Immunocore Holdings PLC (IMCR) 2025 Q4 法說會逐字稿

Greetings, and welcome to the Immunicore conference call and webcast. (Operator Instructions). Please note that this conference is being recorded. I will now turn the conference over to Morgan Morse, Investor Relations. Thank you, Morgan. You may begin.

各位好，歡迎參加 Immunicore 的電話會議和網路直播。（操作說明）請注意，本次會議正在錄影。現在我將把會議交給投資者關係部門的摩根·莫爾斯。謝謝你，摩根。你可以開始了。

Thank you, Darryl. Good morning and good afternoon. Thank you for joining us on our Q4 and full year 2025 earnings call. During today's call, we will make some forward-looking statements, which are qualified by our safe harbour provision under the Private Securities Litigation Reform Act of 1995. Please note that actual results can vary materially from those indicated by these forward-looking statements, including those discussed in our filings with the SEC.

謝謝你，達裡爾。早安，下午好。感謝您參加我們2025年第四季及全年業績電話會議。在今天的電話會議中，我們將做出一些前瞻性陳述，這些陳述受 1995 年《私人證券訴訟改革法案》下的安全港條款的限制。請注意，實際結果可能與這些前瞻性聲明所指出的結果有重大差異，包括我們在提交給美國證券交易委員會的文件中討論的結果。

On today's call, I am joined by Dr. Bahija Jallal, CEO of Immunocore, who will share our 2025 overview and achievements; Ralph Torbay, Head of Commercial, will review our Q4 and full year KIMMTRAK results; Mohammed Dar, our Chief Medical Officer, will provide a pipeline update including our ongoing registrational late line cutaneous melanoma and other highlights across our pipeline. And finally, Travis Coy, our CFO and Head of Corporate Development, will provide some key highlights from our financial results reported earlier this morning.

在今天的電話會議上，我邀請到了 Immunocore 的首席執行官 Bahija Jallal 博士，他將分享我們 2025 年的展望和成就；商業主管 Ralph Torbay 將回顧我們第四季度和全年的 KIMMTRAK 業績；我們的首席醫療官 Mohammed Dar 將介紹產品線的最新亮點，包括我們正在進行的晚期皮膚素瘤以及我們正在進行的其他產品線中的亮點。最後，我們的財務長兼企業發展主管特拉維斯·科伊將介紹我們今天早上公佈的財務業績的一些關鍵亮點。

I will now turn the call to Dr. Bahija Jallal.

現在我將把電話轉給巴希賈·賈拉爾博士。

Thank you, Morgan. Good morning, and good afternoon, and thank you all for joining us. 2025 was a year of consistent execution across every part of our business. I am pleased to share our results and where we're headed as we continue to deliver on our mission. For the year 2025, we generated $400 million in net revenue from KIMMTRAK, up over 29% from the prior year.

謝謝你，摩根。早安，下午好，感謝各位的參與。 2025年是我們業務各環節持續高效執行的一年。我很高興與大家分享我們的成果以及我們為繼續完成使命所採取的方向。2025 年，我們從 KIMMTRAK 獲得了 4 億美元的淨收入，比前一年增長了 29% 以上。

KIMMTRAK is now approved in 39 countries and launched in 30 markets. Growth continues to be driven by deeper US community penetration and continued global expansion. Real world duration of therapy is now 14 months, exceeding our clinical trials experience.

KIMMTRAK 目前已在 39 個國家獲得批准，並在 30 個市場推出。成長持續得益於美國市場滲透率的提高和全球市場的持續擴張。實際治療持續時間為 14 個月，超過了我們的臨床試驗經驗。

Before KIMMTRAK, patients with uveal melanoma diagnosis were given 12 months or less to live. Now with KIMMTRAK, it's not unusual to see patients living three, four, five years or more. This is why we're here, and this is why we come to work every day.

在 KIMMTRAK 出現之前，被診斷為葡萄膜黑色素瘤的患者平均預期壽命為 12 個月或更短。現在有了 KIMMTRAK，患者存活三、四、五年甚至更長時間已經不是什麼稀奇事了。這就是我們來到這裡的原因，也是我們每天來上班的原因。

But we're not stopping here to reach even more patients, we're expanding the reach of KIMMTRAK through a robust life cycle management program with two Phase III trials. TEBE-AM in second-line cutaneous melanoma enrolment on track for the first half of 2026 completion. ATOM in adjuvant uveal melanoma enrolling across multiple sites in Europe and planning to open sites in the US in 2026.

但我們不會止步於此，為了惠及更多患者，我們正在透過一項強大的生命週期管理計劃和兩項 III 期試驗來擴大 KIMMTRAK 的影響範圍。TEBE-AM 二線皮膚黑色素瘤患者入組計畫預計將於 2026 年上半年完成。ATOM 輔助治療葡萄膜黑色素瘤的試驗正在歐洲多個地點進行，並計劃於 2026 年在美國開設試驗點。

This is, to our knowledge, the only active Phase III in this setting. Beyond KIMMTRAK, we have our third Phase III trial. PRISM-MEL-301 with brenetafusp in first-line cutaneous melanoma. The IDMC has selected the 160-microgram dose, which is the highest dose in the last December.

據我們所知，這是目前該領域唯一正在進行的 III 期臨床試驗。除了 KIMMTRAK 之外，我們還有第三項 III 期試驗。PRISM-MEL-301 與 brenetafusp 合併用於第一線治療皮膚黑色素瘤。IDMC 選擇了 160 微克的劑量，這是去年 12 月的最高劑量。

We are also expanding our oncology platform beyond melanoma into ovarian and lung, colorectal cancer and GI cancers. Mohammed will share more details later. And then beyond oncology, we presented promising data for our HIV functional cure program at CROI and our hepatitis B candidate showed encouraging Phase I results at ASLD confirming the potential of our platform in infectious disease.

我們也將腫瘤治療平台從黑色素瘤擴展到卵巢癌、肺癌、大腸癌和胃腸道癌症。穆罕默德稍後會分享更多細節。除了腫瘤學之外，我們還在 CROI 會議上展示了 HIV 功能性治癒計畫的有希望的數據，並且在 ASLD 會議上，我們的乙肝候選藥物也顯示出令人鼓舞的 I 期結果，證實了我們的平台在傳染病領域的潛力。

In autoimmune diseases, we submitted the CTA for our type one diabetes program and expect to dose the first patient in the Phase I in the first half of 2026. Our balance sheet remains strong at approximately $864 million in cash, providing the flexibility to advance the pipeline. I'll now ask Ralph to share more about our commercial performance. Ralph?

在自體免疫疾病方面，我們已提交了 1 型糖尿病計畫的 CTA，預計將於 2026 年上半年在 I 期臨床試驗中給第一位患者用藥。我們的資產負債表依然穩健，擁有約 8.64 億美元的現金，這為我們推動專案研發提供了靈活性。現在我請拉爾夫詳細介紹一下我們的商業表現。拉爾夫？

Thank you, Bahija. Today, I will walk us through KIMMTRAK's full year results and growth opportunities across melanoma. 2025 has been another year of strong commercial execution, marking this our 15th quarter of growth.

謝謝你，巴希賈。今天，我將為大家詳細介紹KIMMTRAK的全年業績以及在黑色素瘤領域的成長機會。 2025年是公司商業營運強勁的一年，這也是我們連續第15季實現成長。

KIMMTRAK generated $400 million in net revenues for the year, representing 29% year-on-year growth. This sustained performance reflects KIMMTRAK's position as the global standard of care in first-line metastatic uveal melanoma with over 70% penetration across all major markets.

KIMMTRAK 當年的淨收入為 4 億美元，年增 29%。這一持續的優異表現反映了 KIMMTRAK 作為一線轉移性葡萄膜黑色素瘤全球標準療法的地位，在所有主要市場的滲透率超過 70%。

This breadth of adoption is a testament to KIMMTRAK's transformative long-term impact, with one in four patients alive at three years, an unprecedented milestone in this disease. Mean duration of therapy remains impressive at 14 months, as Bahija mentioned.

