Immunocore Holdings PLC (IMCR) 2023 Q4 法說會逐字稿

Greetings welcome to the Immunocore fourth quarter financial results conference call. (Operator Instructions) Please note this conference is being recorded. I will now turn the conference over to Clayton Robertson, Head of Investor Relations. Thank you may begin.

歡迎參加Immunocore第四季財務業績電話會議。（操作員說明）請注意，本次會議正在錄製中。我現在將會議交給投資人關係主管克萊頓‧羅伯森 (Clayton Robertson)。謝謝你可以開始了。

Thank you, [Daryl]. Welcome, everyone, to our Q4 and full year 2023 financial results call. Before we begin, I would like to remind you that this call will contain forward-looking statements within the meaning of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995.

謝謝你，[達裡爾]。歡迎大家參加我們的第四季和 2023 年全年財務業績電話會議。在我們開始之前，我想提醒您，本次電話會議將包含 1995 年《私人證券訴訟改革法案》安全港條款含義內的前瞻性陳述。

These include expectations, plans concerning future events, prospects, and performance including with respect to commercialization, clinical development and trials, regulatory approvals, and financial results. Actual events may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those disclosed in our filings with the SEC.

其中包括有關未來事件、前景和業績的預期、計劃，包括商業化、臨床開發和試驗、監管批准和財務業績。由於各種重要因素（包括我們向美國證券交易委員會提交的文件中揭露的因素），實際事件可能與這些前瞻性陳述所顯示的情況有重大差異。

And such statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements.

此類聲明僅代表我們截至本網路廣播之日的觀點，不應被視為代表我們在任何後續日期的觀點。我們明確聲明不承擔更新此類聲明的義務。

With that, I'm now pleased to introduce and [University] Dr. Bahija Jallal.

現在，我很高興向您介紹[大學]Bahija Jallal 博士。

Thank you, Clay. Hello, everyone. With me today, Ralph Torbay, our Head of Commercial; David Berman, our Head of R&D; and Brian Di Donato, our Chief Financial Officer. We will be happy to take your questions at the end.

謝謝你，克萊。大家好。今天和我在一起的是我們的商務主管拉爾夫·托貝 (Ralph Torbay)； David Berman，我們的研發主管；以及我們的財務長布萊恩·迪·多納托 (Brian Di Donato)。最後我們很樂意回答您的問題。

At Immunocore, we are driven by a clear mission to bring transformative immunomodulatory medicines to patients in 2023. We continue to advance our three strategic pillars of maximizing the potential of KIMMTRAK advancing our clinical portfolio and continuing to innovate for sustainable growth.

在Immunocore，我們的明確使命是在 2023 年為患者提供變革性免疫調節藥物。我們繼續推進我們的三大策略支柱，即最大限度地發揮 KIMMTRAK 的潛力，推進我們的臨床產品組合，並繼續創新以實現永續成長。

If you look at the first one on KIMMTRAK last year, we achieved $239 million in net KIMMTRAK sales going into 2024. We see three growth opportunities. First, continue commercial growth driven by the US. Second mid-term growth driven by Q4 data from TEBE-AM trial, and third, long-term growth with the ATOM trial expected to start recruiting this year.

如果您查看去年 KIMMTRAK 上的第一份報告，您會發現，到 2024 年，我們的 KIMMTRAK 淨銷售額達到了 2.39 億美元。我們看到三個成長機會。首先，美國推動的商業成長持續。第二個中期成長是由 TEBE-AM 試驗第四季度數據推動的，第三個是長期成長，ATOM 試驗預計將於今年開始招募。

Second pillar on the portfolio we continue to advance our clinical portfolio with the announcement of our first PRAME Phase 3 trial in first-line advanced cutaneous melanoma. We intend to randomize the first patients in Q1. Preclinical data updates in melanoma, ovarian and lung will come through 2024.

作為產品組合的第二個支柱，我們宣布了針對第一線晚期皮膚黑色素瘤的首個 PRAME 3 期試驗，繼續推進我們的臨床產品組合。我們打算將第一季的第一批患者進行隨機分組。黑色素瘤、卵巢癌和肺癌的臨床前數據更新將於 2024 年完成。

The reflecting our enthusiasm for the PRAME targets. We are advancing two new candidates into the clinic this year. In December, we submitted the CTA for a first-in-class candidate, PIWIL1 in colorectal and GI cancers, and we continue to pursue a potential functional cure in HIV with Phase 1 data for the first half or second half of 2024.

這反映了我們對 PRAME 目標的熱情。今年我們將兩位新候選人推進臨床。去年 12 月，我們提交了針對結直腸癌和胃腸道癌症的一流候選藥物 PIWIL1 的 CTA，並且我們繼續尋求 HIV 的潛在功能性治愈，並在 2024 年上半年或下半年提供一期數據。

The third pillar is an innovation. And last month we announced that we had added two novel tissue targeted autoimmune programs, one for type one diabetes and the second for dermatology indications. You will hear more about each of these exciting programs from David. These additions expand the therapeutic areas we aim to treat to three. And now I'm happy to hand over to Ralph to share more information about KIMMTRAK. Ralph?

第三個支柱是創新。上個月，我們宣布增加了兩項新型組織靶向自體免疫項目，一項針對一型糖尿病，另一項針對皮膚科適應症。您將從 David 那裡聽到更多關於這些令人興奮的節目的資訊。這些補充將我們目標治療的治療領域擴大到三個。現在我很高興由 Ralph 來分享有關 KIMMTRAK 的更多資訊。拉爾夫？

Thank you Bahija. Hello everyone, 2023 was a catalyst year for KIMMTRAK. In less than two years from our first approval, we have transformed medical practice in metastatic uveal melanoma and established as pioneering TCR medicine as the first-line standard of care across all launch markets.

謝謝巴希賈。大家好，2023 年對 KIMMTRAK 來說是催化劑的一年。在我們首次獲得批准後不到兩年的時間裡，我們改變了轉移性葡萄膜黑色素瘤的醫療實踐，並將開創性的 TCR 藥物確立為所有上市市場的一線護理標準。

We have treated over 2,000 patients globally since the start of our first clinical trial. And I'm very proud of this team's achievements and commitment to patients. KIMMTRAK is currently approved in 38 countries and launched and reimbursed in 12. With the publication of KIMMTRAK long term three year overall survival in the New England Journal of Medicine. We continue to raise the bar of survival, and I look forward to the impact the team will have in 2024 leveraging this state.

自首次臨床試驗開始以來，我們已在全球治療了 2,000 多名患者。我為這個團隊的成就和對病人的承諾感到非常自豪。KIMMTRAK 目前已在 38 個國家獲得批准，並在 12 個國家推出並獲得報銷。隨著 KIMMTRAK 長期三年總存活率在《新英格蘭醫學雜誌》上發表。我們繼續提高生存標準，我期待團隊在 2024 年利用這種狀態產生影響力。

I will now take you through the figures and financial performance in more detail. For the full year 2023, KIMMTRAK generated $238.7 million in net revenues, which represents a 70% year-on-year growth. In the fourth quarter, we reported $67.6 million in net revenues, which represents an 8% increase from the prior quarter.

現在我將向您詳細介紹這些數據和財務表現。2023 年全年，KIMMTRAK 淨收入為 2.387 億美元，較去年同期成長 70%。第四季度，我們的淨收入為 6,760 萬美元，比上一季成長 8%。

This growth was primarily driven by continued commercial progress in the United States. In Europe, we launched in six new countries and reached pricing agreements with Italy and Germany. In France, we have been recognizing revenue since day one and have been accruing for an expected negotiated price.

