Immunocore Holdings PLC (IMCR) 2024 Q4 法說會逐字稿

Greetings and welcome to the Immunocore conference call and webcast. (Operator Instructions)

大家好，歡迎參加 Immunocore 電話會議和網路廣播。（操作員指示）

As a reminder, this conference is being recorded. It is now my pleasure to introduce Clayton Robertson, Head of Investor Relations. Thank you. You may begin.

提醒一下，本次會議正在錄製中。現在我很高興介紹投資者關係主管克萊頓羅伯森 (Clayton Robertson)。謝謝。你可以開始了。

Thank you. Good morning and good afternoon. Thank you for joining us on our 4Q and full year 2024 earnings call. During today's call, we will make some forward-looking statements which are qualified by our safe harbor provision under the Private Securities Litigation Reform Act of 1995.

謝謝。早安，下午好。感謝您參加我們的 2024 年第四季和全年財報電話會議。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》的安全港條款的限制。

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. On today's call, I'm joined by Bahija Jallal, CEO of Immunocore, who will share a strategy update. Then Ralph Torbay, Head of Commercial, will review our full year '24 KIMMTRAK sales and KIMMTRAK's life cycle management plans. David Berman, our Head of R&D, will provide some pipeline updates highlighting near-term readouts and infectious diseases. Travis Coy, our CFO and Head of Corporate Development, will also provide highlights on our financial results reported this morning. Bahija?

請注意，實際結果可能與這些前瞻性陳述所示的結果有重大差異，包括我們向美國證券交易委員會提交的文件中討論的結果。在今天的電話會議上，Immunocore 執行長 Bahija Jallal 將與我分享策略更新。然後，商務主管 Ralph Torbay 將回顧我們 24 全年 KIMMTRAK 銷售情況以及 KIMMTRAK 的生命週期管理計劃。我們的研發主管 David Berman 將提供一些管道更新，重點介紹近期讀數和傳染病。我們的財務長兼企業發展主管 Travis Coy 也將重點介紹我們今天上午報告的財務表現。巴希賈？

Thank you, Clay, and good morning. Good afternoon, everyone. Our first order of business today is to welcome Travis Coy, our new CFO. This is Travis's first earnings call for Immunocore, and we are delighted to have him join us. He was on our board previously. Welcome, Travis.

謝謝你，克萊，早安。大家下午好。我們今天的第一項事務是歡迎新任財務長 Travis Coy。這是 Travis 首次為 Immunocore 召開收益電話會議，我們很高興他能加入我們。他以前曾是我們的董事會成員。歡迎光臨，崔維斯。

Today, the team will share the details of our fourth quarter and full year 2024 performance. And the progress of our clinical portfolio.

今天，團隊將分享我們2024年第四季和全年業績的詳細資訊。以及我們的臨床組合的進展。

As always, we have been laser focused on advancing our mission of bringing transformative medicine to patients. I am very proud that 2024 was another year of strong execution thanks to the fantastic work delivered by our teams. We delivered contracts to more patients around the world and achieved 5% growth in Q4 versus Q3 and 30% year on year revenue growth, culminating in a total of $310 million in revenue for the year.

與往常一樣，我們一直專注於推進為患者帶來變革性醫療的使命。我感到非常自豪，由於我們團隊的出色工作，2024 年又是執行力強勁的一年。我們向全球更多患者交付了合同，第四季度較第三季度增長了 5%，同比增長了 30%，全年總收入達到 3.1 億美元。

This continues our great track records of commercial execution. In 2024, we also progressed our deep and diverse clinical pipeline with exciting and promising molecules at all stages of development and across three therapeutic areas which could bring new treatment options to patients. We have advanced our three ongoing Phase 3 trials, including the two Phase 3 melanoma trials, TEBE-AM as we execute on our contract life cycle management.

這延續了我們出色的商業執行記錄。2024 年，我們還推進了深度和多樣化的臨床管線，其中包括處於各個開發階段和三個治療領域的令人興奮和有前景的分子，可以為患者帶來新的治療選擇。我們在執行合約生命週期管理的過程中，推進了三項正在進行的 3 期試驗，包括兩項 3 期黑色素瘤試驗和 TEBE-AM。

We also randomized the first patient in our third Phase 3 trial prison mail. We remain encouraged by the preliminary data in other tumors and we will continue to expand to have the data we need to determine next steps. Our portfolio growth is fueled by an R&D engine that delivered a robust early pipeline.

我們也將第三階段試驗監獄郵件中的第一位患者隨機化。其他腫瘤的初步數據仍然令我們感到鼓舞，我們將繼續擴大研究範圍，以獲得確定下一步所需的數據。我們的投資組合成長得益於研發引擎，該引擎提供了強大的早期產品線。

In 2024, we initiated two Phase 1 trials with two novel molecules that David will talk to you about in a few minutes. Expanding beyond oncology in infectious diseases, we completed the HPV single ascending those trials. And we will be presenting initial data from the multiple ascending those portions of our HIV trials later this quarter.

2024 年，我們啟動了兩項 1 期試驗，試驗對像是兩種新型分子，David 將在幾分鐘後與您討論這些分子。我們的研究範圍從腫瘤學擴展到傳染病，並完成了 HPV 單次上升試驗。我們將在本季稍後公佈 HIV 試驗多個部分的初步數據。

Our modular technology allowed us to expand into a new therapeutic area, tackling autoimmune diseases. We advanced two autoimmune candidates, one targeting Type 1 diabetes and the other atopic dermatitis.

我們的模組化技術使我們能夠擴展到新的治療領域，治療自體免疫疾病。我們開發了兩種自體免疫候選藥物，一種針對第 1 型糖尿病，另一種針對異位性皮膚炎。

These efforts have been delivered by all our employees, guided by an excellent leadership team and supported by a strong balance sheet and disciplined spending.

這些努力是由我們全體員工共同完成的，由優秀的領導團隊指導，並由強勁的資產負債表和有紀律的支出提供支持。

And now ask the team to share additional details. First, Ralph will discuss KIMMTRAK's commercial performance. Ralph, please.

現在請團隊分享更多細節。首先，拉爾夫將討論 KIMMTRAK 的商業表現。請叫我拉爾夫。

Thank you, Bahija and hello, everyone. KIMMTRAK has had another year of exceptional growth, and I continue to be very proud of our team's dedication to reach more patients globally. KIMMTRAK truly embodies our mission of bringing transformative immunotherapies to patients.

謝謝你，Bahija，大家好。KIMMTRAK 又經歷了一年的卓越成長，我為我們團隊致力於在全球範圍內幫助更多患者感到非常自豪。KIMMTRAK 真正體現了我們為患者帶來變革性免疫療法的使命。

We have raised the bar for survival in first line HLA-A*02:01 metastatic uveal melanoma with unprecedented three year overall survival of around 27%. Patients who before KIMMTRAK were given 12 months to live, are now alive two years, even three years later, with KIMMTRAK.

我們提高了 HLA-A*02:01 轉移性葡萄膜黑色素瘤第一線治療的生存標準，三年總存活率達到了前所未有的約 27%。在接受 KIMMTRAK 治療之前，患者的生命只能剩下 12 個月，而接受 KIMMTRAK 治療後，患者可以存活兩年甚至三年。

With 3 Prix Galien award and 2 New England Journal of Medicine publications, among other recognitions, this is what transform transformational innovation looks like.

憑藉 3 項 Prix Galien 獎和 2 項《新英格蘭醫學雜誌》出版物以及其他認可，這就是變革性創新的樣子。

We take the responsibility of commercializing this transformational medicine very seriously, and last year alone, we launched KIMMTRAK in 14 countries for a total of 24 countries launched. We have also established KIMMTRAK, a center of care across most major markets with over 80% share of HLA-A*02:01 positive patients.

我們非常重視將這種轉化藥物商業化的責任，光是去年，我們就在 14 個國家推出了 KIMMTRAK，總共在 24 個國家推出了該產品。我們也建立了 KIMMTRAK，這是一個涵蓋大多數主要市場的護理中心，HLA-A*02:01 陽性患者比例超過 80%。

We're continuing our global expansion with KIMMTRAK, which has now been approved in 39 countries, including most recently in Brazil. We have delivered nearly three years of continuous net revenue growth with KIMMTRAK. For the full year 2024, KIMMTRAK generated $310 million in net revenues, which represents a 30% year on year growth.

我們正透過 KIMMTRAK 繼續進行全球擴張，目前該技術已在 39 個國家獲得批准，包括最近在巴西獲得的批准。我們與 KIMMTRAK 合作已實現了近三年的持續淨收入成長。2024 年全年，KIMMTRAK 淨收入為 3.1 億美元，較去年同期成長 30%。

In the fourth quarter, we've reported $84.1 million in net revenues, representing a 5% increase from the prior quarter. The United States accounted for $226 million, growing at an impressive 34% year on year.

第四季度，我們的淨收入為 8,410 萬美元，較上一季成長 5%。美國出口額達2.26億美元，年增34%。

In 2024, we successfully treated two out of three patients in the community, with nearly half of all [newuchem] track patients starting there. We estimate the market penetration of around 65% in the US with the duration of therapy of approximately 12 months.