KIMMTRAK 的廣泛應用證明了其具有變革性的長期影響，四分之一的患者在三年後仍然存活，這是該疾病治療領域前所未有的里程碑。正如巴希賈所提到的，平均治療持續時間仍然令人印象深刻，為 14 個月。

Continuing the theme of KIMMTRAK's delivering exceptional results, we recently presented real-world data at ESMO IO from 150 patients, showing a median overall survival of 28 months.

KIMMTRAK 延續了其取得卓越成果的主題，我們最近在 ESMO IO 上展示了來自 150 名患者的真實世界數據，顯示中位總生存期為 28 個月。

We plan to build upon this data with the US real-world evidence to be published this year. We also expect to share the five-year overall survival from our registrational clinical trial which will further support KIMMTRAK's long-term benefit. Now as we enter our fifth year on the market, we expect moderating growth through continued commercial execution, further global expansion and increased penetration in the US community setting.

我們計劃利用今年即將發布的美國真實世界證據，對這些數據進行進一步研究。我們也期待分享註冊臨床試驗的五年總存活率，這將進一步支持 KIMMTRAK 的長期療效。如今，我們進入市場第五年，我們預計透過持續的商業執行、進一步的全球擴張以及在美國社區環境中的滲透率提高，成長速度將趨於溫和。

Speaking of the community, KIMMTRAK's adoption is widespread as evidenced by 70% of all KIMMTRAK prescriptions come from the community. Half of all patients starts happening in the community. And in 2025 alone, we activated 150 new accounts, most in the community. This broad adoption is important because it speaks to KIMMTRAK's value proposition of unprecedented survival and manageable safety.

說到社區，KIMMTRAK 的應用非常廣泛，70% 的 KIMMTRAK 處方都來自社區，這足以證明這一點。一半的病例都是在社區中發生的。僅在 2025 年，我們就啟動了 150 個新帳戶，其中大部分來自社群。這種廣泛應用非常重要，因為它體現了 KIMMTRAK 的價值主張，即前所未有的生存能力和可控的安全性。

It also brings KIMMTRAK closer to home for many patients who live in less dense geographic areas. Lastly, it creates a wide foundation for a potential next indication where half of all patients with cutaneous melanoma are treated by physicians experienced with KIMMTRAK. I'm very excited by KIMMTRAK's midterm growth potential.

這也讓居住在人口密度較低地區的許多患者能夠更方便地前往 KIMMTRAK。最後，它為潛在的下一個適應症奠定了廣泛的基礎，即一半的皮膚黑色素瘤患者由接受 KIMMTRAK 治療的醫生進行治療。我對KIMMTRAK的中期成長潛力感到非常興奮。

Today, we're serving approximately 1,000 patients per year in metastatic uveal melanoma, which delivered $400 million in net sales in 2025.

目前，我們每年為約 1,000 名轉移性葡萄膜黑色素瘤患者提供服務，預計到 2025 年將帶來 4 億美元的淨銷售額。

When you look across the horizon, the opportunity is up to sixfold larger with our two Phase III life cycle management trials. The first one TEBE-AM, the only randomized Phase III study in advanced melanoma with an overall survival endpoint that could transform the lives of up to 4,000 patients.

放眼未來，隨著我們兩項 III 期生命週期管理試驗的開展，機會將擴大六倍。第一個是 TEBE-AM，這是唯一一項針對晚期黑色素瘤的隨機 III 期研究，以總存活期為終點，可能會改變多達 4,000 名患者的生活。

Second, ATOM, in adjuvant uveal melanoma that could help up to 1,000 additional patients. I'm confident in our ability to execute on this growth trajectory, and I'm excited about what's ahead for KIMMTRAK and patients we serve.

其次，ATOM 在輔助治療葡萄膜黑色素瘤方面，可以幫助多達 1,000 名額外的患者。我對我們實現這一成長目標的能力充滿信心，我對 KIMMTRAK 和我們服務的患者的未來充滿期待。

I'll now hand over to Mohammed to discuss these trials in more detail as well as our expanding pipeline.

現在我將把發言權交給穆罕默德，讓他更詳細地討論這些試驗以及我們不斷擴大的產品線。

Thank you, Ralph. I'm delighted to join this executive team and look forward to sharing the developments across our clinical programs. At Immunocore, we have built a truly unique and diversified TCR pipeline that now spans three therapeutic areas, and I'm pleased to walk you through our progress today.

謝謝你，拉爾夫。我很高興加入這個管理團隊，並期待與大家分享我們臨床計畫的最新進展。在 Immunocore，我們已經建立了一個真正獨特且多元化的 TCR 產品線，目前涵蓋三個治療領域，今天我很高興向大家介紹我們的進展。

Our R&D engine has delivered a robust portfolio anchored by three ongoing Phase III trials in oncology with data readouts beginning as early as the second half of 2026, with TEBE-AM.

我們的研發引擎打造了一個強大的產品組合，其中以三個正在進行的腫瘤學 III 期試驗為核心，TEBE-AM 的數據最早將於 2026 年下半年開始公佈。

Beyond our late-stage efforts, we look forward to new insights maturing this year across our early-stage oncology and infectious disease programs. In autoimmune, 2026 marks a pivotal milestone for our platform as we initiate our first clinical experience.

除了後期研發工作之外，我們期待今年在早期腫瘤學和傳染病計畫中獲得新的見解。在自體免疫領域，2026 年是我們平台發展歷程中的重要里程碑，因為我們將啟動首次臨床體驗。

I'll now begin by highlighting our three registrational melanoma trials, starting with TEBE-AM. Our first opportunity is in advanced cutaneous melanoma, where there is a high unmet need. No therapy has been proven to extend survival in the second plus cutaneous melanoma setting, falling checkpoint inhibitors and targeted therapy one year overall survival in this setting is approximately 55%.

現在我將首先重點介紹我們的三個黑色素瘤註冊試驗，首先是 TEBE-AM。我們首先有機會攻克晚期皮膚黑色素瘤，因為該領域存在著巨大的未滿足需求。目前尚無任何療法已被證實能夠延長第二期及以上皮膚黑色素瘤患者的存活期，接受檢查點抑制劑和標靶治療的患者一年總存活率約為 55%。

In first-line patients receive either anti-PD-1 with or without additional checkpoints or BRAF-targeted therapy. In second line, patients can switch between these classes where appropriate.

第一線治療患者接受抗 PD-1 治療（可合併或不合併其他檢查點抑制劑）或 BRAF 標靶治療。在二線治療中，患者可以根據情況在這些藥物之間進行轉換。

Beyond second line, there remains a large unmet need: chemotherapy, retreatment with prior therapies and clinical trials remain the primary options. The only new therapy approved in this setting is TIL therapy, which was based on response rate under accelerated approval, not overall survival.

除了二線治療外，仍有大量未滿足的需求：化療、使用先前療法進行再治療以及臨床試驗仍然是主要選擇。目前唯一獲準的新療法是 TIL 療法，該療法是根據加速審批下的反應率而非總生存期批准的。

TEBE-AM is the first Phase III trial aiming to demonstrate an overall survival benefit, the gold standard in the population. If TEBE-AM is positive, KIMMTRAK would be the first new therapy with overall survival benefit in the second line plus cutaneous melanoma setting.

TEBE-AM 是第一個旨在證明整體存活獲益的 III 期試驗，整體存活獲益是該族群的黃金標準。如果 TEBE-AM 檢測結果為陽性，KIMMTRAK 將成為首個在二線及以上皮膚黑色素瘤治療中具有總生存獲益的新療法。

As a reminder, TEBE-AM is a randomized Phase III trial for melanoma patients who have progressed on checkpoint and, if applicable, targeted therapy. Patients are randomized to KIMMTRAK monotherapy, KIMMTRAK plus pembrolizumab or a control arm with a primary endpoint of overall survival.

提醒一下，TEBE-AM 是一項針對接受檢查點抑制劑治療（如果適用，還需接受標靶治療）後病情進展的黑色素瘤患者的隨機 III 期試驗。患者被隨機分配到 KIMMTRAK 單藥治療組、KIMMTRAK 加帕博利珠單抗治療組或對照組，主要終點為總存活期。

Our confidence in this program is supported by promising Phase Ib data showing a 75% one year survival rate compared to the 55% benchmark.

