Iovance Biotherapeutics Inc (IOVA) 2022 Q1 法說會逐字稿

Welcome to the Iovance Biotherapeutics First Quarter 2022 Financial Results. My name is Andrew, and I will be your operator for today's call. (Operator Instructions)

歡迎閱讀 Iovance Biotherapeutics 2022 年第一季度財務業績。我叫安德魯，我將擔任您今天通話的接線員。 （操作員說明）

Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Sara, you may begin.

請注意，本次會議正在錄製中。我現在將把電話轉給 Iovance 投資者和公共關係副總裁 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 Senior Vice President, Commercial; Dr. Friedrich Finckenstein, our Chief Medical Officer; Dr. Madan Jagasia, our Senior Vice President, Medical Affairs; and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine is also on the call to participate in the question-and-answer 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，我們的商務高級副總裁；我們的首席醫療官 Friedrich Finckenstein 博士； Madan Jagasia 博士，我們的醫療事務高級副總裁；以及我們的首席財務官 Jean-Marc Bellemin。我們的監管策略和轉化醫學執行副總裁 Raj Puri 博士也應邀參加問答環節。

This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the 3 months ended on March 31, 2022, as well as recent corporate updates. 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, pre-commercial activities, clinical trials and regulatory plans and results, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, collaboration, 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.

今天下午，我們發布了一份新聞稿，您可以在我們的網站 iovance.com 上找到該新聞稿，其中包括截至 2022 年 3 月 31 日的 3 個月的財務業績以及最近的公司更新。在開始之前，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、預商業活動、臨床試驗和監管計劃和結果、研究和臨床前活動的前瞻性聲明、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、協作、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 our positive start to the year at Iovance during today's conference call. First and foremost, we are moving rapidly towards our first-ever BLA submission for our lead TIL therapy, lifileucel and metastatic melanoma. This is our top priority at Iovance. As we announced last month, we received positive feedback from the FDA regarding our potency assays and assay matrix for lifileucel. For next steps, we intend to hold a pre-BLA meeting in July 2022 and submit the BLA in August 2022. In addition, we continue discussions with the FDA about our registrational strategies in cervical cancer and non-small cell lung cancer so that we may offer TIL therapy to patients with significant unmet need in these additional tumor types. As we prepare to launch lifileucel, we are also making progress in our commercial readiness and internal manufacturing capabilities at the Iovance Cell Therapy Center, or iCTC, in Philadelphia. Our organization is growing to further our mission of innovating, developing and delivering TIL therapies. We now have nearly 400 employees at the company who have on average within 4 years of cell therapy experience. The talent within our organization is a testament to the potential of our Iovance TIL therapy and our global leadership within the field. We're excited about the momentum for our growing TIL pipeline. We continue to enroll patients across 4 Iovance-sponsored clinical trials and plan to initiate 2 additional trials this year. The FDA has allowed an IND to proceed for a clinical trial of our PD-1 inactivated, gene-edited TIL therapy, IOV-4001. We also plan to conduct a Phase III trial of TIL in combination with pembrolizumab in frontline melanoma, where clinical data demonstrated the potential to improve patient outcomes compared with pembrolizumab alone in patients who are naive to immune checkpoint inhibitors. As we prepare to launch the first one-time cell therapy in solid tumors, we believe that our TIL platform, clinical data and people set a strong foundation to establish Iovance TIL therapy as the next class of paradigm-shifting therapies for people with cancer. Manufacturing and managing demand for new cell therapy is key to our success.

謝謝薩拉，大家下午好。我很高興在今天的電話會議上強調 Iovance 今年的積極開局。首先也是最重要的，我們正在快速推進我們的主要 TIL 療法 lifileucel 和轉移性黑色素瘤的首次 BLA 提交。這是我們 Iovance 的首要任務。正如我們上個月宣布的那樣，我們收到了 FDA 關於 lifileucel 效力測定和測定矩陣的積極反饋。下一步，我們計劃於 2022 年 7 月召開 BLA 預審會議，並於 2022 年 8 月提交 BLA。此外，我們將繼續與 FDA 討論我們在宮頸癌和非小細胞肺癌方面的註冊策略，以便我們能夠可能會為這些其他腫瘤類型中未滿足顯著需求的患者提供TIL 治療。在我們準備推出 lifileucel 的同時，我們也在費城 Iovance 細胞治療中心 (iCTC) 的商業準備和內部製造能力方面取得進展。我們的組織正在不斷發展，以進一步推進我們創新、開發和提供 TIL 療法的使命。我們公司現在有近400名員工，平均擁有4年以內的細胞治療經驗。我們組織內的人才證明了我們 Iovance TIL 療法的潛力以及我們在該領域的全球領導地位。我們對 TIL 管道不斷增長的勢頭感到興奮。我們繼續在 Iovance 贊助的 4 項臨床試驗中招募患者，併計劃今年啟動另外 2 項試驗。 FDA 已允許對我們的 PD-1 滅活基因編輯 TIL 療法 IOV-4001 進行 IND 臨床試驗。我們還計劃在一線黑色素瘤中進行TIL 與派姆單抗聯合治療的III 期試驗，其中臨床數據表明，與單獨使用派姆單抗相比，對於未接受過免疫檢查點抑製劑的患者來說，有可能改善患者的預後。當我們準備推出第一個實體瘤一次性細胞療法時，我們相信我們的 TIL 平台、臨床數據和人員為將 Iovance TIL 療法打造成下一類癌症患者的範式轉變療法奠定了堅實的基礎。製造和管理新細胞療法的需求是我們成功的關鍵。

So I'll ask Igor to talk more about our progress in these areas.

所以我會請伊戈爾更多地談談我們在這些領域的進展。

Thank you, Fred. Across our manufacturing network, we continue to focus on patient needs and operational excellence, maintaining a TIL manufacturing success rate of more than 90% in more than 500 patients treated with Iovance TIL therapy. Today, I will summarize key activities of the Iovance Cell Therapy Center, or iCTC, which is our 136,000 square foot cell therapy manufacturing facility. Recently, Iovance was honored by the International Society for Pharmaceutical Engineering with the 2022 Facility of the Year category award for iCTC, a remarkable reflection of what we have accomplished since the initial groundbreaking of this facility only 3 years ago. At iCTC, the main priority remains preparation for the BLA and commercial launch. We designed iCTC to have the capacity to provide commercial and clinical TIL supply for thousands of patients per year. We expect iCTC to handle most of our commercial demand at launch with the added flexibility to use contract manufacturing to optimally manage capacity and address patient demand. We are performing numerous activities to support the BLA submission at iCTC in parallel with clinical manufacturing, which began at iCTC last year. In addition, we are on track in preparing the iCTC and our contract manufacturer facility for BLA, for FDA approval inspections, which we expect to occur as part of the BLA review process. In addition to manufacturing, we have established a strong quality control, or QC Group, at iCTC. The QC team performs release testing of 2 products, which will include commercial release testing of lifileucel upon potential approval. In collaboration with our analytical development group, our QC team has been completing BLA-related activities needed for our 2 potency assays and assay matrix, including our new potency co-culture assay.

謝謝你，弗雷德。在我們的製造網絡中，我們繼續關注患者需求和卓越運營，在 500 多名接受 Iovance TIL 治療的患者中保持 TIL 製造成功率超過 90%。今天，我將總結 Iovance 細胞治療中心 (iCTC) 的主要活動，該中心是我們佔地 136,000 平方英尺的細胞治療製造工廠。最近，Iovance 榮獲國際製藥工程學會 iCTC 2022 年度設施類別獎，這充分反映了我們自三年前該設施奠基以來所取得的成就。在 iCTC，主要優先事項仍然是 BLA 和商業發布的準備工作。我們設計的 iCTC 具有每年為數千名患者提供商業和臨床 TIL 供應的能力。我們預計 iCTC 能夠在推出時滿足我們的大部分商業需求，並增加使用合同製造的靈活性，以優化管理產能並滿足患者需求。我們正在開展大量活動，以支持 iCTC 提交 BLA，同時開展臨床生產（去年在 iCTC 開始）。此外，我們正在為 iCTC 和我們的合同製造商工廠準備 BLA，以接受 FDA 批准檢查，我們預計這將作為 BLA 審查流程的一部分進行。除了製造之外，我們還在 iCTC 建立了強大的質量控製或 QC 小組。 QC 團隊對 2 種產品進行發布測試，其中包括潛在批准後的 lifileucel 商業發布測試。我們的 QC 團隊與我們的分析開發小組合作，完成了 2 個效力測定和測定矩陣所需的 BLA 相關活動，包括我們新的效力共培養測定。

Turning to our Intellectual Property, or IP. We continue to build our robust and growing IP portfolio to support our proprietary manufacturing processes as well as our know-how surrounding TIL therapy. We currently own more than 40 granted or allowed U.S. and international patents. This IP covers TIL compositions and methods of treatment and manufacturing in a broad range of cancers, including Gen 2 patent rights that are expected to provide exclusivity into 2038.

