Iovance Biotherapeutics Inc (IOVA) 2021 Q1 法說會逐字稿

Hello, and welcome to the Iovance Biotherapeutics First Quarter 2021 Financial Results Conference. My name is Michelle, and I will be the operator on today's call. (Operator Instructions)

您好，歡迎參加 Iovance Biotherapeutics 2021 年第一季度財務業績發布會。我叫米歇爾，我將擔任今天通話的接線員。（操作員說明）

I will now turn the call over to Ms. Sara Pellegrino. Ma'am, you may begin.

我現在將把電話轉給薩拉·佩萊格里諾女士。女士，您可以開始了。

Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fardis, our President and Chief Executive Officer; Friedrich Finckenstein, our Chief Medical Officer; and Jean-Marc Bellemin, our Chief Financial Officer. We are also joined by Jim Ziegler, Senior Vice President, Commercial. 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, 2021, as well as corporate update.

謝謝你，接線員。下午好，感謝您加入我們。我們的總裁兼首席執行官瑪麗亞·法迪斯 (Maria Fardis) 在今天的電話會議上發言。 Friedrich Finckenstein，我們的首席醫療官；以及我們的首席財務官 Jean-Marc Bellemin。商務高級副總裁 Jim Ziegler 也加入了我們的行列。今天下午，我們發布了一份新聞稿，可在我們的網站 iovance.com 上找到，其中包括截至 2021 年 3 月 31 日的 3 個月的財務業績以及公司更新。

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, pre-commercial activities, clinical trials and regulatory plans and results, 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.

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、預商業活動、臨床試驗和監管計劃和結果、未來潛在應用的前瞻性聲明。我們的技術、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 intro, I will turn the call over to Maria.

有了這個介紹，我就把電話轉給瑪麗亞。

Thank you, Sara, and good afternoon, everyone. I am pleased to highlight our first quarter 2021 progress at Iovance during today's conference call. During 2021, we have continued to advance and expand our Iovance tumor-infiltrating lymphocytes or TIL platform across multiple indications, including metastatic melanoma, cervical, head and neck and non-small cell lung cancers.

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 2021 年第一季度的進展。2021年，我們繼續推進和擴展我們的 Iovance 腫瘤浸潤淋巴細胞或 TIL 平台，涵蓋多種適應症，包括轉移性黑色素瘤、宮頸癌、頭頸癌和非小細胞肺癌。

For our lead TIL product candidate, lifileucel in metastatic melanoma, we completed the submission of additional information related to our potency assays to FDA in support of a planned Biologics License Application or BLA submission. Resolution of the potency assay with FDA is our top priority for 2021.

對於我們的主要 TIL 產品候選藥物 lifileucel，用於治療轉移性黑色素瘤，我們已完成向 FDA 提交與我們的效力測定相關的其他信息，以支持計劃的生物製劑許可申請或 BLA 提交。與 FDA 解決效力測定問題是我們 2021 年的首要任務。

We also reported new and updated data from our ongoing C-144-01 clinical study demonstrating durable responses in our Cohort 2 for onetime treatment with lifileucel. The Cohort 2 data was presented at AACR 2021, and additional data updates will be presented at ASCO 2021.

我們還報告了我們正在進行的 C-144-01 臨床研究的新數據和更新數據，證明我們的隊列 2 對 lifileucel 一次性治療有持久反應。第 2 組數據已在 AACR 2021 上發布，其他數據更新將在 ASCO 2021 上發布。

In additional indications, we completed patient dosing in Cohort 2 for lifileucel in advanced cervical cancer. For our registration-directed study of LN-145 in non-small cell lung cancer, we continue to activate sites for IOV-LUN-202 and consented multiple patients. We believe that the growing body of Iovance TIL clinical data across multiple late-stage cancers, coupled with results from a combination of our TIL and anti-PD-1 therapy in earlier stages of the disease, validate the significant and broad potential for Iovance TIL therapy. We also continue to execute toward all manufacturing and pre-commercial activities and furthering our commitment to address the critical need of cancer patients.

在其他適應症中，我們在第 2 組中完成了晚期宮頸癌 lifileucel 的患者給藥。對於 LN-145 在非小細胞肺癌中的註冊導向研究，我們繼續激活 IOV-LUN-202 的位點並獲得了多名患者的同意。我們相信，越來越多的 Iovance TIL 涉及多種晚期癌症的臨床數據，加上我們的 TIL 和抗 PD-1 療法在疾病早期階段的聯合治療結果，驗證了 Iovance TIL 的顯著而廣泛的潛力治療。我們還繼續執行所有製造和預商業活動，並進一步履行我們對滿足癌症患者的關鍵需​​求的承諾。

I am very confident in the quality of our internal team to deliver towards this mission. An impressive 76% of our more than 250 employees have at least a year of cell therapy experience. On the call today, I would like to spend a few minutes highlighting our lead indications and manufacturing progress. Then I will let Friedrich review our recent clinical data updates.

我對我們內部團隊實現這一使命的質量非常有信心。我們 250 多名員工中，76% 的員工至少擁有一年的細胞治療經驗，令人印象深刻。在今天的電話會議上，我想花幾分鐘強調我們的主要適應症和製造進展。然後我會讓弗里德里希回顧一下我們最近的臨床數據更新。

I will begin with our first pivotal program, lifileucel for advanced melanoma. As discussed in our previous calls, metastatic melanoma is a common type of skin cancer. In the U.S. alone, metastatic melanoma accounts for approximately 100,000 patients diagnosed and 7,000 deaths each year in the United States. We are focused on the growing population of metastatic melanoma patients that have exhausted their most commonly used available care options and need alternative therapies in our C-144-01 study.

我將從我們的第一個關鍵項目開始，lifileucel 用於治療晚期黑色素瘤。正如我們之前的電話會議中所討論的，轉移性黑色素瘤是一種常見的皮膚癌類型。僅在美國，每年就有約 100,000 名轉移性黑色素瘤患者被診斷，並導致 7,000 人死亡。在我們的 C-144-01 研究中，我們關注的是不斷增長的轉移性黑色素瘤患者群體，他們已經用盡了最常用的可用護理選擇，需要替代療法。

At the American Association for Cancer Research or AACR annual meeting, the updated data for Cohort 2 from C-144-01 clinical study was presented at a clinical trial plenary session. The long-term follow-up data showed that median duration of response was not reached at 28.1 months of median study follow-up. Furthermore, overall response rates remained at 36.4%, and we saw a continued deepening of response in 17% of the patients. We, as well as KOLS, including the physicians who highlighted the data at AACR, continue to be very enthusiastic about the durability of response following onetime treatment with lifileucel in very difficult-to-treat metastatic melanoma patients.

在美國癌症研究協會 (AACR) 年會上，C-144-01 臨床研究第 2 組的更新數據在臨床試驗全體會議上公佈。長期隨訪數據顯示，中位研究隨訪時間為 28.1 個月，但尚未達到中位緩解持續時間。此外，總體緩解率保持在 36.4%，並且我們看到 17% 的患者的緩解持續加深。我們以及 KOLS，包括在 AACR 強調數據的醫生，仍然對非常難以治療的轉移性黑色素瘤患者使用 lifileucel 一次性治療後的持久反應充滿熱情。

For the post anti-PD-1 patient population enrolled in Cohort 2, chemotherapy is the only currently available option and offers a 4% to 10% response rate and overall survival of only 7 to 8 months. Further updates for Cohort 2 will be highlighted at the upcoming American Society of Clinical Oncology or ASCO Annual Meeting in June. Detailed Cohort 2 data has also been accepted for publication in a forthcoming manuscript in a peer-reviewed, high-impact oncology journal.