我們對此計畫的信心源於令人鼓舞的 Ib 期臨床試驗數據，數據顯示一年存活率為 75%，高於 55% 的基準水準。

Beyond efficacy, KIMMTRAK is an off-the-shelf therapy with a predictable and manageable safety profile that is already familiar to the melanoma community. We remain on track and project to complete enrolment in the first half of 2026, with top line data expected as early as the second half of this year.

除了療效之外，KIMMTRAK 還是一種現成的療法，具有可預測和可控的安全性，黑色素瘤患者群體已經對此很熟悉。我們仍按計畫推進，預計 2026 年上半年完成招生工作，並預計在今年下半年獲得初步數據。

Now turning to our second registrational trial. ATOM is the only active registrational Phase III trial in the adjuvant uveal melanoma setting, where there is currently no approved standard of care. High-risk patients are randomized to either KIMMTRAK or observation with recurrence-free survival as the primary endpoint.

現在來看我們的第二次註冊試驗。ATOM 是目前唯一正在進行的輔助性葡萄膜黑色素瘤 III 期註冊試驗，而目前該領域尚無核准的標準治療方案。高風險患者被隨機分配到 KIMMTRAK 組或觀察組，以無復發生存期為主要終點。

The study sponsored by the EORTC is currently activated across multiple European countries and is expected to begin site activations in the US during the first half of 2026.

由歐洲癌症研究與治療組織 (EORTC) 贊助的研究目前已在多個歐洲國家啟動，預計將於 2026 年上半年在美國啟動。

Our goal is to bring the benefit of KIMMTRAK to patients earlier, potentially delaying or even eliminating the onset of metastatic disease.

我們的目標是讓患者更早受益於 KIMMTRAK，這有可能延緩甚至消除轉移性疾病的發生。

As evidence of our robust R&D engine, we now turn to our third registrational opportunity with melanoma, this time, leveraging our TCR targeting PRAME known as brenetafusp. PRISM-MEL is a randomized Phase III trial in first-line cutaneous melanoma, comparing brenetafusp plus nivolumab versus either nivolumab monotherapy or Opdualag, with progression-free survival as the primary endpoint.

為了證明我們強大的研發實力，我們現在轉向第三個針對黑色素瘤的註冊機會，這次，我們將利用我們名為 brenetafusp 的 TCR 靶向 PRAME。PRISM-MEL 是一項針對第一線皮膚黑色素瘤的隨機 III 期試驗，比較了 brenetafusp 加 nivolumab 與 nivolumab 單藥治療或 Opdualag 的療效，以無進展生存期為主要終點。

In November 2025, in line with the FDA's project OPTIMIST, the IDMC completed the dose selection process choosing the highest dose to move forward. We have successfully activated over 200 sites globally and are targeting enrolment completion in 2027.

2025 年 11 月，根據 FDA 的 OPTIMIST 項目，獨立數據監測委員會 (IDMC) 完成了劑量選擇過程，選擇了最高劑量繼續前進。我們已成功在全球範圍內啟動了 200 多個站點，目標是在 2027 年完成招生。

I will now outline how we are strategically applying our platform to address a broader range of high unmet need tumour types. Beyond cutaneous melanoma, we are focused on expanding the PRAME franchise into other tumours, specifically ovarian and non-small cell lung cancer.

接下來，我將概述我們如何策略性地運用我們的平台來解決更廣泛的、未被滿足需求的腫瘤類型。除了皮膚黑色素瘤，我們也致力於將 PRAME 產品線擴展到其他腫瘤，特別是卵巢癌和非小細胞肺癌。

In ovarian, we are building on the monotherapy activity observed in late-line settings by moving into earlier lines of treatment. This includes evaluating brenetafusp in combination with chemotherapy in platinum-resistant ovarian cancer and in combination with bevacizumab in the platinum-sensitive maintenance setting.

在卵巢癌治療中，我們以後期治療中觀察到的單藥治療效果為基礎，逐步推進到早期治療階段。這包括評估 brenetafusp 與化療合併用於鉑金抗藥性卵巢癌，以及與貝伐珠單抗合併用於鉑敏感維持治療。

For lung cancer, our efforts are focused on signal detection across various combinations, including chemotherapy and osimertinib. We expect to present the data from these ovarian and lung cohorts in the second half of 2026, which will inform next steps.

對於肺癌，我們的工作重點是檢測各種組合（包括化療和奧希替尼）中的訊號。我們預計將於 2026 年下半年公佈這些卵巢癌和肺癌隊列的數據，這將為下一步工作提供基礎。

In parallel, we are advancing our PRAME half-life extended candidate, which is currently in dose escalation. Our hypothesis for this molecule is twofold: first, to provide patient convenience through less frequent dosing; and second, to potentially increase the overall response rate. We expect to have a comprehensive data package by the second half of 2026 to determine the optimal path forward for the franchise.

同時，我們正在推進 PRAME 半衰期延長候選藥物的研發，該藥物目前正在進行劑量遞增試驗。我們對這種分子的假設有兩個面向：第一，透過減少給藥頻率為患者提供便利；第二，有可能提高整體反應率。我們預計到 2026 年下半年將獲得一套全面的資料包，以確定該特許經營權的最佳發展路徑。

The modular nature of our platform allows us to expand our reach beyond oncology and unlock significant growth opportunities in infectious disease and autoimmune.

我們平台的模組化特性使我們能夠將業務範圍擴展到腫瘤學以外，並在傳染病和自體免疫疾病領域釋放巨大的成長潛力。

At CROI early last year, we presented initial data from 16 patients enrolled into the multiple ascending dose portion of our HIV study. The data were very well received by investigators and two important findings emerged. First, the treatment was well tolerated. And second, we observed a dose-dependent antiviral effect.

去年年初在 CROI 會議上，我們展示了 16 名參與 HIV 研究中多次遞增劑量部分的患者的初步數據。研究人員對這些數據反應很好，並得出了兩項重要發現。首先，患者對治療的耐受性良好。其次，我們觀察到了劑量依賴性的抗病毒效果。

At the 60-microgram target dose, you can see that when we stop both our compound and the anti-retroviral regimen, viral rebound occurs rapidly. However, at the 120 and 300-microgram target doses, we observed a delay in viral rebound.

在 60 微克的目標劑量下，可以看到，當我們停止使用化合物和抗逆轉錄病毒療法時，病毒會迅速反彈。然而，在 120 微克和 300 微克的目標劑量下，我們觀察到病毒反彈有延遲。

Note the orange lines, providing preliminary clinical evidence that we are impacting the viral reservoir, which is the critical first step toward achieving a functional cure. The clinical data gathered so far confirms the potential of our platform in infectious disease. We are continuing to evaluate higher doses in this study, and we expect to have data from the ongoing dose escalation in the second half of 2026.

請注意橙色線條，它們提供了初步的臨床證據，表明我們正在影響病毒庫，這是實現功能性治癒的關鍵第一步。目前收集到的臨床數據證實了我們的平台在傳染病領域的潛力。我們正在繼續評估該研究中更高的劑量，預計將在 2026 年下半年獲得正在進行的劑量遞增的數據。

Now turning to our third and newest therapeutic area. Our vision for treating autoimmunity is unique. We aim to achieve tissue-specific down modulation of the immune system, thereby avoiding the risks associated with systemic immune suppression, which is the current approach taken in the field.

現在我們來談談第三個也是最新的治療領域。我們治療自體免疫疾病的理念是獨一無二的。我們的目標是實現組織特異性的免疫系統下調，從而避免全身性免疫抑制帶來的風險，而全身性免疫抑制是目前該領域採用的方法。

We are currently advancing two autoimmune candidates. The first is S-118i, which targets the beta cells in the pancreas in patients diagnosed with type one diabetes.

我們目前正在推進兩個自體免疫疾病候選藥物的研發。第一種是 S-118i，它針對的是被診斷為第 1 型糖尿病患者胰臟中的 β 細胞。

The second is U120AI, which targets CD18 on Langerhans cells, specialized antigen presenting cells in the skin for the treatment of atopic dermatitis.