轉向我們的知識產權（IP）。我們繼續構建強大且不斷增長的知識產權組合，以支持我們的專有製造工藝以及 TIL 治療相關的專業知識。我們目前擁有 40 多項已授予或允許的美國和國際專利。該知識產權涵蓋多種癌症的 TIL 組合物以及治療和製造方法，包括預計在 2038 年之前提供排他性的第 2 代專利權。

I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations. Over to you, Jim.

我現在想把電話轉給吉姆·齊格勒，強調我們的商業發布準備工作。交給你了，吉姆。

Thank you, Igor. Our cross-functional team has built the foundation to scale rapidly and efficiently from BLA submission into launch and commercialization. We are partnering with the leading U.S. cancer centers to develop their TIL service line capabilities, and we aim to have at least 40 authorized treatment centers, or ATCs, for launch. The key onboarding and training activities are also aligned with the BLA-related milestones to ensure just-in-time training and readiness at our ATCs. Our market access team continues to engage commercial, state and federal payers such as the Centers for Medicare and Medicaid Services, or CMS, to ensure patients have appropriate and timely access to lifileucel. CMS released the fiscal year 2023 in-patient prospective payment, or IPPS, and proposed rules as part of their annual process in April. In this draft rule, CMS proposes the continued policies that were finalized in the fiscal year 2022 rule making cycle, which expanded DRG 18 for CAR-Ts and other immunotherapies, including lifileucel. This means hospitals will have more appropriate payment for Medicare beneficiaries upon lifileucel approval. In the rule, CMS also summarizes the new technology add-on payment, or NTAP applications, including lifileucel. With the anticipated BLA timelines, we plan to submit our NTAP application in the next fiscal cycle. We appreciate the positive steps CMS has taken to improving Medicare patient access to cell therapies, and we look forward to working with CMS and other key stakeholders to ensure access for the emerging class of cell therapies.

謝謝你，伊戈爾。我們的跨職能團隊已經奠定了從 BLA 提交到啟動和商業化快速高效擴展的基礎。我們正在與美國領先的癌症中心合作開發他們的 TIL 服務線能力，我們的目標是擁有至少 40 個授權治療中心 (ATC) 可供啟動。關鍵的入職和培訓活動也與 BLA 相關的里程碑保持一致，以確保我們的 ATC 及時進行培訓和準備。我們的市場准入團隊繼續與商業、州和聯邦付款人（例如醫療保險和醫療補助服務中心 (CMS)）合作，以確保患者能夠適當且及時地獲得 lifileucel。 CMS 於 4 月份發布了 2023 財年住院患者預期付款 (IPPS) 並提出了規則，作為其年度流程的一部分。在這份規則草案中，CMS 提出了在 2022 財年規則制定週期中最終確定的持續政策，擴大了 CAR-T 和其他免疫療法（包括 lifileucel）的 DRG 18。這意味著在 lifileucel 獲得批准後，醫院將為醫療保險受益人獲得更適當的付款。在規則中，CMS還總結了新技術附加支付，或NTAP應用，包括lifileucel。根據預期的 BLA 時間表，我們計劃在下一個財政週期提交 NTAP 申請。我們讚賞 CMS 為改善醫療保險患者獲得細胞療法的機會而採取的積極步驟，我們期待與 CMS 和其他主要利益相關者合作，確保獲得新興細胞療法。

In addition to supporting access, we are also developing our proprietary IovanceCares program to assist health care providers and patients through every step of their TIL journey. Our goal is to deliver a best-in-class cell ordering, chain of identity, chain of custody and patient support program for launch.

除了支持訪問之外，我們還開發了專有的 IovanceCares 計劃，以幫助醫療保健提供者和患者完成 TIL 旅程的每一步。我們的目標是提供一流的細胞訂購、身份鏈、監管鍊和患者支持計劃以供啟動。

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 share recent updates for our TIL clinical programs. We have made great strides in evolving our TIL technology platform to incorporate additional therapies and technologies to address more cancer patients and new tumor types and indications. The important proof of concept for TIL in combination with pembrolizumab in multiple solid tumors as well as our IND-enabling work to proceed to clinical trials with IOV-4001, are 2 prime examples of our platform expansion and commitment to innovation. Our strategy for TIL in combination with pembrolizumab and checkpoint inhibitor naive patients expand upon the initial opportunity for lifileucel monotherapy after checkpoint inhibitor therapy. In an April 2022 press release, we announced updated clinical data for lifileucel in combination with pembrolizumab from Cohort 1A in our IOV-COM-202 trial. In melanoma patients who are naive to immune checkpoint inhibitor therapy, the overall response rate was 67%. 8 out of 12 patients had a confirmed objective response, including 3 complete responses and 5 partial responses. Overall, a complete response rate for this combination or above published response rates for pembrolizumab in frontline melanoma.

謝謝你，吉姆。今天，我想分享我們 TIL 臨床項目的最新動態。我們在發展 TIL 技術平台方面取得了長足進步，將更多療法和技術納入其中，以應對更多癌症患者和新的腫瘤類型和適應症。 TIL 與 pembrolizumab 聯合治療多種實體瘤的重要概念證明，以及我們開展 IOV-4001 臨床試驗的 IND 支持工作，是我們平台擴展和創新承諾的兩個主要例子。我們的 TIL 聯合派姆單抗和檢查點抑製劑首次治療患者的策略擴展了檢查點抑製劑治療後 lifileucel 單藥治療的初始機會。在 2022 年 4 月的新聞稿中，我們宣布了 IOV-COM-202 試驗中 lifileucel 與隊列 1A 中的派姆單抗聯合用藥的最新臨床數據。在未接受過免疫檢查點抑製劑治療的黑色素瘤患者中，總體緩解率為 67%。 12 名患者中有 8 名獲得確認的客觀緩解，其中 3 名完全緩解，5 名部分緩解。總體而言，該組合的完全緩解率或高於派姆單抗在前線黑色素瘤中公佈的緩解率。

Based on the promising clinical data and to offer possible benefit from TIL therapy to more melanoma patients, we are working with our internal teams and key opinion leaders to finalize the design for a Phase III trial. We currently expect this trial to begin at the end of this year and look forward to providing updates as available. In addition, we are advancing our first genetically modified TIL therapy candidate, IOV-4001, into the clinic. During the first quarter, the FDA allowed our IND to proceed for IOV-4001 for previously treated advanced melanoma or metastatic non-small cell lung cancer. IOV-4001 is a PD-1 inactivated TIL therapy that incorporates the TALEN gene editing technology licensed from Cellectis. Preclinical results for IOV-4001 were recently presented in a poster at the American Association for Cancer Research Annual Meeting, or AACR. In the Murine model of melanoma, the antitumor activity of IOV-4001 was superior to non-edited TIL product, whether alone or in combination with an anti-PD-1 antibody. We are excited about the potential for IOV-4001 to deliver TIL and PD-1 inhibition within a single therapy and look forward to starting a first-in-human study with IOV-4001 later this year.

