 9 月 11 日的總體演示中。

We are also preparing to meet with FDA this year to discuss the Cohort 3A data and our proposed registration trial for lifileucel and frontline advanced non-small cell lung cancer patients which is designed to support full approval in frontline non-small cell lung cancer or to service confirmatory trials supporting full approval in post anti-PD-1 non-small lung cancer. Our goal is to improve frontline non-small cell lung cancer therapies by adding TIL therapy to standard of care pembrolizumab maintenance therapy administered after completion of the initial chemo immunotherapy. Our confidence in this approach is supported by the encouraging responses and response durations for the TIL, pembrolizumab combination in Cohort 3A compared to standard of care benchmarks, even without chemotherapy.

我們還準備今年與 FDA 會面，討論隊列 3A 數據以及我們提議的針對 lifileucel 和一線晚期非小細胞肺癌患者的註冊試驗，該試驗旨在支持一線非小細胞肺癌的全面批准或支持抗PD-1 治療後非小細胞肺癌的完全批准的服務驗證性試驗。我們的目標是通過將 TIL 療法添加到初始化療免疫治療完成後進行的帕博利珠單抗維持治療標準護理中，改善一線非小細胞肺癌治療。即使沒有化療，與標準護理基準相比，隊列 3A 中 TIL 和派姆單抗組合的令人鼓舞的反應和反應持續時間也支持了我們對這種方法的信心。

In cervical cancer, enrollment momentum continues to now expanded Cohort 2 in the ongoing C-145-04 trial. Based on FDA feedback, this cohort is investigating lifileucel following progression on or after chemotherapy and anti-PD-1 therapy to support regulatory submissions. We are also excited about our next-generation approaches to optimize TIL therapy. Several of these programs incorporate genetic modification, utilizing the gene editing TALEN technology licensed from Cellectis to inactivate immune checkpoint proteins that inhibit anti-tumor response.

在宮頸癌方面，在正在進行的 C-145-04 試驗中，入組勢頭仍在繼續擴大第 2 組。根據 FDA 的反饋，該隊列正在研究化療和抗 PD-1 治療期間或之後進展後的 lifileucel，以支持監管提交。我們也對優化 TIL 治療的下一代方法感到興奮。其中一些項目結合了基因改造，利用 Cellectis 授權的基因編輯 TALEN 技術來滅活抑制抗腫瘤反應的免疫檢查點蛋白。

Our lead candidate, IOV-4001, a PD-1 inactivated TIL therapy, is studied in our first in-human IOV-GM1-201 trial in patients with previously treated AVAST melanoma or non-small cell lung cancer. Additional candidates using the TALEN technology, which includes multiple inactivated immune checkpoint targets are expected to enter clinical development in 2024.

我們的主要候選藥物 IOV-4001 是一種 PD-1 滅活 TIL 療法，在我們的首次人體 IOV-GM1-201 試驗中對既往接受過 AVAST 黑色素瘤或非小細胞肺癌治療的患者進行了研究。使用 TALEN 技術的其他候選藥物（包括多個滅活的免疫檢查點靶標）預計將於 2024 年進入臨床開發。

I am available during the question-and-answer session. For now, I will hand the call over to Jean-Marc to discuss our first half and second quarter 2023 financial results.

在問答環節我有空。現在，我將把電話轉給 Jean-Marc，討論我們 2023 年上半年和第二季度的財務業績。

Thank you, Friedrich. My comments will summarize the high-level financial results for the 3 and 6 months ended on June 30, 2023. More details can be found in this afternoon's press release as well as in our SEC filings. Iovance had $317.3 million in cash, cash equivalents, investments and restricted cash as of June 30, 2023 compared to $478.3 million as of December 31, 2022. Use of cash during the period included the upfront consideration to acquire worldwide rights for Proleukin from Clinigen, when the transaction closed in May. The upfront payment was fully financed with existing cash on hand of approximately GBP 167.7 million or approximately USD 200 million as well as approximately GBP 2.4 million or approximately USD 3.1 million for certain Proleukin inventory.

謝謝你，弗里德里希。我的評論將總結截至 2023 年 6 月 30 日的 3 個月和 6 個月的高級財務業績。更多詳細信息可以在今天下午的新聞稿以及我們向 SEC 提交的文件中找到。截至2023 年6 月30 日，Iovance 擁有3.173 億美元的現金、現金等價物、投資和限制性現金，而截至2022 年12 月31 日為4.783 億美元。該期間的現金使用包括從Clinigen 收購Proleukin 全球權利的預付款，當交易於五月份結束時。預付款全部由現有手頭現金約 1.677 億英鎊（約 2 億美元）以及約 240 萬英鎊（約 310 萬美元）的某些 Proleukin 庫存資金提供。

We have also continued to strengthen our balance sheet and remain appropriately funded as we head towards potential commercialization of lifileucel later this year. In July, we raised estimated net proceeds of approximately $161.4 million from a common stock public offering. We continue to prioritize our investments and effectively manage expenses, including of the proceeds from the offering, our current cash position is sufficient to fund our commercial launch preparations, internal manufacturing, clinical pipeline expansion and operating plan until the end of 2024.

我們還繼續加強我們的資產負債表，並保持適當的資金，因為我們將在今年晚些時候實現 lifileucel 的潛在商業化。 7 月份，我們通過普通股公開發行預計籌集了約 1.614 億美元的淨收益。我們繼續優先考慮我們的投資並有效管理費用，包括發行收益，我們目前的現金狀況足以為我們的商業上市準備、內部製造、臨床管道擴張和運營計劃提供資金，直至 2024 年底。

Transitioning to financial results. Net loss for the second quarter ended June 30, 2023, was $106 million or $0.47 per share compared to a net loss of $99.3 million or $0.63 per share for the second quarter ended June 30, 2022. Net loss for the 6 months ended June 30, 2023, was $213.3 million (sic) [$213.9 million] or $0.98 per share compared to a net loss of $191 million or $1.21 per share for the same period ended June 30, 2022.

轉向財務業績。截至2023年6月30日的第二季度淨虧損為1.06億美元，即每股0.47美元，而截至2022年6月30日的第二季度淨虧損為9930萬美元，即每股0.63美元。 截至6月30日的六個月淨虧損2023 年，淨虧損為2.133 億美元（原文如此）[2.139 億美元]，即每股0.98 美元，而截至2022 年6 月30 日的同期淨虧損為1.91 億美元，即每股1.21 美元。

Following the completion of the Proleukin acquisition in May, we recorded revenue for the first time in the second quarter and anticipate significant revenue for Proleukin to begin after the launch of lifileucel. Revenue for the second quarter and 6 months ended June 30, 2023, was $0.2 million, comprised of product sales of Proleukin. There was no revenue for the second quarter and 6 months ended June 30, 2022.