第二種是 U120AI，它靶向朗格漢斯細胞上的 CD18，朗格漢斯細胞是皮膚中專門的抗原呈現細胞，用於治療異位性皮膚炎。

Today, I'm going to focus on our type one diabetes program, which represents the first clinical test of our tissue tethered PD-1 agonist approach. We chose type one diabetes because of the profound unmet medical need with 50,000 patients newly diagnosed every year and data supporting the role of T cells as one of the key mediators of the disease. Our candidate S118i binds to pre-proinsulin, which is expressed exclusively on the beta cells of the pancreas.

今天，我將重點介紹我們的 1 型糖尿病項目，該項目代表了我們組織錨定 PD-1 激動劑方法的首次臨床試驗。我們選擇第 1 型糖尿病是因為存在巨大的未滿足的醫療需求，每年有 5 萬名新患者被診斷出患有這種疾病，而且有數據支持 T 細胞是該疾病的關鍵介質之一。我們的候選藥物 S118i 與胰島素原結合，胰島素原僅在胰臟 β 細胞上表現。

We have already generated compelling ex vivo proof-of-concept data using pancreatic slices from human donors. We demonstrated that S118i binds specifically to beta cells, as shown in the middle panel and successfully rescue them from T cell-mediated killing as seen in the graph on the far right. Importantly, these rescue beta cells remain functional and continue to secrete insulin.

我們已經利用人類捐贈者的胰臟切片產生了令人信服的體外概念驗證數據。我們證明 S118i 能特異性地與 β 細胞結合（如中間圖所示），並能成功地將它們從 T 細胞介導的殺傷中拯救出來（如最右邊的圖表所示）。重要的是，這些被拯救的β細胞仍然具有功能，並繼續分泌胰島素。

Following our CTA filing in December 2025, we are now poised to move into the clinic this year. Our Phase I study is designed to provide early evidence of target engagement and immune modulation. So to recap, we have a robust, diversified pipeline with important readouts later this year, and our R&D teams remain focused as we continue to advance our platform across all three therapeutic areas.

繼我們在 2025 年 12 月提交 CTA 申請後，我們現在已做好準備，今年將進駐診所。我們的 I 期研究旨在提供標靶結合和免疫調節的早期證據。總而言之，我們擁有強大且多元化的產品線，今年稍後將公佈重要數據，我們的研發團隊將繼續專注於推動我們在所有三個治療領域的平台發展。

I will now hand the call to Travis to discuss our financial results.

現在我將把電話交給特拉維斯，讓他來討論我們的財務表現。

Thank you, Mohammed. Good morning, and good afternoon, everyone. Earlier today, we released our financial results for the fourth quarter and year ended 2025. Please refer to the press release and our latest SEC filings on Form 10-K, our full financial results. Let me share some of our key financial highlights for 2025 and then touch upon our expectations for 2026.

謝謝你，穆罕默德。各位早安，各位下午好。今天早些時候，我們發布了截至 2025 年第四季和全年的財務表現。請參閱新聞稿和我們最新的 10-K 表格 SEC 文件，以了解我們的完整財務表現。讓我先和大家分享一下我們 2025 年的一些主要財務亮點，然後再談談我們對 2026 年的預期。

We are pleased to report strong performance for KIMMTRAK with full year net sales reaching $400 million. This represents a 29% increase over 2024 with volume-driven growth across the US, Europe and international regions.

我們很高興地宣布 KIMMTRAK 業績表現強勁，全年淨銷售額達到 4 億美元。與 2024 年相比，這相當於成長了 29%，成長主要由美國、歐洲和國際地區的銷售所推動。

Looking ahead to 2026, as we enter KIMMTRAK 5th year on the market with significant penetration across all major markets, we naturally expect growth to moderate. Our underlying sequential quarterly revenue growth has been in the range of 4% to 7% the last few quarters.

展望 2026 年，隨著 KIMMTRAK 進入市場的第 5 年，並​​在所有主要市場擁有顯著的滲透率，我們自然預期成長速度會放緩。過去幾個季度，我們的基本季度環比收入成長率一直保持在 4% 到 7% 之間。

We are seeing that growth slowdown and expect that trend to continue in 2026. Moving from revenue to expenses. As we continue to maximize global access to KIMMTRAK and advance our pipeline, our operating expenses increased.

我們看到成長速度正在放緩，預計這一趨勢將在 2026 年繼續。從收入轉向支出。隨著我們不斷擴大 KIMMTRAK 的全球市場並推進我們的管道建設，我們的營運費用也隨之增加。

The increase in our R&D spend versus last year was primarily driven by ongoing investments in our three Phase III trials and by advancing our earlier stage programs, including preparations to initiate clinical studies with our autoimmune candidates.

與去年相比，我們研發支出的增加主要是由於我們對三項 III 期試驗的持續投資，以及推進我們早期階段的項目，包括準備啟動我們自身免疫候選藥物的臨床研究。

In 2026, as we continue to invest in our pipeline, we expect R&D expenses to increase modestly year-over-year, although at a slower rate than they did in 2025.

2026 年，隨著我們繼續投資於我們的產品線，我們預計研發費用將逐年小幅成長，儘管成長將低於 2025 年的成長速度。

Turning to SG&A. 2025 expenses were marginally higher versus 2024 as we remain disciplined with this spending. In 2026, we expect only incremental increases to these investments, driven by commercial preparations for the potential expansion of KIMMTRAK into cutaneous melanoma.

接下來談談銷售、一般及行政費用。由於我們繼續嚴格控制這方面的支出，2025 年的支出略高於 2024 年。2026 年，我們預計這些投資只會逐步增加，這是由於 KIMMTRAK 可能擴展到皮膚黑色素瘤領域而進行的商業準備所致。

Overall, we are pleased to have reduced our operating loss in 2025 as revenue grew more than our operating expenses. Our balance sheet remains exceptionally strong. As of year-end, we had $864 million in cash and marketable securities, an increase of more than $40 million versus last year.

總體而言，我們很高興能夠減少 2025 年的營運虧損，因為收入成長超過了營運支出。我們的資產負債表依然非常穩健。截至年底，我們擁有現金和有價證券8.64億美元，比去年增加了4000多萬美元。

Our robust financial position, combined with data-driven investments and expense discipline, provides us with the flexibility and resources to continue advancing our mission of delivering transformative medicines to patients.

我們穩健的財務狀況，加上數據驅動的投資和嚴格的支出控制，使我們擁有足夠的靈活性和資源，繼續推進我們為患者提供變革性藥物的使命。

I'll now turn the call back to Bahija.

現在我將把電話轉回給巴希賈。

Thank you, Travis, and thank you, team. Four years ago, we launched the first ever approved therapy for metastatic uveal melanoma. Today, we're a commercial stage biotech with a validated platform, three Phase III trials and we're expanding into infectious disease and autoimmunity. We're not just treating cancer. We're also redefining what's possible with T cell receptor biology.

謝謝你，崔維斯，也謝謝你們，團隊。四年前，我們推出了首個獲準的轉移性葡萄膜黑色素瘤療法。如今，我們是一家商業化階段的生技公司，擁有經過驗證的平台、三項 III 期試驗，並且我們正在向傳染病和自體免疫領域拓展。我們不僅僅是在治療癌症。我們也正在重新定義T細胞受體生物學的可能性。

2025 was a year of execution and 2026 will be a year of data and continued progress. We thank you all for your support. And now we'll be happy to take your questions. Thank you.

2025年是執行之年，2026年將是資料收集和持續進步之年。感謝大家的支持。現在我們很樂意回答您的問題。謝謝。

(Operator Instructions) Michael Yee, UBS.

（操作說明）Michael Yee，瑞銀集團。

Hey guys, good morning and congrats on the progress. I have a quick question on TEBE-AM. I think that's a really exciting opportunity and the data is coming soon. Can you remind me the general geographic breakdown of your enrolment. Is it half US or Europe, et cetera, et cetera, because I think there's much more limited agents outside the US and that could impact the control arm. And secondly, you are designed KIMMTRAK and also KIMMTRAK plus PD-1. Did you go through a DSMB analysis or a look to test that KIMMTRAK alone is probably doing at least as good as the combo and what insights did you have on that? Thank you.