這一增長主要是由美國持續的商業進步所推動的。在歐洲，我們在六個新國家推出了產品，並與義大利和德國達成了定價協議。在法國，我們從第一天起就一直在確認收入，並按照預期的協商價格進行累積。

In the international region we signed pricing agreements with Canada and Australia, which we are launching through the first half of the year. Our goal in 2024 is to continue our growth momentum in the United States and reach more patients globally, including our next country Spain. We're also excited to potentially expand the benefit of KIMMTRAK to additional indications with our clinical program, which I will take you through in the next slide.

在國際地區，我們與加拿大和澳洲簽署了定價協議，並將在今年上半年推出。我們 2024 年的目標是繼續在美國的成長勢頭，並覆蓋全球更多患者，包括我們的下一個國家西班牙。我們也很高興能夠透過我們的臨床計劃將 KIMMTRAK 的優勢擴展到其他適應症，我將在下一張投影片中向您介紹這項計劃。

We believe KIMMTRAK has significant potential for additional growth in the medium and long term, driven by two registrational clinical trials. The TEBE-AM study builds on the KIMMTRAK phase 1/2 cutaneous melanoma data that has shown a 76% survival rate at one year with an acceptable safety profile.

我們相信，在兩項註冊臨床試驗的推動下，KIMMTRAK 在中長期內具有巨大的額外成長潛力。TEBE-AM 研究建立在 KIMMTRAK 1/2 期皮膚黑色素瘤數據的基礎上，該數據顯示一年的生存率為 76%，且安全性可接受。

Enrollment is going well and we expect top-line results from the Phase 2 portion in the fourth quarter of this year. All the evidence with KIMMTRAK points to our platform being potentially transformative in the early disease settings. We were honored to work with EORTC, to launch the only ongoing registrational adjuvant study in uveal melanoma, the ATOM trial. We anticipate randomization to start in the second half of this year. Let's bring it all together into next slide, please.

註冊工作進展順利，我們預計第二階段部分將在今年第四季取得頂線結果。KIMMTRAK 的所有證據都表明我們的平台在早期疾病環境中具有潛在的變革性。我們很榮幸與 EORTC 合作，啟動唯一正在進行的葡萄膜黑色素瘤註冊輔助研究，即 ATOM 試驗。我們預計隨機化將於今年下半年開始。請讓我們將所有內容放在下一張投影片中。

Today, we're only at the beginning of the KIMMTRAK journey for the benefit is focused on 1,000 patients with metastatic uveal melanoma with the TEBE-AM trial, we see the potential to help 2,000 to 4,000 additional patients with second line plus metastatic cutaneous melanoma. With the ATOM trial, we could be unlocking the early-stage uveal melanoma potential and bringing the benefit of KIMMTRAK to up to 6,000 patients across all three indications.

今天，我們才剛開始 KIMMTRAK 之旅，因為 TEBE-AM 試驗的益處主要針對 1,000 名轉移性葡萄膜黑色素瘤患者，我們看到有可能幫助另外 2,000 至 4,000 名二線加轉移性皮膚黑色素瘤患者。透過 ATOM 試驗，我們可以釋放早期葡萄膜黑色素瘤的潛力，並使 KIMMTRAK 的益處惠及所有三種適應症的多達 6,000 名患者。

On a personal note, I am excited about our future because of this past year, I had the privilege to meet one of the first patients in our clinical trial I've had before that has been taking KIMMTRAK for seven years and is doing well. I also met there our first patient in our early access program remains well and on treatment and the physician who expanded their practice to handle the volume of patients who are now surviving. These people remind us every day of why we need to persevere in helping patients and advancing the science.

就我個人而言，我對我們的未來感到興奮，因為在過去的一年裡，我有幸見到了我們臨床試驗中的第一批患者之一，他已經服用 KIMMTRAK 七年了，並且表現良好。我還在那裡見到了我們早期訪問計劃中的第一位患者，情況仍然良好，正在接受治療，還有一位醫生擴大了他們的業務，以處理目前倖存的患者數量。這些人每天都提醒我們為什麼需要堅持幫助病人和推動科學發展。

I'll now hand it over to David to talk more about our pipeline.

現在我將把它交給 David 來更多地討論我們的管道。

Thank you, Ralph, I'm happy to share an update on our clinical stage portfolio and let's start with PRAME. Our PRAME opportunity stands across multiple solid tumors, including melanoma, ovarian, lung and endometrial carcinoma. By the end of this year, our franchise will include three clinical programs targeting PRAME, including a program for HLA-A02 with the half-life extension and a program for patients or HLA-A24 positive.

謝謝你，Ralph，我很高興分享我們臨床階段產品組合的最新信息，讓我們從 PRAME 開始。我們的 PRAME 機會涉及多種實體瘤，包括黑色素瘤、卵巢癌、肺癌和子宮內膜癌。到今年年底，我們的特許經營權將包括三個針對 PRAME 的臨床項目，包括半衰期延長的 HLA-A02 項目和針對 HLA-A24 陽性患者的項目。

Today, I will focus on the leap program, F106C across four major tumor types we are studying with F106C the melanoma data matured first, and provided confidence to launch the Phase 3, PRISM-MEL301. We will share the melanoma monotherapy and anti-PD1 combination data in second quarter.

今天，我將重點介紹飛躍計劃，F106C，跨越我們正在研究的四種主要腫瘤類型，F106C的黑色素瘤數據首先成熟，並為推出3期PRISM-MEL301提供了信心。我們將在第二季分享黑色素瘤單一藥物治療和抗PD1合併治療的數據。

After melanoma, the ovarian monotherapy and chemotherapy combinations have been maturing, and we are on track to share this data by third quarter for line. We are currently enrolling monotherapy and combinations. Unlike ovarian and melanoma, where we enrolled all comers for lighting, we have focused on select subsets where we would expect to see initial signals before expanding more broadly.

在黑色素瘤之後，卵巢單一療法和化療組合已經成熟，我們預計在第三季之前分享這項數據。我們目前正在招募單一療法和聯合療法。與卵巢癌和黑色素瘤不同，我們將所有參與者納入照明，我們專注於選定的子集，我們希望在更廣泛地擴展之前看到初始訊號。

This data will continue to mature in first half and will be shared by fourth quarter. Additional exploration continues, including endometrial KIMMTRAK combinations and dose confirmation. Several data points led to the initiation of the Phase 3 trial in first-line melanoma, including F106C monotherapy activity in heavily pre-treated patients.

該數據將在上半年繼續成熟，到第四季共享。其他探索仍在繼續，包括子宮內膜 KIMMTRAK 組合和劑量確認。多個數據點導致一線黑色素瘤 3 期試驗的啟動，包括在經過大量預先治療的患者中進行 F106C 單藥治療活動。

The ability to combine with anti-PD1 and insights that our platform works best in early-stage disease. We have opened clinical sites for the Phase three trial and expect to start randomizing patients in the near future. We are pleased to have a clinical trial collaboration and the volume at supply agreement with BMS for this trial.

與抗 PD1 結合的能力和我們的平台在早期疾病中效果最好的見解。我們已經為第三階段試驗開放了臨床中心，並預計在不久的將來開始對患者進行隨機分組。我們很高興與 BMS 就該試驗達成臨床試驗合作和供貨量協議。

I will now turn to highlight the power of our target discovery engine with a novel first-in-class target against PIWIL1. R117C is the first immunotherapy to target PIWIL1, a protein which is expressed in colorectal carcinoma, a tumor that has historically been insensitive to checkpoints.

現在，我將重點介紹我們的目標發現引擎的強大功能，以及針對 PIWIL1 的新型一流目標。R117C 是第一個針對 PIWIL1 的免疫療法，PIWIL1 是一種在結直腸癌中表現的蛋​​白質，結直腸癌歷來對檢查點不敏感。

PIWIL1 is an attractive target since it is not expressed in normal vital tissues is a negative prognostic marker and has broad expression in about a quarter of colorectal cancer patients. The CTA in Europe was submitted in December of last year, and we are on track to start that trial by the second half of this year.

