Immunocore Holdings PLC (IMCR) 2024 Q2 法說會逐字稿

Welcome to the Immunocore conference call and webcast. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to turn the call over to Clayton Robertson, Head of Investor Relations. Thank you. You may begin.

歡迎參加Immunocore 電話會議和網路廣播。（操作員指示）謹此提醒，本次會議正在錄製中。我現在想將電話轉給投資者關係主管克萊頓羅伯森 (Clayton Robertson)。謝謝。你可以開始了。

Good morning and good afternoon. Thank you for joining us on our Q2 and first-half 2024 for earnings call today. During today's call, we will make some forward-looking statements, which are qualified by the Safe Harbor 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.

早安，下午好。感謝您今天參加我們的 2024 年第二季和上半年財報電話會議。在今天的電話會議中，我們將做出一些前瞻性陳述，這些陳述符合 1995 年《私人證券訴訟改革法案》中安全港條款的規定。請注意，實際結果可能與這些前瞻性陳述所顯示的結果有重大差異，包括我們向 SEC 提交的文件中討論的結果。

On today's call, I'm joined by Bahija Jallal, CEO of Immunocore; and Brian Di Donato, CFO and Head of Strategy, who will share a strategy update. Ralph Torbay, Head of Commercial, will review our first half KIMMTRAK sales and additional growth opportunities for KIMMTRAK.

參加今天的電話會議的是，Immunocore 執行長 Bahija Jallal；財務長兼策略主管 Brian Di Donato 將分享策略更新。商務主管 Ralph Torbay 將回顧我們上半年 KIMMTRAK 的銷售情況以及 KIMMTRAK 的其他成長機會。

David Berman, Immunocore's Head of R&D will provide some pipeline updates, including near-term readouts in oncology and infectious diseases. Brian will also provide highlights on our financial results reported this morning. Bahija?

Immunocore 研發主管 David Berman 將提供一些產品線更新，包括腫瘤學和傳染病的近期數據。布萊恩也將重點介紹我們今天早上報告的財務表現。巴希賈？

Thank you Clay. As you may be able to hear, I'm losing my voice. And I have pharyngitis. So to be able to answer your questions at the end, I will ask Brian to pinch hit for me. Brian, please.

謝謝克萊。正如你可能聽到的，我失去了聲音。而且我還有咽喉炎。因此，為了最後能夠回答您的問題，我將請布萊恩為我捏擊。布萊恩，請。

Thank you, Bahija. We hope you feel better. We are pleased to share with you an update on Immunocore through the first half of 2024. We have achieved excellent commercial results while advancing our T-cell engager platform in three therapeutic areas. We appreciate your continued support in advancing our mission of delivering innovative and life-changing medicines to patients.

謝謝你，巴希賈。我們希望您感覺好一點。我們很高興與您分享 2024 年上半年的Immunocore 最新動態。我們在三個治療領域推進 T 細胞接合平台的同時，也取得了出色的商業成果。我們感謝您繼續支持我們推進我們為患者提供創新和改變生活的藥物的使命。

Earlier this year, we outlined our three strategic pillars and our areas of focus for the next 18 to 24 months. Today, we will provide updates on the first two of these pillars. First, we continue to maximize KIMMTRAK performance, complete to report continued sequential revenue growth for the quarter and significant year-over-year growth for the first half of 2024.

今年早些時候，我們概述了未來 18 至 24 個月的三大策略支柱和重點領域。今天，我們將提供前兩個支柱的最新資訊。首先，我們繼續最大限度地提高 KIMMTRAK 業績，並報告本季營收持續成長以及 2024 年上半年年比大幅成長。

This growth was driven by strong US performance. We expanded our customer base and increased market penetration and reported longer duration of therapy. We also continue to increase our global footprint with additional country launches, allowing us to bring KIMMTRAK to more patients around the world.

這一成長是由美國強勁的表現所推動的。我們擴大了客戶群，提高了市場滲透率，並報告了更長的治療時間。我們也繼續透過在更多國家推出產品來擴大我們的全球足跡，使我們能夠將 KIMMTRAK 帶給世界各地的更多患者。

To achieve our longer-term growth objectives for KIMMTRAK, we are simultaneously pursuing label expansion in both late-line cutaneous melanoma with the ongoing TEBE-AM trial and also an adjuvant uveal melanoma with the soon-to-start ATOM trial. If successful, these two expansions may allow up to 6,000 patients to benefit from the survival benefit of KIMMTRAK.

為了實現 KIMMTRAK 的長期成長目標，我們同時透過正在進行的 TEBE-AM 試驗尋求晚期皮膚黑色素瘤的標籤擴展，以及透過即將啟動的 ATOM 試驗的輔助葡萄膜黑色素瘤的標籤擴展。如果成功，這兩次擴展可能會讓多達 6,000 名患者受益於 KIMMTRAK 的存活獲益。

Moving to the second strategic pillar, our aim is to progress our nine clinical programs, all first-in-class leading bispecific TCR therapies are progressing on our innovative research engine to identify additional novel targets and therapeutic. At ASCO, we presented Phase 1 data of brenetafusp, our premium targeted therapy in previously treated cutaneous melanoma patients, which drove the decision to start the Phase 3 registrational trial in first-line cutaneous melanoma patients.

轉向第二個策略支柱，我們的目標是推進我們的九個臨床項目，所有一流的領先雙特異性TCR 療法都在我們的創新研究引擎上取得進展，以確定更多的新標靶和治療方法。在 ASCO 上，我們展示了 brenetafusp 的 1 期數據，這是我們針對既往治療過的皮膚黑色素瘤患者的優質標靶療法，這促使我們決定在一線皮膚黑色素瘤患者中啟動 3 期註冊試驗。

Next month, at ESMO, we will present late-line ovarian cancer data. And in Q4, we are planning to present late-line data in lung cancer at a medical conference. We're also excited about the potential of our platform to treat infectious diseases.

下個月，我們將在 ESMO 上展示晚期卵巢癌數據。在第四季度，我們計劃在一次醫學會議上展示肺癌的最新數據。我們也對我們的平台治療傳染病的潛力感到興奮。

As you recall, our objective is to deliver a functional cure for people living with HIV, and we expect to present the MAD data from our HIV trial early next year. I'll now ask the team to share additional details. First, Ralph will discuss KIMMTRAK's commercial performance. Ralph?

您還記得，我們​​的目標是為 HIV 感染者提供功能性治愈，我們預計明年初公佈 HIV 試驗的 MAD 數據。我現在將要求團隊分享更多詳細資訊。首先，Ralph 將討論 KIMMTRAK 的商業表現。拉爾夫？

Thank you, Brian, and hello, everyone. We've had a strong first half in 2024, delivering $146 million in net sales, which represents a 34% increase compared to the same period last year. I'm proud of our cross-functional team's achievements and commitment as we expanded our reach to more patients.

謝謝你，布萊恩，大家好。2024 年上半年，我們表現強勁，淨銷售額達 1.46 億美元，與去年同期相比成長 34%。當我們將服務範圍擴大到更多患者時，我為我們的跨職能團隊所取得的成就和承諾感到自豪。

We've now launched KIMMTRAK in 19 countries, including nine new launches since the beginning of the year. In the context of a challenging reimbursement environment in Europe, we have made good progress with access, signing two additional reimbursement agreements in Poland and Sweden, which are expected to launch in the fourth quarter.

我們現已在 19 個國家推出 KIMMTRAK，其中自今年年初以來又推出了 9 個新產品。在歐洲報銷環境充滿挑戰的背景下，我們在准入方面取得了良好進展，在波蘭和瑞典簽署了兩項額外的報銷協議，預計將於第四季度啟動。

In Q2, we also announced acceleration of our Phase 3 trial, the TEBE-AM study in advanced cutaneous melanoma. This is an important part of our growth strategy beyond mUM, and we are very pleased with this progress.

在第二季度，我們也宣布加速進行第 3 期試驗，即針對晚期皮膚黑色素瘤的 TEBE-AM 研究。這是我們超越 mUM 的成長策略的重要組成部分，我們對這項進展感到非常高興。

I will now take you through the figures and financial performance in more detail. We delivered $75.3 million in net revenues with KIMMTRAK in the second quarter, which is an increase of 7% compared to the first quarter.

現在我將向您詳細介紹這些數據和財務表現。第二季我們透過 KIMMTRAK 實現了 7,530 萬美元的淨收入，比第一季成長了 7%。

Net revenue growth was driven primarily by the US, where we saw an 11% growth compared to the first quarter. This growth comes from our continued focus on the community and increasing duration of therapy.