各位，早安，祝賀你們的進展。我有一個關於TEBE-AM的簡短問題。我認為這是一個非常令人興奮的機會，相關數據很快就會公佈。可否告知我貴校學生的大致地理分佈？是美國的一半還是歐洲的一半，等等，等等，因為我認為美國以外的代理人數量要少得多，這可能會影響對照組。其次，你們的設計是 KIMMTRAK 和 KIMMTRAK plus PD-1。您是否進行過 DSMB 分析或測試，以證明 KIMMTRAK 單獨使用可能至少與組合使用效果一樣好？您對此有何見解？謝謝。

Great. Mohammed, do you want to take that? Sure, thanks.

偉大的。穆罕默德，你想拿嗎？好的，謝謝。

Sure. Thanks, Michael, for the questions. With regards to enrolment on TEBE-AM, the majority of our enrolment is coming from Europe, in line with other recently completed pivotal trials. We expect between 10% and 15% from US and then the rest from the remaining countries.

當然。謝謝邁克爾提出的問題。關於 TEBE-AM 的入組情況，我們大部分的入組患者來自歐洲，這與其他近期完成的關鍵性試驗的情況一致。我們預計美國將佔10%到15%，其餘部分來自其他國家。

With regards to your question around DSMB and whether we had them look at activity within mono versus combo as you recall, the original TEBE design was a Phase II/III design. Based on enrolment metrics, we converted it all into a Phase III seamless -- a single consolidated trial design. We've never looked at the data, neither did the IDMC. So this is based purely on enrolment metric. And as a result, we saved one year in terms of the conduct of the Phase III trial.

關於您提出的有關 DSMB 的問題，以及我們是否像您記得的那樣讓他們查看單聲道與組合聲道中的活動，最初的 TEBE 設計是二期/三期設計。根據入組指標，我們將所有內容轉換為 III 期無縫銜接的單一整合試驗設計。我們從未查看過這些數據，獨立數據管理中心（IDMC）也沒有。所以這完全是基於入學人數指標的。因此，我們在進行 III 期試驗方面節省了一年時間。

Got it. Thank you.

知道了。謝謝。

Tyler Van Buren, TD Cowan.

泰勒·範·布倫，TD·考恩。

Hey guys, good morning. Thanks for taking the question. Just another on TEBE-AM, given how important the readout is in the second half. Can you just remind us of what both treatment arms are powered for an overall survival and what you believe the likelihood is that the monotherapy arm in addition to TEBE plus pembro combination could succeed?

嘿，各位，早安。感謝您回答這個問題。鑑於下半場的讀數非常重要，TEBE-AM 再添一筆。您能否提醒我們一下，兩種治療方案的整體存活率分別是多少？您認為單藥治療方案加上TEBE加帕博利珠單抗合併治療方案的成功可能性有多高？

Thank you for the question, Tyler. So with regards to the statistical assumptions, we usually don't get into the details, but it's fair to say that we are -- we've designed the study to basically meet both a statistically significant and clinically meaningful threshold difference from the control and that, in my experience, on average, that's at least a 30% difference from the control.

謝謝你的提問，泰勒。所以關於統計假設，我們通常不會深入細節，但可以公平地說，我們設計這項研究的目的是為了達到與對照組在統計上顯著且在臨床上有意義的閾值差異，而且根據我的經驗，平均而言，這至少是與對照組 30% 的差異。

With regards to assumptions between mono and combo, again, we typically don't get into like are detailed at the statistical plan, but needless to say, our data from 201 was based on combo. So certainly, logic would support like the combo may outperform the mono, but that's what I can say.

關於單打和組合打之間的假設，我們通常不會像統計計劃中詳細闡述的那樣深入探討，但毋庸置疑，我們 201 年的數據是基於組合打的。所以，從邏輯上講，組合模式可能會比單模式表現更好，但我只能說這麼多了。

Eric Schmidt, Cantor Fitzgerald.

艾瑞克·施密特，坎托·費茲傑拉。

Maybe to switch gears a little bit toward Ralph and Travis. It feels like we've been talking about or guiding to a deceleration in contract sales for years now, yet growth has been pretty robust as you guys called out 25-ish plus percent year-on-year.

或許可以稍微轉換話題，說說拉爾夫和崔維斯。感覺我們多年來一直在討論或引導合約銷售放緩，但正如你們指出的那樣，增長一直相當強勁，同比增長超過 25%。

I hear you, Travis, you're thinking that quarterly growth rate is going to come down from 4% to 7%. Do you have value in mind that you think is realistic that is substantially less than 25%.

我明白你的意思，崔維斯，你認為季度成長率會從 4% 下降到 7%。你心中是否有一個你認為現實可行的、遠低於 25% 的數值？

Eric, thanks for the question. Obviously, we're pleased that we continue to overperform commercially. So we're excited about that. And we're now entering the fifth year on the market, so we do naturally expect that growth to begin to moderate with significant penetration across all major markets, both US and in Europe.

艾瑞克，謝謝你的提問。顯然，我們很高興公司在商業上繼續取得超乎預期的業績。我們對此感到很興奮。現在我們已經進入市場第五年，因此我們自然預計，隨著在美國和歐洲所有主要市場的顯著滲透，成長速度將開始放緩。

One thing to keep in mind, that year-on-year growth of 29%. We did have some rebate reserves in 2024 and 2025. If you normalize for those rebate reserves, our underlying growth was around 20%. So I just offer that up as a reminder to folks. So you have a little bit of better understanding of where we expect the growth to moderate from.

需要記住的一點是，年成長率為 29%。我們在 2024 年和 2025 年確實有一些退款儲備。如果扣除這些回饋儲備金，我們的基本成長率約為 20%。所以我只是想提醒大家這一點。這樣您就能更了解我們預期成長放緩的起點了。

Thank you, and I see you operate around cash flow breakeven in 2025. Is that a reasonable estimate for '26?

謝謝，我看到你們的營運目標是在 2025 年實現現金流損益平衡。這是 2026 年的合理估計嗎？

Yes. We continue to focus on investment in our 3 Phase IIIs. And so we do expect R&D expenses to modestly increase into 2026 from 2025. From an SG&A perspective, we've been really pleased with how well we've managed those expenses and continue to be disciplined on that front. We've been very consistent really over 2024 and 2025 around that $40 million mark per quarter and only expect incremental increases into 2026 as we prepare for cutaneous melanoma

是的。我們將繼續專注於3個三期項目的投資。因此，我們預計研發支出將從 2025 年到 2026 年略有成長。從銷售、一般及行政費用（SG&A）的角度來看，我們對這些費用的管理情況非常滿意，並將繼續在這方面保持自律。2024年和2025年，我們的季度收入一直穩定在4000萬美元左右，預計到2026年只會略有增長，因為我們正在為皮膚黑色素瘤的防治做準備。

Thank you very much.

非常感謝。

Jack Allen, Baird.

傑克艾倫，貝爾德。

Congrats to the team on the update. I wanted to ask a little bit on the commercial outlook. Pending positive results in the TEBE-AM study, I wanted to ask the team how they thought about pricing in that indication. I know you have a very meaningful price in metastatic uveal melanoma, which is a rare space. How do you think about the larger second-line cutaneous melanoma market and any impact on price moving forward there, pending a launch into that indication? Thank you.

恭喜團隊完成更新。我想稍微了解一下商業前景。在 TEBE-AM 研究取得正面結果之前，我想問該團隊如何看待該適應症的定價。我知道您在轉移性葡萄膜黑色素瘤領域擁有非常有意義的定價，這是一個罕見的領域。您如何看待更大的二線皮膚黑色素瘤市場，以及在進入該適應症之前，該市場價格將受到哪些影響？謝謝。

Thanks, for the good question. So when you consider the unmet need that exists today in advanced melanoma. And the fact that we have a Phase III with an overall survival end point and the fact that we're -- we haven't established safety and this is an off-the-shelf treatment. Really, if the data is positive, and this is all data dependent, we believe that we can potentially defend that price appropriately given the OS endpoint, of course, data dependent.