PIWIL1 是一個有吸引力的靶點，因為它在正常重要組織中不表達，是一種陰性預後標誌物，並且在約四分之一的結直腸癌患者中廣泛表達。歐洲的 CTA 於去年 12 月提交，我們預計在今年下半年開始試驗。

Turning now from oncology to HIV. In addition to redirecting T cells to kill cancer cells. We believe our technology can be used to redirect T cells to kill virally infected cells. For HIV the current standards of care of anti-retroviral therapy block replication that cannot eliminate the virus, which hides in the reservoir in CD4 T cells.

現在從腫瘤學轉向愛滋病毒。除了重新定向 T 細胞來殺死癌細胞。我們相信我們的技術可用於重定向 T 細胞以殺死病毒感染的細胞。對於愛滋病毒，目前的抗病毒治療標準是阻止複製，但無法消除隱藏在 CD4 T 細胞中的病毒。

The single ascending dose portion of theM113V trial, we demonstrated safety and biomarkers indicating target engagement the goals of the ongoing multiple ascending dose portion are to demonstrate antiviral activity, including one, reducing the reservoir in blood. And two delaying the viral rebound.

M113V 試驗的單次遞增劑量部分，我們展示了安全性和指示標靶參與的生物標誌物，正在進行的多次遞增劑量部分的目標是證明抗病毒活性，其中之一是減少血液中的儲存。還有兩個可以延緩病毒反彈。

As we round out the clinical pipeline, I will transition to highlighting further the versatility of our platform. We validated that our impact technology can recruit and activate T cells against cancer, we are using the same T cell activation approach to target HIV and chronic HBV.

當我們完善臨床管道時，我將進一步強調我們平台的多功能性。我們驗證了我們的影響技術可以招募和活化 T 細胞來對抗癌症，我們正在使用相同的 T 細胞活化方法來針對 HIV 和慢性 HBV。

Today, I will share the third platform called ImmTAC, which has a different goal of turning off inflammation and is intended to treat autoimmune and inflammatory diseases. The current standards of care for ANI systemic immune suppression, which can lead to systemic toxicity.

今天，我將分享第三個平台，名為 ImmTAC，它有一個不同的目標：關閉炎症，旨在治療自體免疫和發炎疾病。目前 ANI 全身性免疫抑制的護理標準可能導致全身性毒性。

Our vision for the future is down modulation of the immune system focus only in the organ or tissue, which is under immune attack. As part of our cancer peptide discovery work, we have been mapping the normal human peptide. Therefore, when we want to develop a program to down modulate the ImmTAC in a specific organ, we have a large pre-existing library of peptides, that we know are tissue-specific.

我們對未來的願景是下調免疫系統的調節，只關注受到免疫攻擊的器官或組織。作為我們癌症肽發現工作的一部分，我們一直在繪製正常人類勝肽的圖譜。因此，當我們想要開發一個程序來下調特定器官中的 ImmTAC 時，我們有一個大型的預先存在的勝肽庫，我們知道這些勝肽庫具有組織特異性。

On slide 20, you can see our ImmTAAI molecule, the blue targeting end tethers, the ImmTAAI to the target tissue. The purple effector end is a PD1 agonist which presses on the PD1 break to turn off the T cell, there was also an Fc fusion which prolongs the half-life. And enables less frequent dosing.

在投影片 20 上，您可以看到我們的 ImmTAAI 分子、藍色標靶末端系鏈、與目標組織的 ImmTAAI。紫色效應端是PD1激動劑，它會壓迫PD1斷裂來關閉T細胞，還有一個Fc融合，可以延長半衰期。並且可以減少給藥頻率。

Our first application is for patients with type 1 diabetes, which remains a large unmet need type 1 diabetes results when autoreactive T cells kill pancreatic beta cells, which normally secrete insulin to protect the pancreatic beta cells. We designed an entire that binds to a peptide from the pre-proinsulin protein, which is only expressed in beta cells.

我們的第一個應用是針對第 1 型糖尿病患者，當自身反應性 T 細胞殺死胰臟 β 細胞（通常會分泌胰島素來保護胰臟 β 細胞）時，1 型糖尿病的需求仍然存在很大未得到滿足。我們設計了一個與前胰島素原蛋白的勝肽結合的整體，該蛋白僅在β細胞中表現。

The for PD1 agonist, a factor and will turn off these autoreactive T cells as seen in the data on the rates we see protection against autoreactive T cell killing only when using an ImmTAAI that tethers to the beta cell. Our second candidate is the skin inflammatory diseases, including atopic dermatitis and psoriasis, among others.

對於PD1 激動劑來說，這是一個因素，它將關閉這些自體反應性T 細胞，正如我們在使用與β 細胞相連的ImmTAAI 時看到的針對自身反應性T 細胞殺傷的保護率數據中所見。我們的第二個候選者是皮膚發炎性疾病，包括異位性皮膚炎和牛皮癬等。

We designed an ImmTAAI that bind specifically to a target that is only expressed on antigen-presenting cells in the skin in a T cell stimulation assay, we observed inhibition of T cells only for an ImmTAAI that tethers to the antigen-presenting cell.

我們設計了一種 ImmTAAI，它在 T 細胞刺激測定中特異性結合僅在皮膚中的抗原呈現細胞上表達的靶標，我們觀察到僅針對與抗原呈現細胞結合的 ImmTAAI 對 T 細胞的抑制。

This candidate has another exciting feature it is universal and not HLA restricted. This is an example of how our technology can be broadened to all population, this is certainly an exciting and productive period at Immunocore as we continue to pioneer TCR bispecific for cancer for infectious diseases and now for autoimmune diseases, I will hand over to Brian.

該候選藥物還有另一個令人興奮的特點，它是通用的，不受 HLA 限制。這是我們的技術如何擴展到所有人群的一個例子，這無疑對Immunocore來說是一個令人興奮和富有成果的時期，因為我們繼續開拓針對癌症、傳染病和現在針對自身免疫性疾病的TCR雙特異性技術，我將把工作交給Brian。

Thank you, David. Good morning, everyone. earlier today, we released our financial results for the fourth quarter and year ended 2023. Please refer to the press release and our latest SEC filing on Form 10-K for our full financial results.

謝謝你，大衛。大家，早安。今天早些時候，我們發布了第四季度和截至 2023 年的財務業績。請參閱新聞稿和我們最新的 10-K 表 SEC 備案文件，以了解我們的完整財務表現。

This is the first time that we report financials as a US domestic filer and the comparisons I will discuss are now all in US GAAP. The accounting difference between US GAAP and IFRS is not significant, less than $1 million net in each of the last three years.

這是我們第一次以美國國內申報者身分報告財務狀況，我將討論的比較現在全部採用美國公認會計準則。美國 GAAP 和 IFRS 之間的會計差異並不顯著，過去三年每年的淨額都不超過 100 萬美元。

I will now share some of the key highlights in our second year of launch 2023 has been an impressive year of KIMMTRAK sales, with net revenues growing to $67.6 million in Q4 from $62.6 million in Q3, primarily driven by the 13% growth in the United States.

我現在將分享我們推出第二年的一些關鍵亮點2023 年是KIMMTRAK 銷售令人印象深刻的一年，淨收入從第三季度的6260 萬美元增長到第四季度的6760 萬美元，這主要是由美國13% 的成長推動的狀態。

Total sales for the year, a $238 million or an increase of 70% over 2022. As Ralph mentioned, we continue to make best estimate revenue recognition assumptions and associated accruals for France until we achieve final price agreements. In line with the expansion of our portfolio. We have seen R&D and SG&A expenses increased marginally throughout 2023. With a net loss for the year of $55 million or $1.13 per share. We expect expenses to marginally increase in 2024 as clinical development for late-stage PRAME and KIMMTRAK programs accelerate.