對於加入隊列 2 的抗 PD-1 治療後患者群體，化療是目前唯一可用的選擇，其緩解率為 4% 至 10%，總生存期僅為 7 至 8 個月。第 2 組的進一步更新將在即將於 6 月舉行的美國臨床腫瘤學會或 ASCO 年會上重點介紹。詳細的隊列 2 數據也已被接受在同行評審的高影響力腫瘤學期刊即將發表的手稿中發表。

Turning to TIL in earlier lines of therapy. At the upcoming ASCO 2021 meeting, we are excited about sharing clinical data for lifileucel in combination with pembrolizumab in anti-PD-1-naive metastatic melanoma patients. Combination of Iovance TIL with available therapies in anti-PD-1-naive patients is one of Iovance's main clinical goals towards moving TIL into earlier treatment settings. Melanoma is the second clinical setting in which such combination is tested, and data are being provided.

轉向早期治療中的 TIL。在即將舉行的 ASCO 2021 會議上，我們很高興分享 lifileucel 聯合 pembrolizumab 在抗 PD-1 初治轉移性黑色素瘤患者中的臨床數據。Iovance TIL 與未接受過抗 PD-1 治療的患者的現有療法相結合，是 Iovance 將 TIL 納入早期治療環境的主要臨床目標之一。黑色素瘤是第二種對這種組合進行測試並提供數據的臨床環境。

As previously mentioned, reaching agreement with FDA on the potency assays for lifileucel is a top priority for Iovance. While the length of time until BLA submission depends on feedback from the agency, we continue staying prepared for a BLA submission in 2021. We plan to provide updates when available.

如前所述，與 FDA 就 lifileucel 的效力測定達成一致是 Iovance 的首要任務。雖然提交 BLA 的時間長度取決於機構的反饋，但我們將繼續為 2021 年提交 BLA 做好準備。我們計劃在可用時提供更新。

Our second pivotal program is investigating LN-145, now also known as lifileucel, in the C-145-04 study to support a BLA submission in metastatic cervical cancer. During the first quarter, Cohort 2 patient dosing with lifileucel was completed in post-anti-PD-1 cervical cancer patients. We believe that a BLA submission that includes both pivotal Cohort 1, which is evaluating lifileucel post chemotherapy, in addition to Cohort 2 may strengthen the potential label and reflect the expected upcoming treatment landscapes in cervical cancer.

我們的第二個關鍵計劃是在 C-145-04 研究中研究 LN-145（現在也稱為 lifileucel），以支持轉移性宮頸癌的 BLA 提交。第一季度，第 2 組患者在抗 PD-1 治療後的宮頸癌患者中完成了 lifileucel 給藥。我們認為，除了隊列 2 之外，提交的 BLA 還包括正在評估化療後 lifileucel 的關鍵隊列 1，這可能會強化潛在的標籤，並反映預期的宮頸癌治療前景。

As we have mentioned before, the resolution of the potency assay for lifileucel in melanoma and dialogue with FDA around the amount of clinical data follow-up are key steps toward our BLA submission in the cervical cancer indication. As a reminder, the FDA has previously granted both Breakthrough Therapy and Fast Track designations for lifileucel in cervical cancer.

正如我們之前提到的，lifileucel 在黑色素瘤中的效力測定的解決以及與 FDA 圍繞臨床數據隨訪量的對話是我們在宮頸癌適應症中提交 BLA 的關鍵步驟。提醒一下，FDA 此前已授予 lifileucel 治療宮頸癌的突破性療法和快速通道資格。

Turning to our manufacturing facility. Iovance Cell Therapy Center, or iCTC, we have completed construction of the exterior core and shell as well as initial clean rooms, and we have moved in. Process equipment and necessary utilities are now in place in the available clean room, and activities have commenced to support the start of TIL clinical manufacturing in late 2021.

轉向我們的製造工廠。Iovance細胞治療中心（iCTC），我們已經完成了外部核心和外殼以及初始潔淨室的建設，並且已經搬入。工藝設備和必要的公用設施現已在可用的潔淨室中就位，並且已開始支持 2021 年底啟動 TIL 臨床生產的活動。

Commercial manufacturing of Iovance TIL remains on track for 2022, with capacity to meet the demand for up to thousands of patients in multiple indications. Iovance has transformed TIL manufacturing from a lengthy academic process to a shorter, scalable, centralized GMP process, yielding a cryopreserved product. Our Gen 2 process is 22 days. To date, more than 450 patients have received Iovance TIL with a continuing success rate above 90%.

Iovance TIL 的商業化生產仍將在 2022 年按計劃進行，有能力滿足多達數千名患者多種適應症的需求。Iovance 將 TIL 製造從漫長的學術流程轉變為更短、可擴展、集中的 GMP 流程，生產出冷凍保存的產品。我們的 Gen 2 流程為 22 天。迄今為止，已有超過 450 名患者接受了 Iovance TIL，持續成功率超過 90%。

We are also looking forward to the potential to further improve the TIL manufacturing time lines and efficiencies. A shorter 16-day third-generation Iovance TIL manufacturing process, or Gen 3, is being explored in 2 of our clinical studies. The patients receiving Gen 3 TIL include a cohort of metastatic melanoma patients in the IOV-COM-202 clinical study where patient dosing has initiated as well as a cohort of non-small cell lung cancer patients in the IOV-LUN-202 study.

我們還期待進一步改善 TIL 製造時間線和效率的潛力。我們的兩項臨床研究正在探索縮短 16 天的第三代 Iovance TIL 製造工藝（即 Gen 3）。接受 Gen 3 TIL 的患者包括 IOV-COM-202 臨床研究中已開始患者給藥的一組轉移性黑色素瘤患者，以及 IOV-LUN-202 研究中的一組非小細胞肺癌患者。

We have also built and continue to augment our intellectual property, which is covered by more than 25 granted or allowed U.S. and international patents. Granted patents include composition and methods of treatment in a broad range of cancers relating to the Gen 2 manufacturing process with expected exclusivity through 2038. Iovance patent applications and granted patents are also directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic modification of TIL, tumor digest and fragment composition and methods, including cryopreservation and combination of TIL with checkpoint inhibitors.

我們還建立並繼續增強我們的知識產權，其中包括超過 25 項已授予或允許的美國和國際專利。已授予的專利包括與 Gen 2 製造工藝相關的多種癌症的組合物和治療方法，預計到 2038 年具有排他性。Iovance 專利申請和授權專利還針對 Gen 3 製造、選定的 TIL 產品、TIL 的穩定和瞬時基因修飾、腫瘤消化和片段組成和方法，包括冷凍保存以及 TIL 與檢查點抑製劑的組合。

In addition, as noted in this afternoon's press release, we have licensed additional patent rights from National Institutes of Health, or NIH, for cytokine-tethered TIL technology, including IL-15 and IL-21, and similar technology. We also expanded our worldwide field of use to all cancers. We believe that this expanded license and relationship with NIH may further solidify our leadership in the advancement of TIL and related intellectual property.

此外，正如今天下午的新聞稿中所指出的，我們已從美國國立衛生研究院 (NIH) 獲得了細胞因子束縛 TIL 技術的額外專利權，包括 IL-15 和 IL-21 以及類似技術。我們還將全球使用領域擴展到所有癌症。我們相信，這種擴大的許可以及與 NIH 的關係可能會進一步鞏固我們在 TIL 和相關知識產權發展方面的領導地位。

Turning to our pre-commercial launch preparations. We remain disciplined in our gated approach to commercial readiness. Our core commercial team continues to build the foundation for site training, patient access, payer coverage and other commercialization readiness activities. We are well positioned to rapidly scale and expand efforts across these areas, pending alignment with the FDA on our potency assay.