繼 5 月份完成對 Proleukin 的收購後，我們在第二季度首次錄得收入，並預計在 lifileucel 推出後 Proleukin 將開始出現可觀的收入。截至 2023 年 6 月 30 日的第二季度和 6 個月的收入為 20 萬美元，包括 Proleukin 的產品銷售。截至2022年6月30日的第二季度和六個月沒有收入。

Cost of sales for the second quarter and 6 months ended June 30, 2023, was $2.1 million. Cost of sales related entirely to Proleukin, including $1.9 million of noncash amortization of the acquired intangible assets for developed technology. There was no cost of revenue for the second quarter and 6 months ended June 30, 2022.

截至 2023 年 6 月 30 日的第二季度和 6 個月的銷售成本為 210 萬美元。銷售成本完全與 Proleukin 有關，包括為開發技術而收購的無形資產的 190 萬美元非現金攤銷。第二季度和截至 2022 年 6 月 30 日的 6 個月沒有收入成本。

Research and development expenses were $85.8 million (sic) [$86.3 million] for the second quarter ended June 30, 2023, an increase of $12.9 million compared to $73.4 million for the same period ended June 30, 2022. Research and development expenses were $169.1 million for the 6 months ended June 30, 2023, an increase of $27.4 million compared to $141.7 million for the same period ended June 30, 2022. The increases in research and development expenses over the prior year periods were primarily attributable to growth of the internal research and development team, facility-related and internal research program costs and the initiation of our Phase III TILVANCE-301 trial, which were partially offset by a decrease in stock-based compensation expense.

截至2023年6月30日的第二季度，研發費用為8580萬美元（原文如此）[8630萬美元]，較截至2022年6月30日的同期的7340萬美元增加了1290萬美元。研發費用為1.691億美元截至2023年6月30日止6個月，與截至2022年6月30日止6個月的1.417億美元相比，增加了2740萬美元。研發費用較上年同期增加的主要原因是內部研究的增長和開發團隊、設施相關和內部研究項目成本以及我們第三階段 TILVANCE-301 試驗的啟動，這些成本被股票補償費用的減少部分抵消。

Selling, general and administrative expenses were up $21.9 million for the second quarter ended June 30, 2023, a decrease of $4.4 million compared to $26.3 million for the same period ended June 30, 2022. Selling and general and administrative expenses were $50 million for the 6 months ended June 30, 2023, an increase of only $0.3 million compared to $49.7 million for the same period ended June 30, 2022. The decrease in selling, general and administrative expenses in the second quarter of 2023 compared to prior year periods was primarily attributable to the capitalization of expenses associated with the Proleukin acquisition upon the transaction close.

截至 2023 年 6 月 30 日的第二季度，銷售、一般和管理費用增加了 2190 萬美元，與截至 2022 年 6 月 30 日的同期的 2630 萬美元相比，減少了 440 萬美元。截至2023 年6 月30 日止6 個月，與截至2022 年6 月30 日止同期的4,970 萬美元相比，僅增加30 萬美元。2023 年第二季度銷售、一般和管理費用與去年同期相比減少的主要原因是歸因於交易結束時與 Proleukin 收購相關的費用資本化。

Increase in other costs are explained by the timing of related spend compared to the prior year period, including marketing, advertising, licensing and insurance costs, partially offset by costs associated with the growth in the overall business. The minor increase in selling, general and administrative expense in the first half of 2023, compared to the prior year period was primarily attributable to growth of the internal general and administrative and commercial teams, offset by a decrease in legal fees and other costs. As of June 30, 2023, there were approximately 224.7 million common shares outstanding.

其他成本的增加是由於與上年同期相比相關支出的時間安排，包括營銷、廣告、許可和保險成本，部分被整體業務增長相關的成本所抵消。與上年同期相比，2023 年上半年銷售、一般和行政費用略有增加，主要是由於內部一般、行政和商業團隊的增長，但被法律費用和其他成本的減少所抵消。截至2023年6月30日，已發行普通股約為2.247億股。

I will now hand the call back to the operator to kick off the Q&A session.

我現在將把電話轉交給接線員以開始問答環節。

(Operator Instructions) Our first question comes from the line of Peter Lawson with Barclays.

（操作員說明）我們的第一個問題來自巴克萊銀行的 Peter Lawson。

Great. Maybe a quick question, just around, I guess, Jean-Marc, just around the cash runway. You said kind of into the end of '24 and I felt the prior guidance was early '25, if that was, one, if I got that right; and two, if there are any changes in terms that you were thinking through?

偉大的。也許是一個簡單的問題，我想，讓-馬克，就在現金跑道附近。你說的是 24 年底，我覺得之前的指導是 25 年初，如果是的話，如果我沒說錯的話；第二，您正在考慮的術語是否有任何變化？

Actually, we were guiding before first half of 2024. And with recent ways of -- let's say $162 million net proceeds, we are adding 2 quarters. So that's why we are commenting around into the end of 2024. Of course, this will depend also on the revenue generated by Proleukin on the one side and lifileucel on the other side. But let's say, we have 2 quarters more than what we indicated before.

實際上，我們在 2024 年上半年之前進行了指導。根據最近的方式（假設淨收益為 1.62 億美元），我們將增加 2 個季度。這就是為什麼我們要在 2024 年底之前發表評論。當然，這也將取決於一方面 Proleukin 和另一方面 lifileucel 產生的收入。但假設我們比之前表示的多了兩個季度。

Perfect. And then as we think about the upcoming data at World Lung, just, again, tell us about the number of patients and, in particular, I guess, the follow-up time that we see in the abstract versus the presentation?

完美的。然後，當我們思考世界肺臟即將發布的數據時，請再次告訴我們患者的數量，特別是我想，我們在摘要與演示中看到的隨訪時間？

Yes, Peter, that's still embargoed on the rolls until next week. But there will be, I think, substantial follow-up in the abstract and even more follow-up at the conference. I think it will be significant compared to what you've seen from us typically.

是的，彼得，直到下週，這仍然是禁運的。但我認為，抽象方面將會有實質性的後續行動，甚至在會議上會有更多的後續行動。我認為與您通常從我們這裡看到的相比，這將是重要的。

Got you. And is that also the case in the number of patients, not just follow-up time?

明白你了。不僅僅是隨訪時間，患者數量也是如此嗎？

No, it's primarily follow-up time that you're going to see. We're not going to see a huge increase in number of patients in the abstract or in the presentation.

不，您將看到的主要是後續時間。我們不會在摘要或演示中看到患者數量大幅增加。

Our next question comes from the line of Michael Yee with Jefferies.

我們的下一個問題來自 Michael Yee 和 Jefferies 的對話。

Congrats on the progress. We had 2. One was thinking about the anticipated launch, which I know you guys are excited about. And I went back to my old (inaudible) CAR T numbers and looking at them, [$264 million] or so. And I was just trying to understand, do you generally anticipate because of easier reimbursement and the codes as well as preparation for all the coverage that you talked about that this should be a strong launch and potentially better than some of the things that they had to deal with on the CAR T side? Maybe just talk to that a little bit as people think about the launch?