全年總銷售額達 2.38 億美元，較 2022 年成長 70%。正如拉爾夫所提到的，我們將繼續對法國的收入確認假設和相關應計費用進行最佳估計，直到達成最終價格協議。與我們投資組合的擴展保持一致。我們發現 2023 年研發和銷售、一般行政費用略有增加。全年淨虧損 5,500 萬美元，即每股虧損 1.13 美元。隨著後期 PRAME 和 KIMMTRAK 計畫臨床開發的加速，我們預計 2024 年費用將小幅增加。

On slide 25, you see our net cash position increased to $443 million in 2023. Additionally, in February, we completed a six year $402 million convertible bond offering with a 2.5% interest rate and net proceeds of $389 million.

在投影片 25 上，您可以看到我們的淨現金部位在 2023 年增至 4.43 億美元。此外，2 月份，我們完成了 4.02 億美元的六年期可轉換債券發行，利率為 2.5%，所得淨收益為 3.89 億美元。

We intend to use $50 million of these proceeds to repay our Pharmakon loan in November, which has a rate of 9.75%. Taken together after this financing, we estimate a pro forma cash position of $782 million. Our KIMMTRAK sales and current cash put us in an excellent position to transform outcomes for patients by accelerating this portfolio with multiple clinical opportunities across three therapeutic areas.

我們打算用這些收益中的 5,000 萬美元償還 11 月的 Pharmakon 貸款，該貸款的利率為 9.75%。此次融資後，我們估計預計現金部位為 7.82 億美元。我們的 KIMMTRAK 銷售和當前現金使我們處於有利地位，可以透過三個治療領域的多個臨床機會加速這一產品組合，從而改變患者的治療結果。

I will now pass back to Bahija.

我現在將返回巴希賈。

Thank you, Brian, David, and Ralph. As you have seen, we have multiple data readouts and study starts planned for the remainder of 2024. It will be a very busy year. Reflecting now on the pipeline. The Immunocore has an industry leading bispecific TCR pipeline that now spends three therapeutic areas and reflects the large potential of our KIMMTRAK platform.

謝謝布萊恩、大衛和拉爾夫。正如您所看到的，我們計劃在 2024 年剩餘時間內讀取多個數據並開始研究。這將會是非常忙碌的一年。現在反思管道。Immunocore 擁有領先業界的雙特異性 TCR 管道，目前涵蓋三個治療領域，反映了我們 KIMMTRAK 平台的巨大潛力。

In the last five years, Immunocore has evolved from a research organization to a revenue generating sustainable company. We look forward with excitement to the next five years when we will maximize the value of KIMMTRAK expect to launch our brand targeted therapy and advance our other programs in oncology, infectious disease and autoimmune disease.

在過去五年中，Immunocore 已從研究機構發展成為一家可持續創造收入的公司。我們興奮地期待著未來五年，屆時我們將最大限度地發揮 KIMMTRAK 的價值，期望推出我們的品牌標靶治療，並推進我們在腫瘤學、傳染病和自體免疫疾病方面的其他項目。

Now the full, will be happy to answer questions.

現在已經滿了，很樂意回答問題。

Thank you.

謝謝。

(Operator Instructions) Michael Yee, Jefferies.

（操作員說明）Michael Yee，Jefferies。

Hey guys thanks. Good morning and great update. I had a question on the KIMMTRAK advanced melanoma study, which has a readout at the end of the year. And I wanted to understand, as part of this Phase 2/3 design, how do you think about the primary endpoint? And what you would expect the scenarios to be appreciating that I guess you could sort of go to the Phase 3 where there could be trends and you would still go to the Phase 3, tell me about what types of different outcomes there at the end of the year, given the Phase 2/3 design. Thank you.

嘿夥計們謝謝。早上好，很棒的更新。我對 KIMMTRAK 高級黑色素瘤研究有疑問，研究將於年底公佈。我想了解，作為 2/3 階段設計的一部分，您如何看待主要終點？你所期望的場景是什麼，我想你可以進入第三階段，那裡可能有趨勢，你仍然會進入第三階段，告訴我在結束時有哪些類型的不同結果考慮到 2/3 階段的設計。謝謝。

Thank you, Michael for a question, David, you wanted to take this one?

謝謝麥可提問，大衛，你想接受這個嗎？

Michael Thank you very much for the Phase 2 part of the study has dual primary endpoints of ctDNA and overall survival at the end of the year the ctDNA. will be mature and the survival will be directional, and we believe it will be able to inform us on a couple of key questions Michael One is can we drop one of the arms? Do we really need to include a PD1 or not?

Michael 非常感謝研究的第二階段部分有 ctDNA 和年底總存活期 ctDNA 的雙重主要終點。將會成熟，生存將會有方向性，我們相信它將能夠告訴我們幾個關鍵問題：邁克爾一號，我們可以放下一隻手臂嗎？我們真的需要包含 PD1 嗎？

The second question we're going to ask is can we resize the study is our assumptions, correct. So I think at the end of the year, we'll have a top line of ctDNA. overall survival trend. And what the next steps are in the phase 3.

我們要問的第二個問題是，我們是否可以根據我們的假設調整研究規模，這是正確的。所以我認為到今年年底，我們將擁有 ctDNA 的頂級產品線。整體生存趨勢。第三階段的後續步驟是什麼。

(Operator Instructions) Jessica Fye, JP Morgan.

（操作員說明）Jessica Fye，摩根大通。

Hey, guys, good morning, thanks for taking my question. I was hoping you could walk through in a little more detail the various frame updates we can expect throughout the year with details like the number of additional patients we should expect for cutaneous melanoma, how many patients we'll see for ovarian and maybe a range of patients for how many we'll see in lung and when should we expect any update from the endometrial cohort? Thank you.

嘿，夥計們，早上好，謝謝你回答我的問題。我希望您能更詳細地介紹我們全年可以預期的各種框架更新，其中包括我們預計會出現的皮膚黑色素瘤患者數量、我們將看到多少卵巢患者以及可能的範圍等詳細信息我們將在肺部看到多少患者，我們什麼時候應該期待子宮內膜隊列的任何更新？謝謝。

Thank you, Jess, David, you want to take this one?

謝謝你們，傑西，大衛，你們想買這個嗎？

Yes, just so we haven't commented on numbers, but I'll walk through the different readouts for cutaneous melanoma, which matured the fastest will be presenting the data that supported our decision to move to Phase 3, the data that we shared with the FDA and with some with KOLs, and we can talk more about that if you like.

是的，我們沒有對數字發表評論，但我將介紹皮膚黑色素瘤的不同讀數，成熟最快的皮膚黑色素瘤將提供支持我們決定進入第三階段的數據，這些數據是我們與其他人共享的FDA以及一些KOL 的合作，如果您願意，我們可以更多地討論這一點。

For ovarian, we're still enrolling patients there that was maturing that enrollment was a little bit behind. Melanoma was still enrolling ovarian, but that data will be available in second quarter with line. It has been a little bit different. We're enrolling all comers with ovarian and melanoma with lung. We have taken a methodical approach to focus initially on subsets where we think we'll see signals before it's expanding more broadly for both melanoma and ovarian and lung. In addition to monotherapy, we have combinations for melanoma it's PD1 combinations, for ovarian in line, it's going to be the chemotherapy combinations.