淨收入成長主要由美國推動，與第一季相比成長了 11%。這種增長來自於我們對社區的持續關注和治療持續時間的增加。

We estimate we now have around 65% market share in the US and believe there continues to be opportunity for further growth. In terms of penetration since launch, over 500 unique sites in the US have treated patients with KIMMTRAK, most in the community.

我們估計我們現在在美國擁有約 65% 的市場份額，並相信仍有進一步成長的機會。從推出以來的滲透率來看，美國有超過 500 個獨特的站點使用 KIMMTRAK 治療過患者，其中大多數位於社區。

To continue expanding our reach, we're constantly innovating and recently rolled out our AI-enabled patient finding tool. This has allowed us to find more patients in lower density community centers while keeping our field force footprint unchanged.

為了繼續擴大我們的覆蓋範圍，我們不斷創新，最近推出了支援人工智慧的患者查找工具。這使我們能夠在密度較低的社區中心找到更多患者，同時保持我們的現場人員足跡不變。

Our goal is to continue grow in the US to further market penetration in appropriately supporting duration of therapy, currently trending to 11-plus months. This is exceptional and speaks to a different mechanism of action with the benefit of KIMMTRAK extending beyond the typical RECIST response. Many patients with the best response of stable disease do well and remain on KIMMTRAK two years later, contributing to the growing duration of therapy we observed.

我們的目標是在美國繼續成長，以進一步提高市場滲透率，以適當支持治療持續時間，目前趨勢為 11 個月以上。這是特殊的，說明了一種不同的作用機制，KIMMTRAK 的優勢超越了典型的 RECIST 反應。許多對病情穩定有最佳反應的患者表現良好，並在兩年後繼續使用 KIMMTRAK，這有助於我們觀察到治療持續時間的延長。

Shifting gears to Europe, demand flattened in Q2, and revenues declined net of $6.7 million increase in rebates reserves. The access environment remains remain very challenging across Europe, and we expect incremental demand growth in the second half of the year to come from the launches in Poland and Sweden.

轉向歐洲，第二季需求趨於平緩，扣除回扣準備增加 670 萬美元後，收入下降。整個歐洲的准入環境仍然非常具有挑戰性，我們預計下半年需求的增量成長將來自波蘭和瑞典的推出。

I'm pleased with our team's effort to reach more patients globally with mUM, driving near term growth. KIMMTRAK has the potential to benefit patients beyond mUM and drive midterm growth through label expansion with TEBE-AM study. Following a consultation with the FDA, we converted and accelerated our TEBE-AM study into a Phase 3 registrational trial in second line plus advanced cutaneous melanoma.

我很高興我們的團隊努力透過 mUM 覆蓋全球更多患者，推動近期成長。KIMMTRAK 有潛力使 mUM 以外的患者受益，並透過 TEBE-AM 研究的標籤擴展推動中期成長。在與 FDA 協商後，我們將 TEBE-AM 研究轉變為二線加晚期皮膚黑色素瘤的 3 期註冊試驗，並加速進行。

This is exciting and helps us in two ways, first, to robustly test the PD-1 combination and KIMMTRAK monotherapy arms. And second, by rolling the 120 patients already enrolled into the Phase 2, we accelerated the time to final analysis of the Phase 3 by up to 12 months. We now expect to complete the enrollment in the first half of 2026 and potentially see data in the second half, noting, of course, the event-driven nature of the endpoints.

這令人興奮，並在兩個方面幫助我們，首先，穩健地測試 PD-1 組合和 KIMMTRAK 單藥療法。其次，透過滾動已入組 2 期的 120 名患者，我們將 3 期最終分析的時間縮短了 12 個月。我們現在預計將在 2026 年上半年完成註冊，並可能在下半年看到數據，當然要注意端點的事件驅動性質。

Today, we're only at the beginning of the KIMMTRAK journey. In mUM, we're growing KIMMTRAK double digit year over year as we increase our penetration in the US, support duration of therapy around the world, and launch new markets. Our two ongoing Phase 3 registrational clinical trials position us for continued growth in the mid to long term.

今天，我們才剛開始 KIMMTRAK 旅程。在 mUM 中，隨著我們提高在美國的滲透率、支持世界各地的治療持續時間以及開拓新市場，我們的 KIMMTRAK 逐年增長兩位數。我們正在進行的兩項三期註冊臨床試驗使我們能夠在中長期內持續成長。

With the TEBE-AM trial, we see the potential to extend the benefit of KIMMTRAK to up to 4,000 additional patients with second line plus metastatic cutaneous melanoma. With the ATOM trial, we see this benefit expanded into the adjuvant uveal melanoma setting where all the evidence with KIMMTRAK points to our platform being potentially transformative.

透過 TEBE-AM 試驗，我們看到有可能將 KIMMTRAK 的益處擴展到多達 4,000 名二線加轉移性皮膚黑色素瘤患者。透過 ATOM 試驗，我們看到這種益處擴展到了輔助葡萄膜黑色素瘤治療中，KIMMTRAK 的所有證據都表明我們的平台具有潛在的變革性。

If successful, we could help up to 6,000 patients across all three indications with longer and better lives. I'm very excited about our future, and to tell you more, I'll hand over to David.

如果成功，我們可以幫助多達 6,000 名所有三種適應症的患者獲得更長、更好的生活。我對我們的未來感到非常興奮，為了告訴你更多信息，我將把任務交給大衛。

Thank you, Ralph. I'm really pleased to update you on the strong progress we have made on our pipeline. I'm proud of our R&D team. We have hit all our development milestones and progressing nine clinical programs, including three Phase 3 trials, starting three new Phase 1s and expanding to three therapeutic areas.

謝謝你，拉爾夫。我真的很高興向您介紹我們在管道方面取得的重大進展。我為我們的研發團隊感到自豪。我們已經達到了所有的開發里程碑，並正在推進九個臨床項目，包括三個 3 期試驗、啟動三個新的 1 期試驗並擴展到三個治療領域。

Today, I'm going to focus on the two clinical-stage programs with data readouts over the next 18 months, brenetafusp and HIV. Let's recall our strategy in cutaneous melanoma and the data supporting the Phase 3 trial.

今天，我將重點放在未來 18 個月內有數據讀出的兩個臨床階段項目：brenetafusp 和 HIV。讓我們回顧一下我們在皮膚黑色素瘤方面的策略以及支持 3 期試驗的數據。

The most common therapies used globally are anti-PD-1, either as monotherapy or in checkpoint combination and BRAF therapy for BRAF mutation positive patients. Once patients progress on these available therapies, the only options are clinical trials and pills for select patients. Our strategy is to demonstrate in the Phase 1 trial in third-line patients that brenetafusp is active and well-tolerated and that this activity would support a PFS endpoint in a Phase 3 trial in first line.

全球最常用的療法是抗 PD-1，無論是單一療法或檢查點聯合療法，以及針對 BRAF 突變陽性患者的 BRAF 療法。一旦患者在這些可用療法上取得進展，唯一的選擇就是針對特定患者進行臨床試驗和服用藥物。我們的策略是在三線患者的 1 期試驗中證明 brenetafusp 具有活性且耐受性良好，並且該活性將支持一線 3 期試驗中的 PFS 終點。

Here is a summary of the key data from the Phase 1 trial we presented at ASCO. First, brene has monotherapy activity, something not commonly seen for other biologics in heavily pretreated melanoma. Second, the disease control rate, which is a surrogate of progression-free survival is higher for brenetafusp monotherapy, then the combination of nivolumab plus relatlimab in a similar setting.

以下是我們在 ASCO 上展示的第一階段試驗的關鍵數據的摘要。首先，brene 具有單一治療活性，這是其他生物製劑在經過嚴格預處理的黑色素瘤中不常見的情況。其次，brenetafusp 單藥治療的疾病控制率（無惡化存活期的替代指標）高於類似情況下納武單抗加上 relatlimab 合併治療的疾病控制率。

Third, we see higher activity in PRAME positive versus PRAME negative. This provides biological plausibility as the PRAME negative subset behaves as an internal negative control. And finally, the systemic T-cell fitness data indicates we expect an even higher disease control rate and longer PFS in first line. These data supported our decision to move to Phase 3 in first line.

第三，我們發現 PRAME 陽性的活性高於 PRAME 陰性的活性。這提供了生物學合理性，因為 PRAME 陰性子集充當內部陰性對照。最後，全身性 T 細胞健康數據表明，我們預計一線治療的疾病控制率會更高，且無惡化存活期 (PFS) 會更長。這些數據支持我們決定在第一線進入第三階段。

In our Phase 3 first-line trial, we will combine two biologics, brenetafusp and nivolumab, each with monotherapy activity and with complementary mechanisms of action. Based on the Phase 1 cross-trial comparison I just shared with you, we fully expect that brenetafusp and nivolumab in the first-line setting will be superior to both nivolumab alone and nivolumab plus relatlimab.