祝賀取得的進展。我們有 2 個。其中一個正在考慮預期的發布，我知道你們對此感到興奮。我回到了以前的（聽不清）CAR T 數字並查看了它們，[2.64 億美元]左右。我只是想了解，由於更容易的報銷和代碼以及對您談到的所有覆蓋範圍的準備，您是否普遍預期這應該是一次強有力的發布，並且可能比他們必須做的一些事情更好CAR T方面如何處理？也許只是在人們考慮發佈時稍微討論一下？

And then second question is following up on the lung cancer data. Can you just remind us how to put into context the 47% overall response rate in first line. Do you want to be similar to chemo combo? Do you want to be better? Is it about durability or onetime treatment? Can you just kind of put that into context versus what is already out there for first line and that would help us see the advantages of your therapy.

第二個問題是肺癌數據的跟進。您能否提醒我們如何將第一行 47% 的總體響應率融入到背景中？你想像化療組合一樣嗎？你想變得更好嗎？是關於耐久性還是一次性治療？您能否將其與現有的一線治療方法結合起來，這將有助於我們了解您的治療方法的優點。

Yes, Mike, we do think that our launch can be considerably stronger than what we may have seen from the CAR T products, I don't know exactly what product you're referring to. But as a general matter, we've gotten everything -- the stars are more aligned for us than they were at the time of the CAR T launches because of just a more navigable reimbursement landscape. For example, we've got the Medicare MS-DRG 18 code already established for lifileucel. We've learned a lot from their experience in terms of capacity planning, site onboarding, how to target individual centers and get them up and running, manufacturing capacity and so on. So yes, just as general matter, we anticipate a stronger launch. If I missed your point there, I could have Jim follow up with you on that.

是的，邁克，我們確實認為我們的推出比我們從 CAR T 產品中看到的要強大得多，我不知道你到底指的是哪種產品。但總的來說，我們已經得到了一切——與 CAR T 推出時相比，我們的星星更加一致，因為報銷環境更加便捷。例如，我們已經為 lifileucel 建立了 Medicare MS-DRG 18 代碼。我們從他們在產能規劃、現場啟動、如何定位各個中心並使其啟動和運行、製造能力等方面的經驗學到了很多。所以，是的，就像一般情況一樣，我們預計會有更強勁的發布。如果我沒聽懂你的觀點，我可以讓吉姆跟進你的情況。

On the lung data, I'd be looking at your benchmarks in particular for Cohort 3A. We're looking at the first 2 subgroups, which we call the ICI-naive and the chemo-refractory subgroups. And the comparators for those are the KEYNOTE-47 and KEYNOTE-189 trials, which showed ORRs in the 14% to 15% range with MDORs in the 7 to 11 months range. So I think we're looking at TIL plus pembro plus chemo being superior to that.

關於肺部數據，我會查看您的基準，特別是 3A 組的基準。我們正在研究前 2 個亞組，我們稱之為 ICI 初治亞組和化療難治性亞組。這些試驗的比較對像是 KEYNOTE-47 和 KEYNOTE-189 試驗，這些試驗顯示 ORR 在 14% 至 15% 範圍內，MDOR 在 7 至 11 個月範圍內。所以我認為我們正在考慮 TIL 加 pembro 加化療優於它。

And I think you quoted, by the way, I should add, Mike, you quoted a 47% ORR. That's the ORR across all 3 subgroups. The ORR in the 2 subgroups that are comparable to that is 58.3%. Friedrich mentioned that during his comments earlier.

我認為你引用了，順便說一句，我應該補充一下，邁克，你引用了 47% 的 ORR。這是所有 3 個亞組的 ORR。與之相當的 2 個亞組的 ORR 為 58.3%。弗里德里希在早些時候的評論中提到了這一點。

Our next question comes from the line of Tyler Van Buren with TD Cowen.

我們的下一個問題來自 Tyler Van Buren 和 TD Cowen 的對話。

I have a question on the lifileucel launch. So I'm curious what -- in reference to what the KOL mentioned on the call that you guys recently hosted, I'm curious to see what you guys exactly are doing to overcome the challenges of under-education among the physician community to facilitate more efficient referral upon launch.

我對 lifileucel 的發布有疑問。所以我很好奇——參考 KOL 在你們最近主持的電話會議上提到的內容，我很好奇你們到底正在做什麼來克服醫生社區教育不足的挑戰，以促進啟動後更有效的推薦。

Yes. So that one, I'd probably ask Jim and Brian to speak up there and just give a little bit of a summary what we're doing to work on referral patterns.

是的。因此，我可能會請吉姆和布萊恩在那裡發言，並簡要總結一下我們在推薦模式方面所做的工作。

Sure. This is Jim. Almost 60% of the patients are in the communities and referrals are going to be very important for us beyond the initial months of launch. Here, what we're doing is taking data-driven approaches to understand existing referral patterns as well as build an understanding of where these patients are in the community. We'll use personnel promotions, i.e., the sales force to go out and talk to the physicians with a high concentration of advanced melanoma patients. And then we'll use cost-effective nonpersonnel promotions to expand our reach and frequency to educate on lifileucel among community practices.

當然。這是吉姆。近 60% 的患者來自社區，在啟動的最初幾個月之後，轉診對我們來說非常重要。在這裡，我們正在做的是採用數據驅動的方法來了解現有的轉診模式，並了解這些患者在社區中的位置。我們將利用人員促銷，即銷售人員出去與晚期黑色素瘤患者高度集中的醫生交談。然後，我們將利用具有成本效益的非人事促銷來擴大我們的影響範圍和頻率，以在社區實踐中進行 lifileucel 教育。

Our next question comes from the line of Colleen Kusy with Baird.

我們的下一個問題來自科琳·庫西 (Colleen Kusy) 和貝爾德 (Baird) 的對話。

Congrats on all the progress. So as we're within now a number of months expected approval. Do you have any sense of pent-up demand at this stage? And is there any segmentation of the patient population in the market that you'll prioritize in the early portion of this launch based on patient characteristics or things of that nature?

祝賀所有的進展。因此，我們現在預計將在幾個月內獲得批准。現階段您有感受到被壓抑的需求嗎？在本次發布的早期階段，您是否會根據患者特徵或類似性質的因素優先考慮市場上的患者人群細分？

Yes. Let me add a few comments and then Jim can jump in here. We have a pretty good sense of pent-up demand. It's quite significant. We run an expanded access program, which we can -- which gives us some feel for how the demand is out there, plus we're in contact with all the investigators and patient advocate groups constantly.