轉向我們的商業發布前準備工作。我們仍然嚴格遵守商業準備的封閉方法。我們的核心商業團隊繼續為現場培訓、患者訪問、付款人覆蓋和其他商業化準備活動奠定基礎。我們處於有利地位，可以在這些領域快速擴大和擴大努力，等待 FDA 就我們的效力測定進行協調。

Our medical affairs team maintains clinical site engagement in preparation for commercial launch. This team continues to work with key opinion leaders and patient advocacy groups on TIL awareness and educational programs and to ensure scientific communication at major conferences and in peer review publications.

我們的醫療事務團隊保持臨床現場參與，為商業發布做好準備。該團隊繼續與關鍵意見領袖和患者倡導團體合作開展 TIL 意識和教育計劃，並確保在主要會議和同行評審出版物中進行科學交流。

Commercial team is partnering with the leading U.S. cancer centers to build their TIL service line capabilities. Our training and onboarding program, which we will further expand upon BLA submission, is designed to ensure cross-disciplinary teams can administer the lifileucel treatment regimen upon FDA approval.

商業團隊正在與美國領先的癌症中心合作，建立他們的 TIL 服務線能力。我們的培訓和入職計劃將在 BLA 提交後進一步擴展，旨在確保跨學科團隊能夠在 FDA 批准後實施 lifileucel 治療方案。

Our market access team continues to engage payers to ensure patients have access to lifileucel. Very recently, the Centers for Medicare and Medicaid Services, or CMS, proposed 2 new International Classification of Diseases, 10th revision, Procedure Coding System or ICD-10 code for lifileucel.

我們的市場准入團隊繼續與付款人接觸，以確保患者能夠獲得 lifileucel。最近，醫療保險和醫療補助服務中心 (CMS) 為 lifileucel 提出了 2 個新的國際疾病分類第 10 版程序編碼系統或 ICD-10 代碼。

Additionally, CMS proposed to map lifileucel to existing MS-DRG 18. CMS also proposed to expand MS-DRG 18 from CAR-T cell immunotherapy to CAR-T cell and other immunotherapies, including Iovance TIL.

此外，CMS 提議將 lifileucel 映射到現有的 MS-DRG 18。CMS還提議將MS-DRG 18從CAR-T細胞免疫療法擴展到CAR-T細胞和其他免疫療法，包括Iovance TIL。

We believe that CMS' proposal to include lifileucel in existing MS-DRG 18 is recognition of the value of Iovance TIL and cell therapies for patients and the need to ensure appropriate reimbursement for providers beyond CAR-T. The proposal, if finalized, has the potential to strengthen hospital reimbursement for lifileucel therapy at the time of launch. We appreciate CMS' leadership and commitment to access to care.

我們相信 CMS 將 lifileucel 納入現有 MS-DRG 18 的提議是對 Iovance TIL 和細胞療法對患者價值的認可，以及確保對 CAR-T 以外的提供者進行適當報銷的需要。該提案如果最終敲定，有可能在推出時加強 lifileucel 治療的醫院報銷。我們讚賞 CMS 在獲得護理方面的領導力和承諾。

The Iovance team is also developing our IovanceCares program, which remains on track. Our goal is to deliver a best-in-class chain of custody and chain of identity system, cell ordering platform and patient support capabilities. IovanceCares is designed to be both customer- and patient-centric throughout the lifileucel treatment journey.

Iovance 團隊還在開發我們的 IovanceCares 計劃，該計劃仍在按計劃進行。我們的目標是提供一流的監管鍊和身份系統鏈、細胞訂購平台和患者支持能力。IovanceCares 的設計宗旨是在整個 lifileucel 治療過程中以客戶和患者為中心。

I will now pass the call to Friedrich to outline our clinical update. Friedrich?

我現在將致電弗里德里希，概述我們的臨床最新情況。弗里德里希？

Thank You, Maria. I am pleased to highlight recent and upcoming clinical data updates for Iovance TIL alone and in combination with pembrolizumab in melanoma as well as the status of our 4 ongoing clinical studies. Our drug development strategy focuses on cancer populations with high unmet need with substantial opportunities for TIL to make a meaningful impact.

謝謝你，瑪麗亞。我很高興地重點介紹 Iovance TIL 單獨治療和聯合派姆單抗治療黑色素瘤的近期和即將到來的臨床數據更新，以及我們正在進行的 4 項臨床研究的狀態。我們的藥物開發策略側重於需求未得到滿足的癌症人群，為 TIL 提供大量機會產生有意義的影響。

First, as Maria mentioned, we've provided an update for Cohort 2 and our C-144-01 clinical study at AACR at approximately 28.1 months of median study follow-up, and longer-term updates have been accepted for oral presentation at ASCO. We are also looking forward to an upcoming peer-reviewed publication of detailed Cohort 2 data.

首先，正如 Maria 提到的，我們在 AACR 的中位研究隨訪時間約為 28.1 個月時提供了隊列 2 和 C-144-01 臨床研究的更新，並且長期更新已被接受在 ASCO 進行口頭演示。我們還期待即將發布經過同行評審的第二組詳細數據。

At the upcoming ASCO meeting, we are also looking forward to the poster presentation of initial clinical data in the IOV-COM-202 study from Cohort 1A, which is evaluating lifileucel in combination with pembrolizumab in melanoma. This will represent a second indication with clinical data for Iovance TIL in combination with pembrolizumab in earlier treatment settings following the encouraging data in head and neck cancer presented at last year's Society for the Immunotherapy of Cancer or SITC meeting.

在即將召開的 ASCO 會議上，我們還期待以海報展示來自隊列 1A 的 IOV-COM-202 研究的初始臨床數據，該研究正在評估 lifileucel 與 pembrolizumab 聯合治療黑色素瘤。這將是繼去年癌症免疫療法協會或 SITC 會議上公佈的頭頸癌令人鼓舞的數據之後，Iovance TIL 與派姆單抗聯合用於早期治療的第二個適應症。

While pembrolizumab yields 33% response rate, 6% of which are complete responses in patients with melanoma, 40% to 65% of patients still progress on or after treatment. Therefore, in anti-PD-1-naive metastatic melanoma, there remains a need to increase the overall response rate, and in particular, the complete response rate.

雖然派姆單抗的緩解率為 33%，其中 6% 的黑色素瘤患者完全緩解，但 40% 至 65% 的患者在治療中或治療後仍然出現進展。因此，在抗PD-1初治轉移性黑色素瘤中，仍然需要提高總體緩解率，特別是完全緩解率。

We also continue to recruit patients across 4 clinical studies with Iovance TIL. Our C-145-04 clinical study in advanced cervical cancer has completed patient dosing in the first 2 cohorts. We continue to recruit the third cohort of anti-PD-1-naive patients to receive Iovance TIL plus pembrolizumab.

我們還繼續在 Iovance TIL 的 4 項臨床研究中招募患者。我們針對晚期宮頸癌的 C-145-04 臨床研究已完成前 2 個隊列的患者給藥。我們繼續招募第三組未接受過抗 PD-1 治療的患者接受 Iovance TIL 加派姆單抗治療。

We have now activated a total of 10 sites and consented multiple patients for our registration supporting study, IOV-LUN-202 in second-line non-small cell lung cancer. We believe that the patient population in IOV-LUN-202 as well as the 3 non-small cell lung cancer cohorts in the basket study, allow us to broadly address the unmet needs in non-small cell lung cancer.