基於有前景的臨床數據，並為了讓更多黑色素瘤患者從 TIL 療法中獲益，我們正在與內部團隊和關鍵意見領袖合作，最終確定 III 期試驗的設計。我們目前預計該試驗將於今年年底開始，並期待提供可用的更新。此外，我們正在將第一個轉基因 TIL 候選療法 IOV-4001 推進臨床。第一季度，FDA 允許我們針對先前治療過的晚期黑色素瘤或轉移性非小細胞肺癌開展 IOV-4001 的 IND 申請。 IOV-4001是一種PD-1滅活TIL療法，融合了Cellectis許可的TALEN基因編輯技術。 IOV-4001 的臨床前結果最近在美國癌症研究協會年會 (AACR) 的海報中公佈。在黑色素瘤小鼠模型中，無論是單獨使用還是與抗 PD-1 抗體聯合使用，IOV-4001 的抗腫瘤活性均優於未編輯的 TIL 產品。我們對 IOV-4001 在單一療法中提供 TIL 和 PD-1 抑制的潛力感到興奮，並期待在今年晚些時候開始 IOV-4001 的首次人體研究。

Turning to our strategy for treating non-small cell lung cancer. We're currently enrolling second-line non-small cell lung cancer patients in the IOV-LUN-202 trial at 30 sites. We recently amended the trial protocol to broaden the patient population, a reflection of real-world practice and the unmet need in non-small cell lung cancer. This amended protocol also provides flexibility around the timing of tumor harvest as well as around therapy prior to TIL infusion, which may inform new practices for patients across solid tumors.

轉向我們治療非小細胞肺癌的策略。我們目前正在 30 個地點招募二線非小細胞肺癌患者參加 IOV-LUN-202 試驗。我們最近修改了試驗方案以擴大患者群體，反映了現實世界的實踐和非小細胞肺癌未滿足的需求。這一修訂後的方案還為腫瘤收穫的時間以及 TIL 輸注之前的治療提供了靈活性，這可能為實體瘤患者的新實踐提供信息。

To elaborate on our medical education and outreach efforts, I will hand the call to Madan to discuss.

為了詳細說明我們的醫學教育和外展工作，我將致電馬丹進行討論。

Thank you, Friedrich. Our medicine affairs team has a depth of experience in oncology with long-standing relationships with many of our key opinion leaders. Over the past 2 years, our medical affairs team has been active in engaging centers and physicians of our Iovance TIL therapy. These interactions include scientific exchange at individual and small group meetings or during medical conferences. In total, the team has interacted with approximately 500 health care providers, or HCPs. Among these HCPs, 70% are dedicated to hematology/oncology, 20% are cell therapy specialists and the remaining 10% are surgeons. Our medical affairs team also leads a publication and scientific communication strategy and execution at Iovance. Our goal is to present and publish clinical data and engage with physicians so that we can attract top centers to participate in our clinical trials, increased scientific awareness, drive patient recruitment and increased share of voice for Iovance TIL therapy within the oncology and cell therapy communities. In 2021 alone, our clinical trial data presentations represented 136 patients across 4 tumor types. The venues included 3 major medical meetings, AACR, ASCO and SITC, and one manuscript, which was melanoma Cohort 2 data in the Journal of Clinical Oncology. In addition, our Iovance medical affairs team has interacted with more than 100 centers as we work cross-functionally to facilitate onboarding activities at the authorized treatment centers. Among these centers, 60% are designated cancer centers for the National Cancer Institute and/or Member Institutions of the National Comprehensive Cancer Center Network. The remaining 40% are a mix of academic and large community networks.

謝謝你，弗里德里希。我們的醫學事務團隊在腫瘤學方面擁有豐富的經驗，並與我們的許多關鍵意見領袖保持著長期的關係。在過去的兩年裡，我們的醫療事務團隊一直積極讓中心和醫生參與我們的 Iovance TIL 療法。這些互動包括個人和小組會議或醫學會議期間的科學交流。該團隊總共與大約 500 名醫療保健提供者 (HCP) 進行了互動。在這些 HCP 中，70% 致力於血液學/腫瘤學，20% 是細胞治療專家，其餘 10% 是外科醫生。我們的醫療事務團隊還在 Iovance 領導出版和科學傳播策略及執行。我們的目標是展示和發布臨床數據並與醫生互動，以便吸引頂級中心參與我們的臨床試驗、提高科學意識、推動患者招募並增加 Iovance TIL 療法在腫瘤學和細胞治療界的話語權。僅在 2021 年，我們的臨床試驗數據就代表了 4 種腫瘤類型的 136 名患者。會場包括 AACR、ASCO 和 SITC 3 個主要醫學會議，以及一份稿件，即臨床腫瘤學雜誌上的黑色素瘤隊列 2 數據。此外，我們的 Iovance 醫療事務團隊與 100 多個中心進行了互動，我們跨職能開展工作，以促進授權治療中心的入職活動。在這些中心中，60% 是國家癌症研究所和/或國家綜合癌症中心網絡成員機構的指定癌症中心。剩下的 40% 是學術和大型社區網絡的混合體。

I will now hand the call over to Jean-Marc to discuss our first quarter 2022 financial results.

我現在將把電話轉給 Jean-Marc，討論我們 2022 年第一季度的財務業績。

Thank you, Madan. My comments will reflect the high-level financial results from our first quarter of 2022. Additional details can be found in this afternoon's press release as well as in our SEC filings.

謝謝你，馬丹。我的評論將反映我們 2022 年第一季度的高級財務業績。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。

I will begin with the strength of our cash position. As of March 31, 2022, Iovance held $516 million in cash, cash equivalents, investments and restricted cash compared to $602.1 million on December 31, 2021. Our cash usage from operations included certain annual payments totaling $16 million. We maintained prior guidance that our cash position is sufficient to advance our operating plan into 2024, including pipeline development and expansion, commercial manufacturing readiness and launch preparation.

我將從我們現金狀況的實力開始。截至2022 年3 月31 日，Iovance 持有5.16 億美元的現金、現金等價物、投資和限制性現金，而2021 年12 月31 日為6.021 億美元。我們運營中的現金使用包括總額為1600 萬美元的某些年度付款。我們維持先前的指導，即我們的現金狀況足以將我們的運營計劃推進到 2024 年，包括管道開發和擴張、商業製造準備和上市準備。

Moving to the income statement. Our net loss for the first quarter ended March 31, 2022, was $91.6 million or $0.58 per share. This compared to a net loss of $75.4 million or $0.51 per share for the first quarter ended March 31, 2021. Research and development expenses were $68.3 million for the first quarter ended March 31, 2022, an increase of $12.4 million compared to $55.9 million for the first quarter ended March 31, 2021. The increase in research and development expenses over the prior year period was primarily attributable to the growth of the internal research and development team, including stock-based compensation expense to support our ongoing and planned pipeline activities as well as increased facility-related costs. General and administrative expenses were $23.4 million for the first quarter ended March 31, 2022, an increase of $3.8 million compared to $19.6 million for the first quarter ended March 31, 2021. The increase in general and administrative expenses compared to the prior year period was primarily attributable to the growth of the internal general and administrative team, including stock-based compensation expense, an increase in marketing, intellectual property and legal expenses as well as the build-out of our new corporate headquarter office and information technology infrastructure to support pre-commercialization, launch readiness and our overall growth.

轉到損益表。截至 2022 年 3 月 31 日的第一季度淨虧損為 9160 萬美元，即每股 0.58 美元。相比之下，截至2021 年3 月31 日的第一季度淨虧損為7,540 萬美元，即每股0.51 美元。截至2022 年3 月31 日的第一季度，研發費用為6,830 萬美元，較去年同期的5,590 萬美元增加了1,240 萬美元。截至2021年3月31日的第一季度。研發費用較上年同期增加主要歸因於內部研發團隊的成長，包括支持我們正在進行和計劃的管道活動的股票補償費用以及設施相關成本的增加。截至2022 年3 月31 日的第一季度的一般及管理費用為2,340 萬美元，較截至2021 年3 月31 日的第一季度的1,960 萬美元增加了380 萬美元。與上年同期相比，一般及管理費用的增加為主要歸因於內部一般和行政團隊的增長，包括基於股票的補償費用、營銷、知識產權和法律費用的增加，以及我們新的公司總部辦公室和信息技術基礎設施的擴建，以支持未來的發展。 -商業化、發布準備和我們的整體增長。

As of March 31, 2022, there were approximately 157.2 million common shares outstanding. With the strength of our balance sheet and by managing our focused investments across the pipeline, launch readiness and internal manufacturing, we are well positioned to execute our operating plan while continuing to align our spending with our corporate priorities.