是的。讓我添加一些評論，然後吉姆可以跳到這裡。我們對被壓抑的需求有很好的感覺。這是相當有意義的。我們運行了一個擴大的訪問計劃，我們可以這樣做——這讓我們對那裡的需求有一些了解，而且我們不斷與所有研究人員和患者倡導團體保持聯繫。

Jim, do you want to see if you can take the rest of that question?

吉姆，你想看看你是否能回答這個問題的其餘部分嗎？

Sure. Colleen, we do a very robust segmentation based upon claims data here in the U.S. market. So on the ATC side, we've segmented based upon the volume of patients and we've identified our top 20, 40, 60, et cetera ATCs as well as patients that are concentrated in the community. Because we have studied the CAR T market quite extensively, we know that there is a concentration of patients at the top centers. So those are the targets that we're going for first. And as we have those patients enter the treatment paradigm for lifileucel, we'll start to expand out into the community.

當然。科琳，我們根據美國市場的索賠數據進行了非常穩健的細分。因此，在 ATC 方面，我們根據患者數量進行了細分，並確定了排名前 20、40、60 等的 ATC 以及集中在社區的患者。因為我們對 CAR T 市場進行了相當廣泛的研究，所以我們知道患者集中在頂級中心。這些是我們首先要實現的目標。當我們讓這些患者進入 lifileucel 的治療模式時，我們將開始擴展到社區。

That's helpful. And then any more details you can share on how many centers are participating in the site onboarding process? And can you maybe just share any more details on what that process looks like for centers?

這很有幫助。然後您可以分享更多有關有多少中心參與網站入職流程的詳細信息嗎？您能否分享更多關於中心流程的細節？

Sure. I won't be able to share the exact numbers but I will reinforce our goal is to launch with targeted 40 centers within 3 months of approval and we are on track. What I will say is that there are more centers that are participating in the onboarding. So I think it is reflective of the unmet need and the excitement, again, amongst the ATCs. And I'm sorry, Colleen, can you repeat that second question?

當然。我無法透露確切的數字，但我會強調我們的目標是在批准後 3 個月內啟動 40 個目標中心，我們正在步入正軌。我要說的是，有更多的中心正在參與入職培訓。所以我認為這再次反映了 ATC 中未滿足的需求和興奮。對不起，科琳，你能重複一下第二個問題嗎？

Just any more details you can provide on what that process looks like for centers and how long that might take and how onerous that is.

您可以提供更多詳細信息，說明中心的流程是什麼樣的、可能需要多長時間以及有多繁重。

Sure. There's some administrative things that we do, like IT checks to make sure that the firewalls are compatible for our systems. But the heaviest work is really our medical affairs team, which works with the centers on their capabilities to understand and build workflows, SOPs, make sure that order sets are defined. The whole process, if a center is fully engaged, can be relatively short. If it's a center that's got a lot of competing demands, it could take a bit longer. For centers that are entering the process right now, I'm confident that they could, if they are fully committed, be ready for launch.

當然。我們會做一些管理工作，例如 IT 檢查以確保防火牆與我們的系統兼容。但最繁重的工作實際上是我們的醫療事務團隊，他們與各中心合作，發揮其理解和構建工作流程、SOP 的能力，確保定義訂單集。如果中心全力參與，整個過程可能會相對較短。如果這是一個有很多競爭需求的中心，那麼可能需要更長的時間。對於現在正在進入這一過程的中心，我相信，如果他們全力投入，他們可以為啟動做好準備。

Our next question comes from the line of Yanan Zhu with Wells Fargo.

我們的下一個問題來自朱亞男與富國銀行的對話。

I was wondering if you could give some broad stroke characterization of the ongoing BLA for lifileucel. In general, how is the process going? Are you at or nearing the mid-cycle review stage? Any concerns that might have arisen? And also, when might you have a date for pre-approval inspection?

我想知道您是否可以對 lifileucel 正在進行的 BLA 進行一些大致的描述。總體來說，進展如何？您是否處於或接近週期中期審查階段？可能出現任何問題嗎？另外，您什麼時候可以確定批准前檢查的日期？

Yes, it's going well right now. We're at the mid-cycle. We're past that period now, things continue to go well. Still no ADCOM. FDA has been pretty clear with us from the get-go, there aren't any major review issues. We won't comment publicly on when prelicensing inspections will occur but they typically occur later in the process. That's something obviously, a company like Iovance and our CMOs have -- are heavily (inaudible), working very hard on that right now. But otherwise, it's going very well. The FDA is very engaged. We've got a lot of back and forth that is very productive and we think that things remain on track for the PDUFA date of November 25, 2023.

是的，現在進展順利。我們正處於週期中期。現在我們已經過了那個時期，事情繼續進展順利。仍然沒有 ADCOM。 FDA 從一開始就向我們明確表示，不存在任何重大審查問題。我們不會公開評論何時進行預許可檢查，但它們通常會在流程的後期進行。顯然，像 Iovance 這樣的公司和我們的 CMO 目前正在為此投入大量（聽不清）、非常努力的工作。但除此之外，一切進展順利。 FDA 非常積極參與。我們進行了大量的反复討論，非常富有成效，我們認為在 2023 年 11 月 25 日 PDUFA 日期之前一切仍按計劃進行。

That's terrific to hear. Thanks for that update. Then I do have also a couple of questions on the IOV-LUN-202 and the pivotal program. And I was just wondering any additional color from your interaction with FDA for that setting? What kind of ORR and DOR is the agency looking for, for a pivotal data set? Or in other words, what might be the bar for approval and success for that trial? And could you also talk about the powering assumption for this 120-patient study and whether there is any opportunity for interim update?

聽到這真是太棒了。感謝您的更新。然後我確實還有一些關於 IOV-LUN-202 和關鍵程序的問題。我只是想知道您與 FDA 的互動對這種情況有什麼額外的影響嗎？對於關鍵數據集，該機構正在尋找什麼樣的 ORR 和 DOR？或者換句話說，該試驗獲得批准和成功的障礙是什麼？您能否也談談這項 120 名患者研究的有力假設以及是否有任何中期更新的機會？

Yes. Friedrich, do you want to take that one?

是的。弗里德里希，你想買那個嗎？

Sure. Yes. Thanks. Good questions. So I think one thing that we have to keep in mind is, whenever we're talking about single-arm data like this one, FDA always stresses that they will look at the totality of the data in oncology studies. That's oftentimes because that's the relevant endpoint that you can appropriately address with a design like this response rate. But they will also heavily look at duration of response and safety. So there is really no single number that FDA will tell you. If you repeat that, then you have yourself, again, it's really the totality of the data and they're looking at how, what you are presenting when you submit is comparing to available care.