我們現已啟動總共 10 個站點並同意多名患者參與我們的二線非小細胞肺癌註冊支持研究 IOV-LUN-202。我們相信，IOV-LUN-202 中的患者群體以及籃子研究中的 3 個非小細胞肺癌隊列使我們能夠廣泛解決非小細胞肺癌中未滿足的需求。

Recruitment also continues in our IOV-COM-202 study of Iovance TIL and TIL combinations across melanoma, head and neck and non-small cell lung cancers, in addition to the IOV-CLL-01 study in CLL and SLL. As the impact of the COVID-19 pandemic on hospitals' results, following the rollout of the COVID-19 vaccines and as the virus abates, we hope to be able to provide additional data at future medical meetings.

除了 CLL 和 SLL 的 IOV-CLL-01 研究之外，我們的 Iovance TIL 和 TIL 組合治療黑色素瘤、頭頸癌和非小細胞肺癌的 IOV-COM-202 研究也在繼續招募。由於 COVID-19 大流行對醫院業績的影響，隨著 COVID-19 疫苗的推出以及病毒的減弱，我們希望能夠在未來的醫療會議上提供更多數據。

I will now hand the call over to Jean-Marc to discuss our first quarter 2021 financial results.

我現在將把電話轉給 Jean-Marc，討論我們 2021 年第一季度的財務業績。

Thank you, Friedrich. My comments will reflect the high-level financial results from our first quarter 2021. Additional details can be found in this afternoon's press release as well as in our SEC filings.

謝謝你，弗里德里希。我的評論將反映我們 2021 年第一季度的高級財務業績。更多詳細信息請參閱今天下午的新聞稿以及我們向 SEC 提交的文件。

I will begin with our cash position. As of March 31, 2021, Iovance held $610.2 million in cash, cash equivalents, investments and restricted cash compared to $635 million on December 31, 2020.

我將從我們的現金狀況開始。截至2021年3月31日，Iovance持有現金、現金等價物、投資和限制性現金6.102億美元，而2020年12月31日為6.35億美元。

Our strong cash position is expected to be sufficient into 2023 to deliver on our pipeline programs.

我們強勁的現金狀況預計將足以在 2023 年實現我們的管道計劃。

Moving on to the income statement. Our net loss for the first quarter ended March 31, 2021, was $75.4 million, or $0.51 per share compared, to a net loss of $69.6 million or $0.55 per share for the first quarter ended March 31, 2020.

繼續看損益表。截至2021年3月31日的第一季度淨虧損為7540萬美元，即每股0.51美元，而截至2020年3月31日的第一季度淨虧損為6960萬美元，即每股0.55美元。

Research and development expenses were $55.9 million for the first quarter ended March 31, 2021, a decrease of $1 million compared to $57 million for the first quarter ended March 31, 2020. The year-over-year decrease in research and development expenses was primarily attributable to a decrease in manufacturing and clinical costs following the completion of enrollment in the pivotal cohort for melanoma and cervical cancer.

截至2021年3月31日的第一季度研發費用為5590萬美元，比截至2020年3月31日的第一季度的5700萬美元減少了100萬美元。研發費用同比下降主要歸因於黑色素瘤和宮頸癌關鍵隊列入組完成後製造和臨床成本的下降。

General and administrative expenses were $19.6 million for the first quarter ended March 31, 2021, an increase of $5.8 million compared to $13.9 million for the first quarter ended March 31, 2020. The year-over-year increase in general and administrative expenses was primarily attributable to growth of the internal general and administrative team and higher stock-based compensation expenses. As of March 31, 2021, there were approximately 149.3 million (sic) [147.3 million] common shares outstanding.

截至2021年3月31日的第一季度的一般及管理費用為1,960萬美元，較截至2020年3月31日的第一季度的1,390萬美元增加了580萬美元。一般及行政費用同比增長主要歸因於內部一般及行政團隊的增長以及股票薪酬費用的增加。截至 2021 年 3 月 31 日，已發行普通股約為 1.493 億股（原文如此）[1.473 億股]。

Looking ahead, we remain focused on investment in 4 key areas to ensure the growth and strength of our value creation: first, advancing our current clinical programs and indication; second, scaling up our manufacturing capacity to support our clinical manufacturing while preparing for expected commercial supply in 2022; third, ensuring launch readiness; and fourth, maintaining a strong balance sheet and cash position. I remain confident that by managing our investments across these 4 priorities, we will continue to stay focused and aligned in our spending with our corporate priorities.

展望未來，我們仍然專注於四個關鍵領域的投資，以確保我們價值創造的增長和實力：第一，推進我們當前的臨床項目和適應症；其次，擴大我們的生產能力以支持我們的臨床生產，同時為 2022 年的預期商業供應做好準備；第三，確保發射準備就緒；第四，保持強勁的資產負債表和現金狀況。我仍然相信，通過管理這 4 個優先事項的投資，我們將繼續保持專注，並使支出與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) The first question in the queue comes from Peter Lawson.

（操作員說明）隊列中的第一個問題來自 Peter Lawson。

We'll go to the next question, Michael Yee.

我們將討論下一個問題，Michael Yee。

Can you hear me okay, Maria?

你能聽到我說話嗎，瑪麗亞？

Yes, we can.

我們可以。

In the interest of, I guess, one question, our question was regarding the commentary around the progress in submitting additional data for assays. And the question was around your confidence level that things are absolutely moving on a pace to get an agreement. And if there was an agreement, you would just be able to come out and say that. And if that was not going along the right path, are there mechanisms to be able to either engage with the broader ODAC team or do other things to just be able to go ahead and push a little harder? Sorry for the different questions there, but it's all kind of related to the confidence level and the time lines.

我想，為了一個問題，我們的問題是關於提交額外分析數據進展的評論。問題在於你對事情絕對會以達成協議的速度進行的信心程度。如果達成了協議，你就可以站出來這麼說。如果這沒有沿著正確的道路發展，是否有機制能夠與更廣泛的 ODAC 團隊合作或做其他事情來繼續前進並更加努力？很抱歉提出了不同的問題，但這都與置信水平和時間線有關。

Understood, Michael. Thank you so much, Michael. We have submitted, as we noted, we have submitted our prior responses to the agency to the questions that were issued as part of the Type B meeting. We also have now provided the validation data that we had committed to provide to FDA as part of our responses in Q1 of 2021. We have not heard back from the agency. And I think a degree of confidence would depend on feedback from them. We really do need to hear from them.

明白了，邁克爾。非常感謝你，邁克爾。正如我們所指出的，我們已經向該機構提交了我們之前對 B 類會議中提出的問題的答复。我們現在還提供了我們承諾向 FDA 提供的驗證數據，作為我們 2021 年第一季度回應的一部分。我們還沒有收到該機構的回复。我認為一定程度的信心取決於他們的反饋。我們確實需要聽取他們的意見。

In terms of mechanism of escalation, there are definitely mechanisms by which we can escalate. We have been talking to FDA management to assure that we are able to at least get a response in a timely manner. So yes, there are venues, and we certainly have considered them.

從升級機制來看，我們肯定有升級的機制。我們一直在與 FDA 管理層進行交談，以確保我們至少能夠及時得到答复。所以，是的，有場地，我們當然已經考慮過它們。

And Peter Lawson your line is open.

彼得·勞森（Peter Lawson）您的電話已開通。

Sorry, I joined late, so I apologize if you ran through this. But when -- in lung cancer, when you think about the subsets kind of post TKI and PD-1 high and low and failed, where do you think TIL therapy could potentially fit in? Where do you think you've got the best shot at generating efficacy over both existing and emerging therapies coming through?

抱歉，我加入晚了，如果您遇到了這個問題，我深表歉意。但是，在肺癌中，當您考慮 TKI 和 PD-1 後高、低以及失敗的子集時，您認為 TIL 療法可能適合哪裡？您認為與現有的和新興的療法相比，您在哪些方面最有可能產生療效？

Peter, thank you for the question. The study that was conducted by Moffitt and was published at AACR 2020 was incredibly helpful in showing that there really didn't seem to be a particular subpopulation that was responding to TIL or not responding to TIL. What you might have seen is patients who had a PD-L1 low expression level were still among the responders, or patients that were post TKI if they had an oncogene driver mutation.