截至2022年3月31日，已發行普通股約為1.572億股。憑藉我們的資產負債表實力，並通過管理整個管道、啟動準備和內部製造的重點投資，我們有能力執行我們的運營計劃，同時繼續使我們的支出與我們的公司優先事項保持一致。

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)

（操作員說明）

And our first question comes from the line of Madhu Kumar with Goldman Sachs.

我們的第一個問題來自 Madhu Kumar 與高盛的關係。

I guess our first one is, again, kind of a simple one looking at the calendar. How should we think about the cadence of events in terms of the release of Cohort 4 topline data vis-a-vis this July pre-BLA meeting and the August BLA submission?

我想我們的第一個任務也是一個簡單的查看日曆的任務。相對於今年 7 月的 BLA 前會議和 8 月的 BLA 提交，我們應該如何考慮 Cohort 4 頂線數據發布方面的事件節奏？

Madhu, it's going to be part of that process. We can't really give any more guidances to that. But effectively, as part of that process, we're trying to get the BLA in, and we're trying to talk more about Cohort 4 and complete the process of filing the BLA at the same time. So really, I wouldn't think about it as any particular cadence. It should come in as soon as we're able to go.

Madhu，這將是這個過程的一部分。我們確實無法對此提供更多指導。但實際上，作為該流程的一部分，我們正在努力獲取 BLA，並且我們正在嘗試更多地討論第 4 組，同時完成提交 BLA 的流程。所以說真的，我不認為這是任何特定的節奏。我們一能走它就應該進來。

Okay. And then on non-small cell and cervical cancer, how should we -- you mentioned you plan to have regulatory interactions to discuss kind of making registrational cohorts? In both indications, what do you see as the effective population for unmet need where either TIL monotherapy or TIL plus PD-1 blockade kind of makes sense as a line of therapy for whom you could have a registrational cohort?

好的。然後，關於非小細胞癌和宮頸癌，我們應該如何——您提到您計劃進行監管互動來討論註冊隊列的類型？在這兩種適應症中，您認為什麼是滿足未滿足需求的有效人群，其中TIL 單藥治療或TIL 加PD-1 阻斷作為一種治療方案是有意義的，您可以為其建立一個註冊隊列？

Well, both of the occasions, you have the post checkpoint population available where there's significant unmet medical need today. So that's sort of the short answer to your question. There's obviously much finer points, and we can talk more about the details of each study. And hopefully, after getting our strategy together and regulatory input and sorting out our plans here, we can talk more about this, but that's the general approach. And then, of course, we've got frontline studies running in combination with pembrolizumab as well to look at earlier lines of therapy, as you normally do in oncology trade development.

嗯，在這兩種情況下，檢查站後的人口都可以利用，而今天的醫療需求卻未得到滿足。這就是對你的問題的簡短回答。顯然還有更多的細節，我們可以更多地討論每項研究的細節。希望在整合我們的戰略和監管意見並整理我們的計劃之後，我們可以更多地討論這一點，但這是一般方法。當然，我們還進行了與派姆單抗聯合進行的一線研究，以研究早期的治療方案，就像在腫瘤學貿易發展中通常所做的那樣。

Okay. One last question I got was maybe scientific/philosophical one. How do you think about PD-1 knockout TILs as compared to TILs plus PD-1 as they kind of -- in terms of therapeutic avenues, like where would one -- the PD-1 monoclonal antibody combination make more sense? Where would a PD-1 knockout TIL population make more sense? And I guess kind of which raises the question, how much of TIL efficacy is from the initial TIL product versus kind of epitope spread?

好的。我得到的最後一個問題可能是科學/哲學問題。與 TIL 加 PD-1 相比，您如何看待 PD-1 敲除 TIL？就治療途徑而言，例如 PD-1 單克隆抗體組合在哪裡更有意義？ PD-1 敲除 TIL 群體在哪裡更有意義？我想這提出了一個問題，TIL 功效有多少來自於初始 TIL 產品與表位擴散類型？

Well, let me take the first part of your question, then we can talk a little more about efficacy as we go here. And Madan and Friedrich can jump in as well, if needed. It's untested as of today, but we do believe that knocking down the gene within the T cell may lead to a more efficacious TIL and a more efficacious MOA for PD-1, PD-L1 blockade. There's a number of reasons for this, and there's a number of advantages to knocking down the gene as opposed to giving the patient a antibody. For example, better penetration of the TILs into a tumor stroma layers in the microenvironment as opposed to an antibody, and separately, you can -- that's an efficacy side argument. But on a toxicity side argument, you could argue that less off target effects from the TIL having a knockout versus the antibody being systemically delivered.

好吧，讓我回答你問題的第一部分，然後我們可以在這裡更多地討論功效。如果需要的話，馬丹和弗里德里希也可以加入。截至目前尚未經過測試，但我們確實相信敲除 T 細胞內的基因可能會產生更有效的 TIL 和更有效的 MOA，以阻斷 PD-1、PD-L1。造成這種情況的原因有很多，而且與給患者提供抗體相比，敲除該基因有很多優點。例如，與抗體相比，TIL 可以更好地滲透到微環境中的腫瘤基質層中，並且單獨地，您可以——這是功效方面的爭論。但就毒性方面的爭論而言，您可能會認為，與全身遞送的抗體相比，敲除 TIL 的脫靶效應更小。

On the idea -- on the question of where the TIL efficacy comes from, Steve Rosenberg's Lab has published a lot on this, and it's generally believed that the efficacy of TIL therapies occur in the early period after administration. Although obviously, we see -- from a clinical perspective, we see responses that can originate later after some time. You can have (inaudible) and that kind of thing, but Rosenberg's imaging studies from back 20-plus years ago now show TIL trafficking rapidly the lungs and then the tumor and then generally show signs of tumor clearance early in the process.

關於TIL療效從何而來的問題，Steve Rosenberg的實驗室已經發表了很多這方面的文章，人們普遍認為TIL療法的療效發生在給藥後的早期。顯然，從臨床角度來看，我們看到反應可能會在一段時間後產生。你可以有（聽不清）之類的東西，但 Rosenberg 20 多年前的影像學研究現在表明 TIL 迅速轉移到肺部，然後轉移到腫瘤，然後通常在此過程的早期顯示出腫瘤清除的跡象。

Madan or Friedrich, do you want to add anything to that?

Madan 或 Friedrich，您想補充什麼嗎？

Yes. This is Madan. Just to comment, I think even in the post-TIL infusion TCR persistence, right, in a non-genetically-edited TIL, the TCR, the clonotypes that are persisting have the potential of getting exhausted with repeated antigenic stimulation. But once you knock out the PD-1, the immune surveillance capability of these genetically-edited TILs may hypothetically be much more superior to the current TILs that we have. Again, as Fred said, it's untested, and we have to get into the clinic to test all these hypotheses.

是的。這是馬丹。只是評論一下，我認為即使在 TIL 輸注後 TCR 持續存在，對吧，在非基因編輯的 TIL（TCR）中，持續存在的克隆型也有可能因重複的抗原刺激而耗盡。但是，一旦敲除 PD-1，這些基因編輯 TIL 的免疫監視能力可能會比我們現有的 TIL 優越得多。正如弗雷德所說，它還沒有經過測試，我們必須進入診所來測試所有這些假設。

As you probably saw, Madhu, we're about to get into the clinical net. So that's something that's imminent. Our clinicaltrials.gov posting went up yesterday.

正如您可能看到的那樣，Madhu，我們即將進入臨床網絡。所以這是迫在眉睫的事情。我們的 ClinicalTrials.gov 帖子​​昨天上升了。

And 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。

This is Dennis on for Mike. Two for me. One on the BLA, can you discuss any other gating factors we should be thinking about? Like assay validation or project in CMC? What else needs to happen between now and when you submit in August? And then my second question is on single-line lung cancer. I mean you talked about using the LUN-202 study as a registrational. Do you need to include a docetaxel arm? Or can you get approval on just ORR? Or do you think you need PFS?