謝謝你的好問題。所以，當你考慮到目前晚期黑色素瘤領域存在的未被滿足的需求。而且，我們目前進行的是以總存活期為終點的 III 期臨床試驗，但我們尚未確定其安全性，而且這是一種現成的治療方法。實際上，如果數據是積極的（這一切都取決於數據），我們相信，考慮到操作系統終端，我們有可能合理地捍衛這個價格，當然，這也取決於數據。

Great, thanks for the call.

太好了，謝謝你的來電。

Sean Laaman with Morgan Stanley.

摩根士丹利的肖恩拉曼。

Good morning everyone. Hope everyone's well and thank you for taking my question. I have a question on your autoimmune entry, so first candidate entering Phase I in 2026. How do you evaluate our success in the early autoimmune studies relative to oncology benchmarks? And how capital-intensive could the platform become? Thank you.

大家早安。希望大家一切都好，謝謝你們回答我的問題。我有一個關於你們自體免疫疾病入選的問題，第一個進入 I 期臨床試驗的候選藥物將於 2026 年上市。您如何評估我們在早期自體免疫研究中取得的成功與腫瘤學基準相比如何？該平台可能需要多少資本投入？謝謝。

Yes. So thank you for this question. I'll take that. We chose type one diabetes exactly for that reasons that we can determine very early on if two questions that will answer right away, does the drug bind the target and that we will look at that with the soluble PD-1, for instance, and other things.

是的。謝謝你的提問。我接受。我們選擇第 1 型糖尿病正是出於這個原因，我們可以很早就確定兩個問題，這兩個問題可以立即得到解答：藥物是否與標靶結合，我們將用可溶性 PD-1 等來研究這個問題，以及其他一些因素。

And the second is we do have the surrogate C peptide that we can measure. Once we have the dose, we can measure that, and that's a surrogate for efficacy. So exactly that we can find out basically early on if this has the potential to be active or not. And that's really the reasoning before we engage into big Phase IIbs or something like that.

第二點是，我們確實有可以測量的替代 C 肽。一旦確定了劑量，我們就可以測量劑量，而劑量可以作為療效的替代指標。這樣我們就能儘早發現它是否有可能活躍起來。這就是我們在進行大型 IIb 期臨床試驗或其他類似計畫之前需要考慮的真正原因。

Wonderful, thank you.

太好了，謝謝。

Jonathan Chang with Leenik Partners.

Jonathan Chang 與 Leenik Partners 合作。

Hi guys, thanks for taking my question. How are you thinking about the learnings from the success of KIMMTRAK in uveal melanoma? And how could those apply to a potential commercial launch in cutaneous melanoma, what similarities and differences are you considering? Thank you.

大家好，感謝你們回答我的問題。您如何看待KIMMTRAK在葡萄膜黑色素瘤治療中取得的成功所帶來的經驗教訓？那麼，這些因素如何應用於皮膚黑色素瘤的潛在商業化推廣？您認為兩者之間有哪些相似之處和不同之處？謝謝。

Yes. Great question. Ralph, do you want to take that?

是的。問得好。拉爾夫，你想拿那個嗎？

Sure. Jonathan, thank you for the question. So -- we -- in cutaneous melanoma, you have half of these physicians treating patients who -- half of the patients with cutaneous melanoma are being treated by physicians who are experienced with KIMMTRAK today. So this is a great foundation upon which we will build. In addition to that, the team is very well trained, has executed recently in the launch and has a track record of successful launches. So all of this together will lead into, I think, a good data dependent, of course, potential launch.

當然。喬納森，謝謝你的提問。所以——我們——在皮膚黑色素瘤方面，有一半的醫生正在治療患者——目前有一半的皮膚黑色素瘤患者正在接受有 KIMMTRAK 經驗的醫生的治療。所以，這是我們未來發展的良好基礎。除此之外，該團隊訓練有素，最近在產品發布中表現出色，並且擁有成功發布產品的記錄。所以我認為，所有這些因素加在一起，最終會促成一次良好的、當然取決於數據的、潛在的發布。

A strong medical team. I think that's following with the science.

一支強大的醫療團隊。我認為這符合科學原理。

Got it, thanks.

明白了，謝謝。

Greg Suvannavejh, Mizuho Securities.

Greg Suvannavejh，瑞穗證券。

Thanks for taking my question and congrats on the progress. I was curious about your PRAME portfolio, you've got several different programs going on there. And I'm wondering, you've got a lot of combinations for lung cancer and also ovarian cancer. I'm wondering what are the different scenarios that we could see coming out of the company when we get the data update in the second half? Would you be willing to share if you would be advancing potentially two assets if you had good data? Or is a view that there is going to be one asset coming out of that pipeline review.

感謝您解答我的問題，也祝賀您的進展。我對您的 PRAME 專案組合很感興趣，您在那裡開展了好幾個不同的專案。我想知道，你們有很多治療肺癌和卵巢癌的組合藥物。我想知道，當我們在下半年獲得公司數據更新時，可能會看到哪些不同的情況？如果您有可靠的數據，您是否願意分享您是否會推動兩項資產的投資計畫？或者有人認為，該管道審查最終只會推出一項資產。

Any color there on how you're thinking about what the outcome could be of that update in the second half?

對於下半年的更新可能帶來的結果，您有什麼想法嗎？

Yes. Before I leave it to Mohammed, I'll just say this is a typical Phase 1 exploration, Phase Ib that we are doing, especially when you know that the target is validated. And I think to just address a lot of questions in the early phase before engaging in a late phase, at least when it comes outside of melanoma. But Mohammed, do you want to comment.

是的。在把發言權交給穆罕默德之前，我只想說，這是我們正在進行的典型的 1 期探索，也就是 Ib 期，尤其是在你知道目標已經得到驗證的情況下。我認為，至少在黑色素瘤以外的領域，應該在早期階段解決很多問題，然後再進入後期階段。穆罕默德，你想發表一下看法嗎？

Sure. Thanks, Greg, for the question. Look, I think we're in a unique position where we've been in the clinic with brene for several years, and we've now enrolled several hundred patients. So we're certainly mining that data, which will help guide next steps for the brene program. But in addition, as Bahija mentioned , we have the PRAME HLE trial that's ongoing.

當然。謝謝格雷格的提問。我認為我們處於一個獨特的地位，我們已經和布琳一起在診所工作了好幾年，現在我們已經招募了數百名患者。因此，我們肯定會挖掘這些數據，這將有助於指導布雷尼計劃的下一步工作。此外，正如巴希賈所提到的，我們還有正在進行的 PRAME HLE 試驗。

And so we're going to be in a good position by the end of the year to look at the totality of the data to guide us with regards to next steps. It just provides us optionality basically.

因此，到今年年底，我們將處於一個有利的位置，可以查看所有數據，從而指導我們採取下一步行動。它基本上只是給我們提供了選擇餘地。

Rajan Sharma, Goldman Sachs.

Rajan Sharma，高盛集團。

Hi, just one on the HIV program that we're expecting an update for later this year. Could you just maybe frame expectations there in terms of number of patients that we should expect that data set to be in? And maybe if you could just talk to how high you think you can push the dose there. Thank you.

您好，關於愛滋病防治項目，我們預計今年稍後會收到更新資訊。您能否具體說明一下，我們應該預期該資料集包含多少名患者？或許你可以跟我說說你覺得你能把劑量提高到多高。謝謝。

Yeah, Mohammed, do you want to take that? Sure.

穆罕默德，你想拿嗎？當然。

Thanks, Rajan, for the question. Just as a reminder, obviously, the HIV trial is in a multiple ascending dose portion. We shared data last year that showed early dose-dependent effects. So we're continuing to escalate. It's still a Phase I dose escalation.

謝謝拉詹的提問。再次提醒一下，愛滋病毒試驗採用的是多劑量遞增方案。我們去年分享的數據顯示了早期劑量依賴性效應。所以我們正在繼續升級行動。這仍然是 I 期劑量遞增試驗。

So cohorts are small sizes, but we anticipate by the end of this year to be able to identify the right dose and look at the impact on the viral reservoir as well as the viral rebound.