當然。是的。謝謝。好問題。因此，我認為我們必須記住的一件事是，每當我們談論像這樣的單臂數據時，FDA 總是強調他們將查看腫瘤學研究中數據的整體性。這通常是因為這是相關的端點，您可以通過像這樣的響應率這樣的設計來適當地解決這個問題。但他們也會認真考慮響應的持續時間和安全性。所以FDA實際上不會告訴你一個單一的數字。如果你重複這一點，那麼你就再次擁有了自己，這實際上是數據的整體，他們正在研究你提交時所呈現的內容如何與可用的護理進行比較。

Right now, again, for response rates, that means docetaxel, (inaudible) might be something that they're looking at, where you have a range of ORRs but you have definitely short durability of responses. And that's something that they're looking at, which is exactly why we are excited about the data in LUN-202 right now where the durability looks really promising and safety is obviously an aspect as well. In a study like this, with a single arm design you would usually not do an interim analysis because it's really the final data that gives you the totality of data that is informative, you wouldn't necessarily stop based on in between reads with a smaller sample size. Does that your answer your question?

現在，對於反應率，這意味著多西紫杉醇（聽不清）可能是他們正在考慮的東西，其中您有一系列的 ORR，但您的反應持續時間肯定很短。這正是他們正在關注的東西，這正是我們現在對 LUN-202 中的數據感到興奮的原因，其中耐用性看起來非常有希望，而且安全性顯然也是一個方面。在這樣的研​​究中，採用單臂設計，您通常不會進行中期分析，因為它實際上是最終數據，為您提供信息豐富的數據總量，您不一定會基於較小的讀取之間停止樣本大小。這回答了你的問題嗎？

Yes, yes. It does. It does. I was also lastly, wondering, are you in a position to comment whether those patients who were -- who had a response and were ongoing as of the date of cutoff are still in ongoing response?

是的是的。確實如此。確實如此。最後，我想知道，您是否有權評論那些在截止日期之前有反應並且仍在持續反應的患者是否仍在持續反應中？

Yes. I can respond to this. What we shared just a short while ago was very hot off the press. So the data set that we disclosed was basically cross-checked a couple of days prior to when we shared. So that -- maybe that gives you a good idea on where we stand on that.

是的。我可以對此做出回應。不久前我們分享的內容在媒體上非常熱門。因此，我們披露的數據集基本上是在我們共享之前幾天進行了交叉檢查。所以——也許這能讓你更好地了解我們在這方面的立場。

Our next question comes from the line of Reni Benjamin with JMP Securities.

我們的下一個問題來自 JMP 證券公司的雷尼·本傑明 (Reni Benjamin)。

Congrats on the progress. Maybe just starting off, this might be for Jim. You talked about the 40 ATCs. Jim, about how many patients do you figure each -- I don't know, ATC could handle in a month or in a quarter. I think you mentioned that bed capacity is sufficient. Can you maybe help quantify what sufficient is, according to each of these ATCs? And do they vary significantly, for example, the top 20 versus the top 40 versus the top, call it, 60 or 80 in terms of capacity or are they all right around the same?

祝賀取得的進展。也許剛剛開始，這可能是為吉姆準備的。您談到了 40 個 ATC。吉姆，你估計每人有多少病人——我不知道，ATC 可以在一個月或一個季度內處理。我想你提到床位容量是足夠的。您能否根據這些 ATC 幫助量化什麼是充足？它們的差異是否很大，例如，前 20 名、前 40 名、前 40 名、前 40 名、前 60 名或 80 名的容量，還是都差不多？

Reni, thanks for the question. It's a terrific question. So we've looked at both the CAR T market as well as our own data. What we know is that there is a concentration. So the number is going to vary. Your top centers are going to have more patients compared to centers that are beyond 40 to 60, et cetera. And therefore, bed capacity is going to vary to some degree. What I'm not saying is that all hospitals will always have sufficient capacity but in general, as we've engaged the ATCs, they have reported that they would have sufficient capacity.

雷尼，謝謝你的提問。這是一個很棒的問題。因此，我們研究了 CAR T 市場以及我們自己的數據。我們所知道的是，有一個濃度。所以這個數字會有所不同。與超過 40 至 60 人等的中心相比，您的頂級中心將擁有更多的患者。因此，床位容量會有所不同。我並不是說所有醫院總是有足夠的能力，但總的來說，當我們與 ATC 接觸時，他們報告說他們將有足夠的能力。

In our corporate slide deck, we provided some numbers, both from HHS in the healthdata.gov, which characterizes hospital capacity overall and in our own internal team as we've been engaging with these ATCs for a while now we engage them on the number of beds often broken down to the various levels, various floors. So when I say that hospitals have sufficient capacity, it's based upon both of these data points.

在我們的公司幻燈片中，我們提供了一些數據，這些數據均來自healthdata.gov 中的HHS，這些數據描述了醫院的整體能力以及我們自己的內部團隊的能力，因為我們已經與這些ATC 合作了一段時間，現在我們與他們合作了解這些數字床位通常分為不同層次、不同樓層。因此，當我說醫院有足夠的能力時，這是基於這兩個數據點。

Got it. And just sticking with sales and marketing for a second, how big is the sales and marketing team right now? And by the time November 25 comes along, how big will it be?

知道了。繼續討論銷售和營銷，現在的銷售和營銷團隊有多大？到 11 月 25 日到來時，規模會有多大？

Sure. I won't give you a specific number but we're probably in the 30-plus range right now. About half of my team members come with previous cell therapy experience, including nurses and advanced nurse practitioners who've actually joined us from the ATCs themselves. We have a number of very experienced nurses who've actually onboarded and helped to treat patients on CAR T. So they've got a lot of experience on the team.

當然。我不會給你具體的數字，但我們現在可能在 30 多個範圍內。我的團隊成員中約有一半具有細胞治療經驗，其中包括實際上從 ATC 加入我們的護士和高級執業護士。我們有許多經驗豐富的護士，他們實際上已經加入並幫助治療過 CAR T 患者。所以他們在團隊中擁有豐富的經驗。

In terms of the onboarding right now, the existing team between commercial and medical affairs is sufficient to drive the onboarding process. So I won't need to hire the actual sales team until we get a little bit closer.

就目前的入職而言，現有的商業和醫療事務團隊足以推動入職流程。因此，在我們更接近之前，我不需要雇用真正的銷售團隊。

Got it. Okay. And you guys provided a little bit of a goalpost for the non-small cell pivotal study in terms of completing enrollment at the, call it, second half of 2024. Can you give us any sense as to how the cervical cancer trial is going and whether you have an idea as to when enrollment may complete there?

知道了。好的。你們為非小細胞關鍵研究提供了一點目標，即在 2024 年下半年完成註冊。您能給我們介紹一下宮頸癌試驗的進展情況嗎？您是否知道那裡的註冊何時可以完成？

No, we haven't guided on that study. That -- obviously, we had to restart that entire program after the approval of pembrolizumab in frontline setting and other companies had to withdraw their BLAs. So it's going. We try to leverage the existing sites and it's running. But it's not the type of study where we can project enrollment right now. We're trying to just enroll as fast as we can. And now this new patient population has been created by the approvals.