這是丹尼斯替邁克發言。給我兩個。關於 BLA，您能否討論一下我們應該考慮的其他任何限制因素？喜歡 CMC 中的測定驗證或項目嗎？從現在到八月份提交時還需要做什麼？我的第二個問題是關於單線肺癌。我的意思是您談到使用 LUN-202 研究作為註冊。您需要添加多西他賽臂嗎？或者僅 ORR 就能獲得批准嗎？或者您認為您需要 PFS？

Sure. Why don't I take the first one and Friedrich, can you take the second one? On the validation on -- activities like validation and anything else we do in the CMC sphere to get ready for the BLA, we're not talking about the details of this publicly, but you can assume that a lot of that's happening has already happened, and we're making great progress as we've already completed most of those tasks. There is a tremendous amount of work to be done here, but nothing that rises to the level of the potency assay situation that we were in before, where there was less gating item type of thing there that we had to resolve. So the teams at Iovance, employees at Iovance and all our partners are working really hard to get all these things done. Yes, there's tons of validations. There's tons of PPQs and comparability and all the stuff that needs to be run and succeed, but that's stuff that we think we can handle.

當然。為什麼我不拿第一個，弗里德里希，你可以拿第二個嗎？關於驗證活動以及我們在 CMC 領域為準備 BLA 所做的任何其他活動，我們不會公開談論此細節，但您可以假設很多事情已經發生了，我們正在取得巨大進展，因為我們已經完成了大部分任務。這裡有大量的工作要做，但是沒有任何東西可以達到我們之前所處的效力測定情況的水平，在那裡我們必須解決的門控項目類型較少。因此，Iovance 的團隊、Iovance 的員工以及我們所有的合作夥伴都在非常努力地完成所有這些事情。是的，有大量的驗證。有大量的 PPQ 和可比性以及所有需要運行並取得成功的東西，但這些都是我們認為我們可以處理的東西。

Friedrich, do you want to talk a little bit more about LUN-202 and docetaxel as a comparator and registrational against -- study registrational?

Friedrich，您想多談談 LUN-202 和多西紫杉醇作為比較劑和註冊研究的註冊情況嗎？

Yes, sure. Good question. So one thing to keep in mind here is that the FDA is happy to review single-arm data. It looks as single-arm clinical trial data in a somewhat different way than randomized studies, and we'll have preferences for where they would prefer which type of data, but they are looking at single-arm data. They are looking at those data in the context of risk-benefit assessed by the totality of the data, which does include available therapy at that time. But they are generally happy to look at that data. Keep in mind, docetaxel, it is not a great drug. It's not popular with (inaudible) doctors. It has low response rates, short durability, a lot of toxicity. So there certainly is an unmet medical need and that does certainly support bringing single-arm data forward with the FDA. Generally, we'll look at that.

是的，當然。好問題。因此，這裡要記住的一件事是 FDA 很樂意審查單臂數據。它看起來是單臂臨床試驗數據，其方式與隨機研究有些不同，我們會優先考慮他們喜歡哪種類型的數據，但他們正在研究單臂數據。他們正在通過整體數據評估風險效益的背景下查看這些數據，其中確實包括當時可用的治療方法。但他們通常很樂意查看這些數據。請記住，多西紫杉醇，它不是一種很好的藥物。它不受（聽不清）醫生的歡迎。其反應率低、持續時間短、毒性大。因此，肯定存在未滿足的醫療需求，這確實支持向 FDA 提交單臂數據。一般來說，我們會看看這個。

One thing to add. Let me just add one more time. The other point to add is, we're not -- because it's not a combination therapy, right? In a combination therapy that then gets a little more complicated because the FDA usually likes to look at data that will identify and pinpoint the contribution of components. Our therapy is the monotherapy that you can compare with historical data from available therapy.

要補充一件事。讓我再補充一次。另一點需要補充的是，我們不是——因為它不是聯合療法，對吧？在聯合療法中，情況會變得更加複雜，因為 FDA 通常喜歡查看數據來識別和查明成分的貢獻。我們的療法是單一療法，您可以將其與現有療法的歷史數據進行比較。

Our next question comes from the line of Peter Lawson with Barclays.

我們的下一個問題來自巴克萊銀行的彼得勞森。

Just kind of curious on just going back to the kind of sequence of events for the BLA submission. When will we get the first feedback from the FDA regarding that when we can see that?

只是有點好奇回到 BLA 提交的事件順序。我們什麼時候可以得到 FDA 的第一個反饋？

Peter, probably the first real feedback comes at the time of acceptance of the BLA, which is 60 days after submission.

Peter，第一個真正的反饋可能是在接受 BLA 時出現的，即提交後 60 天。

Got you. And would there be any commentary around the alignment around the potency assay?

明白你了。圍繞效價測定的比對會有任何評論嗎？

I can't say for sure what FDA is going to say at that stage. But typically, at that stage, they're going to tell you that the BLA has been accepted and then later during the review process, they may -- they typically make requests where they could ask for more details about all sorts of things, including assay information. And we think we've addressed all that upfront and our goal is to address all that upfront with the idea that any request to come in (inaudible).

我無法確定 FDA 在此階段會說什麼。但通常情況下，在那個階段，他們會告訴您 BLA 已被接受，然後在審核過程中，他們通常會提出請求，要求提供有關各種事情的更多詳細信息，包括化驗信息。我們認為我們已經預先解決了所有這些問題，我們的目標是預先解決所有這些問題，並提出任何請求（聽不清）。

Got you. And then as that communication kind of unfolds or your keep us in the loop of like how that communication is evolving, whether you need additional questions, et cetera. Is that the plan?

明白你了。然後，隨著這種溝通的展開，或者您讓我們了解這種溝通是如何演變的，您是否需要其他問題等等。是這樣的計劃嗎？

I think we'll probably get a lot of questions about during that period, Peter, as you can imagine, but we'll do our best to keep everybody informed. I don't think companies typically go blow-by-blow as everything comes in from the FDA. But I'm sure you'll hear us talk about this as people check in -- let's say, it's November on the earnings call and people are checking in on how things are going, and we'll hopefully be able to give some updates as to how we see the BLA review progressing at that stage.

我想，正如你想像的那樣，彼得，在那段時間我們可能會收到很多問題，但我們會盡力讓每個人都了解情況。我認為公司通常不會逐一進行，因為一切都來自 FDA。但我確信您會在人們查看時聽到我們談論這個問題 - 比方說，現在是 11 月的財報電話會議，人們正在查看事情的進展情況，我們希望能夠提供一些最新消息我們如何看待現階段BLA 審查的進展。

Got you. And then just the final question just around when the BLA is submitted, will we get kind of more information around the potency assay? And will we see, I guess, IP filings as well around the potency assays?

明白你了。然後就是提交 BLA 時的最後一個問題，我們是否會獲得有關效力測定的更多信息？我想，我們還會看到有關效力測定的知識產權申請嗎？

Ultimately, we'll see IP filings. I can't tell you exactly when because it's a little sensitive right now. But as you probably know, that filings eventually become public typically around 18 months or greater after the first priority date. So there's some -- there could be information out there at some level. I don't think that -- I've tried to caution analysts to think that we're going to put details out on some of the stuff that is competitively sensitive, and I think we'll probably continue to talk about the quarter.

最終，我們將看到知識產權申請。我不能告訴你具體時間，因為現在有點敏感。但您可能知道，申請最終通常會在第一優先權日期後 18 個月或更長時間內公開。因此，在某種程度上，可能存在一些信息。我不這麼認為——我試圖提醒分析師，我們將公佈一些競爭敏感內容的細節，而且我認為我們可能會繼續討論本季度的情況。

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。

Have you received confirmation of the scheduling of the July meeting? Or what is the likelihood that might slip and could further delay your BLA filing?

您收到 7 月份會議安排的確認了嗎？或者，有什麼可能性會出現下滑並進一步延遲您的 BLA 提交？

Colleen, we don't -- a pre-BLA meeting is a type B meeting. So they're requested 60 days in advance. We're not putting out details exactly what's going on there, but right now, the July timing is, we just announced it. So we're very comfortable with that timing.

Colleen，我們不認為——BLA 前的會議是 B 類會議。因此，他們需要提前 60 天提出要求。我們沒有確切地公佈那裡發生的事情的細節，但現在，七月的時間，我們剛剛宣布了。所以我們對這個時機非常滿意。

Okay. That's helpful. And what is your latest understanding on whether the BLA submission in late line melanoma would support accelerated or a full approval?