因此，雖然每個隊列的規模較小，但我們預計到今年年底將能夠確定合適的劑量，並觀察其對病毒庫的影響以及病毒反彈情況。

The other part of the study is that we can trigger expansion based on the data that we see. And so that can allow us to build on any signals we see during those deletions.

研究的另一部分是，我們可以根據我們看到的數據觸發擴張。這樣一來，我們就可以基於在這些刪除過程中看到的任何訊號進行分析。

[Fessel Kurshid], Jefferies.

[Fessel Kurshid]，傑富瑞。

I just want to ask how are you thinking about the upcoming competitor readout in frontline uveal from IDEA. I understand it's HLA negative, but do you think there could be any read-through or any impact to your stronghold in frontline HLE-positive uveal? Thank you.

我只是想問您對即將由IDEA發布的Frontline Uveal競爭對手數據有何看法。我知道它是 HLA 陰性，但您認為這會對您在 HLE 陽性葡萄膜的一線治療中的優勢地位產生任何影響嗎？謝謝。

Ralph, you want to take it? Sure.

拉爾夫，你想拿嗎？當然。

Sure. Thank you for the question. So look, we need to see some randomized Phase III data from the competitor. Currently, we've seen only 42 patients with 11 of those patients being HLA-0201 positive. What I'll be personally looking for, in addition to response rate, of course, is the hazard ratio because standard of care has evolved since the beginning of that trial and the safety because small molecules can have tolerability challenges. We've seen another indication. So those are the two that I'll be looking for in the data readout.

當然。謝謝你的提問。所以，我們需要看看競爭對手的一些隨機 III 期臨床試驗數據。目前，我們只見過 42 名患者，其中 11 名患者為 HLA-0201 陽性。除了反應率之外，我個人還會關注風險比，因為自該試驗開始以來，治療標準已經發生了變化；此外，我還會關注安全性，因為小分子藥物可能存在耐受性方面的挑戰。我們看到了另一個跡象。所以，這兩個就是我要在資料讀取中尋找的內容。

And we are very much confident that KIMMTRAK is standards of care with very robust data from not only from the clinical trials, but also from the real-world evidence and will bring a five year evidence basically that's extending life of patients.

我們非常有信心，KIMMTRAK 是治療標準，其數據非常可靠，不僅來自臨床試驗，也來自真實世界的證據，並且基本上可以提供五年的證據，證明其可以延長患者的生命。

Great. Thank you.

偉大的。謝謝。

James Shin, Deutsche Bank.

James Shin，德意志銀行。

Hey, good morning, guys. Thank you for the question. One for Mohammed. I want to follow up on the TEBE-AM question on geographic breakdown. Can you lay out the percentage mix in the control arm as in what percent maybe on TILs versus recycled PD-1s and whether that mix may impact historic OS levels.

嘿，各位早安。謝謝你的提問。獻給穆罕默德。我想就TEBE-AM關於地理細分的問題進行後續討論。能否詳細說明對照組中TILs與回收PD-1s的比例，以及此比例是否會影響歷史OS水準？

Thank you.

謝謝。

Yeah, thanks, James, for the question. So no, it's a really important question. It's one that we've obviously been thinking about throughout the context of the study. What I can tell you is that we've looked at recent real-world data. And that confirms our original assumptions that about 1/3 of the patients likely in the control and will get retreated with checkpoint.

好的，謝謝你的提問，詹姆斯。所以，這的確是一個非常重要的問題。顯然，在整個研究過程中，我們一直在思考這個問題。我可以告訴你們的是，我們已經查看了最近的真實世界數據。這證實了我們最初的假設，即大約 1/3 的患者可能處於對照組，並將接受檢查點抑制劑治療。

Those that are BRAF-mutant, typically, get retreated with a BRAF-based regimen. And then the remaining are treated with chemotherapy or clinical trial, reflecting the high unmet need and the lack of an accepted standard. In terms of TIL, your question, as I mentioned in my original response, to Michael, majority of the patients are being enrolled in Europe where TILs are not approved. And so I think we remain confident in the original assumptions of our trial regards to control.

對於 BRAF 突變的患者，通常採用基於 BRAF 的治療方案進行再治療。其餘患者則接受化療或參與臨床試驗，反映出巨大的未滿足需求和缺乏公認的標準。關於 TIL，正如我在最初回覆 Michael 時提到的，大多數患者都在歐洲接受治療，而 TIL 在歐洲尚未獲得批准。因此，我認為我們仍然對我們試驗中關於控制的最初假設充滿信心。

Paul Jeng, Guggenheim Securities.

Paul Jeng，古根漢證券公司。

Oh, good. Thanks for taking the question. I wanted to ask about the second-line cutaneous melanoma opportunity for KIMMTRAK and how you view the evolving landscape, maybe two to three years down the road where there could be some other therapies on the market, including for the HLA-positive segment. Where do you sort of see KIMMTRAK fitting into that paradigm in the future? Are there any factors like patient baseline characteristics or sites of care that could drive more utilization for KIMMTRAK versus some of those competing therapies. Thank you.

哦，太好了。感謝您回答這個問題。我想詢問 KIMMTRAK 在二線皮膚黑色素瘤治療方面的機會，以及您如何看待未來兩到三年內可能出現的其他療法（包括針對 HLA 陽性患者的療法）的演變前景。您認為 KIMMTRAK 未來在這個模式中會扮演怎樣的角色？與某些競爭療法相比，是否存在一些因素（例如患者基線特徵或治療地點）可以推動 KIMMTRAK 的使用率更高？謝謝。

Well, I can start, of course, Mohammed, you can add to this. So currently, the only approved therapy in the monotherapy of treatment is TILs. And of course, that is highly selective of patients because of the entire process that patients have to undergo through.

當然，我可以先開始，穆罕默德，你可以補充。因此，目前唯一核准的單藥治療療法是 TILs。當然，由於患者必須經歷整個治療過程，因此對患者的篩選非常嚴格。

Similarly, you mentioned the HLA2-positive TCRT. That is also a highly selective patient population. And of course, KIMMTRAK is -- has -- will have an OS endpoint, right?

同樣，您提到了 HLA2 陽性 TCRT。這也是一個經過高度篩選的患者族群。當然，KIMMTRAK 現在、將來都會有一個作業系統端點，對吧？

Keep in mind, TILs and the TCRT will have response rate potentially PFS end points, we'll have an overall survival endpoint, which is the golden standard in that indication. And importantly, we're off the shelf. We'll have also long-term safety, safety already in melanoma patients of obviously, uveal melanoma. And importantly, we have a great base of experience. We have half of the cutaneous melanoma patients are being treated in centres that are experienced with KIMMTRAK.

請記住，TILs 和 TCRT 可能會以 PFS 終點來衡量緩解率，而我們將以總生存期終點來衡量，這是該適應症的黃金標準。更重要的是，我們已不再是擺設。我們還將提供長期安全性數據，在黑色素瘤患者（顯然包括葡萄膜黑色素瘤患者）中已經證實了安全性。更重要的是，我們擁有豐富的經驗基礎。我們有一半的皮膚黑色素瘤患者正在接受 KIMMTRAK 治療中心的治療。

So all of this together, I think, gives us a significant leg up in this setting. Anything to add?

因此，我認為所有這些因素加在一起，使我們在這種環境下擁有了巨大的優勢。還有什麼要補充的嗎？

Yes. The only other thing I would add is that, ultimately, it's good for patients who -- in a setting where there's no high unmet need and no options. It's good for patients to have options. Ultimately, I think what drives the physician choice is based on the data.

是的。我唯一要補充的是，最終，這對於那些沒有很高的未滿足需求也沒有其他選擇的患者來說是有益的。對患者來說，有多種選擇是件好事。歸根結底，我認為醫生的選擇取決於數據。

And so as Ralph mentioned, our trial is a randomized Phase III trial looking at OS, which is the gold standard. And so I think the data will drive ultimate practice.

正如拉爾夫所提到的，我們的試驗是一項隨機 III 期試驗，研究的是總生存期（OS），這是黃金標準。所以我認為數據將最終指導實踐。

Eva Fortea, Wells Fargo.