在我們的 3 期一線試驗中，我們將結合兩種生物製劑 brenetafusp 和 nivolumab，每種製劑都具有單一治療活性並具有互補的作用機制。根據我剛剛與您分享的 1 期交叉試驗比較，我們完全預期 brenetafusp 和 nivolumab 在一線治療中將優於單獨使用 nivolumab 和 nivolumab 加 relatlimab。

We are pleased to announce that the Phase 3 PRISM-MEL-301 study has started and we are focused on activating more sites globally. With the PRISM-MEL-301 in first line I just shared and with the TEBE-AM in second line that Ralph shared, we are really proud to be one of the few companies to have multiple Phase 3 investments in cutaneous melanoma, both backed by strong data.

我們很高興地宣布，第三階段 PRISM-MEL-301 研究已經開始，我們的重點是在全球範圍內激活更多站點。憑藉我剛剛分享的第一線PRISM-MEL-301 和Ralph 分享的第二線TEBE-AM，我們非常自豪能夠成為少數幾家在皮膚黑色素瘤方面進行多項3 期投資的公司之一，這兩項投資均由強大的數據。

I will now turn to brenetafusp in ovarian cancer. Women with ovarian carcinoma are cycled through platinum regimens, shown in the blue, until they become resistant or refractory, shown in the green, at which point they received non platinum chemotherapies or for the folate alpha receptor positive tumors, antibody-drug conjugate.

我現在將轉向 brenetafusp 在卵巢癌中的應用。患有卵巢癌的女性接受鉑類治療方案（以藍色顯示），直到她們變得抗藥性或難治（以綠色顯示），此時她們接受非鉑類化療或針對葉酸α受體陽性腫瘤的抗體藥物偶聯物。

Unlike melanoma, ovarian cancer, has historically not been sensitive to immunotherapy. In heavily pretreated platinum-resistant, which is the population in our Phase 1 trial, the outlook is poor with non-platinum chemotherapies, having response rates less than 10% and disease control rates between 40% to 50%.

與黑色素瘤不同，卵巢癌歷來對免疫療法不敏感。在我們第一期試驗中經過嚴格預處理的鉑類抗藥性族群中，非鉑類化療的前景不佳，緩解率低於 10%，疾病控制率在 40% 至 50% 之間。

In our Phase 1 trial, we aim to demonstrate in the platinum-resistant setting that brenetafusp is clinically active and can be combined with non-platinum chemo. This will be the subject of ESMO poster next month

在我們的第一期試驗中，我們的目標是在鉑類抗藥性的情況下證明 brenetafusp 具有臨床活性，並且可以與非鉑類化療結合。這將是下個月 ESMO 海報的主題

We have learned for our platform that clinical benefit manifest as disease control. That activity is even higher in earlier lines and that combinability with standard of care may enable at least additive activity. In addition, unlike melanoma, ovarian cancer is more complex with two distinct disease segments that are treated very differently, which requires us to study more combinations.

我們從我們的平台了解到，臨床效益表現為疾病控制。該活性在早期產品線中甚至更高，並且與護理標準的結合可能至少能夠實現附加活性。此外，與黑色素瘤不同，卵巢癌更為複雜，有兩種不同的疾病部分，治療方法也截然不同，這需要我們研究更多的組合。

Therefore, our next step in ovarian is two-fold. First in that heavily pretreated platinum-resistant disease we will expand our patient data set of combinations with non-platinum chemotherapy. And second, in the earlier line platinum-sensitive disease setting, we will test the combinations with bevacizumab and with platinum chemotherapy.

因此，我們在卵巢方面的下一步有兩個面向。首先，在經過嚴格預處理的鉑類抗藥性疾病中，我們將擴大與非鉑類化療組合的患者資料集。其次，在早期鉑敏感疾病環境中，我們將測試貝伐珠單抗和鉑化療的組合。

Let's now turn to lung cancer. Late-line lung cancer is a heterogeneous disease with patients generally having rapid progression. With line, we are still in the signal detection phase. Later this year, we plan to share monotherapy in heavily pretreated lung cancer selected for PRAME suppression and combinations with late-line chemotherapies enrolled without regard to selection for PRAME expression.

現在讓我們轉向肺癌。晚期肺癌是一種異質性疾病，患者通常進展迅速。就線路而言，我們還處於訊號偵測階段。今年晚些時候，我們計劃對選擇進行 PRAME 抑制的經過嚴格治療的肺癌進行單一療法，並與登記的晚期化療聯合使用，而不考慮 PRAME 表達的選擇。

The next steps are additional combinations with osimertinib in the EGFR mutant patients and with docetaxel. This will then be followed by first-line platinum combinations.

下一步是在 EGFR 突變患者中與奧希替尼以及多西他賽進行其他組合。隨後將推出一線鉑金組合。

PRAME is a promising target across multiple tumor types and brenetafusp is a first-in-class PRAME ImmTAC. When you pioneer a novel platform, you have to be ready to look, to learn, and to adjust. And in fact, frankly, this is the exciting part of drug development. We did this for brenetafusp in melanoma, and we'll follow the same thoughtful approach for brenetafusp in ovarian and lung.

PRAME 是跨多種腫瘤類型的有前景的靶點，brenetafusp 是一流的 PRAME ImmTAC。當你開創一個新穎的平台時，你必須做好觀察、學習和調整的準備。事實上，坦白說，這是藥物開發中令人興奮的部分。我們對黑色素瘤中的 brenetafusp 進行了此操作，並且我們將對卵巢和肺部的 brenetafusp 採用相同的深思熟慮的方法。

I will now close by updating on HIV. HIV is currently managed by anti-retroviral therapy, but when ART is stopped the virus rebounds on average within two weeks. By week eight, after treatment interruption, 98% of people will have a viral load of at least 200 copies per ml. This is the threshold commonly used to denote risk for viral transmission.

最後我將介紹有關愛滋病毒的最新情況。目前，愛滋病毒透過抗病毒療法進行治療，但當停止抗愛滋病毒治療後，病毒平均會在兩週內反彈。到第八週，治療中斷後，98% 的人的病毒量將至少為每毫升 200 個拷貝。這是通常用來表示病毒傳播風險的閾值。

The next frontier in HIV treatment is functional care, where the goal is to reduce or eliminate the viral reservoir, which would then delay or prevent viral rebound. To date, no therapy has convincingly demonstrated either of these endpoints. This is the goal of our 113V program called STRIVE.

HIV治療的下一個前沿是功能性護理，其目標是減少或消除病毒庫，從而延遲或防止病毒反彈。迄今為止，還沒有任何治療方法能夠令人信服地證明這些終點中的任何一個。這是我們名為 STRIVE 的 113V 計畫的目標。

The MAD portion of the STRIVE study is ongoing. We are treating with 113V plus ART for 12 weeks and then stopping both therapies. The objectives of this study are twofold, first, to determine whether we can reduce the viral RNA reservoir during the treatment phase. And second whether we can delay viral rebound or alter the kinetics of viral rebound after treatment interruption.

STRIVE 研究的 MAD 部分正在進行中。我們使用 113V 加 ART 治療 12 週，然後停止兩種療法。這項研究的目的有兩個，首先是確定我們是否可以在治療階段減少病毒 RNA 庫。其次，我們是否可以在治療中斷後延遲病毒反彈或改變病毒反彈的動力學。

As of June, we have enrolled 15 people living with HIV across three cohorts, the highest at 300 micrograms. The 300-microgram dose is biologically active. The next step is to enroll more people living with HIV to better characterize the activity and to explore higher doses. This will move the data release into the first quarter of '25.

截至 6 月，我們已在三個隊列中招募了 15 名愛滋病毒感染者，最高劑量為 300 微克。300微克的劑量具有生物活性。下一步是招募更多愛滋病毒感染者，以便更好地描述這項活動並探索更高的劑量。這將使數據發布推遲到 2025 年第一季。

I'm very proud of our R&D team. We pioneered the world's first TCR therapeutic. We saw the value of KIMMTRAK early in Phase 1. And we followed that vision to bring a fantastic new medicine to metastatic uveal melanoma patients.

我為我們的研發團隊感到非常自豪。我們開創了世界上第一個 TCR 療法。我們在第一階段初期就看到了 KIMMTRAK 的價值。我們遵循這個願景，為轉移性葡萄膜黑色素瘤患者帶來一種神奇的新藥。

We saw that value for KIMMTRAK in cutaneous melanoma and the potential in adjuvant uveal and these programs are underway. We see that value in brenetafusp, and we are excited to follow through on that vision as well. Brian, I'm going to hand back to you now.