2024 年，我們成功治療了社區中三分之二的患者，幾乎一半的 [newuchem] 追蹤患者都是從那裡開始治療的。我們估計美國的市場滲透率約為 65%，治療持續時間約為 12 個月。

These numbers speak to our efforts and as importantly, to KIMMTRAK safety and exceptional efficacy. Looking ahead at 2025, we continue to expect KIMMTRAK incremental growth driven by three main factors. First, US community expansion focused on less dense areas, leveraging the AI tools we launched last year. Second, duration of therapy, which continues to increase beyond clinical trial experience, highlighting KIMMTRAK's benefit beyond typical resist progression. And third, new launches ex, including the recent launch in the UK and Poland.

這些數字證明了我們的努力，同樣重要的是，也證明了 KIMMTRAK 的安全性和卓越的功效。展望 2025 年，我們預期 KIMMTRAK 將持續實現增量成長，主要受三大因素推動。首先，美國社區擴張重點是人口密度較低的地區，利用我們去年推出的人工智慧工具。其次，治療持續時間超出了臨床試驗經驗，凸顯了 KIMMTRAK 超越典型抵抗進展的優勢。第三，新產品的推出，包括最近在英國和波蘭的推出。

We're also excited to potentially expand the benefit of KIMMTRAK to additional indications with our life cycle management program, which I will take you through in the next slide. No therapy has been proven to extend survival in second line metastatic cutaneous melanoma post checkpoint inhibitors. Patients survival in the setting is poor and hovers at around 55% at one year.

我們也很高興能夠透過我們的生命週期管理計劃將 KIMMTRAK 的優勢擴展到更多適應症，我將在下一張投影片中向您介紹。目前尚無任何療法被證實能夠延長檢查點抑制劑治療後二線轉移性皮膚黑色素瘤的存活期。該環境下患者的存活率很低，一年存活率徘徊在 55% 左右。

TEBE-AM is the first Phase 3 trial aiming to show improved overall survival in this setting. There are strong reasons to believe in the potential of KIMMTRAK in this patient population based on Phase one trial data that showed 75% survival rate at one year, as well as an acceptable safety profile.

TEBE-AM 是第一個旨在證明這種情況下整體存活率提高的 3 期試驗。根據第一階段試驗數據顯示，一年存活率為 75%，且安全性可接受，因此有充分理由相信 KIMMTRAK 在該患者群體中具有潛力。

The TEBE-AM trial has three arms KIMMTRAK monotherapy, KIMMTRAK in combination with Pembro, and a control arm which includes options such as investigator choice of chemotherapy, retreatment with anti-PD1 or BRAF therapy, or clinical trials.

TEBE-AM 試驗分為三個組別：KIMMTRAK 單一療法、KIMMTRAK 與 Pembro 聯合療法以及對照組，對照組包括研究者選擇的化療、使用抗 PD1 或 BRAF 療法進行再治療或臨床試驗等選項。

We have line of sight on data within the next 18 months. Enrollment is on track to finish in the first-half of '26, and data in the second-half of '26. The ATOM trial is the only registrational Phase 3 trial in the adjuvant uveal melanoma setting with the potential to prolong time to progression and survival.

我們對未來 18 個月內的數據有清楚的了解。入學工作預計將於 26 年上半年完成，數據預計將於 26 年下半年完成。ATOM 試驗是輔助性葡萄膜黑色素瘤領域中唯一一項註冊性 3 期試驗，具有延長疾病進展時間和存活期的潛力。

There remains a huge unmet need for patients at high risk of recurrence after definitive treatment, which is often radiation or removal of the eye. Patient patients currently have no other option but to watch and worry. Yet we know for half of these patients, Metastasis will occur within three years.

對於復發風險較高的患者，在接受確定性治療（通常是放射治療或眼球摘除）後，仍存在巨大的未滿足需求。患者目前除了看著和擔心之外沒有其他選擇。然而我們知道，這些患者中有一半會在三年內出現轉移。

The ATOM trial in collaboration with the EORTC aims to treat patients during this period with the goal of delaying or eliminating metastases. EORTC enrolled the first patient in the fourth quarter of 2024, and the trial is currently recruiting patients globally. As we look to the future for KIMMTRAK. We strongly believe in its potential to help up to 6,000 patients with melanoma live longer.

ATOM 試驗與 EORTC 合作，旨在對這段時期的患者進行治療，以延緩或消除轉移。EORTC 於 2024 年第四季招募了第一位患者，該試驗目前正在全球招募患者。我們展望 KIMMTRAK 的未來。我們堅信它有潛力幫助多達 6,000 名黑色素瘤患者延長生命。

This vision is built upon robust clinical data, groundbreaking Phase 3 trials, and a proven track record in the clinic.

這個願景建立在可靠的臨床數據、開創性的 3 期試驗以及臨床驗證的良好記錄之上。

We're steadfast on our commitment to transforming patient outcomes and so defying KIMMTRAK's position as a leading therapy in the melanoma landscape.

我們堅定不移地致力於改變患者的治療結果，從而鞏固 KIMMTRAK 在黑色素瘤治療領域的領先地位。

Now I'd like to pass the baton to David to discuss our promising pipeline. David.

現在我想把接力棒交給大衛來討論我們有前景的管道。大衛。

Thank you, Ralph. I am pleased to share an update on our clinical portfolio. 2024 was an execution rich Europa R&D team.

謝謝你，拉爾夫。我很高興與大家分享我們臨床組合的最新進展。 2024 年是一支執行力極強的 Europa 研發團隊。

We started two Phase 3 trials, Prismel and Adam, two Phase 1 trials, and PRISM-MEL-301, the mad Phase of HIV and we completed the SAD of our HPV trial. Over the next 12 to 18 months, we hope to have data readouts, including potentially for TEBE-AM that will guide next steps for these programs.

我們啟動了兩個 3 期試驗、Prismel 和 Adam、兩個 1 期試驗以及 PRISM-MEL-301、HIV 的瘋狂階段，並且完成了 HPV 試驗的 SAD。在接下來的 12 到 18 個月內，我們希望獲得數據讀數，包括可能包括 TEBE-AM 的數據，以指導這些項目的下一步。

Ralph has just presented the KIMMTRAK clinical trial updates and so I will provide brief updates on PRAME, PLWH, HIV, and our autoimmune programs.

拉爾夫剛剛介紹了 KIMMTRAK 臨床試驗的最新情況，因此我將簡要介紹 PRAME、PLWH、HIV 和我們的自身免疫計劃的最新情況。

Let's talk about PRAME. We are actively randomizing patients into the Phase 3 study in newly diagnosed metastatic cutaneous melanoma, studying brenetafusp plus nivolumab versus a nivolumab regimen.

讓我們來談談PRAME。我們正在積極地將患者隨機分配到新診斷的轉移性皮膚黑色素瘤的 3 期研究中，研究 brenetafusp 加 nivolumab 與 nivolumab 方案的對比。

The goal for this year is for the Independent data monitoring Committee to review data on the first 90 randomized patients in order to select between the 40 mcg and the 160 mcg as they go forward dose.

今年的目標是讓獨立數據監測委員會審查前 90 名隨機患者的數據，以便在他們進一步服用劑量時在 40 微克和 160 微克之間進行選擇。

Beyond cutaneous melanoma, we have focused on three goals this year. First, building on the initial signals of activity in ovarian carcinoma, we will study brenetafusp in chemo combinations in platinum resistant ovarian and in earlier lines in combinations in platinum sensitive ovarian carcinoma.

除了皮膚黑色素瘤之外，我們今年還專注於三個目標。首先，基於卵巢癌的初始活動訊號，我們將研究 brenetafusp 在鉑抗藥性卵巢癌的化療組合中的作用以及在鉑敏感型卵巢癌的早期組合中的作用。

Second, we will continue signal detection in lung cancer with osimertinib and docetaxel.

其次，我們將繼續使用奧希替尼和多西他賽進行肺癌訊號檢測。

And third, we will continue dose escalation of our PRAME path life extended impact. All three will be reviewed together over the next 12 to 18 months to determine next steps.

第三，我們將持續提高 PRAME 路徑壽命延長影響的劑量。我們將在未來 12 至 18 個月內對這三項措施進行綜合審查，以確定下一步措施。

PRAME and GP 100 are both well-known targets for TCI therapies. In contrast, ImmTAV is a novel first in class target, and our ongoing Phase 1 program here demonstrates the power of our discovery engine.

PRAME 和 GP 100 都是 TCI 療法的知名目標。相比之下，ImmTAV 是一個新穎的同類首創目標，我們正在進行的第一階段計劃展示了我們發現引擎的強大功能。

Colorectal carcinoma has an increasing incidence and a high unmet need. R117 is the first immunotherapy to target PIWIL1, a protein expressed in colorectal carcinoma, which we know has historically been insensitive to checkpoints. PIWIL1 is an attractive target since it's not expressed in normal vital tissues, is a negative prognostic marker, and has broad expression in about 25% of colorectal cancer patients.