不，我們還沒有指導這項研究。顯然，在派姆單抗在一線環境中獲得批准後，我們​​必須重新啟動整個計劃，而其他公司則必須撤回其 BLA。所以就這樣了。我們嘗試利用現有網站並且它正在運行。但這不是我們現在可以預測入學人數的研究類型。我們正在努力盡快註冊。現在，這個新的患者群體已經通過批准而創建了。

Got it. And just one final one for me. As we think about the next-generation TILs, genetically modified TILs, how should we be thinking about it in terms of how those products exist with the -- what will hopefully be currently approved TIL products? And how do we think about potential cannibalization? Or is there a way to position those second-generation drugs so that both can kind of coexist in the same commercial space?

知道了。對我來說，這只是最後一件事。當我們考慮下一代 TIL（轉基因 TIL）時，我們應該如何考慮這些產品如何與當前批准的 TIL 產品共存？我們如何看待潛在的蠶食？或者有沒有辦法定位這些第二代藥物，以便兩者可以在同一個商業空間中共存？

Well, you're asking about the second generation and beyond drugs that we're developing based on the TIL platform at Iovance. We don't necessarily have to cannibalize our indications. We can develop those other genetically modified TIL therapies, for example, into different indications. It's not like we have to continuously launch in melanoma. There's plenty of solid tumor indications out there that look to be promising that show some signs of responsiveness to either IPI or TILs are combined but need additional efficacy to get over the hurdle and that will be where we're focused. And that necessarily -- not necessarily are the same indications that we would be seeking approval in or getting approval in the near future.

嗯，您問的是我們基於 Iovance 的 TIL 平台開發的第二代及後續藥物。我們不一定要蠶食我們的指示。例如，我們可以開發其他轉基因 TIL 療法，用於不同的適應症。我們並不需要不斷地針對黑色素瘤開展研究。有很多實體瘤適應症看起來很有希望，顯示出對 IPI 或 TIL 組合的一些反應跡象，但需要額外的功效來克服障礙，這將是我們關注的重點。這不一定是我們將在不久的將來尋求批准或獲得批准的相同跡象。

Our next question comes from the line of Ben Burnett with Stifel.

我們的下一個問題來自本·伯內特 (Ben Burnett) 和斯蒂菲爾 (Stifel) 的對話。

This is Carolina Ibanez-Ventoso on for Ben Burnett. In a scenario where lifileucel gets approved and you treat an initial bolus of melanoma patients who have already progressed on an anti-PD-1 and then separately, lifileucel is also available in combination with pembro through the TILVANCE trial, how do you think physicians will treat newcomers? Will they treat the new coming patients with a sequence of pembro and then if the patient progresses with lifileucel? Or do you think there will be situations where doctors may want to try to keep the tumor hard from the onset with lifileucel and pembro combination?

我是本·伯內特 (Ben Burnett) 的卡羅萊納·伊巴內斯·文托索 (Carolina Ibanez-Ventoso)。如果 lifileucel 獲得批准，您對接受抗 PD-1 治療後病情已出現進展的黑色素瘤患者進行初始推注治療，然後通過 TILVANCE 試驗單獨使用 lifileucel 與 pembro 聯合​​使用，您認為醫生會如何看待對待新人？他們會用一系列 pembro 治療新來的患者，然後如果患者使用 lifileucel 治療病情進展嗎？或者您認為在某些情況下，醫生可能會嘗試使用 lifileucel 和 pembro 組合從一開始就使腫瘤保持堅硬？

So it's a good question. We will have this Phase III study up and running and it's a clinical trial. So I would -- we anticipate majority of doctors will be wanting to treat their post-PD-1 patients on lifileucel commercially approved, which is going to be much more available than what one can get from a clinical trial setting. However, sites that have access to the trial or more have a deeper understanding of how ICIs and TILs combine, might be interested in using the TILVANCE study more preferably. And that's why we'll have it open it United States as well as outside the U.S. to drive that enrollment.

所以這是一個好問題。我們將啟動並運行這項第三期研究，這是一項臨床試驗。因此，我們預計大多數醫生會希望使用商業批准的 lifileucel 來治療他們的 PD-1 後患者，這將比從臨床試驗環境中獲得的藥物更容易獲得。然而，能夠參與該試驗或對 ICI 和 TIL 如何結合有更深入了解的網站可能有興趣更好地使用 TILVANCE 研究。這就是為什麼我們將其開放給美國以及美國以外的地區，以推動招生。

Okay. Understood. And then a quick clarification question for Jean-Marc. On the (inaudible) guidance, the extension to second half 2024, does it include any potential revenues from Proleukin and lifileucel?

好的。明白了。然後向讓-馬克提出一個快速澄清的問題。關於（聽不清）指導意見，即延長至 2024 年下半年，是否包括 Proleukin 和 lifileucel 的任何潛在收入？

Yes, we are taking into account only Proleukin revenue at this stage because, of course, we cannot -- although we are very positive about the approval, we don't want to take lifileucel revenue into account. So it's only Proleukin that I take into account in my [quotation].

是的，我們現階段只考慮 Proleukin 的收入，因為我們當然不能——儘管我們對批准非常積極，但我們不想考慮 lifileucel 的收入。所以我在[引文]中只考慮了Proleukin。

Our next question comes from the line of Asthika Goonewardene with Truist.

我們的下一個問題來自 Asthika Goonewardene 與 Truist 的對話。

I'll echo my positive sentiment for the progress we made here. First off, just want to direct the question at Fred. Fred, when we spoke last at Symposia Cell conference a couple of months ago, when we discussed centers building capacity, you mentioned that some centers were building capacity at about -- to treat about 25 or more patients a month. So I want to just maybe check back (inaudible) on this. Can you quantify what proportion of these 40 centers that you're targeting in the first 3 months after approval are gearing up the capacity to treat this number of about 25 patients a month? Is it a majority, a significant proportion or a minority? And then I've got a couple more questions.

我將表達我對我們在這裡取得的進展的積極看法。首先，我想向 Fred 提問。 Fred，幾個月前，當我們在 Symposia Cell 會議上最後一次發言時，當我們討論中心建設能力時，您提到一些中心正在建設能力，每月大約治療 25 名或更多患者。所以我想也許再檢查一下（聽不清）這一點。您能否量化您在批准後的前 3 個月內瞄準的 40 個中心中，有多少比例正在提高每月治療約 25 名患者的能力？是多數、相當大的比例還是少數？然後我還有幾個問題。

Yes. So that -- Jim partially answered that question a little bit earlier. There's a slide in our deck, I believe it's Slide 38 that has in it some data that we collected. And that's where the 25 number is coming from that I would have mentioned at the conference, when we were there speaking. It's basically the number -- it's the average number of beds for target ATC per month suitable for lifileucel patients. That's what the number is.