對於卵巢，我們仍在招募那些正在成熟的患者，但招募有點落後。卵巢黑色素瘤仍在招募中，但數據將於第二季發布。情況有些不同了。我們正在招募所有患有卵巢癌和肺癌的黑色素瘤患者。我們採取了一種有條不紊的方法，首先關注我們認為在黑色素瘤、卵巢癌和肺癌更廣泛擴展之前我們會看到信號的子集。除了單一療法之外，我們還有針對黑色素瘤的組合療法，即 PD1 組合療法，針對卵巢癌的組合療法，則為化療組合療法。

(Operator Instructions) Tyler Van Buren with TV Cowen.

（操作員說明）Tyler Van Buren 與 TV Cowen。

Hey, guys, thanks for taking the question and congrats on another great KIMMTRAK quarter. Just to follow up on the second quarter PRAME melanoma update, if I'm not mistaken, there was only one cutaneous melanoma patient ongoing as of the update during the second quarter '23 earnings.

嘿，夥計們，感謝您提出問題，並祝賀 KIMMTRAK 又一個精彩的季度。只是為了跟進第二季 PRAME 黑色素瘤更新，如果我沒記錯的話，截至 23 年第二季收益更新時，只有一名皮膚黑色素瘤患者仍在治療中。

So should we expect more cutaneous monotherapy patients with the second quarter update or not. And regarding the PD1 combo data, how heavily pretreated are these patients so we can understand what the bar should be that we should compare to.

因此，我們是否應該期待第二季更新後會有更多的皮膚單藥治療患者出現。關於 PD1 組合數據，這些患者的預處理程度如何，這樣我們就可以了解我們應該比較的標準應該是什麼。

Thank you, Tyler another one for David.

謝謝你，泰勒又給大衛一份了。

Yeah so for the first question, at the update last year, we just shared the update of the original asthma patients. So we certainly will have more cutaneous melanoma patients and it will be sufficient to inform and provide reasons believe for the Phase 3 trial.

是的，對於第一個問題，在去年的更新中，我們剛剛分享了原始氣喘患者的更新。因此，我們肯定會有更多的皮膚黑色素瘤患者，這足以為第三階段試驗提供資訊和理由。

With regards to the second question, which I missed which tumor you were?

關於第二個問題，我漏掉了，你是哪一種腫瘤？

PRAME melanoma, PD1 combination data, how heavily pre-treated will they basically (inaudible)?

PRAME黑色素瘤，PD1組合數據，他們基本上會接受多少預處理（聽不清楚）？

Others are the place to be?

其他地方都可以去嗎？

Yes, Tyler, I can I can address that. So it's a mixture. So there were some patients because the pembrolizumab is indicated they could be pembrolizumab naive, but many of them were previously exposed to some mixed population because the primary endpoint is safety and feasibility.

是的，泰勒，我可以，我可以解決這個問題。所以它是一種混合物。因此，有一些患者因為帕博利珠單抗表明他們可能未接受過帕博利珠單抗治療，但他們中的許多人之前曾接觸過一些混合人群，因為主要終點是安全性和可行性。

And that was Mohammad, our CMO.

那就是穆罕默德，我們的首席行銷長。

(Operator Instructions) Eric Schmidt, Cantor Fitzgerald.

（操作員說明）Eric Sc​​hmidt、Cantor Fitzgerald。

Thanks for taking my question and congrats on the quarter. Maybe one on KIMMTRAK in the Phase 2/3 relapsed refractory melanoma study and the Phase 2 readout toward year end. I think you've commented that if the data are favorable from the Phase 2 portion that could support a compendia listing, how should we think about a compendia listing with an endpoint that's survival driven as opposed to response rate driven? Thanks

感謝您提出我的問題並祝賀本季。也許是 KIMMTRAK 的 2/3 期復發難治性黑色素瘤研究和年底的 2 期讀數。我想您已經評論過，如果第二階段部分的數據是有利的，可以支持概要列表，那麼我們應該如何考慮具有生存驅動而非響應率驅動端點的概要列表？謝謝

David you want to pick?

大衛你想選嗎？

Eric, very good question. So this is something that we'll have to decide on a data dependent fashion. The survival data will mature in 2025 and we will typically what happens.

埃里克，非常好的問題。因此，我們必須根據數據依賴的方式來決定這一點。生存數據將於 2025 年成熟，我們通常會知道會發生什麼。

Eric, is that you submit that you write a paper of our presentation, you submit that to NCCN. So we will trial and submit it and it's up to NCCN to decide whether or not to accept that the benefit of course, is we already have a therapy which has shown a survival benefit, [albeita] in a different type of melanoma.

Eric，您提交了我們的簡報的論文，您將其提交給 NCCN。因此，我們將進行試驗並提交它，由 NCCN 決定是否接受這一好處，當然，我們已經有了一種療法，該療法已顯示出對不同類型黑色素瘤的生存益處。

(Operator Instructions) Michael Schmidt, Guggenheim.

（操作員說明）邁克爾·施密特，古根漢。

I think for taking our question, this is Paul on for Michael. Minor also on frame. So maybe for David, what is your current thinking on the planned registrational opportunity in mind, cutaneous melanoma. Is this still a focus area given your initiation of the frontline Phase 3? And if so, how do you think about response benchmarks of the recent accelerated approval for TEBE-AM of impact review on the setting?

我認為，在回答我們的問題時，這是保羅代替邁克爾。框架上也有輕微的變化。那麼對於大衛來說，您目前對計劃的註冊機會有何想法，皮膚黑色素瘤。鑑於你們啟動了前線第三階段，這仍然是一個重點領域嗎？如果是這樣，您如何看待最近加速批准 TEBE-AM 對環境影響審查的回應基準？

And then just a quick follow-up on PRAME in lung can you expand on which particular subsets on focus and overall strategy?

然後，您可以對肺部 PRAME 進行快速跟進，以擴展重點和整體策略的特定子集嗎？

So maybe, David, thank you, Michael, for the question. Maybe, David, to start and then Mohammad.

所以也許，大衛，謝謝你，邁克爾，提出這個問題。也許，大衛，先開始，然後是穆罕默德。

Sorry, Paul? Yes. So in terms of the PRAME, we as a small company, you have to focus. And so what we have decided is to focus where we believe is both the best opportunity from a technical point of view, but also which is the largest opportunity. And so for PRAME, we're focused on first line in the late-line setting where the tolls was originally put caps where we have KIMMTRAK in an opportunity and that trial is accruing well. And that trial has a survival endpoint, which will lead to a full approval, whereas the recent sales was an accelerated approval.

對不起，保羅？是的。所以就PRAME而言，我們作為一家小公司，你必須專注。因此，我們決定將重點放在我們認為從技術角度來看最好的機會，也是最大的機會的地方。因此，對於 PRAME，我們專注於晚線設置中的第一條線，其中通行費最初設置了上限，我們有 KIMMTRAK 的機會，而且試驗進展順利。該試驗有一個生存終點，這將導致完全批准，而最近的銷售是加速批准。

With regards to the lung of your question?

關於你的問題的肺？

Mohammed you want to take that?

穆罕默德，你想接受這個嗎？

Happy to do that. So with lung, we know it's a very heterogeneous disease and there's distinct molecular subsets of based on well-known and well described subsets to the cohorts that David alluded to that we're exploring are sort of run along those lines.

很高興這樣做。因此，對於肺部，我們知道這是一種非常異質的疾病，並且基於眾所周知和充分描述的子集，大衛提到我們正在探索的隊列有不同的分子子集，這些子集有點沿著這些思路運行。

(Operator Instructions) Graig Suvannavejh, Mizuho.

（操作員說明）Graig Suvannavejh，Mizuho。

Hi, this is Avantika for Graig. Congrats on the quarter. I just had a question on KIMMTRAK, it appeared that the ex U.S. sales were a little bit flat, I would say. And is there a reason for this? And how do you intend to keep growing this? And how do you also intend or how much more growth do you see in the US? Thank you.