大腸直腸癌的發生率不斷上升，且未滿足的治療需求較高。R117 是第一個針對 PIWIL1 的免疫療法，PIWIL1 是一種在結腸直腸癌中表現的蛋白質，我們知道它對檢查點不敏感。PIWIL1 是一個很有吸引力的靶點，因為它在正常生命組織中不表達，是一種負面預後標誌物，並且在約 25% 的結腸直腸癌患者中廣泛表達。

We designed the Phase 1 dose escalation, which started last year based on all the insights from our earlier ImmTAAI programs. We have learned which signals are markers of activity for our platform, and we hope to see these mature in the next 12 to 18 months.

我們設計了第一階段的劑量遞增，該計劃於去年啟動，基於我們早期 ImmTAAI 項目的所有見解。我們已經了解哪些訊號是我們平台活動的標誌，我們希望在未來 12 到 18 個月內看到這些訊號成熟。

We know that our ImmTAAI platform is validated in cancer and therefore we have been excited to test whether the same approach of redirecting T-cells can be used for chronic viral diseases such as HIV and HPV. While antiretroviral therapy or [art] has turned HIV into a chronic disease, there remains a large unmet need for functional care.

我們知道我們的 ImmTAAI 平台已在癌症領域得到驗證，因此我們很高興測試重定向 T 細胞的相同方法是否可以用於治療 HIV 和 HPV 等慢性病毒疾病。儘管抗病毒療法或[ART]已將愛滋病毒轉變為慢性疾病，但對功能性照護的需求仍有很大未滿足的需求。

We estimate over 0.5 million people living with HIV and across G7 could be eligible for an MTA that could deliver a functional cure for HIV. The challenge for people living with HIV is that while art does control the virus, when art is stopped or interrupted, the virus rapidly rebounds and is detectable in the blood at 50 copies per mL, the threshold for detection, on average within two weeks.

我們估計，七國集團中超過 50 萬名愛滋病毒感染者可能有資格獲得 MTA，從而實現愛滋病毒的功能性治癒。愛滋病毒感染者面臨的挑戰是，雖然抗逆轉錄病毒療法確實可以控制病毒，但當抗逆轉錄病毒療法停止或中斷時，病毒會迅速反彈，平均兩週內血液中的病毒含量即可達到每毫升 50 份，這是檢測的閾值。

Furthermore, eight weeks after interruption, the vast majority of people will have over 200 copies per ml. This is the level of virus associated with risk of transmission or infection.

此外，中斷八週後，絕大多數人每毫升的拷貝數將超過 200。這是與傳播或感染風險相關的病毒等級。

However, the fact that some people can control the virus is reason to believe that the immune system may be able to recognize and target HIV infected cells and supports the hypothesis of our NTA immune therapy approach.

然而，有些人能夠控制病毒這一事實有理由相信免疫系統可能能夠識別和瞄準愛滋病毒感染細胞，並支持我們的 NTA 免疫治療方法的假設。

In the most recent meta-analysis, which was just published last month, one of the best predictors of HIV control was whether the person started art early versus late in their infection.

在上個月剛發表的最新統合分析中，愛滋病毒控制的最佳預測因子之一是患者是在感染早期還是晚期開始接受抗病毒治療。

The population in our Phase 1 trial. Generally started art later after initial HIV infection. And here the historical rate of HIV control at week 12 is very rare. Our Phase 1 trial is called Strive, and we are treating people living with HIV with M113 on the background of arc for 12 weeks and then stopping both therapies.

我們第一階段試驗的族群。通常在初次感染 HIV 後才開始進行抗病毒治療。這裡第 12 週的 HIV 控制率歷史非常低。我們的第一階段試驗名為 Strive，我們在弧光背景下使用 M113 治療 HIV 感染者 12 週，然後停止兩種療法。

The objectives are to determine whether we can reduce the viral RNA reservoir during the treatment Phase and then whether we can alter the kinetics or delay viral rebound after treatment interruption. We'll present the initial mad data from 16 people living with HIV at a conference next month. Over the next 12 months, we will continue dose escalation to be followed by expansion.

目標是確定我們是否可以在治療階段減少病毒 RNA 庫，然後確定我們是否可以在治療中斷後改變動力學或延遲病毒反彈。我們將在下個月的會議上展示 16 名愛滋病毒感染者的初步瘋狂數據。在接下來的 12 個月裡，我們將繼續增加劑量並隨後進行擴大。

We know that our tissue targeting platform works based on the KIMMTRAK survival benefit. We came up with the idea of using our tissue targeting platform to turn down the immune system. For the treatment of autoimmune disease.

我們知道，我們的組織標靶平台是基於 KIMMTRAK 生存優勢而運作的。我們想出了利用組織標靶平台來抑制免疫系統的想法。用於治療自體免疫疾病。

Over the next 12 to 18 months, we will bring our two lead autoimmune candidates, one for Type 1 diabetes, the second for atopic dermatitis into the clinic. Our vision for treating autoimmunity is unique, and that is tissue specific down modulation of the immune system which would avoid systemic immune suppression.

在接下來的 12 到 18 個月內，我們將把兩種主要的自體免疫候選藥物（一種用於治療第 1 型糖尿病，另一種用於治療異位性皮膚炎）引入臨床。我們對治療自體免疫的願景是獨一無二的，那就是對組織進行特異性的免疫系統下調，以避免全身性免疫抑制。

We accomplished this with our emti molecule which has three features. First, the targeting arm, which binds strongly or tethers the inti to the target tissue. This provides tissue specificity. Second is a PD1 agonist that turns off T cells by checkpoint agonism, which is the opposite of checkpoint blockade. And third is an FC fusion to enable longer half-life for infrequent dosing. These three features are designed to realize our vision of tissues specific immune suppression.

我們利用具有三個特徵的 emti 分子實現了這一目標。首先，靶向臂將內皮細胞牢固地結合或束縛在目標組織上。這提供了組織特異性。第二種是 PD1 激動劑，它透過檢查點激動來關閉 T 細胞，這與檢查點阻斷相反。第三種是 FC 融合，可以延長半衰期，進而減少給藥次數。這三個功能旨在實現我們對組織特異性免疫抑制的願景。

The hallmark of our approach is that the ImmTAC will only inhibit T cell activity when tethered or bound to the target cell or target tissue. For example, when the ImmTAC is not tethered, that is free floating in blood or other tissues, it is not brought into the T cell synapse and so does not inhibit T cell activation. This avoids systemic immune suppression.

我們方法的特點是，ImmTAC 僅當與目標細胞或目標組織束縛或結合時才會抑制 T 細胞活性。例如，當 ImmTAC 沒有被束縛，即自由漂浮在血液或其他組織中時，它就不會進入 T 細胞突觸，因此不會抑制 T 細胞活化。這避免了全身免疫抑制。

However, When ImmTAC binds to the target cell, it is brought into the T cell synapse where the PD1 agonist factor potently inhibits T cell activity. This will result in tissue-specific immune suppression.

然而，當 ImmTAC 與目標細胞結合時，它會被帶入 T 細胞突觸，其中 PD1 激動劑因子會強效抑制 T 細胞活性。這將導致組織特異性免疫抑制。

Type 1 diabetes is a terrible autoimmune disease that requires lifelong insulin replacement and carries risks and morbidities. There remains a high and met need for well tolerated medicines to delay or prevent progression of T1D. This is the goal of our first program, S-118. T1D is caused when auto reactive T cells kill the beta cell in the pancreas. These are the cells that normally secrete insulin.

1 型糖尿病是一種可怕的自體免疫疾病，需要終生補充胰島素，並伴隨風險和疾病。人們仍然迫切需要耐受性良好的藥物來延緩或預防第 1 型糖尿病的進展。這是我們的第一個專案 S-118 的目標。當自體反應性 T 細胞殺死胰臟中的 β 細胞時，就會引起第 1 型糖尿病 (T1D)。這些細胞通常會分泌胰島素。

S118 protects against auto-reactive T cell killing only when tethered to the beta cell. When not tethered, the anti is unable to prevent the killing of the beta cell.

S118 僅當與 β 細胞結合時才能防止自身反應性 T 細胞殺死。當不受束縛時，抗體無法阻止β細胞被殺死。

We have recently generated exciting ex vivo proof of confidence for S118 in pancreatic slices from a deceased donor who had recent onset of P1D prior to their death. We demonstrated that S118 binds specifically to beta cells and that it can have an inhibitory effect on the T cells within the pancreatic slice.

我們最近在一位去世前曾患過 P1D 的捐贈者的胰腺切片中獲得了令人興奮的體外信心證明，證明 S118 有效。我們證明 S118 特異性地與 β 細胞結合，並且可以對胰臟切片內的 T 細胞產生抑製作用。

S118 is on track for CTA later this year. I will now turn to our second autoimmune program that uses the same PD1 agonist but employs a different targeting domain and is intended for atopic dermatitis. Langerhans cells and an HLA-like molecule called CD1A that is expressed on Langerhans cells, both play key roles in triggering allergic inflammation in the skin.