是的。所以——吉姆早些時候部分回答了這個問題。我們的幻燈片中有一張幻燈片，我相信是幻燈片 38，其中包含我們收集的一些數據。這就是 25 這個數字的來源，當我們在那裡講話時，我會在會議上提到這個數字。它基本上是數字——目標 ATC 每月適合 lifileucel 患者的平均床位數量。就是這個數字。

So that -- obviously, that's an average and you're going to have a minimum and maximum there and there's a whole series of statistics there but that's the average. We have the data. We're trying to keep some of that confidential because some of that is confidential sites. But the average is about 25 beds for targeting ATC per month that are suitable for lifileucel patients. Like Jim said earlier, there could be some that are lower, there could be some that are higher. The big centers are going to have more. It all comes down to the amount of investment the hospital is making in its BMT, CAR-T and TIL service lines.

所以，顯然，這是一個平均值，那裡會有最小值和最大值，並且那裡有一系列統計數據，但這就是平均值。我們有數據。我們正在努力對其中一些內容保密，因為其中一些是機密網站。但平均每月大約有 25 張適合 lifileucel 患者的靶向 ATC 床位。正如吉姆之前所說，可能有一些較低，也可能有一些較高。大型中心將會有更多。這一切都取決於醫院在 BMT、CAR-T 和 TIL 服務領域的投資金額。

Got it. Okay, that's helpful. And then when you stress tested your production facility and gone full production, about how many batches of cells can you manufacture at full capacity?

知道了。好的，這很有幫助。然後當你對你的生產設施進行壓力測試並全面投產時，你大約可以滿負荷生產多少批次的電池？

We haven't disclosed how much we can manufacture in what you call stress tests. We do things called capacity demonstrations, as part of what we do to demonstrate to the regulatory authorities that we can manufacture at scale here. And what we've done so far is consistent with what we've disclosed for the site -- the sites, both Iovance and our CMO, in terms of the capacity that we're projecting for the market.

我們還沒有透露在你們所說的壓力測試中我們可以生產多少。我們會做一些叫做產能演示的事情，這是我們向監管機構展示我們可以在這里大規模生產的一部分。就我們為市場預測的容量而言，我們迄今為止所做的與我們為該站點（Iovance 和我們的 CMO）所披露的內容是一致的。

So if you go to our deck and look at the number of patients, we said we can accommodate at our facilities. You could assume that we've got capacity that's within those boundaries or ramping up to those boundaries. We haven't put the exact number out but that's something that we're focused very much on internally and work with FDA on.

因此，如果您到我們的甲板上查看患者數量，我們會說我們的設施可以容納。您可以假設我們的容量在這些邊界內或正在增加到這些邊界。我們還沒有公佈確切的數字，但這是我們內部非常關注並與 FDA 合作的事情。

Got it. Okay. And then I don't know if Raj is available on the call here. But I appreciate there hasn't been a request for an ADCOM but maybe if Raj can comment based on experience, what would be a scenario that would prompt the FDA to ask for an ADCOM?

知道了。好的。然後我不知道 Raj 是否可以接聽這裡的電話。但我很高興還沒有提出建立 ADCOM 的請求，但也許如果 Raj 可以根據經驗發表評論，那麼什麼情況會促使 FDA 要求建立 ADCOM？

This is Raj. So thanks for the question. I don't expect that FDA will seek any ADCOM at this point. Based on our -- as Fred mentioned earlier in the call, that we have a frequent interaction with the FDA and it's all -- it's a routine as a part of the BLA review process, nothing we have identified or FDA so far that will take it to ADCOM. So late in the review cycle and so I'm not expecting any outcome at this point.

這是拉吉。謝謝你的提問。我預計 FDA 目前不會尋求任何 ADCOM。正如 Fred 之前在電話會議中提到的那樣，我們與 FDA 經常進行互動，這只是 BLA 審查流程的一部分，到目前為止，我們沒有發現任何情況，FDA 也不會採取任何行動。到 ADCOM。審查週期已經很晚了，所以我目前不期望有任何結果。

Great. I like the confidence there, Raj. And then last one, if I can, to Friedrich. On 4001, is there any possibility of an update this year? Apologies if I missed this, if you mentioned this earlier but that's my last question.

偉大的。我喜歡那裡的自信，拉傑。最後一位，如果可以的話，寫給弗里德里希。 4001今年有更新的可能嗎？如果我錯過了這一點，如果你之前提到過這一點，我深表歉意，但這是我的最後一個問題。

Yes, I think I already -- and thanks for the question. We haven't provided guidance on the timing on updates on that study. So I think bear with us, we will once there's something to update on.

是的，我想我已經——謝謝你的提問。我們尚未就該研究的更新時間提供指導。因此，我認為請耐心等待，一旦有需要更新的內容，我們就會進行更新。

Our next question comes from the line of Joe Catanzaro with Piper Sandler.

我們的下一個問題來自喬·卡坦扎羅和派珀·桑德勒的對話。

Maybe a couple of follow-ups on a couple of things that's been covered. Maybe first on cervical. Does another FDA interaction need to happen there to firm up some things? Or is the challenge simply around projecting time lines because of enrollment pace?

也許對已經討論過的幾件事進行一些後續行動。也許首先是頸椎。是否需要與 FDA 進行另一次互動來確定某些事情？或者挑戰僅僅是因為招生速度而導致的預計時間線？

And then second question, just wondering if you could say anything about the progress you've made on TILVANCE-301. And whether you have expectations that the FDA might ask for a status report of that trial ahead of the November PDUFA?

然後是第二個問題，只是想知道您是否可以談談您在 TILVANCE-301 上取得的進展。您是否預計 FDA 可能會在 11 月 PDUFA 之前要求提供該試驗的狀態報告？

Yes, I can take this. The -- so in cervical, it's more about the size of the patient population. It's not a large patient population than it is about regulatory interactions. We've already had a lot of regulatory interactions with FDA on that. We feel pretty comfortable where we are at. It doesn't mean we won't have additional interactions leading into a potential BLA there but we need to focus right now on just enrolling.

是的，我可以接受這個。因此，對於頸椎病，更重要的是患者群體的規模。這並不是一個龐大的患者群體，而是監管相互作用的問題。我們已經就此與 FDA 進行了很多監管互動。我們現在所處的位置感覺很舒服。這並不意味著我們不會有額外的互動導致潛在的 BLA，但我們現在需要專注於註冊。

With respect to TILVANCE-301, the FDA remains in close contact with us about that study to make sure it's well underway and we feel quite comfortable with where we are and what we disclose to them. They do ask about that and we have given them updates.

關於 TILVANCE-301，FDA 仍就該研究與我們保持密切聯繫，以確保該研究順利進行，並且我們對我們的現狀以及我們向他們披露的內容感到非常滿意。他們確實詢問了這一點，我們已經向他們提供了最新情況。

Our next question comes from the line of Mara Goldstein with Mizuho.