大家好，我是 Graig 的 Avantika。恭喜本季。我剛剛對 KIMMTRAK 有一個問題，我想說的是，美國前的銷售額似乎有點持平。這是有原因的嗎？您打算如何繼續發展這一點？您還有什麼打算或您認為美國的成長幅度是多少？謝謝。

Thank you Avantika, Ralph you want to take this one?

謝謝阿凡提卡，拉爾夫，你想買這個嗎？

Avantika, thank you for your question. So look, we've had a very successful set of years a couple of years in Europe where we've launched in Germany, France, significantly, but as well as Italy and six other countries. So we're really at this phase where we've established KIMMTRAK as standard of care, and we are well penetrated. So we do see a relatively flat future with some of the launches incrementally adding to the growth there.

阿凡提卡，謝謝你的提問。所以看，我們在歐洲已經取得了非常成功的幾年，我們在德國、法國、義大利和其他六個國家推出了重要產品。因此，我們確實處於這個階段，我們已將 KIMMTRAK 確立為護理標準，並且我們的滲透率很高。因此，我們確實看到了一個相對平坦的未來，一些產品的推出逐漸促進了那裡的成長。

Now the primary driver of growth will be the United States and that will be driven really mainly by us continuing to penetrate into the community and identifying patients earlier.

現在成長的主要驅動力將是美國，這實際上主要是由我們繼續滲透到社區並更早地識別患者來推動的。

And as, in Europe, it's about the country by country for pricing. And so that's the word continuing that.

在歐洲，定價取決於各國。這就是繼續這個詞。

(Operator Instructions) Peter Lawson, Barclays.

（操作員說明）Peter Lawson，巴克萊銀行。

Please proceed with your question great thank you. Thanks for taking my questions and congratulations on the quarter.

請繼續您的問題，非常感謝。感謝您回答我的問題並對本季表示祝賀。

Just as we think about revenues this quarter, kind of what drove the growth in US business, any one-time we should think about and any guidance around that we should be thinking about one queue.

正如我們考慮本季的收入（推動美國業務成長的因素）一樣，我們應該考慮的任何一次性情況以及圍繞該問題的任何指導都應該考慮一個隊列。

Great, Peter, great question, Ralph.

太好了，彼得，好問題，拉爾夫。

So, Peter we had a great 30% quarter-over-quarter growth in the US on the main drivers that if you recall at the beginning of the year, we said we're going to be focusing on the community and that community penetration.

所以，彼得，我們在美國的主要驅動因素實現了 30% 的季度環比增長，如果你還記得年初的話，我們說過我們將重點關注社區和社區滲透率。

And that's what we did. And now the majority of our scripts are coming from the community. And that's what's driving really the main part of our growth. We're also seeing duration of therapy being sustained with physicians treated beyond progression.

這就是我們所做的。現在我們的大部分腳本都來自社群。這才是真正推動我們成長的主要因素。我們也看到，醫生的治療持續時間超過了進展。

So what we expect in 2024 is the growth to incrementally continue to the US and beyond 2024. And in the midterm. We're expecting the as David has mentioned ImmTAAI and study data as well as in the long term, the ATOM trial, which we're very excited about.

因此，我們預計 2024 年美國及 2024 年後將持續逐步成長。並且在中期。我們期待著 David 提到的 ImmTAAI 和研究數據，以及長期的 ATOM 試驗，我們對此感到非常興奮。

(Operator Instructions) Jack Allen, Baird.

（操作員說明）Jack Allen、Baird。

Hi, this is Charlie on for Jack. I was just wondering if -- for the ovarian in the brain franchise, would you be able to give us a little more color in terms of the size of the dataset you're expecting as well as duration of follow-up and what you would consider the bar for success?

嗨，我是傑克的查理。我只是想知道，對於大腦中的卵巢特許經營權，您能否就您期望的數據集大小以及隨訪持續時間以及您想要的內容向我們提供更多信息考慮成功的標準嗎？

Great. Thank you. David, you want to take this question?

偉大的。謝謝。大衛，你想回答這個問題嗎？

yeah, Charlie, the with regard to size, we haven't been commenting on number of patients. But what we have said is that we will show data that is sufficient in order to inform the level of activity and the duration of follow-up, we believe will also be sufficient in terms of the bar for success.

是的，查理，關於規模，我們還沒有評論患者的數量。但我們所說的是，我們將提供足以告知活動水平和後續持續時間的數據，我們相信就成功的標準而言也足夠了。

We're looking at answering two questions, which is the traditional. What we do in drug development is the drug active and does that clinical activity support registrational trial. So we know the drug is active. And then here in terms of clinical activity, we'll be looking at partial responses, durable tumor reduction, PFS disease control and of course, CTD and a reduction which is emerging as a consistent theme for our platform.

我們正在考慮回答兩個傳統問題。我們在藥物開發中所做的是藥物活性以及臨床活性是否支持註冊試驗。所以我們知道該藥物具有活性。然後就臨床活動而言，我們將專注於部分緩解、持久腫瘤減少、PFS 疾病控制，當然還有 CTD 和減少，這是我們平台的一致主題。

(Operator Instructions) Jeet Mukherjee, BTIG.

（操作員指令）Jeet Mukherjee，BTIG。

Thanks for taking our question. This is Jeet on for Justin.

感謝您提出我們的問題。這是賈斯汀的傑特。

Was hoping you could just help us think about the efficacy bar for relapse-free survival for the adjuvant setting?

希望您能幫助我們考慮輔助治療無復發生存的療效標準​​嗎？

And just any thoughts around the neoadjuvant setting as well for uveal melanoma? Thanks.

關於葡萄膜黑色素瘤的新輔助治療有什麼想法嗎？謝謝。

Right, Jeet and David, do you want to take this one and maybe you can comment as well about.

好的，Jeet 和 David，你們想接受這個嗎？

Yeah. I'll focus on the neoadjuvant some first step in that. Interestingly, in the original trial, when we looked back, we did have a couple of patients with residual melanoma in the eye. And interestingly, when we looked at those lesions, there was actually a reduction in those tumor lesions. So I think neoadjuvant is an exploratory program, and we have a couple of ESRs with regard to that.

是的。我將重點放在新輔助治療的第一步。有趣的是，在最初的試驗中，當我們回顧時，我們確實有幾位患者的眼睛裡殘留著黑色素瘤。有趣的是，當我們觀察這些病變時，這些腫瘤病變實際上有所減少。所以我認為新輔助治療是一個探索性計劃，我們有一些與此相關的 ESR。

In terms of your first question, which was the what is the bar for success in terms of relapse-free survival? And what would the control arm? This is a high-risk population.

就您的第一個問題而言，無復發生存成功的門檻是什麼？控制臂又是什麼？這是一個高危險群。

Yeah I think Mohammad can comment on that.

是的，我認為穆罕默德可以對此發表評論。

Yeah, sure. I'm happy to comment. So really you know, the way to think about this is that there is no standard in the adjuvant setting. And so the bar there is no established far what we know is that the median time to relapse in this high-risk population, which is the target population, is about three years. And so the bar is that we have to improve above that. So this is the way to conduct a trial in the adjuvant setting, which is a randomized trial that's global that focuses on the high-risk population.

好，當然。我很高興發表評論。所以你真的知道，思考這個問題的方法是輔助設定沒有標準。因此，據我們所知，目前還沒有確定的標準是，在這個高風險族群（即目標族群）中，復發的中位數時間約為三年。因此，我們必須在此基礎上進行改進。這就是在輔助環境中進行試驗的方法，這是一項針對高風險族群的全球隨機試驗。

(Operator Instructions) Patrick Trucchio, H.C. Wainwright.