我們看到了 KIMMTRAK 在皮膚黑色素瘤中的價值以及在輔助葡萄膜中的潛力，這些項目正在進行中。我們看到了 brenetafusp 的價值，並且我們也很高興能夠實現這個願景。布萊恩，我現在要把東西還給你。

Thank you, David. Earlier today, we released our financial results for the second quarter ended June 30, 2024. Please refer to the press release and our latest SEC filing on Form 10-Q for our full financial results. I'll now share some of the key highlights.

謝謝你，大衛。今天早些時候，我們發布了截至 2024 年 6 月 30 日的第二季財務業績。請參閱新聞稿和我們最新的 10-Q 表格向 SEC 提交的文件，以了解我們的完整財務表現。現在我將分享一些關鍵亮點。

In Q2, global KIMMTRAK unit sales and net sales have both continued to grow sequentially, even with the challenging reimbursement environment in Europe. Net revenue grew to $75.3 million in Q2 from $70.3 million in Q1, a 7% increase, driven primarily by the 11% growth in the United States.

第二季度，儘管歐洲報銷環境充滿挑戰，但全球 KIMMTRAK 單位銷售額和淨銷售額均持續較上季成長。第二季淨收入從第一季的 7,030 萬美元增至 7,530 萬美元，成長 7%，這主要是由美國市場 11% 的成長推動的。

The US has consistently contributed over 70% of global net sales. In Q2, we increased rebate reserves by $6.7 million in Europe as we continue to make best estimate revenue recognition assumptions and associated accruals. For the remainder of 2024, we anticipate global unit sales will continue to grow on a sequential basis as we continue to expect solid demand in the US market and new country contributions from non-US markets.

美國一直貢獻全球淨銷售額的 70% 以上。第二季度，我們在歐洲增加了 670 萬美元的回扣準備金，因為我們繼續做出最佳估計收入確認假設和相關應計費用。在 2024 年剩餘時間內，我們預計全球銷售將繼續環比成長，因為我們繼續預期美國市場的需求強勁以及非美國市場的新國家貢獻。

For both SG&A and R&D expenses declined sequentially this quarter, they have increased 31% in the first half over the same period in 2023. We expect R&D expenses to marginally increase in the second half compared to the first half as clinical development for late-stage PRAME and KIMMTRAK Phase 3 programs continue to accelerate.

本季的銷售、行政管理 (SG&A) 和研發費用均較上季下降，但與 2023 年同期相比，上半年成長了 31%。隨著後期 PRAME 和 KIMMTRAK 3 期計畫的臨床開發持續加速，我們預計下半年研發費用將較上半年小幅增加。

In aggregate, our net loss for the first half of $36.1 million or $0.72 a share was roughly unchanged from 2023, given our increase in sales revenue. As you can see on this slide, our net cash and marketable securities position increased $860 million as of June 30 or $770 million net of the planned $50 million loan repayment and an expected $40 million in European sales rebate payments, both expected in the second half of '24.

總的來說，考慮到銷售收入的增加，我們上半年的淨虧損為 3,610 萬美元，即每股 0.72 美元，與 2023 年基本持平。正如您在這張幻燈片中看到的那樣，截至6 月30 日，我們的淨現金和有價證券頭寸增加了8.6 億美元，扣除計劃的5000 萬美元貸款償還和預計的4000 萬美元歐洲銷售回扣付款（預計在下半年）淨增加了7.7 億美元'24.

I'd like to congratulate the teams on continued KIMMTRAK sales growth as we reach progressively more patients globally. This cash flow enables us to accelerate the broader portfolio we're delivering transformative outcomes to patients. For the remainder of 2024, we will be presenting the brenetafusp Phase 1 late-line ovarian data at ESMO and then in Q4, the initial Phase 1 lung data at a medical conference.

隨著我們在全球接觸到越來越多的患者，我要祝賀各團隊 KIMMTRAK 銷售持續成長。這種現金流使我們能夠加速更廣泛的投資組合，為患者提供變革性的結果。在 2024 年剩餘時間內，我們將在 ESMO 上展示 brenetafusp 1 期晚期卵巢數據，然後在第四季度在醫學會議上展示最初的 1 期肺部數據。

Looking over the next four years, we expect numerous data readouts, including additional data from brenetafusp, our HIV Phase 1 study, data from our three Phase 3 trials with KIMMTRAK and brenetafusp and data from several new trial starts across our three therapeutic areas.

展望未來四年，我們預計會有大量數據讀出，包括來自我們的HIV 1 期研究brenetafusp 的額外數據、我們使用KIMMTRAK 和brenetafusp 進行的三項3 期試驗的數據以及來自我們三個治療領域的幾項新試驗的數據。

With a strong balance sheet, a robust and diversified portfolio, our talented and dedicated teams, and a clear and compelling vision for the future, we are confident we can continue to deliver significantly for patients and shareholders. Thank you. We will now take questions.

憑藉強大的資產負債表、穩健且多元化的投資組合、才華橫溢且敬業的團隊，以及對未來清晰而引人注目的願景，我們有信心能夠繼續為患者和股東提供顯著的服務。謝謝。我們現在將接受提問。

(Operator Instructions) Michael Yee, Jefferies.

（操作員說明）Michael Yee，Jefferies。

Hey, guys, thanks. Good morning. Congrats on great progress. We have two questions. On KIMMTRAK, I know you made a few comments about the challenges about reimbursement in Europe. Can you just help us understand in the second quarter there that the reserve was for? Was that a specific country? And what does that mean for the go-forward third and fourth quarters?

嘿，夥計們，謝謝。早安.祝賀取得巨大進步。我們有兩個問題。在 KIMMTRAK 上，我知道您對歐洲報銷挑戰發表了一些評論。您能否幫助我們了解第二季儲備金的用途？那是一個特定的國家嗎？這對於接下來的第三季和第四季意味著什麼？

Do we go back to adjusting for that? And was that a onetime reserve? So help us understand the second quarter and then third and fourth quarter adjustments.

我們要回去調整嗎？那是一次性儲備嗎？所以幫助我們了解第二季以及第三季和第四季的調整。

And then on the pipeline, I thought you made a very, very interesting comment about HIV. Can you just expand on that a little bit? You're saying you're enrolling more patients at a higher dose and that's biologically active. Have you been working at the prior doses? Is the study all blinded or what are you seeing there? And what gives you that confidence to enroll more patients? Thank you.

然後在管道中，我認為你對愛滋病毒做了非常非常有趣的評論。能稍微擴充一下嗎？你說你正在以更高的劑量招募更多的患者，這具有生物活性。您是否按照之前的劑量進行工作？這項研究是盲目的還是你在那裡看到了什麼？是什麼讓您有信心招募更多病患？謝謝。

Thank you, Michael. Brian or Ralph for the first question, and David for the HIV, please.

謝謝你，麥可。請布萊恩或拉爾夫回答第一個問題，請大衛回答愛滋病毒問題。

Great. Ralph, why don't you take the European question?

偉大的。拉爾夫，你為什麼不回答歐洲問題？

Sounds good. Thank you, Michael, for the question. So look, we've had successes with reimbursement as proven by the nine launches that we've had so far in the first half of the year. We increased the estimated reserves by 6.6 -- $6.7 million. This should be a one-time thing based on the latest assumptions that we have on the negotiations.

聽起來不錯。謝謝邁克爾的提問。所以看，我們在報銷方面取得了成功，今年上半年迄今我們已推出的九次產品就證明了這一點。我們將估計儲備金增加了 660 至 670 萬美元。根據我們對談判的最新假設，這應該是一次性的事情。

Now in terms of looking forward, I would caution you against just adding the $6.7 million because the erosion is both backward looking and forward looking and it's mainly on our negotiations with France and Germany.

現在就展望未來而言，我要提醒您不要只增加 670 萬美元，因為侵蝕既是向後看的，也是前瞻性的，而且主要是我們與法國和德國的談判造成的。

Michael, so with the HIV program, we're in the dose escalation phase of the multiple ascending dose. And as mentioned, we've gotten up to 300 micrograms. And we'll continue to dose higher. There's a couple of some important first year that we're that we're looking at. This is the first time we've taken our platform into a setting with such a low peptide target density and where we have such a low, in fact, cell target density.

邁克爾，對於愛滋病毒項目，我們正處於多次劑量遞增的劑量遞增階段。如前所述，我們的含量高達 300 微克。我們將繼續增加劑量。我們正在關注第一年的一些重要事件。這是我們第一次將我們的平台引入肽目標密度如此低的環境中，而且實際上細胞目標密度也如此低。

And so it was an important question for us to ask, can we actually see anything? And then of course, there's never been a functional cure. There's never been a therapy that can reduce the reservoir or delay the rebound. So these were all really important first.