S118 將於今年稍後開通 CTA 線路。現在我將介紹我們的第二個自體免疫項目，該項目使用相同的 PD1 激動劑，但採用不同的標靶域，旨在治療異位性皮膚炎。朗格漢斯細胞和在朗格漢斯細胞上表達的類似 HLA 的分子 CD1A 都在引發皮膚過敏性發炎方面發揮關鍵作用。

Langerhans cells are sentinels in the skin. They monitor and are the initial triggers to alert the immune system. Two important ways they alert the immune system are by presenting lipids via CD1A and by presenting peptides by a class 1 and class 2.

朗格漢斯細胞是皮膚中的哨兵。它們進行監測並作為警告免疫系統的初始觸發器。它們向免疫系統發出警報的兩種重要方式是透過 CD1A 呈現脂質以及透過 1 類和 2 類呈現勝肽。

Preventing long on cells from initiating pathogenic inflammation by blocking both lipid and peptide presentation may have therapeutic benefit in several important inflammatory diseases, including atopic dermatitis.

透過阻斷脂質和勝肽的呈現來防止長細胞引發致病性發炎可能對幾種重要的發炎疾病（包括異位性皮膚炎）具有治療益處。

Our candidate U-120 is designed to achieve this goal of dual blockade. The targeting domain recognizes and binds CD1A and thus tethers the two Langerhans cells. When it does find CD1A, it sterically blocks lipid presentation, and this prevents lipid sensing T cells from being activated.

我們的候選U-120就是為了實現雙重封鎖的目標而設計的。靶向域識別並結合 CD1A，從而束縛兩個朗格漢斯細胞。當它找到 CD1A 時，它會在空間上阻止脂質呈現，阻止脂質感應 T 細胞被活化。

By now coating the long [han] cell in thousands of PD1 agonist spikes, which is the effector arm. U 120 will turn off any T cell that approaches the long cells to be activated by peptides. In fact, in vitro, U120 is more efficacious than persolamab, a PD1 agonist that is not tethered and has lower potency for PD1 agonism.

現在，長 [han] 細胞上覆蓋著數千個 PD1 激動劑刺突，這就是效應臂。U 120 將關閉任何接近長細胞並被勝肽活化的 T 細胞。事實上，在體外，U120 比 persolamab 更有效，persolamab 是一種不受束縛的 PD1 激動劑，對 PD1 激動劑作用的效力較低。

The next 12 to 18 months is an exciting time for our R&D teams as we look forward to the conclusion of the Phase 3 heavy AM trial. Decisions on the next steps for praying, PLWH, HIV, and HPV. And beginning our journey into developing our platform for autoimmune disease.

接下來的 12 到 18 個月對於我們的研發團隊來說是一個令人興奮的時刻，我們期待第三階段重型 AM 試驗的結束。關於祈禱、愛滋病毒感染者、愛滋病毒和人類乳突病毒感染者的下一步決定。並開始開發自體免疫疾病平台的旅程。

I would like to welcome and now hand over to Travis.

我歡迎特拉維斯，現在把時間交給他。

Thank you, David. Good morning. Good afternoon, everyone. Earlier today we released our financial results for the 4th quarter, and the year ended 2024. 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。早安.大家下午好。今天早些時候，我們發布了第四季度和 2024 年度的財務表現。請參閱新聞稿和我們最新的 SEC 10-k 表格文件，以了解我們的完整財務表現。

Let me share some of our key financial highlights for 2024 and then touch upon our expectations for 2025. As Ralph mentioned, 2024 was a strong year for KIMMTRAK sales, with net sales growing to $84 million in Q4. A 5% increase versus Q3. Primarily driven by volume growth in the US and continued launches outside of the US.

讓我分享一下我們 2024 年的一些主要財務亮點，然後談談我們對 2025 年的期望。正如拉爾夫所提到的，2024 年是 KIMMTRAK 銷售強勁的一年，第四季淨銷售額成長至 8,400 萬美元。與第三季相比成長了 5%。主要受美國國內銷售成長和美國境外持續推出的推動。

For the first time, we exceeded full year sales of $300 million with total sales for the year of $310 million which represents growth of 30% over 2023. It is worth noting that the reimbursement environment in Europe remains challenging.

我們的全年銷售額首次超過 3 億美元，全年總銷售額達到 3.1 億美元，比 2023 年成長 30%。值得注意的是，歐洲的報銷環境仍充滿挑戰。

And we continue to make our best estimates for revenue recognition as we finalize price negotiations. As we continue to invest in our portfolio, SG&A and R&D expenses have increased versus 2023. R&D expenses increased primarily due to investments in our three Phase 3 trials. The Phase 1/2 chord expansions in ovarian and lung for Bermetous also contributed to the increase. Our SG&A expenses increased slightly, primarily due to an increase in general business functions needed to support our operations.

在完成價格談判時，我們將繼續對收入確認做出最佳估計。隨著我們繼續投資於我們的投資組合，銷售、一般及行政費用和研發費用較 2023 年增加。研發費用的增加主要是因為我們對三項 3 期試驗的投資。Bermetous 卵巢和肺部的 1/2 期弦擴張也導致了這種增加。我們的銷售、一般及行政費用 (SG&A) 略有增加，主要是由於支援我們營運所需的一般業務職能增加。

Moving to 2025, let me provide some comments on how to think about KIMMTRAK sales growth expectations and our SG&A and R&D expenses for this year. For KIMMTRAK, we expect revenue to grow incrementally in 2025, led primarily by growth in the US by further penetration into the community setting, and by growth to a lesser extent from launches in the EU and international markets.

展望 2025 年，讓我就如何看待 KIMMTRAK 今年的銷售成長預期以及銷售、一般及行政費用 (SG&A) 和研發費用提供一些評論。對於 KIMMTRAK，我們預計 2025 年營收將逐步成長，主要得益於美國進一步滲透到社區環境帶來的成長，以及較小程度上得益於在歐盟和國際市場的推出所帶來的成長。

We anticipate that R&D expenses will increase relative to 2024 as we further advance our clinical and pre-clinical pipeline candidates. And shifting to SG&A expenses, we expect those investments to be mostly consistent with Q4 2024 levels over the course of 2025, while anticipating typical quarterly variability.

我們預計，隨著我們進一步推進臨床和臨床前候選藥物的研發，研發費用將相對於 2024 年增加。至於銷售、一般及行政費用，我們預計這些投資在 2025 年期間將與 2024 年第四季的水平基本保持一致，同時預計會出現典型的季度波動。

Turning briefly to our cash position, I am pleased to report that we had $820 million in cash and marketable securities at the end of the year.

簡單談談我們的現金狀況，我很高興地報告，截至年底，我們擁有 8.2 億美元的現金和有價證券。

As a reminder, we repaid our $50 million loan with Pharmakon in November. We believe our robust financial position, coupled with prudent expense discipline and data-driven investments, enables us to advance our portfolio to deliver transformative medicines to patients across all three of our therapeutic areas.

提醒一下，我們在 11 月償還了 Pharmakon 的 5000 萬美元貸款。我們相信，我們穩健的財務狀況，加上審慎的支出紀律和數據驅動的投資，使我們能夠推進我們的產品組合，為我們所有三個治療領域的患者提供變革性藥物。

And I'll pass the call back to Bahija.

我會把電話轉回 Bahija。

Thank you, Travis. Thank you, David and Ralph. We entered 2025 with an eye towards delivering significant results in the next 12 to 18 months, starting with the HIV MAD data this quarter. This year, we expect incremental growth of KIMMTRAK will continue enrolling patients in our three Phase 3 melanoma trials, pursue additional opportunities in our PAM franchise, and continue to develop the next generation of transformative immunomodulating therapies.

謝謝你，崔維斯。謝謝你，大衛和拉爾夫。我們邁入 2025 年，著眼於在未來 12 到 18 個月內取得重大成果，從本季的 HIV MAD 數據開始。今年，我們預計 KIMMTRAK 的增量成長將繼續招募我們三項 3 期黑色素瘤試驗的患者，在我們的 PAM 特許經營中尋求更多機會，並繼續開發下一代變革性免疫調節療法。

Our strong financial position, a deep differentiated portfolio, our dedicated teams, and a clear line of sight for the future, we are confident in our ability to continue delivering significant value to both patients and shareholders.

我們擁有強大的財務狀況、深度差異化的產品組合、專業的團隊以及清晰的未來規劃，我們有信心能夠繼續為患者和股東創造巨大的價值。

Thank you, and will now open the floor for questions.

謝謝，現在開始提問。

(Operator Instructions)

（操作員指示）

Michael Yee, Jefferies.

麥可‧餘 (Michael Yee)，傑富瑞集團 (Jefferies)。

Hey, good morning. Thanks for the question. We had a question on the upcoming HIV results, which David made a bunch of comments on coming up, and we want to understand in the 16 patients what they all have 12 weeks or so off therapy off all the therapy, and so you would have a clear picture of whether there would be viral rebound over an extended period of time and what you would deem to be a good rate of patients not rebounding. And then a follow up question is a quick housekeeping question. Maybe the company could comment on the European sales, which appeared to be down sequentially Q4 to Q1. Was there some one-time adjustment on price or lumpy ordering patterns? What was going on there? Thank you.