（操作員說明）Patrick Trucchio, H.C.溫賴特。

Thanks. Good morning and congrats on all the progress. I have a follow up on the previous Phase 3 program. I'm wondering if you can discuss in more detail the strategy around pursuing first line treatment as well as the design that includes the combination with nivo. How should we think about contribution of PRAME this regimen and understanding the study is expected to randomize the first patient this quarter?

謝謝。早上好，恭喜所有的進展。我對之前的第三階段計劃進行了跟進。我想知道您是否可以更詳細地討論圍繞一線治療的策略以及包括與 nivo 聯合的設計。我們該如何思考 PRAME 這項方案的貢獻，並了解研究預計將在本季隨機分配第一位患者？

When do you anticipate initial data like ctDNA data to emerge? And what read-through should we anticipate from that data to potential for the program's success on the primary endpoint of PFS?

您預期 ctDNA 資料等初始資料何時會出現？我們應該從這些數據中預測哪些通讀內容，以了解該專案在 PFS 主要終點上取得成功的潛力？

Patrick, and thank you for the question. I think David and Mohammad.

派崔克，謝謝你的提問。我認為是大衛和穆罕默德。

Yeah so Patrick, I will try answer a couple of your questions. I hope I get them all. But in terms of the Phase 3 PRAME for planned trial. I think that's what your question was with regard to cost, multiple data points that lead to that, the monotherapy activity of epilepsy which we'll share the ability to combine with anti-PD1 and their knowledge for our platform. And it's true with immunotherapies in general that you always see higher activity as you move from late first line effect with ctDNA clearance and KIMMTRAK we see a tripling of clearance as we go from second line to first line.

是的，派崔克，我會試著回答你的幾個問題。我希望我能得到它們。但就計劃試驗的第三階段 PRAME 而言。我認為這就是你的問題是關於成本、導致這一點的多個數據點、癲癇的單一治療活動，我們將分享與抗 PD1 結合的能力以及他們在我們平台上的知識。一般來說，對於免疫療法來說，當您從晚期一線效應與ctDNA 清除和KIMMTRAK 轉移時，您總是會看到更高的活性，當我們從二線轉到一線時，我們會看到清除率增加了三倍。

In terms of the design and the contribution of components. The design end is prime plus nivolumab versus nivolumab. So that already has built in the contribution of components because we have PRAME on top of the nivolumab.

在設計和組件的貢獻方面。設計最終是prime加納武單抗與納武單抗。因此，這已經內建了組件的貢獻，因為我們在納武單抗之上有 PRAME。

Now there will be a minority of patients in the control arm. We do get up to a lag, but until we'll be able to draw a point us from it. But most of the patients in comparison to feel like for most of the patients will have received nivo monotherapy.

現在對照組中將有少數患者。我們確實遇到了滯後，但直到我們能夠從中得出結論。但相較之下，大多數患者感覺大多數患者都接受了 nivo 單一療法。

So we'll have contribution of components there. And the primary endpoint is progression-free survival, which is globally accepted for approval for regulatory approval. The secondary endpoint is overall survival. We do have an exploratory endpoint of ctDNA, but that won't be available until the trial is open.

所以我們將在那裡貢獻組件。主要終點是無惡化存活期，這是全球公認的監管機構批准的指標。次要終點是總存活期。我們確實有 ctDNA 的探索性終點，但要等到試驗開放後才能實現。

(Operator Instructions) Gil Blum, Needham.

（操作員說明）Gil Blum，Needham。

Good morning, and thanks for squeezing me in maybe a quick on your new PIWIL1 asset and CRC.

早安，感謝您讓我快速了解您的新 PIWIL1 資產和 CRC。

So generally, CRC is an immune desert. Could that be a potential issue for agents of this type. I mean, we've seen a lot of activity for TEBE-AM and then the PRAME asset and more T cell infiltrated tumors.

所以總的來說，大腸直腸癌是一個免疫沙漠。對於此類代理商來說，這可能是一個潛在問題嗎？我的意思是，我們已經看到 TEBE-AM 的大量活性，然後是 PRAME 資產和更多 T 細胞浸潤的腫瘤。

Yeah, thank you Gil for this question, I'll pass it on to Mohammed that I just want to remind you that the uveal melanoma is a complete cold tumor as cold as it gets. So that's I think where our platform, you want to talk a little bit more Mohammed about that?

是的，謝謝吉爾提出這個問題，我會將其轉告給穆罕默德，我只是想提醒您，葡萄膜黑色素瘤是一種完全冷的腫瘤。所以我想這就是我們的平台，你想多談談穆罕默德嗎？

Yeah, this is part of the reason why we are so excited about the PIWIL1 program in our mechanism, which is very distinct from checkpoints where we don't need pre-existing immunity or infiltration by the immune system into the tumor.

是的，這就是我們對我們機制中的 PIWIL1 程序如此興奮的部分原因，它與我們不需要預先存在的免疫或免疫系統滲透到腫瘤中的檢查點非常不同。

We what -- we've shown with TEBE-AM user was alluding to is that we just need functional T cells in the periphery and our mechanism drives T cells into a non-inflamed or immune desert. So this is one of the reasons why we're excited about this program and its potential application in CRC.

我們向 TEBE-AM 使用者展示的內容暗示，我們只需要外圍有功能性 T 細胞，而我們的機制可驅動 T 細胞進入非發炎或免疫沙漠。這就是我們對這個程式及其在 CRC 中的潛在應用感到興奮的原因之一。

And I will let the data tell us.

我會讓數據告訴我們。

(Operator Instructions) Noreen Calabria, Capital One Securities.

（操作員指示）Noreen Calabria，第一資本證券。

Hi, good morning. Congrats on the quarter and thanks for taking my question. So I guess just a follow-up on the KIMMTRAK, Phase 2/3, TEBE-AM study, obviously you're going to be looking at the ctDNA and trends with the OS. I'm just curious what kind of reduction in ctDNA do you expect and in this setting, sort of to help you inform the decision to drop one arm. How big of a delta are you looking at and again, be comparing between the two arms or is it just baseline from the Pacific arm?

早安.恭喜本季度，感謝您提出我的問題。所以我想這只是 KIMMTRAK 第 2/3 階段 TEBE-AM 研究的後續，顯然您將關注 ctDNA 和 OS 的趨勢。我只是好奇你期望 ctDNA 減少多少，在這種情況下，這可以幫助你做出放棄一隻手臂的決定。您要再次比較兩個臂之間的三角洲有多大，還是只是太平洋臂的基線？

Great Noreen, and thank you very much, David, you want to take it from here?

偉大的諾琳，非常感謝你，大衛，你想從這裡拿走它嗎？

Yeah, so hope you looking, so we have three arms. Just as a reminder, we have prevented us monotherapy dependent those plus pembrolizumab. And then, of course, the control arm and the primary the dual endpoints of ctDNA and survival.

是的，所以希望你能看到，所以我們有三隻手臂。提醒一下，我們已經阻止了依賴單藥治療的患者加派姆單抗（pembrolizumab）。當然，還有對照組和主要的 ctDNA 和存活的雙重終點。

In terms of ctDNA, we believe it directionally gives us information. But since it's still exploratory in cutaneous melanoma, we will rely on survival as well. And although the survival will not be fully mature, we have done some simulations showing that we will have sufficient power to see trends in order to drop one of the arms. The size is about 40 patients per arm and so we think we have enough power in order to make that decision, take the integrating ctDNA and survival.

就ctDNA而言，我們相信它可以定向為我們提供資訊。但由於它在皮膚黑色素瘤中仍處於探索階段，因此我們也將依賴生存。雖然生存還沒有完全成熟，但我們已經做了一些模擬，表明我們將有足夠的能力看到趨勢，以便放下其中一隻手臂。每隻手臂大約有 40 名患者，因此我們認為我們有足夠的權力來做出決定，整合 ctDNA 和生存率。

(Operator Instructions) Jeffrey Hung, Morgan Stanley.