因此，我們要問的一個重要問題是，我們真的能看到任何東西嗎？當然，從來沒有功能性治癒的方法。從來沒有一種療法可以減少儲存量或延遲反彈。所以這些首先都非常重要。

And we do see evidence of biological activity during the MAD portion, but it's still early and there only a few patients per cohort. And so we think it's prudent to get some more patients in that cohort and also to continue to go higher. And we will discuss more of what biological activity means as we approach the full data release, which will be in the first quarter of next year.

我們確實在 MAD 部分看到了生物活性的證據，但現在還為時過早，而且每個隊列中只有少數患者。因此，我們認為謹慎的做法是在該群組中增加更多患者，並繼續提高水準。當我們即將於明年第一季發布完整數據時，我們將更多地討論生物活性的含義。

Thank you.

謝謝。

Jessica Fye, JP Morgan.

潔西卡法耶，摩根大通。

This is Nick on for Jess. Thanks for taking our questions. First, on the brand-new ovarian update, we should expect at ESMO, can you just help set the stage for how many patients with the data we should expect, the split between mono and combo, that I believe you stated should be more combo?

這是尼克替傑西發言。感謝您回答我們的問題。首先，關於全新的卵巢更新，我們應該在ESMO 上期待，您能否幫助為我們應該期待的數據的多少患者奠定基礎，單藥和組合之間的劃分，我相信您所說的應該是更多組合？

And maybe add some more detail around what we see as promising data that supports continued evaluation here in this setting based on some of those benchmarks you provided.

也許還可以根據我們認為有希望的數據添加一些更多細節，這些數據支援在此設定中根據您提供的一些基準進行持續評估。

Yeah, happy to. So in terms of size, it's going to be roughly the same number as the continuous melanoma dataset at ASCO. It will be mostly monotherapy. But in contrast to the ASCO melanoma, we will have more combinations because there is more chemotherapy options to test here. So we'll be mostly mono with combination as well.

是的，很高興。因此，就大小而言，它將與 ASCO 的連續黑色素瘤資料集的數量大致相同。它將主要是單一療法。但與 ASCO 黑色素瘤相比，我們將有更多的組合，因為這裡有更多的化療選擇可供測試。所以我們也將主要採用單聲道和組合。

In terms of the questions that we're going to be asking, so number one is -- and these are the standard questions I've been asking throughout my drug development career in the space. Is there monotherapy activity? Can you combine with the intended registrational partner if you plan to do a combination? And can you have confidence that the drug activity can meet whatever registrational endpoint? So those are the types of questions we're asking in order to progress.

就我們要問的問題而言，第一個問題是——這些是我在該領域的藥物開發生涯中一直在問的標準問題。是否有單一療法活動？如果您打算進行合併，您可以與預期的註冊合作夥伴合併嗎？您是否有信心藥物活性能滿足任何註冊終點？這些就是我們為了取得進展而提出的問題類型。

In terms of the metrics or the benchmarks, I think you were asking, yes, so there aren't a lot of good benchmarks in this heavily pretreated platinum-resistant setting or a few published chemotherapy trials. And so the chemotherapy benchmarks there, the response rates are in the single digits and the disease control rate is about 40% to 50%.

就指標或基準而言，我認為您問的是，是的，因此在這種經過嚴格預處理的鉑耐藥環境或一些已發表的化療試驗中，沒有很多好的基準。所以那裡的化療基準，有效率是個位數，疾病控制率大約是40%到50%。

Great. And then in addition to that in bringing the platinum-resistant ovarian cancer patients, you noted some evaluation in the platinum-sensitive setting as well. So can you provide a little more detail the progress there? And when we can expect an update from that data set?

偉大的。除了引入鉑類抗藥性卵巢癌患者之外，您還注意到對鉑類敏感的環境進行了一些評估。您能否提供更詳細的進展？我們什麼時候可以期待該資料集的更新？

Mohammed, do you want to take that?

穆罕默德，你想接受這個嗎？

Sure. Happy to do that. So as David mentioned, obviously, ovarian is more heterogeneous and complex than melanoma. So we've been exploring mostly in the platinum-resistant setting, but now the study does allow us to move to earlier lines and combine with therapies that are used in sensitive. And those include bev and also will include platinum doublet.

當然。很高興這樣做。正如大衛所提到的，顯然，卵巢比黑色素瘤更異質、更複雜。因此，我們主要在鉑類抗藥性環境中進行探索，但現在這項研究確實使我們能夠轉向更早的產品線，並與敏感人群使用的療法相結合。其中包括 bev，也將包括鉑金雙合成峰。

Great. Thank you.

偉大的。謝謝。

Tyler Van Buren, TV Cowen. .

泰勒範布倫，考恩電視台。。

Good morning. Thanks very much for the presentation. I have a couple of follow-ups on the ovarian updated ESMO. So I understand that the bar for beating non platinum chemo in platinum resistant patients is low. But for the brene combo -- chemo combo specifically isn't ELAHERE here or mirvetuximab data, the bar.

早安.非常感謝您的介紹。我對卵巢更新的 ESMO 有一些後續行動。所以我知道，在鉑類抗藥性患者中擊敗非鉑類化療的門檻很低。但對於布雷尼組合 - 化療組合具體不是 ELAHERE 這裡或 mirvetuximab 數據，酒吧。

And then the second question is, if you can combined with non-platinum chemo with good safety, do you believe that the likelihood of combining with platinum chemo in the frontline with platinum sensitive patients is high.

那麼第二個問題是，如果可以安全性好的非鉑化療，你認為第一線鉑敏感病患結合鉑化療的可能性很高嗎？

David and Mohammed?

大衛和穆罕默德？

Yeah, So I'll address the first one and then Mohammed you can talk about the plat. So Tyler, mirve, it's good to see that there's a new medicine for these patients, and it's not -- this mirve is a targeted chemotherapy. We know chemotherapies do work there.

是的，所以我將解決第一個問題，然後穆罕默德，您可以談談平台。所以泰勒，米爾韋，很高興看到有一種針對這些患者的新藥，但事實並非如此——這種米爾韋是一種靶向化療。我們知道化療在那裡確實有效。

So the key differences, I would say, Tyler, for us, is that the mirve strategy is in the PROC setting is to replace chemotherapy. Our strategy is to add on to chemotherapy, not to replace chemotherapy. And so our approach is going to be an add-on to chemotherapy. And of course, eventually, there also could be an add-on to mirvetuximab as well. And do you want to comment on the platinum sensitivity?

所以，我想說，Tyler，對我們來說，關鍵的區別是 mirve 策略在 PROC 環境中是取代化療。我們的策略是補充化療，而不是取代化療。因此，我們的方法將成為化療的補充。當然，最終，也可能有米維妥昔單抗的附加藥物。您想對鉑金敏感性發表評論嗎？

Sure. Happy to do that. So I would say, Tyler, this is early days. This is the first time we're actually combining our platform with chemotherapy and we're learning. But so far, the expectations that we should be able to combine and the plan is to then move from the non platinum-based chemotherapies to the platinum-based chemotherapies over the coming months and into next year.

當然。很高興這樣做。所以我想說，泰勒，現在還為時過早。這是我們第一次真正將我們的平台與化療結合，我們正在學習。但到目前為止，我們應該能夠結合的期望和計劃是在未來幾個月和明年從非鉑類化療轉向鉑類化療。

Thank you.

謝謝。

Eric Schmidt, Cantor Fitzgerald.

埃里克·施密特，康托·菲茨傑拉德。

Well, thanks for taking my question. Maybe back to KIMMTRAK for a moment. It sounds like you've crossed the $300 million annualized run rate for the first time. You've grown now for several quarters at 30% or more year on year. You've spoken of more patients out there than you thought previously and longer duration, of course than you had assumed.

嗯，謝謝你回答我的問題。也許暫時回到 KIMMTRAK。聽起來您似乎第一次突破了 3 億美元的年化運行率。現在，您已經連續幾個季度實現了 30% 或以上的同比增長。您提到那裡的患者數量比您之前想像的要多，而且持續時間當然比您想像的要長。

So I guess the question is what's the ceiling for this drug and the current uveal melanoma indication? Do you think it's a $500 million, $600 million, $700 million drug? Where is this going to end?

所以我想問題是這種藥物和目前葡萄膜黑色素瘤適應症的上限是多少？你認為這是一個價值5億美元、6億美元、7億美元的藥物嗎？這將在哪裡結束？

Thank you, Eric. Ralph, do you want to take that and maybe, Brian, you can comment also at the end.