嘿，早安。謝謝你的提問。我們對即將公佈的 HIV 結果有一個疑問，David 對此發表了許多評論，我們想了解這 16 名患者中，他們都是在 12 週左右的時間內停止了所有治療，這樣您就可以清楚地了解在較長時間內是否會出現病毒反彈，以及您認為不反彈的患者比例是多少。然後接下來的問題是一個快速的內部問題。該公司或許可以對歐洲的銷售額發表評論，歐洲的銷售額似乎從第四季到第一季連續下降。是否有一次性的價格調整或大量訂購模式？那裡發生了什麼事？謝謝。

Great, thank you, David. Do you want to take the.

太好了，謝謝你，大衛。你想拿嗎？

First one, Michael, thank you very much. Yes, all patients will have been off of therapy and entered the ATI, and all will have been available to see whether there is antiviral activity and of course whether there is a viral reservoir reduction during the treatment Phase. In terms of your question of what rate is good, I would just remind you that this is a Phase 1 dose escalation with five to six people per cohort.

首先，邁克爾，非常感謝你。是的，所有患者都將停止治療並進入 ATI，並且所有患者都將能夠觀察是否存在抗病毒活性，當然還有治療期間病毒庫是否減少。關於您問的什麼劑量比較合適，我只想提醒您，這是第一階段的劑量遞增，每組有五到六人。

So I wouldn't focus necessarily on rates at this point. I think we need to get to a top dose and then expand. But in terms of a TPP, Michael, I would point you to a recent publication a few years ago in terms of what they would like to see in terms of rates and in terms of what good looks like, and essentially it is copies they would like to see suppression of viral copies to less than 200 copies per ml for two years in about 20% to 30% of people. That's the minimum commercially successful TPP.

因此，目前我不一定會關注利率。我認為我們需要達到最高劑量，然後再擴大。但就 TPP 而言，邁克爾，我想向您指出幾年前的一份最新出版物，其中說明了他們希望看到的速率和良好外觀，本質上是複製品，他們希望看到在兩年內將大約 20% 到 30% 的人的病毒拷貝數抑製到每毫升 200 份以下。這是最低限度的商業成功TPP。

Ralph, you want to. So.

拉爾夫，你想。所以。

As Travis mentioned, Michael, Europe is having a challenging reimbursement environment and as we are negotiating prices with Germany and France. We actually have li in sight on those negotiations.

正如崔維斯所提到的，邁克爾，歐洲正面臨著充滿挑戰的報銷環境，我們正在與德國和法國協商價格。事實上，我們已經看到了這些談判的前景。

We had 14 successors worldwide, which speaks to sort of how well we're doing. And you know we have some incremental growth as we've been guided basically in Europe, which is what is reflected in our numbers.

我們在全球有 14 位繼任者，這足以說明我們的表現有多好。你知道，我們在歐洲基本上實現了增量成長，這也反映在我們的數據上。

Jessica Fye, JP Morgan.

傑西卡費伊 (Jessica Fye)，摩根大通 (JP Morgan)。

Hey guys, good morning, thanks for taking my question. So maybe following up on Mike's question, for HIV, can you elaborate on what factors are going to help you determine a go forward dose, and how you would think about next steps once dose escalation is complete? Would you move directly to a registrational trial? What could something like that look like? Thank you.

大家好，早安，感謝您回答我的問題。因此，也許可以繼續回答 Mike 的問題，對於 HIV，您能否詳細說明哪些因素將幫助您確定下一步的劑量，以及劑量增加完成後您將如何考慮下一步？您會直接進入註冊試驗嗎？那樣的東西會是什麼樣子的呢？謝謝。

Yeah, Jess, thank you for the question. So in terms of the factors we would use to select the go-for, there's, of course, safety. This is a relatively healthy population, so it needs to be a well-tolerated regimen. And then we need to be, we need to see that we have evidence of antiviral activity that, gives us reason to believe that we can achieve a functional cure. Right now we've selected 12 weeks of dosing. We're focused on the dose. There might need to be to optimize frequency. There might need to be duration. We'll also look, of course, at biological activity, so we'll use all of those and there might, by the way, be two doses that we take forward into an expansion.

是的，傑西，謝謝你的提問。因此，就我們用來選擇目標的因素而言，當然有安全性。這是一個相對健康的人群，因此需要一種耐受性良好的治療方案。然後我們需要，我們需要看到我們有抗病毒活性的證據，讓我們有理由相信我們可以實現功能性治癒。目前我們選擇了 12 週的給藥時間。我們關注的是劑量。可能需要優化頻率。可能需要持續一段時間。當然，我們也會關註生物活性，因此我們會利用所有這些，順便說一下，我們可能會將兩劑藥物帶入擴展階段。

In terms of the next steps after an expansion, once we've confirmed the signal, typically there's a randomized Phase 2 with the placebo, and that would then lead to a Phase 3 trial. Now interestingly, the meta-analysis that was just published, and I refer everyone to that last month, they're trying to argue that you don't need to do a placebo controlled randomized Phase 2 anymore because the historical rate of control is actually quite low, so that. That meta-analysis argued for doing single arm trials, but that's something we'll consider as we approach them.

就擴展後的下一步而言，一旦我們確認了訊號，通常會進行安慰劑的隨機第 2 階段試驗，然後進行第 3 階段試驗。有趣的是，剛發表的薈萃分析，我上個月向大家推薦過，他們試圖爭辯說，你不再需要進行安慰劑對照的隨機第 2 階段試驗，因為歷史控制率實際上相當低，所以。這個薈萃分析主張進行單臂試驗，但這是我們在進行研究時會考慮的事情。

Yeah, and we definitely will talk to the regulatory authorities before we do anything.

是的，我們在採取任何行動之前肯定會與監管機構溝通。

Tyler Van Buren, TD Cowen.

泰勒範布倫 (Tyler Van Buren)，TD Cowen。

Hey guys, good morning. Thanks very much. I'll ask another one on HIV just for additional clarity. It's been very helpful what you've said already, but just the 12 week time point of patients being controlled following ART interruption. Is that enough to have confidence that they would maintain control over the longer term, or do you need to follow them longer, and at which point would you have confidence based upon [KOL] feedback and I guess related to that, have strategics told you what profile they would like to see demonstrated in the clinic or what level of follow up is required as well?

大家好，早安。非常感謝。我將向另一個有關 HIV 的人詢問，以獲得更清晰的答案。您所說的非常有幫助，但這只是 ART 中斷後患者得到控制的 12 週時間點。這是否足以讓您有信心他們會在長期內保持控制，或者您是否需要跟踪他們更長時間，在什麼時候您會根據 [KOL] 反饋有信心，我想與此相關，戰略人員是否告訴過您他們希望在診所看到什麼樣的概況，或者還需要什麼程度的跟進？

Tyler, the 12 weeks is 12 weeks of interruption is historically being used in these initial Phase 1 trials to get a sense of whether you have any activity because based on the meta-analysis that I mentioned, the percentage of people who will have viral control of 12 weeks is. About 1%, so it's extremely low when you're conducting these trials, you don't want to keep the people off of therapy for too long, especially in the initial Phases.

泰勒，12 週是 12 週的中斷期，這些初始第 1 階段試驗歷來用於了解您是否有任何活動，因為根據我提到的薈萃分析，12 週內病毒控制率的人的百分比是。大約 1%，所以當你進行這些試驗時，這個比例非常低，你不想讓人們長時間不接受治療，特別是在最初階段。

So you first want to look for 12 weeks to see if you have evidence of antiviral control. You then move to expand those 12 weeks. In terms of what is commercially acceptable our target product profile, and I would add that no one, no therapy or company or anyone has been able to demonstrate viral control reliably. So this is a new area that, there is no precedence to it on. I would really refer you to that that white paper that published what a commercially successful TPP, what the minimum case is and what the base case is.

因此，您首先要觀察 12 週，看看是否有抗病毒控制的證據。然後你就可以擴展這 12 週了。就我們的目標產品概況在商業上可接受的程度而言，我想補充一點，沒有任何人、任何療法、任何公司或任何人能夠可靠地證明病毒控制。所以這是一個新領域，沒有先例。我真的想向你推薦那份白皮書，其中公佈了什麼是商業上成功的TPP、什麼是最低情況以及什麼是基本情況。

Eric Schmidt, Cantor Fitzgerald.

艾瑞克·施密特、康托·費茲傑拉。

Thanks for taking my question. Maybe I'll mix it up a little bit and ask a question on Brene and the Prism me study, the dose selection that's going to happen I guess later this year.

感謝您回答我的問題。也許我會稍微混合並詢問有關 Brene 和 Prism me 研究的問題，我猜劑量選擇將在今年晚些時候進行。

On those first 90 patients, what kind of follow up will you have in terms of duration, and I assume you're going to make a decision on early disease control. Is that feasible given the follow up? I'm also kind of curious as to whether we'll see updated Phase 1 data already in in second line melanoma this year. Thank you.