（操作員指示）Jeffrey Hung，摩根士丹利。

Hi, this is Michael Riad on for Jeff Hung. Thank you for taking our question on. Could you talk a little bit more about ctDNA predictive power on or less and advanced cutaneous versus uveal melanoma. How far in the treatment course, do you need to go to have confidence in its predictive power? And does that power gets stronger as you move into earlier lines? Thank you.

大家好，我是傑夫·洪 (Jeff Hung) 的邁克爾·裡亞德 (Michael Riad)。感謝您回答我們的問題。能多談談 ctDNA 對晚期皮膚黑色素瘤與葡萄膜黑色素瘤的預測能力嗎？在治療過程中，您需要進行到什麼程度才能對其預測能力充滿信心？當你進入較早的線路時，這種力量會變得更強嗎？謝謝。

Thank you, Michael. David, you want to take it?

謝謝你，麥可。大衛，你想接受嗎？

Yeah, Michael. So the current the association with survival. We have validated in uveal melanoma in two independent trials. So when it comes to uveal melanoma ctDNA we have really strong confidence with cutaneous melanoma, we have emerging confidence, but we, of course, don't have randomized trials and we don't have long-term survival.

是的，邁克爾。所以當前與生存的連結。我們在兩項獨立試驗中對葡萄膜黑色素瘤進行了驗證。因此，當涉及葡萄膜黑色素瘤 ctDNA 時，我們對皮膚黑色素瘤非常有信心，我們的信心正在顯現，但當然，我們沒有隨機試驗，也沒有長期生存。

So we will be looking both at ctDNA directionally as an early potential surrogate and we'll be looking at survival in parallel. We hope that this trial will begin to set up the associations that we have seen in uveal in cutaneous melanoma. If we acknowledge that we'll need to see both ctDNA and survival and integrate both of those at this early time.

因此，我們將定向研究 ctDNA 作為早期潛在替代品，並同時研究存活。我們希望這項試驗將開始建立我們在葡萄膜與皮膚黑色素瘤中所看到的關聯。如果我們承認，我們需要同時觀察 ctDNA 和存活率，並儘早整合這兩者。

(Operator Instructions) Ahu Demir, Ladenburg.

（操作員指令）Ahu Demir，拉登堡。

Good morning, thank you so much for taking my questions and congrats on the quarter. Two questions for my first one is the on the PRAME melanoma, the that in the second quarter in terms of the patient follow up, could you give us a sense of the majority of patients, how long they were followed up for?

早安，非常感謝您回答我的問題，並祝賀本季。我的第一個問題是關於 PRAME 黑色素瘤的兩個問題，即第二季度患者隨訪情況，您能否讓我們了解大多數患者的情況，他們隨訪了多長時間？

And the second question I have is expectation for the HIV MAD study with them. What's that look like?

我的第二個問題是對他們的 HIV MAD 研究的期望。那是什麼樣子的？

Thank you, Ahu, David, and maybe Mohamed as well?

謝謝你，阿胡、大衛，也許還有穆罕默德？

Yeah, in terms of the PRAME melanoma, I do think we have sufficient follow-up in order to show durability. I don't have the exact follow-up with me right now. But I would say I believe that it's going to be sufficient in order to interpret the data. And that's because the reason I say it because we enrolled a lot of those patients throughout 2023.

是的，就 PRAME 黑色素瘤而言，我確實認為我們有足夠的後續行動來顯示耐久性。我現在還沒有確切的後續行動。但我想說，我相信這足以解釋數據。我之所以這麼說是因為我們在 2023 年招募了許多這樣的病人。

In terms of HIV, it's a good question because no one has ever been able to show a reduction in the reservoir or a functional cure. So for the reduction of the reservoir, we'll be looking in the blood to see whether we can reduce CD4 T cells with HIV and in terms of what success looks like that I think we're going to have to generate the data sharing with the KOLs, and then we'll share that data and we'll be able to interpret what success looks like.

就愛滋病毒而言，這是一個很好的問題，因為沒有人能夠證明病毒庫的減少或功能性治癒。因此，為了減少儲存庫，我們將在血液中觀察是否可以減少 HIV 的 CD4 T 細胞，就成功的情況而言，我認為我們必須與以下機構共享數據： KOL，然後我們將分享這些數據，我們將能夠解釋成功是什麼樣子的。

In terms of delay of the viral rebound that also, as, a very novel, no one has been able to show that. So I think we're going to have to look at the data, discuss with KOLs, and then we'll share the data. I think any sign of the delay and rebound that we can attribute biologically to the drug would be a success as an initial step in HIV treatment.

在病毒反彈的延遲方面，這也非常新穎，沒有人能夠證明這一點。所以我認為我們必須查看數據，與 KOL 討論，然後我們將共享數據。我認為任何可以從生物學角度歸因於該藥物的延遲和反彈跡像都將是愛滋病毒治療的成功第一步。

(Operator Instructions) Raj Sharma, Goldman Sachs.

（操作員指示）Raj Sharma，高盛。

Hi. I'm just a quick one on KIMMTRAK and just kind of thinking about, how confident you are in maintaining pricing in a scenario where you do get these additional settings that you've talked to each was potentially significantly increase the number of patients on therapy on its kind you flagged 6,000 potential patients exercising currently, and I'd be keen to understand how you see that playing out?

你好。我只是簡單介紹一下 KIMMTRAK，只是想一下，如果您確實獲得了與每個人交談過的這些額外設置，可能會顯著增加接受治療的患者數量，那麼您對維持定價有多大信心？下，您標記了目前正在鍛鍊的6,000 名潛在患者，我很想知道您如何看待這種情況？

Yeah Raj, thank you, I think it will be a good problem to have, but (technical difficulty).

是的，拉吉，謝謝你，我認為這將是一個很好的問題，但是（技術難度）。

I agree thank you for the question. So look, the way we look at pricing is really the framework that we use is the value that it brings to patients value every society. So as Bahija said, it's a little bit early for us to comment on that. So once we see the data, we hope that this is bringing significant value for it. The price version would be minimal.

我同意謝謝你的提問。所以看，我們看待定價的方式其實是我們使用的框架，它為病人帶來的價值重視每個社會。正如巴希賈所說，我們現在對此發表評論還為時過早。因此，一旦我們看到這些數據，我們希望這能為其帶來重大價值。價格版本將是最低的。

Thank you. There are no further questions at this time. I would now like to hand the call back over to Bahija Jallal, for any closing remarks.

謝謝。目前沒有其他問題。現在，我想將電話轉回巴希賈·賈拉勒 (Bahija Jallal)，讓其發表結束語。

Thank you very much. So in closing, I would like to express my gratitude to our patients, our shareholders and to the team this past year has been a testament to our drive to bring KIMMTRAK to patients. Our innovation into bringing more novel targets and entering new therapeutic areas. And as always, our commitment to patients by working with a sense of urgency. And as we move forward into the next fiscal year will remain steadfast in our mission to drive growth, create value, and deliver results.

非常感謝。最後，我要向我們的病患、股東和團隊表達感謝，過去的一年證明了我們將 KIMMTRAK 帶給病患的努力。我們的創新帶來更多新穎的標靶並進入新的治療領域。一如既往，我們以緊迫感開展工作，對患者做出承諾。當我們進入下一個財年時，我們將堅定不移地履行推動成長、創造價值和交付成果的使命。

I would like to end this call by thanking all of you for your support. Thank you.

在結束這通通話時，我想感謝大家的支持。謝謝。

Thank you that does conclude today's teleconference. We appreciate your participation and you may disconnect your lines at this time and enjoy the rest of your day.

謝謝大家，今天的電話會議到此結束。我們感謝您的參與，您可以在此時斷開線路並享受剩下的一天。