彼得，謝謝你的提問。由 Moffitt 進行並在 AACR 2020 上發表的這項研究非常有幫助，它表明似乎確實沒有特定的亞群對 TIL 做出反應或對 TIL 沒有反應。您可能會看到的是，PD-L1 低表達水平的患者仍然是有反應者，或者是 TKI 治療後的患者（如果他們有癌基因驅動突變）。

So that's highly encouraging. It's quite consistent with the signature of TIL, where there's not a specific subpopulation that may not respond to TIL.

所以這是非常令人鼓舞的。這與 TIL 的特徵非常一致，沒有特定的亞群可能對 TIL 沒有反應。

Now our study design, such as the specific IOV-COM-202 or LUN-202 is more designed with a registration program in mind. So LUN-202 is specifically is potentially supportive of registration. And so the subpopulation that we selected there is trying to identify a patient population that is both an unmet medical need and yet early enough in lines of therapy that the patients have an opportunity to benefit from TIL. It's not selected based on where we think TIL may be active or not active. It's really what we see is TIL seems to be active regardless of the subpopulation to the degree we have data in non-small cell.

現在我們的研究設計，例如特定的IOV-COM-202或LUN-202，更多是在設計時考慮到註冊程序。因此，LUN-202 特別可能支持註冊。因此，我們在那裡選擇的亞人群試圖確定既具有未滿足的醫療需求，又在治療中足夠早的患者群體，使患者有機會從 TIL 中受益。它不是根據我們認為 TIL 可能處於活動狀態或不活動狀態而選擇的。事實上，我們看到的是，無論亞群如何，TIL 似乎都很活躍，就我們在非小蜂窩中擁有的數據而言。

Got you. And then this may be addressed. But when was the last time you spoke to the FDA? I know the FDA does not honor a time clock with you. But when was the last time you spoke and -- about the BLA? And when do you anticipate speaking again? And do you think things are moving forward? Or have they paused? Or just your sense around that dialogue?

明白你了。然後這個問題就可以得到解決。但您最後一次與 FDA 交談是什麼時候？我知道 FDA 不尊重你的打卡時間。但您最後一次談論 BLA 是什麼時候？您預計什麼時候再次發言？您認為事情正在向前發展嗎？或者說他們已經暫停了？或者只是你對對話的感覺？

Sure. So FDA is a pretty large body. The review team or formal meetings is one venue for communication. There certainly are informal other ways of talking to FDA, through either regulatory project managers or other venues. So the dialogue with the agency is very much ongoing. It doesn't necessarily mean this is a -- standard sort of review type of a meeting, like a Type B meeting. But there definitely is dialogue between our regulatory team and the FDA to make sure that they have received the package, that they set aside time to review it, and they will respond to us in a timely manner.

當然。所以 FDA 是一個相當大的機構。審查小組或正式會議是溝通的場所之一。當然還有其他非正式的方式與 FDA 交談，可以通過監管項目經理或其他場所。因此，與該機構的對話一直在持續進行。這並不一定意味著這是一種標準的審查類型會議，例如 B 類會議。但我們的監管團隊和 FDA 之間肯定會進行對話，以確保他們已經收到該包裹，並留出時間進行審查，並且他們會及時回复我們。

The next question in the queue comes from Mark Breidenbach.

隊列中的下一個問題來自馬克·布雷登巴赫。

Just switching over to the upcoming data from lifileucel combined with pembrolizumab in frontline melanoma. I'm curious how many patients we're likely to see in that presentation, maybe ballpark? How much follow-up we can expect?

只是切換到即將發布的 lifileucel 聯合派姆單抗治療一線黑色素瘤的數據。我很好奇我們可能會在這次演示中看到多少患者，大概是多少？我們可以期待多少後續行動？

And Maria, I'm also curious to get your thoughts on what you see as likely next steps for development in an early line setting. Would this basket trial cohort potentially balloon into a randomized study versus single-agent pembro? Or what do you have in mind, assuming these initial data look good?

瑪麗亞，我也很想知道您對早期生產線設置中可能的下一步開發的想法。這個籃子試驗隊列是否有可能發展為一項與單藥 pembro 相比的隨機研究？或者假設這些初始數據看起來不錯，您有什麼想法？

Sounds good. Thank you, Mark. The number of patients has not quite been disclosed. Once the abstracts come out away from embargo, we can certainly discuss how many patients are in there. What I can say is that the cohort itself was designed for 12 patients, and the cohort is still open. So it's still continuing to enroll into the cohort.

聽起來不錯。謝謝你，馬克。患者人數尚未完全披露。一旦摘要解除禁運，我們當然可以討論其中有多少患者。我能說的是，該隊列本身是為 12 名患者設計的，並且該隊列仍在開放中。因此，它仍在繼續加入該隊列。

In terms of what the next steps would be, it is important for us to understand with larger number of patients and longer follow-up, what the real data is. These early looks are really helpful for us to understand what the potential may be. But at the same time, we recognize that we want to make sure we have large enough sample size, that we understand what the product is or is not doing.

就下一步而言，重要的是我們要了解更多患者和更長隨訪時間的真實數據是什麼。這些早期的觀察確實有助於我們了解其潛力。但與此同時，我們認識到我們要確保我們有足夠大的樣本量，以便我們了解產品正在做什麼或沒有做什麼。

In terms of next steps, I think once the data is visible, it's a little bit easier to speak to it. In general, I'll speak -- I'll answer your question in a general sense. Typically, when you have a combination in early line, the next step typically is a randomized study that would show the contribution of elements. I do not rule out single arms in general. If the contribution of elements is extremely high in that single arm there may be possibilities of talking to the agency and defining the registration path with a single arm. It's not very common, though. So typically, a randomized Phase III test would be a next step to take.

就下一步而言，我認為一旦數據可見，就更容易對其進行交流。總的來說，我會從一般意義上回答你的問題。通常，當您在早期就有組合時，下一步通常是一項隨機研究，以顯示元素的貢獻。一般來說，我不排除單臂。如果元素的貢獻在該單臂中非常高，則可能有可能與該機構交談並用單臂定義註冊路徑。不過，這並不常見。因此，下一步通常會進行隨機 III 期測試。

And the next question in the queue comes from Boris Peaker.

隊列中的下一個問題來自鮑里斯·皮克。

Just wanted to ask in terms of the lung cancer cohorts, when should we be expecting updates from those? And what are some of the factors that go into kind of deciding the timing of those updates?

只是想問一下關於肺癌隊列的問題，我們什麼時候應該期待這些隊列的更新？決定這些更新時間的因素有哪些？

Yes, absolutely. So we have really 2 cohorts that have lung cancer patients. One is in our basket study. The COM-202 study has 2 cohorts, Cohort 3A and 3B. The Cohort 3A, which is early line patients, the treatment-naive -- well, actually PD-1-naive patients, has been a little bit slower to enroll during COVID. And this may very well be the impact of hospitals having been impacted by COVID as well as the fact that these patients obviously have available therapies to receive at their local institutions.

是的，一點沒錯。所以我們確實有兩個肺癌患者隊列。其中之一在我們的籃子研究中。COM-202 研究有 2 個隊列：隊列 3A 和 3B。隊列 3A 是早期一線患者，即未接受過治療的患者，實際上是未接受過 PD-1 治療的患者，在新冠肺炎期間入組的速度稍慢一些。這很可能是受新冠疫情影響的醫院的影響，以及這些患者顯然可以在當地機構接受治療的事實。

In Cohort 3B, we do have some patients. We have not committed to a specific data flow time line. We drew the conclusion that patients that are second line are certainly much better in terms of non-small cell. The patient attrition from first line to second line in non-small cell lung cancer is quite large, unfortunately. Many patients, around 70% of the patients don't make it to second line.