謝謝你，埃里克。拉爾夫，你想接受嗎？

Happy to. Thank you, Eric, for the question. So look, we're very proud of the growth that we've had. A lot of it has been driven, as we've stated, by the US growth where we're 65% penetrated.

很高興。謝謝埃里克提出的問題。所以看，我們對我們所取得的成長感到非常自豪。正如我們所說，其中很大一部分是由美國的成長推動的，我們的滲透率為 65%。

It's important to keep in mind two aspects. One is the reimbursement landscape in Europe is such and the challenges are such that we expect really minor to very incremental growth coming from Europe moving forward. So a lot of the growth will be driven by the US -- a lot of the incremental growth will be driven by the US. That's for mUM.

重要的是要記住兩個方面。一是歐洲的報銷格局如此，挑戰如此之大，我們預期歐洲未來將出現微小到非常增量的成長。因此，很大一部分成長將由美國推動——許多增量成長將由美國推動。那是給mUM的。

But really, I think where we get very much excited is when we think about the label expansions that are possible with the TEBE-AM study, which expects data in 2026 as I mentioned. And from the ATOM study, a little bit further down the line, that also would bring us into the adjuvant setting, would bring the platform to the adjuvant setting. So I think there is still significant growth for KIMMTRAK, up to 6,000 patients potentially benefiting from it.

但實際上，我認為當我們想到 TEBE-AM 研究可能進行的標籤擴展時，我們感到非常興奮，正如我所提到的，該研究預計在 2026 年獲得數據。從 ATOM 研究來看，再往前走一點，這也會把我們帶入輔助設置，也會把平台帶入輔助設置。因此，我認為 KIMMTRAK 仍有顯著成長，多達 6,000 名患者可能從中受益。

Brian, do you want to add anything?

布萊恩，你想補充什麼嗎？

The only thing I'd add, Eric, is that we're really pleased that given the survival benefit of KIMMTRAK that the duration of therapy continues to extend. The mean duration of therapy is now over 11 months approaching 12 months, maybe plus.

Eric，我唯一要補充的是，鑑於 KIMMTRAK 的生存益處，治療持續時間不斷延長，我們真的很高興。目前治療的平均持續時間超過 11 個月，接近 12 個月，甚至可能更長。

And as patients stay on longer and the tail is pronounced as we see in the three-year survival follow-up, it's still unclear how long the duration of therapy can extend. So that's one of the upside potentials in KIMMTRAK. And as Ralph said, 73% of net sales are coming from the United States. We'd expect that to continue going forward.

隨著患者的治療時間延長，並且正如我們在三年生存隨訪中看到的那樣，尾部明顯，目前尚不清楚治療的持續時間可以延長多長時間。這就是 KIMMTRAK 的上行潛力之一。正如拉爾夫所說，73% 的淨銷售額來自美國。我們預計這種情況會持續下去。

Thank you.

謝謝。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hi, guys. Thanks for taking my questions. I had another one for David, just on the PRAME program again, could you just provide us with your updated views on the opportunity in the lung cancer indication? Are there any particular patient subsets and focus for the development strategy.

嗨，大家好。感謝您回答我的問題。我為 David 準備了另一份報告，剛剛再次參加 PRAME 計劃，您能否向我們提供您對肺癌適應症機會的最新看法？開發策略是否有任何特定的患者子集和重點？

Are you enriching certain patients into this cohort? Any particular genotypes perhaps that might benefit most from PRAME in lung cancer? And what should our expectations be for the scope of that data readout later this year? Thanks so much.

您是否正在將某些患者豐富到這個隊列中？任何特定的基因型可能最能從 PRAME 治療肺癌中獲益？我們對今年稍後數據讀出的範圍應該有什麼期望？非常感謝。

Yeah. Thanks, Michael. So with lung, of course it's a lot more heterogeneous disease on multiple levels than ovarian and melanoma. And so we have been very interested in looking at those key subsets in order to first see the initial signal before we start.

是的。謝謝，麥可。因此，對於肺部來說，它在多個層面上當然是比卵巢癌和黑色素瘤更異質的疾病。因此，我們對查看這些關鍵子集非常感興趣，以便在開始之前首先看到初始訊號。

So one example of the key subset of course are actionable gene mutation-positive patients because those are in a sense checkpoint and so that would make an interesting place for us to look, but there are other potential subsets as well.

因此，關鍵子集的一個例子當然是可採取行動的基因突變陽性患者，因為這些患者在某種意義上是檢查點，因此這將成為我們觀察的一個有趣的地方，但還有其他潛在的子集。

We have initially for the monotherapy, as I talked about in the presentation. We focused on enrolling PRAME positive because about half of the adenocarcinoma patients are PRAME negative, half are positive. And for the initial signal, of course you want to make sure that the patients are PRAME positive.

正如我在演講中談到的，我們最初採用單一療法。我們專注於 PRAME 陽性的患者，因為大約一半的腺癌患者是 PRAME 陰性，一半是陽性。對於初始訊號，您當然要確保患者的 PRAME 呈陽性。

And so we have been doing this double screening, looking for the right patients. And so the monotherapy data later this year will be smaller probably than what we're seeing for ovarian and for melanoma. But it's a little too soon to guide to the numbers of that. The combinations of course is where we're also interested because that's where we believe our platform is going to work best in terms of combinations.

所以我們一直在進行雙重篩選，尋找合適的患者。因此，今年稍後的單一療法數據可能會小於我們所看到的卵巢和黑色素瘤的數據。但現在判斷這個數字還為時過早。當然，我們也對組合感興趣，因為我們相信我們的平台在組合方面將發揮最佳作用。

So it will be a monotherapy and it will be mostly a chemotherapy combination initially. As I talked about, Michael, going into next year we expect to move into earlier lines with a docetaxel combination and with the osimertinib combination. Mohammed, anything you want to add?

因此，這將是一種單一療法，最初主要是化療組合。正如我所說，邁克爾，進入明年，我們預計將進入早期的多西他賽組合和奧希替尼組合產品線。穆罕默德，您還有什麼要補充的嗎？

No, I guess we also have chemo -- platinum-based chemotherapy options that will come a little bit later after osi and doce.

不，我想我們還有化療——以鉑類為基礎的化療方案，會在 OSI 和 Doce 之後稍後出現。

Thank you.

謝謝。

Jack Allen, Baird.

傑克艾倫、貝爾德。

Thanks a lot for taking the question and congratulations on the progress.

非常感謝您提出問題並祝賀取得的進展。

I wanted to ask a little bit about the earlier stage pipeline. I know the PIWIL program recently cleared CTA and is expected to enter the clinic in the second half of this year and you also submitted the CTA for the half-life extended PRAME and have plans to submit the CTA for the PRAME-A24 program. I guess my question here is when can we start to see the pipeline kind of build out and see clinical data from some of these earlier assets?

我想問一些有關早期階段管道的問題。我知道PIWIL計畫最近通過了CTA，預計今年下半年進入臨床，你們也提交了半衰期延長的PRAME計畫的CTA，並計畫提交PRAME-A24計畫的CTA。我想我的問題是我們什麼時候可以開始看到管道的建構並看到這些早期資產的臨床數據？

Thank you, Jack. Mohammed?

謝謝你，傑克。穆罕默德？

Yes, thanks for the question, Jack. So you're absolutely right. We're quite excited about the progress we're making with the early-stage pipeline. So for PIWIL, following submission, we're now in the stage of activating sites and then hopefully, we'll be able to meet our target of enrolling the first patient before the end of the year.

是的，謝謝你的提問，傑克。所以你是完全正確的。我們對早期管道所取得的進展感到非常興奮。因此，對於 PIWIL 來說，提交後，我們現在處於激活站點的階段，希望我們能夠在年底前實現招募第一位患者的目標。

With HLE, we've made the submission. So we're waiting for on health authority feedback and with A24 we remain on track. We're making the health authority submissions by the end of the year. In terms of data, I mean, these are first-in-human trials, right? So we need to get the trials open and start accruing. I'm sorry, it's too early to guide to when we would expect data from these trials.

透過 HLE，我們已經提交了意見。因此，我們正在等待衛生當局的回饋，並且 A24 計劃仍將保持在正軌上。我們將在今年年底前向衛生當局提交意見。就數據而言，我的意思是，這些都是首次人體試驗，對嗎？因此，我們需要開放試驗並開始累積。抱歉，現在判斷我們何時會收到這些試驗的數據還為時過早。

And if I could just add one other point, Tom Jack, is Mohammed's team has really baked in important learnings that we've made from our entire platform from KIMMTRAK and from brenetafusp. So the PIWIL study is now designed in colorectal cancer with all the best knowledge we have about where this platform is going to work.