好的。這很有幫助。您對晚期黑色素瘤 BLA 提交是否支持加速批准或完全批准有何最新理解？

We don't know for sure. We think that with the size of the data set we're coming in with, with Cohort 4 and Cohort 2 being sort of, there's a good chance of full approval, and we've spoken about that a few times on calls recently. We do have the option of the Phase III study that we've been talking about also serving as a confirmatory trial should that need to be there. So we're planning for every scenario.

我們不確定。我們認為，根據我們即將獲得的數據集的規模，即隊列 4 和隊列 2，獲得完全批准的機會很大，而且我們最近在電話會議上多次談到過這一點。我們確實可以選擇我們一直在談論的第三階段研究，如果需要的話也可以作為驗證性試驗。因此，我們正在針對每種情況進行規劃。

Okay. Great. And one more follow-up, if I can. The comments on the call around potentially using a CMO, if needed upon launch. Would you expect that, that would be driven more by limited capacity at the iCTC early on or more due to any sort of indication you're seeing of high demand at launch?

好的。偉大的。如果可以的話，還有一個後續行動。電話會議上的評論圍繞著可能使用首席營銷官（如果啟動時需要的話）進行。您是否認為這將更多地受到 iCTC 早期容量有限的推動，或者更多地是由於您在發佈時看到的高需求的任何跡象？

It's probably a demand at launch issue first. We're trying to learn as much as we can from the launches of the 2 BCMA CAR-Ts right now and just make sure we've got a really, really flexible footing when we go to launch. So the iCTC obviously bears the brunt of the capacity, but having the CMO available to help is going to just allow us to potentially do better than what happened with some of the -- with 2 BCMA products (inaudible).

這可能首先是啟動時的需求。我們正在努力從目前推出的 2 款 BCMA CAR-T 中學習盡可能多的知識，並確保我們在推出時擁有真正非常靈活的立足點。因此，iCTC 顯然首當其衝，但有了 CMO 的幫助，我們可能會比某些 2 BCMA 產品（聽不清）做得更好。

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

您的下一個問題來自泰勒·範布倫 (Tyler Van Buren) 和考恩 (Cowen) 的對話。

The first one on Dr. Puri, great to have you on board, and congratulations on the new role. I'd love to hear why you decided to join Iovance at this stage in your career and the confidence you have in lifileucel receiving approval? And then the second question is related to LN-145 in lung cancer. When should we expect to get the next data update with earlier-stage second-line patients? Could we get an update later in the year?

第一篇關於 Puri 博士的文章，很高興您加入，並祝賀您擔任新角色。我很想知道您為什麼在職業生涯的這個階段決定加入 Iovance，以及您對 lifileucel 獲得批准有何信心？第二個問題與LN-145在肺癌中的作用有關。我們什麼時候可以獲得早期二線患者的下一次數據更新？我們可以在今年晚些時候得到更新嗎？

Sure. Why don't you take the second one? Go ahead. Raj, go ahead, why don't you take the first one. I'll come back around if you want to it, too. Go ahead.

當然。為什麼不拿第二個呢？前進。 Raj，來吧，你為什麼不選擇第一個呢？如果你也願意的話我會回來的。前進。

Yes. I just want to say after a significant number of years at the FDA, 19 as Division Director, I was interested in the better career goals. And I see that T cells, TILs a great potential for solid cancer compared to other modalities such as checkpoint inhibitors or CAR-T cell, which only works in the hematological malignancies and checkpoint inhibitors had limited effect on 15% to 20% of the cases. So vast majority of the patients with solid cancer has no other option, and TIL cells with the broad reactive T cell CD4, CD8 cells have a great potency to -- in the solid cancer. So I think that was one of the main goal to join the company, and Iovance is an important of this therapy. So that's the reason I joined the Iovance.

是的。我只想說，在 FDA 工作了很長一段時間（19 歲擔任部門主管）後，我對更好的職業目標很感興趣。我發現，與檢查點抑製劑或CAR-T 細胞等其他治療方法相比，T 細胞、TIL 具有治療實體癌的巨大潛力，後者僅適用於血液惡性腫瘤，檢查點抑製劑對15% 至20 % 的病例效果有限。因此，絕大多數實體癌患者沒有其他選擇，而TIL細胞與廣泛反應性T細胞CD4、CD8細胞在實體癌中具有巨大的效力。所以我認為這是加入公司的主要目標之一，而 Iovance 是這種療法的重要組成部分。這就是我加入 Iovance 的原因。

And then with respect to LUN-202 and data possibly later this year, we haven't said specifically. Obviously, we're trying to optimize enrollment in that trial and get more data there to bolster what we think of a clean efficacy signal until therapy announcement for lung. And if we get some data that we think is worth putting out, I think we would try to put that out as soon as we can. We try to do that specifically with lung last year. So all I can say, there is just hang tight and let us continue to enroll and generate data.

然後關於 LUN-202 和可能在今年晚些時候的數據，我們還沒有具體說。顯然，我們正在努力優化該試驗的入組情況，並獲取更多數據，以支持我們認為的明確療效信號，直到宣布針對肺部的治療為止。如果我們得到一些我們認為值得發布的數據，我想我們會盡快發布。去年我們專門針對肺部進行了嘗試。所以我只能說，堅持住，讓我們繼續註冊和生成數據。

Our next question comes from the line of Mark Breidenbach with Oppenheimer.

我們的下一個問題來自馬克·布雷登巴赫和奧本海默的對話。

Just a quick one for me with respect to the new trial of IOV-4001. Can you just remind us why the protocol is focused on melanoma and non-small cell lung cancer only and is not inclusive of some of the other tumor types? You've investigated TIL therapy. And also, will this trial kind of be competing at all with the LUN-202 trial in terms of trying to enroll the same types of lung cancer patients? Or are they more or less distinct populations?

我簡單介紹一下 IOV-4001 的新試驗。您能否提醒我們為什麼該方案僅關注黑色素瘤和非小細胞肺癌，而不包括其他一些腫瘤類型？您已經研究過 TIL 療法。此外，在嘗試招募相同類型的肺癌患者方面，該試驗是否會與 LUN-202 試驗競爭？或者他們或多或少是不同的群體？

Friedrich, do you want to take this one?

弗里德里希，你想買這個嗎？

Yes, sure. Good question. Thanks. So there's really 2 strategies here in the same trial. Number one, the cohort on melanoma patients is an opportunity to enroll and generate clinical data fast because we know there is demand for access to TIL therapy. This is an attractive new approach really promising based on the preclinical data and the rationale that Fred and Madan spoke about earlier. So we'll be able to generate data in a population that they know very well based on our own data and the academic data, which then allows us to compare and draw some conclusions as soon as possible. So that's really the strategy for melanoma here. Non-small cell lung cancer is a really important indication in tumor type for us. We have generated data in Cohort 3b that indicates activity in TIL therapy and non-small cell lung cancer. We hope that with the technological approach of PD-1 knockout, we are improving on both response rates and duration. And in addition, if you look at the population, we are going to a broader patient population than the population we're targeting in LUN-202, both in regards to allow the numbers of prior therapy as well as drive mutations in the patient's tumor. So there is really an opportunity to and take another shot at those later line patients and start and exploring activity and driver mutation positive patients. Around -- so that also speaks to your question about overlap with the existing study for melanoma, we do think that because we are going to enroll rather quickly, but there's little risk of overlap with other efforts in melanoma that are taking.

是的，當然。好問題。謝謝。所以在同一個試驗中實際上有兩種策略。第一，黑色素瘤患者隊列是快速招募和生成臨床數據的機會，因為我們知道存在對 TIL 療法的需求。根據臨床前數據以及 Fred 和 Madan 之前談到的基本原理，這是一種有吸引力的新方法，確實很有前途。這樣我們就可以根據我們自己的數據和學術數據，在他們非常了解的人群中生成數據，然後讓我們盡快進行比較並得出一些結論。這確實是治療黑色素瘤的策略。非小細胞肺癌對我們來說是一個非常重要的腫瘤類型適應症。我們在隊列 3b 中生成了表明 TIL 療法和非小細胞肺癌活性的數據。我們希望通過 PD-1 敲除的技術方法，我們能夠提高緩解率和持續時間。此外，如果你看一下人群，我們將針對比 LUN-202 的目標人群更廣泛的患者人群，無論是允許先前治療的數量還是驅動患者腫瘤的突變。因此，確實有機會對後來的患者進行另一次嘗試，並開始探索活動和驅動突變陽性患者。這也說明了您關於與現有黑色素瘤研究重疊的問題，我們確實認為，因為我們將很快入組，但與正在進行的黑色素瘤其他研究重疊的風險很小。

And our next question comes from the line of Mara Goldstein with Mizuho Securities.