在第 3B 組中，我們確實有一些患者。我們尚未承諾具體的數據流時間線。我們得出的結論是，二線患者在非小細胞方面肯定要好得多。不幸的是，非小細胞肺癌從一線到二線的患者流失相當大。許多患者，大約 70% 的患者沒有進入二線。

So we are trying to limit our subsequent upcoming cohorts to second-line non-small cell, but we do have some patients in that, they were 3B, which once we have long-enough follow-up, we could disclose the data. We haven't committed to a specific venue or a time frame yet.

因此，我們正在嘗試將後續即將到來的隊列限制為二線非小細胞，但我們確實有一些患者，他們是 3B，一旦我們有足夠長的隨訪時間，我們就可以披露數據。我們尚未承諾具體地點或時間範圍。

And the next question in the queue comes from Mara Goldstein.

隊列中的下一個問題來自瑪拉·戈德斯坦。

Just a couple of things. First, I just wanted to circle back to make sure that I understood correctly on the submission that was made to the FDA around the assay. That the FDA is not obligated to respond to you within a specific time frame for that submission.

只是幾件事。首先，我只是想回顧一下，以確保我對向 FDA 提交的有關該檢測的提交材料的理解正確。FDA 沒有義務在提交的具體時間範圍內回复您。

And on the cervical program, can you give us a bit more background on how the decision was made to combine the 2 cohorts? And was that made based on discussions with FDA? And where does that leave a potential filing time line?

關於宮頸計劃，您能否給我們提供更多背景信息，說明如何做出合併這兩個隊列的決定？這是根據與 FDA 的討論制定的嗎？那麼潛在的申請時間表在哪裡呢？

And then the last thing I had was just a curiosity more than anything. On the reimbursement front in the -- and the determinations that have been made around codes and whatnot, is there a specific time limit in which those must be made active such that you don't have to reapply back to the agencies?

然後我的最後一件事只是好奇心。在報銷方面——以及圍繞代碼等做出的決定，是否有一個特定的時間限制，在該時間限制內必須激活這些限制，以便您不必重新向機構申請？

Mara, I understood your first 2 questions. Let me answer them. But I didn't catch quite your third question. Let me try and answer the first 2, and then I'll ask you to repeat #3.

瑪拉，我理解你的前兩個問題。讓我來回答他們。但我沒聽清你的第三個問題。讓我嘗試回答前 2 個問題，然後我會請您重複第 3 個問題。

In terms of the assay, you're correct. The agency is not on a PDUFA clock to answer in a given time line. However, when a CMC IND amendment is submitted to the agency, there's guidelines that typically limit the duration of timely review. It's usually 1 to 2 months. And so that guideline is what we are sort of referring to and waiting for the agency to respond within that window of opportunity.

就化驗而言，你是對的。該機構沒有按 PDUFA 時鐘在給定的時間內答复。然而，當 CMC IND 修正案提交給該機構時，有一些指導方針通常會限制及時審查的持續時間。一般是1到2個月。因此，我們正在參考該指南，並等待該機構在這個機會之內做出回應。

In terms of cervical, we have been quite committed to combining the cohorts. I just want to be sure that we are clear. We gave the visibility to investors that we have the possibility of combining Cohorts 1 and 2. It's certainly subject to discussion with FDA. Cohort 1 were patients that were post chemotherapy in a metastatic setting, and Cohort 2 were patients that also could have received anti-PD-1 in a metastatic study.

在宮頸方面，我們一直致力於將隊列合併起來。我只是想確保我們清楚。我們向投資者表明我們有可能合併第 1 組和第 2 組。這當然需要與 FDA 進行討論。第 1 組是在轉移性環境中接受化療後的患者，第 2 組是在轉移性研究中也可能接受過抗 PD-1 治療的患者。

Now the reason we kind of went down that path is we wanted to make sure that the investors are aware that there's a possibility, given the potential change in the landscape of cervical cancer, there's a possibility that the agency may request cohort 2 and/or Iovance may want to include that data. So it's very much subject to discussion with the FDA. If that addresses your questions 1 and 2, do you mind repeating your question 3?

現在，我們走這條路的原因是，我們希望確保投資者意識到，考慮到宮頸癌形勢的潛在變化，該機構有可能要求隊列 2 和/或Iovance 可能希望包含該數據。因此，這非常需要與 FDA 進行討論。如果這解決了您的問題 1 和 2，您介意重複您的問題 3 嗎？

Sure, not a problem. But on question 2, if you do -- if the determination is that those cohorts will be combined from a potential filing perspective, is that -- what does that do to sort of the internal time line that you have or the one that you shared?

當然，不是問題。但在問題 2 上，如果你這樣做——如果決定從潛在的申請角度來看這些群組將被合併，那麼——這會對你擁有的或你共享的內部時間線進行排序？

Understood. Understood. From a timing perspective, just to kind of lay out what is required to reach a cervical BLA, let me just sort of lay out the steps that are needed. First and foremost, we absolutely want to make sure that our potency assay issue is resolved with the melanoma team, which is right now the dialogue that is ongoing. As a next step, we still do need to meet with the cervical review team to discuss the amount of follow-up you're going to request and whether Cohort 1 plus Cohort 2 is something they want or they want to stay just with Cohort 1.

明白了。明白了。從時間的角度來看，為了列出達到宮頸 BLA 所需的條件，讓我列出所需的步驟。首先也是最重要的，我們絕對希望確保我們的效力測定問題得到黑色素瘤團隊的解決，這是目前正在進行的對話。下一步，我們仍然需要與宮頸審查團隊會面，討論您要要求的隨訪量，以及他們想要隊列 1 加隊列 2 還是只留在隊列 1 。

And subsequent to that, we can -- we can think about sort of the BLA time line. A scenario during which this submission can happen later part of this year is still in the picture from my perspective. It really depends on when we get the potency assay results.

接下來，我們可以考慮 BLA 的時間線。從我的角度來看，這種提交可能會在今年晚些時候發生的情況仍然存在。這實際上取決於我們何時獲得效力測定結果。

Okay. That's it. And then I was just curious, as you were discussing in the top of the call around having determinations from CMS and whatnot around potential codes, such that you could get reimbursed, I know typically, those need to be in the books, I believe, by August. And so I'm just curious, do you have to have a commercialized product within a certain amount of time? If those are still valid? So would you have to go through this exercise again next year?

好的。就是這樣。然後我只是很好奇，正如您在電話會議的頂部討論的那樣，關於CMS 的決定以及潛在代碼的相關內容，這樣您就可以得到報銷，我知道通常情況下，這些需要記錄在書中，我相信，到八月。所以我很好奇，你必須在一定時間內擁有商業化的產品嗎？如果這些仍然有效？那麼明年您是否需要再次進行此練習？

Sure. Let me ask Jim to actually address that question. He's in the room with me.

當然。讓我請吉姆實際回答這個問題。他和我在房間裡。

Thanks, Maria. With respect to the DRG, if it's approved, it will be approved upon product approval. I think your real question is around NTAP. So for products or technologies that are approved by July 1, they would be implemented in the next fiscal year, beginning 1 October, so in this case, 2022. For products that don't meet that 1 July approval date, would have to resubmit with the NTAP. They are 2 separate processes, right? So one is the DRG, the other one...