對於最初的 90 名患者，您將進行什麼樣的持續跟踪，我認為您將對早期疾病控製做出決定。從後續情況來看是否可行？我也有點好奇我們是否會看到今年二線黑色素瘤治療中更新的第一階段數據。謝謝。

Yeah, I'm happy to take that. So the way the 90 patient do selection. Analysis is set up is that those patients will be followed up for between 8 and 12 weeks. So really it's looking at a high level for both safety as well as initial response rate, and it's really set up to look for big differences because we know that both doses are active.

是的，我很樂意接受。所以 90 名患者都是這樣選擇。分析表明，這些患者將接受 8 至 12 週的追蹤。因此，它實際上是在高水平上關注安全性和初始反應率，並且它確實是為了尋找巨大的差異，因為我們知道兩種劑量都是有效的。

Justin Zelin, BTIG.

BTIG 的 Justin Zelin。

Good morning and thanks for taking our question and congrats on all the progress. So it's great to see the progress in the pipeline outside of oncology. I want to ask how you expect the safety and tolerability profile of both impacts outside of the ecology settings, such as the infectious disease or autoimmune disease settings to shake out, and what would be the minimum commercially successful TPP that would be in these settings in regards to adverse events such as CRS. Thank you.

早安，感謝您回答我們的問題，並祝賀您的所有進展。因此，看到腫瘤學以外的領域取得進展真是令人欣慰。我想問一下，您認為在生態環境之外，例如傳染病或自體免疫疾病環境中，這兩種影響的安全性和耐受性概況會如何發展，以及在這些環境中，就 CRS 等不良事件而言，最低限度的商業上成功的 TPP 是什麼。謝謝。

I'm happy to take that's a very good question. In terms of infectious disease, what we would expect to see, of course, is cytokine relief syndrome because that's the mechanism. T cell activation leads to cytokine. But in contrast to oncology, we can't really have moderate or severe CRS. So we really need to only have mild CRS, and we think that's really achievable.

我很高興回答這個問題，這是一個非常好的問題。就傳染病而言，我們當然期望看到細胞因子緩解綜合徵，因為這就是機制。T 細胞活化導致細胞激素的產生。但與腫瘤學不同的是，我們實際上不可能出現中度或重度的 CRS。因此，我們確實只需要輕度 CRS，我們認為這確實是可以實現的。

We don't expect to have any on target of viral activity because these are viral peptides that don't that aren't in the body. So in contrast to GP 100, we see rash. We don't expect to see any other toxicity aside from mild cytokine relief syndrome, and I think that's what would be needed in HIV and HPV, where the people are generally healthy. In terms of autoimmune, actually we don't expect to have any right now. We don't expect to have cytokine relief syndrome because we're turning off the immune system. We're not turning it on.

我們預計不會有任何針對病毒活動的目標，因為這些是病毒勝肽，它們不在體內。因此與 GP 100 相比，我們看到的是皮疹。除了輕微的細胞激素緩解症候群外，我們預計不會看到任何其他毒性，我認為這就是 HIV 和 HPV 所需要的，因為人們通常是健康的。就自體免疫而言，實際上我們現在並不認為會出現任何問題。由於我們正在關閉免疫系統，因此我們不希望出現細胞激素緩解症候群。我們沒有打開它。

And the other nice feature of our platform is it's intended to be tissue specific. So any immune suppression we see will be localized in the target tissue. We shouldn't expect to see broad systemic immune suppression. In fact, that's one of the differentiating features. So we're looking. But in the autoimmune we're looking in autoimmune and in ID we're looking for very infrequent dosing that is that is very well tolerated.

我們的平台的另一個優點是它針對特定組織。因此，我們看到的任何免疫抑制都將局限於目標組織。我們不應該期望看到廣泛的系統性免疫抑制。事實上，這是差異化特徵之一。所以我們正在尋找。但在自體免疫中，我們正在尋找自體免疫，而在 ID 中，我們正在尋找非常低頻率的給藥，即耐受性非常好的給藥。

Yeah, I just want to add to that, I think you see in HIV we did actually share that we are escalating beyond 300 mcg just to give you an idea. So I think the safety profile is very good.

是的，我只是想補充一點，我想你會看到，在 HIV 方面，我們確實分享了我們正在升級到 300 微克以上，只是為了給你一個概念。所以我認為安全性非常好。

Graig Suvannavejh, Mizuho Securities.

Graig Suvannavejh，瑞穗證券。

Hi, this is Sam on for Greg. Thank you for taking our questions. Maybe going back to Brene, can you provide an update on the current efforts to generate data in ovarian and lung cancers? What were the changes that have been made in patient recruitment and those indications and when might you be able to share the next data? Thank you.

大家好，我是 Sam，代表 Greg。感謝您回答我們的問題。也許回到 Brene，您能否提供有關當前在卵巢癌和肺癌中生成數據的最新努力？在病患招募和適應症方面做了哪些改變？何時可以分享下一個數據？謝謝。

I'm happy to take that, Sam. So with ovarian, we're building up the initial signals. It was clear that Brene had monotherapy activity and [lateline] platinum resistance, but we needed to see a path forward, and that path forward is in earlier lines and in combinations. We saw an interesting signal for chemo combinations in the platinum resistance, so we need to expand platinum resistant chemo combo, and then we need to study platinum sensitive bevacizumab, and those are ongoing now. In the lung setting, we're more in the signal detection Phase here. And so here we're looking at combinations with acimertinib and docetaxel, which are generally earlier lines than the late lane PR.

我很高興接受這個，山姆。因此，透過卵巢，我們正在建立初始訊號。很明顯，Brene 具有單一療法活性和 [晚期] 鉑類抗藥性，但我們需要找到一條前進的道路，而這條前進的道路是在早期治療和聯合治療中。我們在鉑類抗藥性中看到了化療組合的一個有趣訊號，因此我們需要擴展鉑類抗藥性化療組合，然後我們需要研究鉑類敏感貝伐單抗，這些現在正在進行中。在肺部環境中，我們更處於訊號檢測階段。因此，我們在這裡研究阿西替尼和多西他賽的組合，這些組合通常比晚期 PR 更早。

And so we hope to see signals there in terms of when we're going to share the data. We're going to share the data when there's a complete understanding of what's going on and we have a story that we can put together. So I don't want to nail it down presumably in the next 12 to 18 months.

因此，我們希望看到有關何時共享資料的訊號。當我們完全了解正在發生的事情並且有一個可以整理的故事時，我們將會分享數據。所以我不想在未來 12 到 18 個月內就確定。

Jonathan Chang, Leerink Partners.

Jonathan Chang，Leerink Partners。

Hi guys. Thanks for taking the question. How are you guys thinking about business development opportunities for 2025? Thank you.

嗨，大家好。感謝您回答這個問題。你們如何看待 2025 年的商業發展機會？謝謝。

Great, thank you. Travis?

太好了，謝謝。崔維斯？

And thanks for the question. First of all, we're obviously very excited about the opportunities we have in the pipeline currently. At the same time, we do continuously look for opportunities to enhance the value of the portfolio. Those opportunities need to be a good strategic fit that leverage our expertise and our our capabilities, but we're in a strong position with what we have today and having that optionality to pursue partnerships at the same time is a great benefit.

感謝您的提問。首先，我們顯然對目前正在籌備的機會感到非常興奮。同時，我們確實不斷尋找機會來提升投資組合的價值。這些機會需要有良好的策略契合度，才能充分利用我們的專業知識和能力，但憑藉目前所擁有的資源，我們處於有利地位，同時擁有尋求合作的選擇權，這也是一大優勢。

Michael Schmidt, Guggenheim Partners.

古根漢合夥公司的麥可‧施密特。

Hi, thanks for taking our question. This is Paul on for Michael. For KIMMTRAK, just on the commercial performance, I believe you've been at or around 65% US penetration for the past couple quarters. How much additional headroom do you see there in terms of share of that market with your push into the community setting? Where do you see that share in the US market plateauing? And then on treatment duration, you mentioned trending over 12 months. What's your best estimate of where that could land on the term? Thank you.

您好，感謝您回答我們的問題。這是保羅代替麥可。對於 KIMMTRAK，僅從商業表現來看，我相信過去幾季你們在美國的滲透率已經達到或接近 65%。隨著你們進軍社區環境，你們認為市佔率還能增加多少？您認為美國市場的市佔率在哪裡會趨於穩定？然後關於治療持續時間，您提到了 12 個月內的趨勢。您對於該術語的最佳估計是什麼？謝謝。

Ralph, I think it's 65%, but go ahead.

拉爾夫，我認為是 65%，但請繼續。

Well, thank you for the question and as you said, we are at 65% penetrated, which is, good news because we've been growing significantly, 34% growth, last year in the US. And look, we, we're continuing our work into the community where the good news is that, half of our prescriptions are coming of our new start prescriptions are coming from the community.

嗯，謝謝您的提問，正如您所說，我們的滲透率是 65%，這是個好消息，因為去年我們在美國實現了顯著增長，增長率為 34%。瞧，我們正在繼續在社區開展工作，好消息是，我們一半的新處方都來自社區。

In fact, two-third of our prescriptions are coming from the community, so we just have to continue that work. There is still a lot of patients out there and so unmet needs, so we're going to continue that work.