我們的下一個問題來自瑞穗證券 (Mizuho Securities) 的瑪拉·戈爾茨坦 (Mara Goldstein)。

This is Jerry on for Mara Goldstein. So first is also on IOV-4001. How do you anticipate prioritizing the 2 melanoma and a CLC cohorts?

這是傑瑞為瑪拉·戈德斯坦配音。首先也是 IOV-4001。您預計如何優先考慮 2 個黑色素瘤和一個 CLC 隊列？

How do we anticipate prioritizing? They're both going to be open at the same time, and they're different patient populations and different investigators. So we -- I kind of view them as equal priority, but Friedrich just mentioned a little bit earlier that we do expect melanoma to enroll rapidly because of the demand in that area right now. So I can't tell you for sure exactly how enrollment will go in one versus the other, but (inaudible) shouldn't roll faster, I would think. That doesn't mean we're prioritizing it.

我們如何預測優先級？它們都將同時開放，並且它們是不同的患者群體和不同的研究人員。所以我們——我認為它們是同等重要的，但弗里德里希剛才提到，由於目前該領域的需求，我們確實預計黑色素瘤會迅速入組。因此，我無法確切地告訴您其中一個與另一個的註冊情況如何，但我認為（聽不清）不應該滾動得更快。這並不意味著我們會優先考慮它。

These 2 cohorts are open simultaneously. They're expecting different enrollment rates, but there's really no overlap or competition. We're certainly not held back by having limited manufacturing slots or anything like that. So we don't -- we don't have to derive which patient is next because of any sort of concerns around having to for these patients. So there is no need to prioritize based on that.

這兩個隊列同時開放。他們期望不同的入學率，但實際上不存在重疊或競爭。我們當然不會因為有限的製造槽位或類似的事情而受到阻礙。所以我們不需要——我們不必因為對這些患者的任何擔憂而推斷出下一個患者是哪位患者。所以沒有必要以此為基礎來確定優先級。

Got you. Next one is on LN-145. With the slight trial protocol change, do you expect the similar strategy to be able for other tumor types as well?

明白你了。下一個是在 LN-145 上。隨著試驗方案的輕微改變，您是否期望類似的策略也適用於其他腫瘤類型？

Are you talking about LUN-202?

您是在談論 LUN-202 嗎？

Yes.

是的。

Yes. Yes, there is going to be potential for that, yes.

是的。是的，會有這樣的潛力，是的。

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。

Just a couple of commercial questions. I guess, first, is there any color you can provide just at this point in terms of securing IL-2? Just commercially, will this be procured kind of on an as-needed basis real-time or otherwise? And I guess how confident are you that your IL-2 supplier can handle the initial commercial demand?

只是幾個商業問題。我想，首先，在保護 IL-2 方面，您目前可以提供任何顏色嗎？就商業而言，這是根據需要實時採購還是以其他方式採購？我想您對您的 IL-2 供應商能夠滿足最初的商業需求有多大信心？

This is Jim Ziegler. We've met with the folks from Clinigen that supply IL-2 in the past. As you know, they're going through a transition right now. We'll be working with them as we approach our BLA and coordinating forecast needs with them to ensure that we have supply -- adequate supply across the board. We have looked at all of the potential ATCs that we're working with and all of them basically have the ability to order IL-2 with their current wholesalers.

這是吉姆·齊格勒。我們過去曾與 Clinigen 供應 IL-2 的人員會面。如您所知，他們現在正在經歷轉變。我們將在接近 BLA 時與他們合作，並與他們協調預測需求，以確保我們有供應——全面供應充足。我們已經研究了所有正在與我們合作的潛在 ATC，他們基本上都有能力向其當前的批發商訂購 IL-2。

Okay. So they would order IL-2 on their own. You wouldn't be ordering IL-2 and then supplying it yourselves?

好的。所以他們會自己訂購IL-2。您不會訂購 IL-2 然後自己提供嗎？

Correct.

正確的。

Okay. Okay. And then if I could, just another question really, I guess, just on the sort of the patient journey that you're expecting, if lifileucel is approved. I guess like specifically, do you -- are you expecting cardiac and pulmonary functions that need to be verified? And if so, does that happen -- does it happen after the biopsy is taken?

好的。好的。然後，如果可以的話，我想，這只是另一個問題，只是關於您所期待的患者旅程，如果 lifileucel 獲得批准的話。我想具體來說，您是否期待需要驗證的心臟和肺功能？如果是這樣，這種情況是否會發生——是否會在活檢後發生？

This is Madan Jagasia. It's a very valid question. So the conduct of the clinical trial, patients have to obviously meet eligibility criteria prior to the tumor harvest. I suspect that will be the same pattern of practice once we are in the commercial landscape. HCPs will need to ensure the patients have adequate cardiopulmonary reserve before they go in for a tumor harvest, which then subsequently leads to the TIL cell therapy. So that's a pretty standard practice in the world of stem cell therapy, in the world of CAR-T cell therapy as well today.

這是馬丹·賈加西亞。這是一個非常有效的問題。因此，在進行臨床試驗時，患者必須在腫瘤收穫之前明顯符合資格標準。我懷疑一旦我們進入商業領域，這將是相同的實踐模式。 HCP 需要確保患者在進行腫瘤收穫之前有足夠的心肺儲備，然後進行 TIL 細胞治療。因此，這在幹細胞治療領域和當今的 CAR-T 細胞治療領域都是相當標準的做法。

Got it. Okay. And would they -- I guess, would they go through those tests again after the manufacturing process when it's ready -- when TIL fusion is ready?

知道了。好的。我想，當製造過程準備就緒時，當 TIL 融合準備就緒時，他們會再次進行這些測試嗎？

Not necessarily. Obviously, they have had any further cytotoxic therapy, which may influence their cardiac or pulmonary reserve, which is highly unlikely given the agents that are in use for metastatic melanoma. So typically, it is done once. And unless the clinical situation changes, it's typically not repeated.

不必要。顯然，他們接受了任何進一步的細胞毒性治療，這可能會影響他們的心臟或肺儲備，考慮到用於治療轉移性黑色素瘤的藥物，這種情況極不可能發生。因此，通常只完成一次。除非臨床情況發生變化，否則通常不會重複。

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

你的下一個問題來自 Asthika Goonewardene 和 Truist 的對話。

This is (inaudible) for Asthika today. Just one question on lung and then one on cervical. So on the 202 study protocol amendment, if you gather resections for a patient they haven't yet progressed, how do you determine when to manufacture TIL product? And will you guys have TIL manufactured and stored somewhere until needed?

這是（聽不清）今天的 Asthika。只有一個關於肺部的問題，然後是一個關於頸部的問題。因此，在 202 研究方案修正案中，如果您收集尚未取得進展的患者的切除情況，您如何確定何時生產 TIL 產品？你們會在需要時製造 TIL 並將其存儲在某個地方嗎？

Yes. This is Madan. Good question. So I think what you're referring to is what we alluded to as a pre-progression resection. So yes, the patients will have -- their tumor resected and the TILs manufactured. We expect most of these patients to eventually progress because the chance that a patient is going to "respond for perpetuity" and non-small cell lung cancer is very small. So we do expect most of these patients to progress on their frontline therapy and does the probability of using the TILs that have been manufactured approaches at a very, very high number.

是的。這是馬丹。好問題。所以我認為你指的是我們提到的進展前切除術。所以，是的，患者的腫瘤將被切除並製造 TIL。我們預計這些患者中的大多數最終會取得進展，因為患者“永久緩解”和非小細胞肺癌的機會非常小。因此，我們確實預計這些患者中的大多數會在一線治療中取得進展，並且使用已生產的 TIL 的可能性會非常非常大。

And would that be a gating factor from presenting data from the study? And any other gating factors that you can mention in terms of just presenting the data would be very helpful as well.