謝謝，瑪麗亞。對於DRG，如果獲得批准，將在產品批准時獲得批准。我認為你真正的問題是關於 NTAP 的。因此，對於 7 月 1 日之前批准的產品或技術，它們將在下一個財年（10 月 1 日開始）實施，在本例中是 2022 年。對於未滿足 7 月 1 日批准日期的產品，必須向 NTAP 重新提交。它們是兩個獨立的進程，對嗎？所以一個是 DRG，另一個......

And the next question in the queue comes from Asthika Goonewardene.

隊列中的下一個問題來自 Asthika Goonewardene。

This is Avi for -- on for Asthika. Can you hear me?

這是 Asthika 的 Avi。你能聽到我嗎？

Yes, we can.

我們可以。

So one quick question about this license agreement with the NIH. Can you just give a little color on -- so this -- these are exclusive agreements. And every time there's a BLA approval, you're subject to paying out a low single-digit million dollar payment, right?

關於與 NIH 簽訂的許可協議，有一個簡單的問題。您能否稍微說明一下——這些是排他性協議。每次獲得 BLA 批准時，您都需要支付數百萬美元的低額付款，對吧？

That's correct.

這是正確的。

Okay. Got it. And one last thing, just circling back with the FDA. A lot of clarity today. But one -- so you mentioned that it was a 1 to 2 month general guidelines, but it's not required like a typical PDUFA date. So your last -- when -- can you give a little more clarity on like the day or the week you guys submitted the most recent data back to them?

好的。知道了。最後一件事，就是回到 FDA。今天清楚了許多。但有一點——所以你提到這是一個 1 到 2 個月的一般準則，但不像典型的 PDUFA 日期那樣需要。那麼，您的最後一次（何時）能否更清楚地說明一下你們向他們提交最新數據的日期或星期？

Thank you, Avi, for the question. So we didn't disclose the exact date, but we did say that we have submitted the validation package to the agency in Q1. We had committed to investors to do that and that was completed on time.

謝謝阿維的提問。所以我們沒有透露確切的日期，但我們確實說過我們已經在第一季度向該機構提交了驗證包。我們已向投資者承諾這樣做，並且已按時完成。

The next question in the queue comes from Madhu Kumar.

隊列中的下一個問題來自 Madhu Kumar。

Can you guys hear me okay?

你們能聽到我說話嗎？

Yes, we can.

我們可以。

Okay, great. So kind of thinking about the frontline Melanoma trial a little bit. I just kind of had a very simple question. Where do you think are the gaps in frontline melanoma on PD-1 blockade where TILs can provide specific benefit, like duration of response, complete response? Where do you think there's a kind of window for TILs plus PD-1 to get edge?

好的，太好了。稍微思考一下前線黑色素瘤試驗。我只是有一個非常簡單的問題。您認為一線黑色素瘤在 PD-1 阻斷方面的差距在哪裡，TIL 可以提供特定的益處，例如反應持續時間、完全反應？您認為 TIL 加上 PD-1 的優勢窗口在哪裡？

That's a great question, Madhu. So melanoma is a disease that is fairly well addressed with checkpoint inhibitors. However, I think that it really depends on the data itself. And I think we can comment a little bit more once the data for TIL plus pembro shows up at ASCO.

這是一個很好的問題，馬杜。因此，黑色素瘤是一種可以通過檢查點抑製劑很好地解決的疾病。然而，我認為這實際上取決於數據本身。我認為一旦 TIL 加 pembro 的數據出現在 ASCO 上，我們就可以多發表一些評論。

There's certainly -- there's always room for improvement if the patients are not reaching a complete response or that their duration of response could be improved. So from my perspective, a patient that experiences a deep, durable response in frontline really offers a lot of benefit to the patients.

當然，如果患者沒有達到完全緩解或者他們的緩解持續時間可以延長，那麼總是有改進的空間。因此，從我的角度來看，在前線經歷深刻、持久反應的患者確實會給患者帶來很多好處。

The clear second unmet need is exactly what we have been doing, which is the post-PD-1 patient population. I'm going to ask Friedrich to comment if he has anything to add. Did you want to add to this?

顯然，第二個未滿足的需求正是我們一直在做的，即 PD-1 後患者群體。如果弗里德里希有什麼要補充的，我會請他發表評論。您想對此進行補充嗎？

No, I think I agree, Maria. What we shouldn't forget that although a lot of progress has been made with the checkpoint inhibitors in various indications, the majority of patients still will progress either primarily or secondarily because of resistance mechanisms. You will make that less likely and you will increase benefit by pushing down the responses even deeper. And complete responses are a real, real good goal here. So I think I totally agree with Maria, that, that is really where there is room for improvement.

不，我想我同意，瑪麗亞。我們不應忘記，儘管檢查點抑製劑在各種適應症方面取得了很大進展，但由於耐藥機制，大多數患者仍會出現原發性或繼發性進展。你將降低這種可能性，並且通過將響應推得更深來增加收益。完整的回復是一個真正非常好的目標。所以我認為我完全同意瑪麗亞的觀點，這確實是有改進空間的地方。

Okay. Great. And kind of the follow-up on some of the questions around the cell potency assay issues. I mean I guess, kind of ultimately, to what extent is this whole situation about kind of educating the FDA about the differences between TILs and kind of earlier-generation cancer cell technologies, like CAR-T? And to what extent is this about kind of -- you mentioned having a panel of cytokine-type factors that demonstrate kind of T cell potency beyond just a single type of factor assay to demonstrate T cell potency?

好的。偉大的。以及有關細胞效力測定問題的一些問題的後續行動。我的意思是，我想，最終，整個情況在多大程度上是為了讓 FDA 了解 TIL 和早期一代癌細胞技術（如 CAR-T）之間的差異？您提到有一組細胞因子類型因子可以證明 T 細胞效力，而不僅僅是通過單一類型的因子測定來證明 T 細胞效力，這在多大程度上是這樣的？

So great question, Madhu. I don't know if I can comment on educating the agency. I mean the agency, certainly on our review team, there are members who have been at NCI before. Now how much internal communication there is, it's a little hard for me to sort of comment on that.

這是一個很好的問題，Madhu。我不知道我是否可以對教育機構發表評論。我的意思是該機構，當然在我們的審查團隊中，有一些成員以前曾在 NCI 工作過。現在有多少內部溝通，我很難對此發表評論。

I can tell you that the requests that they have made so far have been reasonable in the sense that they're not asking, for example, for a go find yourself an antigen-specific assay. That would have told me that well, for TIL, it's going to be very difficult to do. But that type of a request hasn't come through, which tells you that they do understand the power of TIL, the fact that it ultimately addresses multiple neoantigens, and it is highly, highly polyclonal.

我可以告訴你，他們到目前為止提出的要求是合理的，因為他們並沒有要求，例如，去尋找抗原特異性檢測。這會告訴我，對於 TIL 來說，這將是非常困難的。但這種類型的請求還沒有通過，這告訴你他們確實了解 TIL 的力量，事實上它最終能解決多種新抗原，而且它是高度、高度多克隆的。

So I think that maybe education is not the right word. Maybe the way is to better define a first-in-class product with this sponsor. There definitely is some time that needs to be spent between both the agency and the sponsor in trying to define how do we define such a complex product? I think that's probably the true statement.

所以我認為也許“教育”這個詞並不合適。也許方法是與這個贊助商一起更好地定義一流的產品。代理機構和讚助商之間肯定需要花費一些時間來嘗試定義我們如何定義如此復雜的產品？我認為這可能是真實的說法。

And the next question in the queue comes from Nick Abbott.

隊列中的下一個問題來自尼克·阿博特。

Maria and co., so in the current JCO, Jason Luke and colleagues have reported encouraging data for the combination of PD-1 and CTLA-4 in patients who really are considered primary PD-1 failures, and acknowledging these are largely second-line CTLA-4-naive patients. And so clearly, not apples-to-apples with lifileucel and resulting cohort. Do you think these data change the use of that doublet in the sort of second-line setting in -- does it create a barrier for lifileucel use?