Tom Jack，如果我可以補充一點的話，Mohammed 的團隊確實吸收了我們從 KIMMTRAK 和 brenetafusp 的整個平台中學到的重要知識。因此，PIWIL 研究現在針對結直腸癌進行設計，我們掌握了有關該平台將在何處發揮作用的所有最佳知識。

Likewise with the PRAME Half Life Extension, which is essentially the same molecule as brenetafusp but with an Fc half-life extended. All of the wall of data we're building in terms of combinations and translational insights are directly applicable to the PRAME Half Life Extension. So we see acceleration in our Phase 1 trials based on these learnings.

PRAME 半衰期延長也是如此，它與 brenetafusp 本質上是相同的分子，但 Fc 半衰期延長了。我們在組合和轉化見解方面所建構的所有資料牆都直接適用於 PRAME 半衰期延長。因此，基於這些經驗，我們看到第一階段試驗正在加速進行。

Got it. Thank you.

知道了。謝謝。

Justin Zimmerman, BTIG.

賈斯汀·齊默爾曼，BTIG。

Thanks for taking my question and congrats on the progress. I'll ask a question about the autoimmune disease programs. It looks like you're kicking off CMC manufacturing here for your candidates. Any thoughts on timeline for entering the clinic on these programs?

感謝您提出我的問題並祝賀我的進展。我會問一個有關自體免疫疾病計畫的問題。看起來您正在為您的候選人開始 CMC 製造。對於進入這些計畫的診所的時間表有什麼想法嗎？

Thank you, Justin. We're hoping by next year, so the CMC is going well and we take it from there. But yes, we're excited about this program as well.

謝謝你，賈斯汀。我們希望到明年，CMC 進展順利，我們就從那裡開始。但是，是的，我們也對這個計劃感到興奮。

Great. Thanks for taking my question.

偉大的。感謝您提出我的問題。

Jonathan Chang, Leerink securities.

Jonathan Chang，Leerink 證券公司。

Hi, guys, thanks for taking my questions. Our first question, how do you see the uveal melanoma competitive landscape potentially evolving in the future and what gives you confidence in the ability to continue and potentially expand the successful commercial story in the event of potential new entrants?

嗨，夥計們，感謝您回答我的問題。我們的第一個問題是，您如何看待未來葡萄膜黑色素瘤的競爭格局，以及是什麼讓您對在潛在新進入者出現時繼續並可能擴大成功商業故事的能力充滿信心？

And second question, I guess just out of curiosity for the lower tech people like myself, can you provide more color on the AI-enabled patients finder and how is this facilitating commercial story? Thank you.

第二個問題，我想只是出於對像我這樣的技術水平較低的人的好奇，您能否為支持人工智能的患者查找器提供更多信息，以及這如何促進商業故事？謝謝。

Great. Thank you so much for the great questions. So I'll start with David and maybe then Ralph, you can comment more.

偉大的。非常感謝您提出的好問題。所以我將從大衛開始，也許然後是拉爾夫，你可以發表更多評論。

Yes, Jonathan, in terms of the landscape, I think there are two ways to look at it. First, in the metastatic setting. In the HLE-A02 positive, of course we now have the three-year survival benefit. It's a global standard of care. And so we're continuing to build on that.

是的，喬納森，就景觀而言，我認為有兩種看待它的方式。首先，在轉移環境中。在 HLE-A02 陽性中，我們現在當然擁有三年存活效益。這是全球護理標準。因此，我們將繼續在此基礎上繼續發展。

We know that in the HLE-A02 negative, there are studies going on and by the way, it's great to see options. But that registrational study is in the HLE-A02 negative setting.

我們知道，針對 HLE-A02 陰性的研究正在進行中，順便說一句，很高興看到一些選擇。但該註冊研究是在 HLE-A02 陰性環境中進行的。

In terms of the adjuvant, we have the ATOM trial, which is a well-designed standard relapse-free survival endpoint. It's a standard endpoint used globally for full approval. So this is a trial that we believe will give us a full approval label with high confidence in the adjuvant setting. We are aware that there's competition in the neoadjuvant setting. And I think it's too early for us to comment in terms of that. Ralph, do you want to talk about the AI?

在佐劑方面，我們有ATOM試驗，這是一個精心設計的標準無復發生存終點。它是全球使用的獲得完全批准的標準端點。因此，我們相信這項試驗將為我們帶來充分的核准標籤，並對佐劑環境充滿信心。我們知道新輔助治療領域存在競爭。我認為我們對此發表評論還為時過早。拉爾夫，你想談談人工智慧嗎？

Thank you, David. So we're very excited about this tool actually because when you recall, we were discussing initially how our approach to addressing the market, particularly in the US. We talked about the fact that there's a higher density of academic accounts. And then after that, it tails off with very low density in the community.

謝謝你，大衛。因此，我們實際上對這個工具感到非常興奮，因為當你還記得時，我們最初正在討論我們如何應對市場，特別是在美國的市場。我們討論了學術帳戶密度更高的事實。之後，社區的密度就逐漸降低。

And one of the challenges is how do you address that low density, those patients that pop up once a year or once every other year? And really now that AI has gotten to the place where some of the predictive models have become very good, we're leveraging that ability to predict based on historical data where the patients and when the patients might pop in some of the different practices. And that's enabled us to find patients and send beds on a just-in-time basis, which allowed us to basically keep our rep footprint the same.

其中一個挑戰是如何解決低密度問題，即每年或每隔一年出現一次的患者？事實上，現在人工智慧已經達到了一些預測模型變得非常好的水平，我們正在利用這種能力根據歷史數據來預測患者在哪裡以及何時患者可能會出現在一些不同的實踐中。這使我們能夠及時找到患者並發送床位，從而使我們的代表性足跡基本保持不變。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Hey, good morning. This is Alex on for Peter and thank you for taking our questions. Just had two on the ovarian update. So assuming data is supportive, would you pursue a monotherapy or a chemo combination approval in the platinum-resistant setting? Or would the goal be to maybe try to go sort of directly into earlier lines of therapy in combination with chemo?

嘿，早安。我是亞歷克斯（Alex）為彼得（Peter）發言，感謝您回答我們的問題。剛剛有兩個關於卵巢的更新。因此，假設數據支持，您會在鉑類抗藥性的情況下尋求單一療法還是聯合化療？或者目標是嘗試直接進入早期療法與化療結合？

Thank you, Alex. DavId?

謝謝你，亞歷克斯。大衛？

So Alex, I guess it's important to understand to remind about what insights we've made. First of all, our platform works really well with disease control. It works very well in increased activity in earlier lines. And we think it works best in combinations.

所以亞歷克斯，我想重要的是要了解並提醒我們所做的見解。首先，我們的平台在疾病控制方面效果非常好。它對於增加早期生產線的活動非常有效。我們認為它的組合效果最好。

In ovarian cancer, which is different from cutaneous, there's these two major disease segments and of course multiple different combinations. So, we have to generate the data before we decide on what the next step is. So, the immediate next steps are more chemotherapy combinations in the platinum-resistant setting. And then as we talked about, more platinum combinations and bevacizumab combinations in the platinum sensitive. This is the data set that we think will enable us to make the best decision on what the next study is, PROC or PSOC.

與皮膚癌不同，卵巢癌有這兩種主要疾病部分，當然還有多種不同的組合。因此，在決定下一步要做什麼之前，我們必須產生資料。因此，接下來的步驟是在鉑類抗藥性環境中使用更多的化療組合。然後，正如我們所討論的，更多的鉑類組合和貝伐單抗組合出現在鉑類敏感人群中。我們認為這個資料集將使我們能夠就下一項研究是 PROC 還是 PSOC 做出最佳決定。

Okay, great. And do we actually see any bev combination patients in the 3Q update.

好的，太好了。我們是否真的在第三季更新中看到任何 BEV 組合患者？

No, there won't be any bevacizumab combinations in this update.

不，本次更新中不會有任何貝伐單抗組合。

Okay. Thank you.

好的。謝謝。

Ahu Demir, Ladenburg Thalmann.

阿胡·德米爾，拉登堡·塔爾曼。

Good morning. Thank you for taking my questions. Two questions from us. First one is on the lung cancer program. When you present data for us disclose data from (technical difficulty)

早安.感謝您回答我的問題。我們提出兩個問題。第一個是關於肺癌計畫。當您向我們提供數據時，披露來自（技術難度）

I was asking how many patients disclosure that you would have from the lung cancer? And what percentage would have monotherapy versus combination? And I have another question after that.