這會成為展示研究數據的限制因素嗎？您在展示數據時提到的任何其他門控因素也將非常有幫助。

No. That should not be a gating factor for data from the study. We view that as actually something that we think will lead to improved enrollment and more flexibility, and it could be something that we explore, like I said earlier, and other indications, too.

不。這不應該成為研究數據的限制因素。我們認為這實際上會導致入學率的提高和靈活性的提高，並且這可能是我們正在探索的事情，就像我之前所說的，以及其他跡象。

Okay. Great. And then on cervical cancer, when can we expect an update just on the regulatory discussions that you've been having with the FDA? It seems like based on the cadences, these earnings releases that you've been talking to them for somewhere between like 2 to 5 months. And yes, when can we get an update on that?

好的。偉大的。那麼關於宮頸癌，我們什麼時候可以期待您與 FDA 進行的監管討論的最新情況？從這些收益發布的節奏來看，你似乎已經與他們討論了大約 2 到 5 個月的時間。是的，我們什麼時候可以得到最新消息？

Bear in mind that the announcement with pembrolizumab approval came at the very end of last year. So Yes, it's been a few months, but it does take some time to get in front of the regulator and then also build a strategy. So we haven't guided to a specific date here because we don't have one yet, but we are working hard on cervical, and hopefully, we'll be back with more information soon.

請記住，派姆單抗獲得批准的公告是在去年年底發布的。是的，已經過去幾個月了，但確實需要一些時間才能面對監管機構，然後製定策略。因此，我們在這裡沒有指導具體的日期，因為我們還沒有確定的日期，但我們正在努力研究宮頸疾病，希望我們很快就會回來提供更多信息。

The final one, would you expect a similar sort of timeline with longer? Is there anything different there versus your conversations on cervical?

最後一個，您是否期望類似的時間線更長？與你們關於宮頸癌的談話有什麼不同嗎？

There are separate conversations. And so I can't say the timelines would be the same, but it's similar in the sense that we're having those discussions separately with the FDA and setting the strategy for those things. But other than that, I can't really link them.

有單獨的對話。所以我不能說時間表是相同的，但從某種意義上說是相似的，我們正在與 FDA 單獨進行這些討論並為這些事情制定策略。但除此之外，我無法真正將它們聯繫起來。

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

您的下一個問題來自 JMP 證券的雷尼·本傑明 (Reni Benjamin)。

I think I heard this right. I'm not sure in the prepared remarks, I believe you said that there would be data at ASCO and SITC. If I did hear that right, can you give us an idea as to what are the most likely trials that might be updated at those conferences?

我想我沒聽錯。我不確定在準備好的發言中，我相信你說過 ASCO 和 SITC 會有數據。如果我沒聽錯的話，您能否告訴我們哪些最有可能在這些會議上更新的試驗？

This is Madan. So I think what we mentioned in the prepared statement is our data that we had presented in 2021 at ASCO, SITC and AACR on the 136 patients across 4 tumor indications.

這是馬丹。因此，我認為我們在準備好的聲明中提到的是我們於 2021 年在 ASCO、SITC 和 AACR 上提交的關於 4 個腫瘤適應症的 136 名患者的數據。

And we do have a site for ASCO coming this year, which you can see, but we can't really say much more about that right now.

今年我們確實有一個 ASCO 網站，您可以看到，但我們現在不能透露更多。

Okay. And then with the potency assays, I'm just kind of curious, are those assays already integrated into the new iCTC facility? Or is that something that's done sort of outside the facility?

好的。然後，對於效力測定，我只是有點好奇，這些測定是否已經集成到新的 iCTC 設施中？或者這是在設施之外進行的事情？

That's something that we do at our facility, and we can do it elsewhere as well, but that's something that the facility -- Reni, I can't remember if you joined us for any of our open houses, but if you have come and seen it, you'll see it's fully integrated in terms of QC and that includes the ability to do the potency matrix that we talk about a lot.

這是我們在我們的工廠所做的事情，我們也可以在其他地方做，但這是工廠的事情——雷尼，我不記得你是否參加了我們的任何開放日活動，但如果你來了並且看到它，您會發現它在 QC 方面完全集成，其中包括我們經常談論的效力矩陣的能力。

Yes. Got it. Okay. That makes sense. And then just a couple of other ones. I don't know if you've mentioned this in the past, but how are you thinking about a potential sales force? And how big could it or small could it possibly be?

是的。知道了。好的。這就說得通了。然後還有其他幾個。我不知道您過去是否提到過這一點，但是您如何看待潛在的銷售人員？它可能有多大或有多小？

I think you can think of it on a comparison basis to the existing cell therapy field forces for the other CAR-Ts. The way that we'll be operating is through the potential authorized treatment centers, there's a pretty high concentration of care and then the community referrals will come in through the ATC. So I would say, if you benchmark the current CAR-T field forces, you're right in the ballpark.

我認為你可以將其與其他 CAR-T 的現有細胞治療領域進行比較。我們的運作方式是通過潛在的授權治療中心，提供高度集中的護理，然後社區轉診將通過 ATC 進行。所以我想說，如果你對當前的 CAR-T 現場部隊進行基準測試，你就在大致範圍內。

Okay. And then I guess one final one for me. It has -- in your discussions with the regulatory agencies, have they brought up anything in particular that could be a review issue? Or do you think that since this is the first time that a TIL going through that it's most definite that you'll have (inaudible) now?

好的。然後我猜對我來說最後一個。在您與監管機構的討論中，他們是否提出了任何可能成為審查問題的具體內容？或者您是否認為由於這是 TIL 第一次經歷，所以您現在肯定會擁有（聽不清）？

We don't know that for sure. It's possible because it is the first therapy in this class that we could get in a committee -- advisory committee. But TIL therapy is also very well known, and it's well known from (inaudible) experience as well as plenty of other academic centers experience, and we've got tons of data at Iovance, too. So that doesn't mean we have to get advisory committee, we may not get one. So your -- to the bigger part of your question, basically, are there any other things? No. Right now, we feel pretty comfortable with our timings and all the things we're doing. We have to -- obviously, it's -- for biotech, it's a big thing that follows first BLA, so we have to execute on that. But other than that, we think we're in good shape.

我們不確定。這是可能的，因為這是我們可以在委員會——諮詢委員會——中獲得的第一種療法。但 TIL 療法也非常出名，它是從（聽不清）經驗以及許多其他學術中心的經驗中眾所周知的，而且我們在 Iovance 也有大量數據。因此，這並不意味著我們必須設立諮詢委員會，我們可能不會設立。所以你的問題的大部分，基本上，還有其他事情嗎？不。現在，我們對我們的時間安排和我們正在做的所有事情感到非常滿意。顯然，我們必須——對於生物技術來說，這是繼 BLA 之後的一件大事，所以我們必須執行它。但除此之外，我們認為我們的狀況良好。

And I'm showing no further questions. So with that, I'll turn the call back over to Interim President and CEO, Fred Vogt for any closing remarks.

我沒有再提出任何問題。因此，我將把電話轉回給臨時總裁兼首席執行官 Fred Vogt，讓他發表結束語。

Thank you again for joining the Iovance Biotherapeutics First Quarter 2022 Financial Results Conference Call. It's an exciting time to be part of Iovance as we move towards our first BLA submission, continue our ongoing clinical trials and expand our growing TIL pipeline into new clinical trials, including the clinical trial of IOV-4001 that just posted to clinicaltrials.gov yesterday. I would like to recognize the patients and physicians who are participating in our clinical studies as well as our employees and cross-functional teams for their hard work in moving (inaudible). I would also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to our Investor Relations team if you wish to follow up.

再次感謝您參加 Iovance Biotherapeutics 2022 年第一季度財務業績電話會議。成為Iovance 的一員是一個激動人心的時刻，因為我們正朝著第一個BLA 提交、繼續我們正在進行的臨床試驗並將我們不斷增長的TIL 管道擴展到新的臨床試驗，包括昨天剛剛發佈到ClinicalTrials.gov 的IOV-4001 臨床試驗。我要感謝參與我們臨床研究的患者和醫生，以及我們的員工和跨職能團隊在搬家過程中所做的辛勤工作（聽不清）。我還要感謝我們的股東和分析師的支持。如果您想跟進，請隨時聯繫我們的投資者關係團隊。

Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。