Maria 和同事，在當前的JCO 中，Jason Luke 和同事報告了在確實被認為是原發性PD-1 失敗的患者中聯合使用PD-1 和CTLA-4 的令人鼓舞的數據，並承認這些患者主要是二線治療未接受 CTLA-4 治療的患者。很明顯，lifileucel 和由此產生的隊列不是同類的。您認為這些數據是否會改變該雙聯體在第二行設置中的使用——它是否會為 lifileucel 的使用造成障礙？

Nick, thank you for the question. I'll do my best to give you preliminary answers, and I'm going to invite Friedrich to also comment. I do -- we have seen the manuscript. I'm glad you're -- it's getting noticed. I highlight a few differences between the manuscript in terms of the patient population, the end points with what Iovance is doing.

尼克，謝謝你的提問。我會盡我所能給你初步的答案，並且我將邀請弗里德里希也發表評論。我知道——我們已經看過手稿了。我很高興你——它正在受到關注。我強調了手稿之間在患者群體、終點與 Iovance 正在做的事情方面的一些差異。

The end point that is reported with the manuscript is irRECIST, not RECIST 1.1. RECIST 1.1 is a regulatory end point that has been very well understood and requested by FDA. irRECIST is an immune-mediated type of end point and has not been really accepted by the agency as an appropriate end point.

手稿中報告的終點是 irRECIST，而不是 RECIST 1.1。RECIST 1.1 是 FDA 充分理解和要求的監管終點。irRECIST 是一種免疫介導的終點類型，尚未被該機構真正接受為適當的終點。

In terms of the patient population, this is strictly speaking, second line and in some cases, frontline metastatic patients, because they could have had adjuvant therapy. And subsequent to that, they would have entered the study.

就患者群體而言，嚴格來說，這是二線患者，在某些情況下是一線轉移患者，因為他們本可以接受輔助治療。之後，他們就會進入研究。

I highlight a couple of other points. Their amount of time on prior anti-PD-1 as the median was reported at 4.8 months. That's a pretty short duration of time. It probably looks like a primary refractory patient population. What was also remarkable from my perspective was the time from prior anti-PD-1, which was quite short. And that may yield to the previous product still being on board given the long half-life of prior anti-PD-1.

我強調其他幾點。據報導，他們先前使用抗 PD-1 藥物的時間中位數為 4.8 個月。這是一個相當短的持續時間。它可能看起來像是原發性難治性患者群體。從我的角度來看，同樣值得注意的是先前抗 PD-1 的時間非常短。鑑於先前的抗 PD-1 藥物半衰期較長，這可能會導致先前的產品仍在使用中。

The median duration of response had been [reached]. It was reported. And some of the patients, as I noted, were coming from an adjuvant setting. So I think that there's meaningful differences, both between the end points as well as the patient population, making it very difficult to compare. Friedrich, did you want to add any comment to this?

已[達到]中位緩解持續時間。據報導。正如我所指出的，有些患者來自輔助治療環境。因此，我認為終點和患者群體之間都存在有意義的差異，因此很難進行比較。Friedrich，您想對此添加任何評論嗎？

I think maybe a couple of comments, kind of compare and contrast also. This is an academic paper. This was generated in 7 U.S. sites. The data that we are presenting for our program is a global, multicenter study. I think that is relevant in this context as well.

我想也許有一些評論，還有一些比較和對比。這是一篇學術論文。這是在 7 個美國站點生成的。我們為我們的項目提供的數據是一項全球性、多中心研究。我認為這在這種情況下也是相關的。

And maybe one -- just one quick comment on the nature of the therapy. The treatment that was explored in this manuscript still requires continuation of pembrolizumab for up to 2 years, which is a big contrast to a onetime treatment with the lifileucel regimen. I think that is meaningful as well. And other than that, I think Maria summarized the differences very well.

也許還有一個——只是對這種療法的性質的一個簡短評論。本手稿中探討的治療方法仍然需要持續使用派姆單抗長達 2 年，這與 lifileucel 方案的一次性治療形成鮮明對比。我認為這也是有意義的。除此之外，我認為瑪麗亞很好地總結了這些差異。

Yes. Just maybe one more point, Nick, that I was reminded. Again, strictly speaking, they're second line at the latest. Many of the patients, the percent of the patients were first line sort of systemic therapy, and then some of them were second line. The patients had not received prior anti-CTLA-4 or other therapeutics, which is pretty much a reality of life for these patients nowadays, and outpatients never receive them.

是的。也許還有一點，尼克，我被提醒了。再說一次，嚴格來說，他們最遲是第二線。許多患者，一定比例的患者接受了一線全身治療，然後其中一些接受了二線治療。這些患者之前沒有接受過抗 CTLA-4 或其他治療，這對這些患者來說幾乎是現實的生活，而且門診患者也從未接受過這些治療。

And we have one more question in the queue, and that question comes from Ben Burnett.

我們還有一個問題在隊列中，這個問題來自本·伯內特。

This is Carolina Ibanez-Ventoso on for Ben Burnett. My call dropped earlier. So my apologies if you already touched on this. We were wondering if you could talk a bit more on the Cohort 3 arm of the cervical cancer study. And if you expect this would be needed for approval?

我是本·伯內特 (Ben Burnett) 的卡羅萊納·伊巴內斯·文托索 (Carolina Ibanez-Ventoso)。我的電話早些時候掛斷了。如果您已經觸及這一點，我深表歉意。我們想知道您是否可以多談談宮頸癌研究的第 3 組。如果您預計這需要獲得批准？

If I understand -- let me make sure I understand the question. Were you asking about Cohort 3 of cervical?

如果我理解了——讓我確保我理解了這個問題。您問的是頸椎病第 3 組嗎？

Yes, correct.

是，對的。

So Cohort 3 is patients that are PD-1 naive, and they get 2 plus anti-PD-1. Is that the cohort you're asking? Or are you asking about Cohort 2?

因此，第 3 組是未接受過 PD-1 治療的患者，他們接受了 2 組加抗 PD-1 治療的患者。你問的是那群人嗎？或者你是在問第二組嗎？

No. I'm asking about Cohort 3 and if you find that this will be needed for approval.

不。我詢問的是有關第 3 組的情況，以及您是否發現這需要獲得批准。

Great question. I don't believe so. That was really an exploratory cohort that we started trying to understand what a combination of TIL plus pembro in PD-1-naive patients would yield. So this has not been subject to any regulatory discussions. The patient population is an earlier-line patient compared to Cohorts 1 and 2.

很好的問題。我不相信是這樣。這確實是一個探索性隊列，我們​​開始嘗試了解 TIL 加 pembro 的組合在 PD-1 初治患者中會產生什麼效果。因此，這尚未受到任何監管討論。與隊列 1 和隊列 2 相比，患者群體是較早就診的患者。

Cohort 1 was discussed with the FDA. Cohort 2 is a patient population which is post PD-1 as well as post chemotherapy, and we think this is the landscape of patients that is coming. So we have added that cohort into the program, and we think it might be also important in submission of the BLA.

與 FDA 討論了隊列 1。第 2 組是 PD-1 治療後和化療後的患者群體，我們認為這就是即將到來的患者的情況。因此，我們已將該群體添加到該計劃中，我們認為這對於提交 BLA 也可能很重要。

Okay. We have no further questions at this time. Thank you, ladies and gentlemen. This will conclude today's teleconference. Thank you for participating. You may now disconnect.

好的。目前我們沒有進一步的問題。謝謝你們，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。