伊娃‧福特亞，富國銀行。

Good morning. Thanks for taking our question and congrats on the progress. A quick one from us, just on Brene. What do you need to see in the coming ovarian and lung readouts to move forward in development? Are you looking for anything specific in terms of efficacy?

早安.感謝您解答我們的問題，並祝賀您的進展。我們來簡單介紹一下布琳·布朗。為了推進研發工作，您希望在即將進行的卵巢和肺部檢測結果中看到什麼？您在功效方面有什麼具體要求嗎？

Mohammed, you want to say?

你想說的是穆罕默德嗎？

Sure, thanks, Eva, for the question. So we -- as I mentioned earlier we've been in the clinic for now a number of years and treated several hundred patients. We already have seen a clear signal of activity in ovarian. We shared that data in '24 at ESMO. But there obviously wasn't a clear line of sight for monotherapy accelerated approval.

當然，謝謝你的提問，伊娃。正如我之前提到的，我們已經在診所工作好幾年了，治療了數百名患者。我們已經看到卵巢中出現了明顯的活動訊號。我們在 2024 年的 ESMO 會議上分享了這些數據。但顯然，單藥療法加速審批並沒有明確的前景。

So we pivoted to earlier lines, the maintenance setting, which we believe plays to the strength of the platform, which is disease control and a very favourable safety profile.

因此，我們轉向了更早的生產線，即維護設置，我們認為這發揮了該平台的優勢，即疾病控制和非常有利的安全性能。

So the data that we're planning to share will be predominantly safety cohorts so smaller than the monotherapy data we shared earlier, but focused on safety and potentially early signals in this maintenance setting, lung we're still signal searching. This is a heterogeneous population. And so the data that we're planning to share will include a data set that's similar to what we've shared with ovarian and melanoma, but it's across multiple heterogeneous subsets. And then, of course, we have safety cohorts looking at chemo combo.

因此，我們計劃分享的數據主要來自安全性隊列，規模比我們之前分享的單藥治療數據要小，但重點關注安全性以及維持治療中的早期信號，我們仍在尋找信號。這是一個異質性很強的群體。因此，我們計劃分享的數據將包括一個與我們分享的卵巢癌和黑色素瘤數據類似的數據集，但它涵蓋多個異質子集。當然，我們還有針對化療聯合方案的安全隊列研究。

Ultimately, Eva, what I would say is that it's going to be the totality of the data. And then in addition, we have the PRAME HLE. So we'll look at the total data to help guide our next steps.

伊娃，我最終想說的是，這將取決於所有數據。另外，我們還有 PRAME HLE。因此，我們將查看所有數據，以指導我們下一步的工作。

Romy O'Connor, Lanschot Kempen.

羅密·奧康納，蘭肖特·肯彭。

Hi, team. Thank you for taking my question. Just backing on to eva's here, focusing on the half-life extended PRAME. I just want to ask if you can point us to what we need to see here to inform any major changes to the PRAME program in totality. You mentioned convenience and improved response. Should we be benchmarking this against what brenetafusp already shown? Thank you.

大家好。感謝您回答我的問題。回到 eva 的觀點，聚焦半衰期延長的 PRAME。我只想請問，您能否指出我們需要看到哪些信息，以便對 PRAME 項目進行全面重大修改？您提到了便利性和更快的反應速度。我們是否應該將此與 Brenetafusp 已經展示的內容進行比較？謝謝。

Great question, Mohammed?

問得好，穆罕默德？

Thanks, Romy, for the question. Yes. No, exactly. I mean as we said, we're in a very good position where we have our brenetafusp data and essentially PRAME HLE is brene with the Fc added on. And so we're doing the right experiment in the clinic asking those 2 basic questions.

謝謝羅米的提問。是的。沒錯，正是如此。我的意思是，正如我們所說，我們現在處境非常好，我們有 Brenetafusp 數據，PRAME HLE 本質上就是 Brenet 加上 Fc。因此，我們在診所進行的實驗是正確的，我們提出了這兩個基本問題。

And based on the data, it will provide us optionality in terms of which molecule to carry forward in which setting.

根據數據，我們可以選擇在何種情況下推進哪一種分子的研究。

Yes. I think the when we started is really look at convenience because we see with KIMMTRAK with short half-life an amazing hazard ratio of 0.51. Now I think with the other data out there, if we see also an increase in ORR or something like that, then I think that's what Mohammed was talking about is looking at the totality of the data, and then we'll determine the next steps. But we are very -- we'll do the experiments, and we'll get the data.

是的。我認為我們最初確實更關注便利性，因為我們看到 KIMMTRAK 的半衰期很短，但風險比卻低至 0.51。現在，我認為結合其他數據，如果我們也看到 ORR 或其他類似指標的提高，那麼我認為這就是 Mohammed 所說的，我們需要綜合考慮所有數據，然後再決定下一步的行動。但是我們非常有信心——我們會進行實驗，我們會得到數據。

Great. Thank you.

偉大的。謝謝。

Patrick Trucchio, H.C. Wainwright.

派崔克·特魯基奧，H.C. 溫賴特。

Thanks, good morning. Just a couple of follow-ups on TEBE-AM. I'm just wondering, given the OX primary endpoint, what was the assumed median OS in the control arm? And has anything in the real-world evolution of the treatment landscape changed that assumption since trial initiation. And then just separately, just regarding the timing of the data as early as second half '26. Maybe you can give us an idea of what the event assumptions are driving that and the probability that the data perhaps looks into 2027.

謝謝，早安。關於 TEBE-AM，還有幾點後續問題。我想知道，考慮到 OX 的主要終點，對照組的假設中位總存活期是多少？自試驗開始以來，現實世界治療格局的發展是否改變了這個假設？然後，單獨來看，關於數據的時間安排，最早可以追溯到 2026 年下半年。或許您可以告訴我們，驅動這一事件假設的是什麼，以及數據可能追溯到 2027 年的機率。

Okay. I'll take the second part, and then Mohammed will take the first part. So because it is an OS endpoint, it is event driven. So we'll have a little bit better idea maybe when the trial is done, but it's going to depend on the event. That's why just doing the calculation that we did and the assumptions that will basically we see it today as early as the second half of 2026.

好的。我負責第二部分，然後穆罕默德負責第一部分。由於它是作業系統端點，因此它是事件驅動的。所以，等審判結束後，我們或許就能更清楚地了解狀況，但這取決於事件的進展。這就是為什麼我們根據我們所做的計算和假設，最早在 2026 年下半年就能看到這種情況的原因。

So we'll get a little bit better once we finish the trial and depending on the events. But Mohammed, do you want to take the first part?

所以，審判結束後，情況會好轉一些，具體還要看審判結果。但穆罕默德，你想先做第一部分嗎？

Sure. Thanks for the question, Patrick. So with regards to OS assumptions for the control arm in TEBE, the assumptions we made at the start of the trial really haven't changed because ultimately, there has been no randomized trial that's actually established in improvement in survival in this setting. So those assumptions essentially were a median overall survival between 12 and 13 months and a one year survival rate of around 55%. Things haven't really moved from that regard.

當然。謝謝你的提問，派崔克。因此，關於TEBE對照組的OS假設，我們在試驗開始時所做的假設實際上並沒有改變，因為最終還沒有隨機試驗真正證實這種情況下生存率的提高。因此，這些假設基本上是：整體存活期中位數為 12 至 13 個月，一年存活率約為 55%。在這方面，情況並沒有什麼實質的進展。

Great, thanks so much.

太好了，非常感謝。

Thank you. We have reached the end of our question-and-answer session, and with that, I would like to turn the floor back over to Morgan Morse for any closing comments.

謝謝。我們的問答環節到此結束，接下來，我想把發言權交還給摩根·莫爾斯，請他作最後的總結發言。

Thank you for joining us today we appreciate all of your support.

感謝各位今天蒞臨，我們非常感謝大家的支持。

Thank you.

謝謝。

Thank you, ladies and gentlemen. This does now conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.

謝謝各位女士、先生。今天的電話會議到此結束。感謝您的參與。您可以在此時斷開線路。祝您今天餘下的時間愉快。