我們的下一個問題來自 Mara Goldstein 和 Mizuho 的關係。

I had a question on the LUN-202 study, then just a follow-up on Proleukin. On the study, you're going to enroll PD-01 patients with scores greater than 1% and less than 1%, are they prestratified into set numbers or is it (inaudible)?

我有一個關於 LUN-202 研究的問題，然後是關於 Proleukin 的後續問題。在這項研究中，您將招募分數大於 1% 和小於 1% 的 PD-01 患者，他們是否被預先分層到設定的數字中，還是（聽不清）？

No. It's going to be a total sample size of 120 we're going into across the 2 cohorts.

不會。我們對 2 個隊列進行的總樣本量為 120 個。

Okay. So there's no particular number of one versus the other in that trial?

好的。那麼在那場審判中，沒有具體的一人與另一人的人數嗎？

No, we expect it to be relatively evenly balanced.

不，我們希望它能夠相對均衡。

Okay. And then Jim, can you really help us understand a little bit about Proleukin ex, obviously, commercialization with lifileucel given the revenue that you recognized in the short period of time that you're open relative to the COGS and just how we should think about that on a go-forward basis?

好的。然後，Jim，您能否真正幫助我們了解一些有關 Proleukin ex 的信息，顯然，考慮到您在相對於 COGS 開放的短時間內確認的收入，以及我們應該如何考慮 lifileucel 的商業化是在前進的基礎上嗎？

So you're asking -- Mara, you're asking about ex U.S. revenues without lifileucel?

所以你問——Mara，你問的是沒有 lifileucel 的情況下美國前的收入？

Yes. In terms of focusing (inaudible).

是的。在聚焦方面（聽不清）。

Yes. So Proleukin outside the United States is priced at relatively modest numbers right now and the sales were not particularly high. So that's not something we look at as a major revenue driver for us, if that's what you're asking.

是的。因此，Proleukin 目前在美國以外的定價相對適中，銷量也不是特別高。因此，如果您想問的話，我們並不將其視為主要收入驅動因素。

Now upon launch of lifileucel that could become more significant but it's still a lot different outside the U.S. than it is in the U.S. because of the pricing difference.

現在，隨著 lifileucel 的推出，這可能會變得更加重要，但由於價格差異，在美國以外的地區與在美國仍然有很大不同。

Right. But it's still, on its own, profitable, correct?

正確的。但它本身仍然有利可圖，對嗎？

Outside the U.S., is it profitable? I don't know. It's a -- it can make a -- you can make a profit on it outside the U.S. but it's nowhere near like it in the United States.

在美國以外的地區是否有利可圖？我不知道。你可以在美國以外的地方從中獲利，但這與在美國的情況相差甚遠。

Our question comes from the line of Kelsey Goodwin with Guggenheim.

我們的問題來自凱爾西·古德溫與古根海姆的關係。

I guess, first, could you just remind us maybe of the efficacy bar in cervical cancer, kind of given the evolving landscape that you mentioned and especially since the last time we saw a data cut there.

我想，首先，考慮到您提到的不斷變化的情況，特別是自從我們上次看到那裡的數據削減以來，您能否提醒我們宮頸癌的療效欄。

And then maybe just to confirm based on your interactions with the FDA, are we still leaning towards the label, including the pooled data of Cohorts 2 and 4? And that's it for me.

然後也許只是根據您與 FDA 的互動來確認，我們是否仍然傾向於標籤，包括隊列 2 和隊列 4 的匯總數據？對我來說就是這樣。

Yes. While I take the second part and then I'll hand -- ask Friedrich to take the first part. Yes, the FDA has given us favorable feedback, including at the pre-BLA meeting on the full data. And so yes, we do continue to think that there is a possibility we can get that on the label, a good possibility that we'll have some indication of full data on the label. That's something we're working towards, obviously.

是的。當我接受第二部分時，然後我會請弗里德里希接受第一部分。是的，FDA 給了我們有利的反饋，包括在 BLA 前會議上就完整數據提供的反饋。所以，是的，我們確實繼續認為我們有可能在標籤上得到這些信息，很有可能我們會在標籤上顯示完整數據的一些指示。顯然，這就是我們正在努力的方向。

Friedrich, do you want to take the question about the bar for cervical?

Friedrich，您想回答有關頸椎棒的問題嗎？

Sure. The bar is low. Where we are right now, we're basically similar to how we're seeing this happen in lung cancer where checkpoint inhibition has moved into frontline in combination with chemo. Now the post PD-1 and the post frontline setting is wide open again. The data that are available from time where folks were then looking at second and third line therapy for cervical cancer with other chemotherapeutics, either as monotherapy or other combinations were pretty dismal, with response rates reported between, like between 3% and below 10%. So the bar is really low and the unmet medical need is high.

當然。門檻很低。我們現在的情況基本上與我們在肺癌中看到的情況類似，檢查點抑制已與化療結合進入前線。現在，後PD-1和後前線設置再次敞開。當時人們在尋找與其他化療藥物聯合治療宮頸癌的二線和三線療法（無論是單一療法還是其他組合療法）時獲得的數據相當慘淡，報告的反應率介於 3% 和 10% 以下之間。所以門檻確實很低，而未滿足的醫療需求很高。

And I'm currently showing no further questions at this time. I'd now like to turn the call back over to Fred Vogt for closing remarks.

目前我沒有提出任何進一步的問題。現在我想將電話轉回給 Fred Vogt，讓其作結束語。

Thank you, again, for joining the Iovance Biotherapeutics Second Quarter 2023 Financial Results and Corporate Updates Conference Call. We've had an exciting start to 2023 with the acceptance of the BLA, the close of the Proleukin agreement, the important updates in lung cancer while delivering on our key regulatory commercial, manufacturing and pipeline activities.

再次感謝您參加 Iovance Biotherapeutics 2023 年第二季度財務業績和公司動態電話會議。隨著 BLA 的接受、Proleukin 協議的結束、肺癌方面的重要更新，同時開展我們關鍵的監管商業、製造和管道活動，我們在 2023 年有了一個令人興奮的開端。

I'm grateful for the patients, physicians and regulators as well as our employees and cross-functional teams in advancing our mission to be a global leader in TIL therapy. I would also thank our shareholders and covering analysts for their support. Please feel free to reach out to our Investor Relations team for follow-up. Thank you.

我感謝患者、醫生和監管機構以及我們的員工和跨職能團隊，感謝他們推動我們成為 TIL 治療全球領導者的使命。我還要感謝我們的股東和分析師的支持。請隨時聯繫我們的投資者關係團隊進行跟進。謝謝。

This concludes today's conference call. Thank you for joining. You may now disconnect.

今天的電話會議到此結束。感謝您的加入。您現在可以斷開連接。