事實上，我們的三分之二的處方來自社區，所以我們必須繼續這項工作。仍有許多患者和未滿足的需求，因此我們將繼續這項工作。

In terms of the duration of therapy, this is the duration of therapy is performing better than we've seen in clinical trials, so it's difficult for me to predict where this is going to land, and we'll see it hopefully grow together.

就治療持續時間而言，這種治療持續時間比我們在臨床試驗中看到的要好，所以我很難預測它最終會達到什麼程度，我們希望看到它一起成長。

Yeah, which is really unusual actually. It speaks highly of the treatment. The impacts of contract.

是的，這確實很不尋常。它高度評價了這種治療方法。合約的影響。

Jack Allen, Baird.

傑克艾倫，貝爾德。

Hey, this is Nick. Thanks for taking my question. Surrounding the pivotal first [lineriSL] study of [radiate] and melanoma, it appears you're now specifying timeline for the selection decision. Second half of 2025. It seems like 8 to 10 weeks minimum follow up is expected to be reviewed by the IDMC. What metrics do you expect the IDMC will use to make a selection decision, whether that's OR CCDNA or PFS, and to what extent? Will the interim data be communicated to the company and finally, can you comment as to whether there will be a there's a futility analysis included as part of the selection decision and thanks.

嘿，我是尼克。感謝您回答我的問題。圍繞著 [radiate] 和黑色素瘤的關鍵首個 [lineriSL] 研究，您現在似乎正在指定選擇決策的時間表。2025年下半年。看起來 IDMC 預計至少需要 8 到 10 週的後續審查。您預期 IDMC 將使用什麼指標來做出選擇決定，無論是 OR CCDNA 還是 PFS，以及在多大程度上？中期數據是否會傳達給公司？最後，您能否評論一下在選擇決策中是否會包含無效性分析？謝謝。

So I can start, so we are not intending to release the data just for the integrity of the trial that's going to be the IDMC looking at them, they're the only ones looking at the trial, but David, you want to comment?

所以我可以開始了，我們不打算只是為了試驗的完整性而發布數據，IDMC 會查看它們，他們是唯一查看試驗的人，但是大衛，你想評論一下嗎？

Thank you. There will not be a futility analysis. The analysis is strictly to choose a dose, and that will be done by the IDMC in terms of what will be used.

謝謝。不會進行無效性分析。分析嚴格來說是為了選擇劑量，這將由 IDMC 決定使用什麼。

The IDMC will use both efficacy and safety. I will just remind you that in the Phase 1 trial, we both doses were active and well tolerated 40 and 160, and we didn't really see a dose response. So they're going to be looking for large differences. And if they don't see large differences, then we're going to be, they'll be using modeling. We'll be providing support by modeling to help select the dose.

IDMC 將同時使用功效和安全性。我只是想提醒您，在第 1 階段試驗中，兩種劑量均有效且耐受性良好，40 和 160，我們並沒有真正看到劑量反應。所以他們會尋找巨大的差異。如果他們沒有發現很大的差異，那麼我們就會使用建模。我們將透過建模提供支援以幫助選擇劑量。

Gil Blum, Needham and Company.

吉爾布魯姆，尼德漢姆公司。

Yeah, hi, thanks for taking my question. This is Ethan on for Gil. So you mentioned some reimbursement challenges in Europe for KIMMTRAK, which isn't very surprising, but I know it's early on, but do you anticipate similar challenges for [Buranaifest] in Europe, or are these challenges more product indication specific to KIMMTRAK? Thank you.

是的，你好，謝謝你回答我的問題。這是 Ethan 代替 Gil 上場的。所以您提到了 KIMMTRAK 在歐洲面臨的一些報銷挑戰，這並不奇怪，但我知道現在還為時過早，但您是否預計 [Buranaifest] 在歐洲也會面臨類似的挑戰，或者這些挑戰是否更多是 KIMMTRAK 特有的產品指示？謝謝。

Yeah, I think I'll start in the rough please comment, I think we are actually I'll look at the cup hassle, we had so far, good negotiations and 14 approvals for the drug, but as Europe in general is country by country, and that's what you have to do and it's more challenging right now, but I want to point out to the fact that we actually overturned the nice decision and we get now we're launching in the UK. That's one of the toughest markets, but Ralph, you want to comment?

是的，我想我會從粗略的角度開始，請評論一下，我認為我們實際上會研究杯子的麻煩，到目前為止，我們已經進行了良好的談判，並獲得了 14 項藥物批准，但由於歐洲總體上是逐個國家進行的，這就是你必須做的事情，而且現在更具挑戰性，但我想指出的事實是，我們實際上推翻了這個好的這款產品，現在我們正在推出英國。這是最艱難的市場之一，但是拉爾夫，你想評論一下嗎？

So, as just said, yes, we've had a lot of successes with KIMMTRAK, and that speaks to the valid proposition of KIMMTRAK. Look, I think the market is challenging or the reimbursement landscape is challenging for all companies, and you've seen this communicated by everybody. So, all we can do is expect good data and keep working to create access for patients across Europe and, hopefully we'll have the same successes of the data with the like.

所以，正如剛才所說，是的，我們在 KIMMTRAK 方面取得了許多成功，這證明了 KIMMTRAK 的合理主張。你看，我認為市場充滿挑戰，或者說報銷情勢對所有公司來說都充滿挑戰，而且你已經看到每個人都傳達了這一點。因此，我們所能做的就是期待良好的數據並繼續努力為整個歐洲的患者創造機會，並希望我們能夠獲得相同數據的成功。

For Brene, we expect the same thing, I think if we if we are lucky and have an OS end point that facilitate things in Europe. That's exactly what happened with KIMMTRAK.

對於 Brene 來說，我們期待同樣的事情，我想如果我們夠幸運並且擁有一個可以促進歐洲發展的作業系統端點。KIMMTRAK 的情況正是如此。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

Great. Thank you so much. I apologize, I joined the call late, but I'd just love to know around the HIV data that's coming up, how we should be thinking about the buzz for success, whether it's around reservoir reduction or the delay in viral rebound, and if anything you can say around that kind of doses we should expect to see and a number of patients in each dose. Thank you.

偉大的。太感謝了。抱歉，我加入電話會議晚了，但我很想了解即將公佈的愛滋病毒數據，我們應該如何看待成功的因素，是減少病毒庫還是延遲病毒反彈，以及您是否可以透露一下我們預期會看到的劑量以及每次劑量的患者數量。謝謝。

Peter, we expect we will show three doses, five to six people per dose. We are, by the way, continuing to dose escalate now that that data is just not ready for the data cut for the presentation. In terms of what success would look like, this is a setting both viral reservoir reduction during the treatment Phase and then demonstrating viral control after interruption. It's never been reliably shown.

彼得，我們預計將展示三劑，每劑五到六人。順便說一句，我們現在正在繼續增加劑量，因為這些數據還沒有準備好用於演示的數據剪切。就成功而言，這是一種在治療階段減少病毒庫，然後在中斷後展示病毒控制的設定。它從未被可靠地證明過。

For any therapy. So for us, what we're looking for in a Phase 1 dose is do we have signals of activity? Can we reliably reduce the reservoir and can we alter the kinetics? To me, that would be a huge success for the field actually, because no one's been able to show this. Once we complete. Dose escalation, we then move to expansion and there we want to get a better sense of percentage of patients who would have antiviral control and is there enough strength to move forward to randomized Phase 2 trial. So that information will come later this year.

對於任何療法。因此對我們來說，我們在第一階段劑量中尋找的是是否有活動訊號？我們能否可靠地減少儲層並改變動力學？對我來說，這實際上是該領域的巨大成功，因為沒有人能夠證明這一點。一旦我們完成。劑量增加後，我們進入擴展階段，我們希望更了解能夠獲得抗病毒控制的患者百分比，並了解是否有足夠的實力進入隨機第 2 階段試驗。因此該資訊將於今年稍後公佈。

Patrick Trucchio, H.C. Wainwright & Co.

特魯基奧（Patrick Trucchio），H.C. Wainwright & Co.

Thanks. Good morning. My question is also on the HIV program. I was just curious if, based on the data that's generated in this mad portion of the strive trial, if you might see a potential for a combination strategy for M1 and 3V. Such as pairing it with LRAs and separately just based on the outcome of this mad portion, is there a possibility that M113B could qualify for a priority review or other regulatory incentives for potential accelerated development path.

謝謝。早安.我的問題也是關於愛滋病項目。我只是好奇，根據努力試驗的這個瘋狂部分產生的數據，您是否可以看到 M1 和 3V 的組合策略的潛力。例如，將其與 LRA 配對，並單獨基於這部分瘋狂的結果，M113B 是否有可能獲得優先審查或其他監管激勵，以獲得潛在的加速發展路徑。

Yeah, Patrick, thank you for that question, and it's a good one because it reminds me to that pretty much our entire platform oncology, ID, and potentially autoimmune is combinable. In fact, the Phase one trial that we'll share data within the next few weeks is on the background of ART and certainly this could be combined with LRAs. It could be combined with anything essentially, but the goal for here is not to have chronic long-term treatment.

是的，派崔克，謝謝你提出這個問題，這是一個很好的問題，因為它提醒我，幾乎我們的整個平台腫瘤學、ID 和潛在的自身免疫都是可以結合的。事實上，我們將在未來幾週內分享數據的第一階段試驗是在 ART 的背景下進行的，當然這可以與 LRA 結合。它本質上可以與任何東西結合，但這裡的目標不是進行慢性長期治療。

It's for to have a finite dosing regimen so that we can stop treatment and the patients can be off all therapies for two to three years. I think that would be kind of our eventual in terms of. Health authority interactions and priority reviews. I think that is certainly something we would consider once we need to, but we need to generate the data and so that would come with, it's still too early I think to comment on that.

這是為了製定一個有限的給藥方案，以便我們可以停止治療，並且患者可以在兩到三年內停止所有治療。我認為這將是我們的最終目標。衛生當局互動和優先審查。我認為，一旦我們需要，我們肯定會考慮這一點，但我們需要產生數據，因此，我認為現在對此發表評論還為時過早。

Rajan Sharma, Goldman Sachs.

高盛的拉詹·夏爾馬。

Hi, thanks for taking the question. Just a couple left from my side. Atopic dermatitis, I know that it's a way out until we see the initial data, but just at this point in kind of thinking about your planning for the asset, how are you thinking about potential benchmarks longer term? And then secondly, just on HPV, countries where we obviously have the HIV update coming relatively imminently, is there anything from the HIV data set? That you'd be looking to maybe increase confidence in the platform more broadly, and if there's any crossroads to HPV there. Thank you.

你好，謝謝你回答這個問題。我這邊就剩下幾個了。異位性皮膚炎，我知道在我們看到初步數據之前這是一種解決方法，但就在此刻，在考慮資產規劃時，您如何考慮長期的潛在基準？其次，僅就 HPV 而言，在那些 HIV 更新顯然相對較快的國家，有沒有什麼來自 HIV 資料集的資訊？您可能希望更廣泛地增強對該平台的信心，以及是否存在 HPV 十字路口。謝謝。

Yeah, in terms of the atopic dermatitis, I think right now we have a lot of excitement about the mechanism in atopic dermatitis because of the role that CD1A and Langerhan cells play in skin inflammation. Our initial entry point will be in patients who have who are refractory to all therapy because we're going to be looking for a signal, and I think after that, at that point we'll probably be in a better sense to understand what a commercially acceptable TPP is.

是的，就異位性皮膚炎而言，我認為現在我們對異位性皮膚炎的機制非常感興趣，因為 CD1A 和朗格漢斯細胞在皮膚發炎中發揮作用。我們的初始切入點是針對那些對所有療法均有抵抗力的患者，因為我們將尋找信號，我認為在此之後，我們可能會更好地理解什麼是商業上可接受的 TPP。

In terms of the HIV data, which is next month, and then the HPV, I think you asked about that sad data. I actually looked at them as a package and I think they do, they are both important because they are the first time PCR therapy has been used in HIV and first time off the shelf, he's got therapy and HPV and so I think although the HPV is SAD data, the question there is we're going to be asking, can we see anything right after a single dose. I think it's a hard hurdle, but can we see anything? So I think those two data pieces this year will be important to understand whether our [ITAF] can work in chronic viral diseases. Yeah.

至於下個月的 HIV 數據，以及 HPV 數據，我想您問的是那些令人悲傷的數據。我實際上將它們視為一個整體，我認為它們確實如此，它們都很重要，因為這是 PCR 療法首次用於治療 HIV，也是首次現成的，他同時進行了治療和 HPV 檢測，因此我認為，儘管 HPV 是 SAD 數據，但問題是我們要問，單劑量後我們能立即看到任何效果嗎？我認為這是一個很難克服的障礙，但我們能看到什麼嗎？因此，我認為今年的這兩項數據對於了解我們的 [ITAF] 是否能夠治療慢性病毒性疾病非常重要。是的。

Just to add, I think on CD1 there are multiple indications, and I think that's the attractiveness about the about the mechanism. And both HIV, HPV gives us higher confidence to -- for the platform to work in infectious disease and lot of learning there.

補充一下，我認為 CD1 有多個指示，我認為這就是該機制的吸引力。HIV 和 HPV 都讓我們對該平台在傳染病領域的工作和學習更有信心。

David Dai, UBS.

瑞銀集團戴維戴（David Dai）。

Great. Hey, thanks for taking my questions. Just one from me. So regarding HIV program, just want to dig into the mechanism of action. Could you need to highlight some of the preclinical data that gives you confidence of potential viral control, for the Phase 1 trial. Thanks.

偉大的。嘿，謝謝你回答我的問題。我只有一個。因此，關於愛滋病毒計劃，我只想深入研究其作用機制。您是否需要強調一些臨床前數據，這些數據可以讓您對第一階段試驗的潛在病毒控制充滿信心。謝謝。

David, sure. So we've actually published several papers on the pre-clinical data. It's actually quite fascinating. So we've shown that this molecule can redirect T cells to kill HIV infected CD4 T cells. So we've shown that in vitro. We've actually shown imaging. A microscopy showing that the impass can bridge a T cell to an infected CD4 T cell, so a CD8 killer cell to an infected CD4 T cell, and we've shown that this can work even when you don't stimulate when you don't when you don't kit with the HSA inhibitor, you don't have to activate the T cell to induce transcription of the HIV expression. So we do have some interesting pre-clinical data we're happy to share those publications, but there is a body of evidence we've already published.

大衛，當然。因此，我們實際上已經發表了幾篇關於臨床前數據的論文。這確實非常有趣。因此，我們已經證明這種分子可以重新定向 T 細胞來殺死受 HIV 感染的 CD4 T 細胞。我們已經在體外證明了這一點。我們實際上已經展示了成像。顯微鏡顯示，這種抑制劑可以將 T 細胞與受感染的 CD4 T 細胞連接起來，從而將 CD8 殺傷細胞與受感染的 CD4 T 細胞連接起來，我們已經證明，即使在不使用 HSA 抑制劑進行刺激的情況下，這種方法也可以發揮作用，您不必激活 T 細胞來誘導 HIV 表達的轉錄。因此，我們確實有一些有趣的臨床前數據，我們很樂意分享這些出版物，但我們已經發表了大量證據。

Yeah, and I think the one reason, for this platform. And for the HIV, we know that the reservoir has very low expression, if you will, of the target, and we know that our technology can go can kill cells down to 5 to 10 targets or copies per cell. So that's another reason to believe.

是的，我認為這是這個平台的一個原因。對於 HIV，我們知道病毒庫中的目標表現量非常低，我們知道我們的技術可以殺死每個細胞中低至 5 到 10 個目標或拷貝的細胞。所以這是另一個值得相信的理由。

Jeff Jones, Oppenheimer & Co.

傑夫瓊斯，奧本海默公司

Hi guys, and thanks for taking the question. Just one from us in terms of the autoimmune program, and AD being your first universal program, how are you thinking about applicability of that to the oncology programs? Thanks.

大家好，感謝你們回答這個問題。關於自體免疫計劃，我們只提一個，AD 是您的第一個通用計劃，您如何看待它對腫瘤學計劃的適用性？謝謝。

Yeah, I would say that it's, what they have in common is the tissue targeting part that that we can show exquisite tissue targeting with our cancer program and we believe we'll get exquisite tissue targeting with our autoimmune program where they differ, of course, is in the effector side in oncology, we're activating T cells in the autoimmune, we're turning T cells off and so they differ in that regard, but they both have. In common, the TCR targeting and in fact our pre-clinical toxicology risking program that we're going to use for autoimmune does incorporate many of the aspects we use for oncology.

是的，我想說的是，它們的共同點在於組織靶向部分，我們可以透過我們的癌症計劃展示精確的組織靶向，並且我們相信我們將通過我們的自身免疫計劃獲得精確的組織靶向，當然，它們的不同之處在於腫瘤學的效應方面，我們在自身免疫中激活 T 細胞，我們關閉 T 細胞，所以它們在這方面有所不同，但它們都有。共同的是，TCR 標靶以及我們用於自體免疫的臨床前毒理學風險計劃確實包含了我們用於腫瘤學的許多方面。

Yeah, the way I think about it is the yin and yang, if you will, of the oncology and autoimmune, and that's another reason why we are in both areas, therapeutic areas.

是的，我的看法是，腫瘤學和自體免疫學是陰陽，如果你願意的話，這也是我們涉足這兩個治療領域的另一個原因。

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

謝謝。目前沒有其他問題。現在我想請 Bahija Jallal 做最後發言。

Yeah, thank you, operator. I just want to thank you again for dialling in for excellent questions and for your support and, have a great day.

是的，謝謝您，接線生。我只想再次感謝您撥打電話提出出色的問題並給予支持，祝您有美好的一天。

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

謝謝。今天的電話會議到此結束。感謝您的參與。現在您可以斷開線路。享受剩餘的一天。