我問有多少病患透露自己罹患肺癌？單一療法與合併療法的比例是多少？之後我還有另一個問題。

Thank you. I would say it's too early to say, but I'll give it to Mohammed to tell you.

謝謝。我想說現在說還太早，但我會把它交給穆罕默德來告訴你。

Sure. Thanks for the question on. In terms of lung cancer, as you know, David mentioned, it is obviously a more -- it's a more heterogeneous setting compared to melanoma, and we are still in the initial signal detection mode.

當然。感謝您提出的問題。大衛提到，就肺癌而言，如你所知，與黑色素瘤相比，它顯然是一個更異質的環境，而且我們仍處於初始訊號檢測模式。

But in terms of patient, it will be likely a smaller dataset than melanoma and ovarian, and we will likely have more combo patients than mono patients for the reason David mentioned that for monotherapy, we have to select for PRAME and with combo, we are allowing regardless of PRAME tests.

但就患者而言，它的數據集可能比黑色素瘤和卵巢癌更小，而且我們可能會比單一患者擁有更多的組合患者，因為David 提到，對於單一療法，我們必須選擇PRAME，而對於組合療法，我們允許無論 PRAME 測試如何。

And so that's helpful. And my second question is on the HIV program. You touched on the viral load and also the rebound rate. What would give you confidence to move forward from the MAD data? Would you be looking for -- what data would you be looking for and (technical difficulty) combinations for that program?

這很有幫助。我的第二個問題是關於愛滋病毒計畫。您談到了病毒量和反彈率。什麼能讓您有信心從 MAD 數據中繼續前進？您會尋找 - 您會尋找該程式的哪些數據和（技術難度）組合嗎？

Yes, David.

是的，大衛。

Yes, it's a really good question because, of course, we're pioneering this area here. No one's generated the data thresholds for what surprise to move forward. I would say at this stage, any evidence of activity that is definitely related to antiviral would be really intriguing to us because no one has been able to show that.

是的，這是一個非常好的問題，因為我們當然是這個領域的先驅。沒有人為接下來的驚喜產生數據閾值。我想說，在現階段，任何與抗病毒藥物肯定相關的活動證據都會引起我們的興趣，因為沒有人能夠證明這一點。

So we're looking at, can you reduce the viral reservoir, and can you delay or alter the rebound kinetics? Anything I think here would be interesting for us to continue. Of course at the end of the day, it's going to have to be an antiviral delay and rebound that is going to be the endpoint. But I think any insights we make here are going to be important for us. So immediate next steps are for us to generate more data and to get to higher doses because we only have a few patients per cohort.

所以我們正在研究，你能減少病毒儲存嗎？我認為這裡的任何事情對我們來說都會很有趣，可以繼續下去。當然，最終，抗病毒藥物的延遲和反彈才是終點。但我認為我們在這裡提出的任何見解對我們來說都很重要。因此，我們接下來要做的就是產生更多數據並獲得更高劑量，因為每個隊列只有少數患者。

And I would just add one thing. I think you talked about combination just to remind you that we do it. The first part is on top of the anti-retroviral.

我只想補充一件事。我想你談到組合只是為了提醒你我們這樣做。第一部分是抗愛滋病毒藥物。

Yes. Thanks.

是的。謝謝。

Avantika Joshi, Mizuho.

阿凡提卡·喬希，瑞穗。

Hi. This is Avantika on for Greg. I just had a question. Are you still looking at brenetafusp in tumors beyond melanoma, ovarian, and non-small cell?

你好。這是 Greg 的 Avantika。我只是有一個問題。您還在關注黑色素瘤、卵巢癌和非小細胞瘤以外的腫瘤中的 brenetafusp 治療嗎？

Yes, we certainly are. And there's strong scientific rationale. As a team, I've asked them to focus, right? We're launching a global Phase 3 cutaneous melanoma. We are committed to following up on the signals in ovarian and to look for signals in line. And we've certainly had the sites focus on those as well. We do have ongoing Phase 1 exploration in other tumors, but we've had to focus. And so we are certainly interested in continuing to be interested in other tumors like endometrial.

是的，我們當然。而且有很強的科學根據。作為一個團隊，我要求他們集中註意力，對嗎？我們正在全球啟動皮膚黑色素瘤第三期臨床試驗。我們致力於追蹤卵巢內的訊號並尋找符合的訊號。當然，我們也讓網站專注於這些內容。我們確實正在對其他腫瘤進行一期探索，但我們必須集中精力。因此，我們當然有興趣繼續對子宮內膜等其他腫瘤感興趣。

And one more question was for the earlier stage assets for P115C and T119C, are you initially running basket studies? Are you focusing on specific tumors? Thank you.

還有一個問題是，對於 P115C 和 T119C 的早期資產，你們最初是否進行籃子研究？您專注於特定腫瘤嗎？謝謝。

Go ahead, Mohammed. I have to admit that I'm not -- I don't retain the numbers, but go ahead.

繼續吧，穆罕默德。我必須承認我不會——我不保留這些數字，但繼續吧。

Are those numbers referring to the half-life extended and the A24?

這些數字是指延長的半衰期和 A24 嗎？

Yeah, the half-life extended and the A24.

是的，半衰期延長了，還有 A24。

We would have to simplify that.

我們必須簡化它。

As David mentioned earlier, we are certainly applying all of the learnings from our F106C PRAME program to those two programs. We know where PRAME is expressed. So yes, those trials are designed expressively so we have multiple options in terms of the types of patients that we can enroll.

正如 David 之前提到的，我們當然會將 F106C PRAME 程式中的所有知識應用到這兩個程式中。我們知道 PRAME 在哪裡表達。所以，是的，這些試驗的設計是明確的，因此我們在可以招募的患者類型方面有多種選擇。

Okay. Thank you.

好的。謝謝。

Jeffrey Hung, Morgan Stanley.

傑弗裡洪，摩根士丹利。

Hello. This is Lina on for Jeff. Two questions here on PRAME. For the melanoma data, ctDNA responders were defined as 0.5 log reduction. Do you expect the threshold for meaningful correlation to longer survival to be similar across indications like in ovarian and lung? And the second question was when might we expect an update from the endometrial cohort? Thank you.

你好。這是莉娜為傑夫代言的。關於 PRAME 有兩個問題。對於黑色素瘤數據，ctDNA 應答者被定義為 0.5 log 減少。您認為與較長存活期有意義相關的閾值在卵巢和肺臟等適應症中是否相似？第二個問題是我們什麼時候可以期待子宮內膜隊列的更新？謝謝。

Yeah, I'm happy to take both of those. So ctDNA response criteria is still in the early stages. Externally, companies have looked in lung cancer for example at a 0.5 log reduction. So there's precedence of that called the molecular response.

是的，我很樂意接受這兩個。因此 ctDNA 反應標準仍處於早期階段。例如，在外部，公司已經研究了肺癌的對數減少 0.5。因此，有一個優先事項，稱為分子反應。

In our cutaneous melanoma data, that 0.5 log reduction did seem to -- in our uveal melanoma data that 0.5 log reduction did seem to be a good threshold cutoff for correlating with survival. We saw the same correlation in cutaneous melanoma, and we'll share that data on ctDNA on the ovarian data at ESMO.

在我們的皮膚黑色素瘤數據中，0.5 個對數減少似乎確實是——在我們的葡萄膜黑色素瘤數據中，0.5 個對數減少似乎確實是與生存相關的良好閾值截止值。我們在皮膚黑色素瘤中發現了同樣的相關性，我們將在 ESMO 的卵巢數據中分享 ctDNA 數據。

But it does look like that 0.5 log reduction I think is a good threshold for us based on the data we have today. In terms of the endometrial timeline, I think it's a little too soon to guide because, as I mentioned, we've asked the team to focus on ovarian, lung, and cutaneous melanoma. We'd ask the sites to focus on that as well too.

但根據我們今天掌握的數據，我認為 0.5 對數減少確實對我們來說是一個很好的閾值。就子宮內膜時間線而言，我認為現在指導還為時過早，因為正如我所提到的，我們已要求團隊專注於卵巢、肺部和皮膚黑色素瘤。我們也要求網站也關注這一點。

Okay.

好的。

Naureen Quibria, Capital One Securities.

諾琳‧奎布里亞，第一資本證券。

Hi, good morning. Congrats on all the progress. And I guess my first question sort of follows up on that last one. In terms of the PRAME results that you'll be on presenting at ESMO, you've observed benefit with KIMMTRAK outside of Rhesus response. Right?

嗨，早安。祝賀所有的進步。我想我的第一個問題是最後一個問題的後續。就您將在 ESMO 上展示的 PRAME 結果而言，您已經觀察到 KIMMTRAK 在 Rhesus 反應之外的益處。正確的？

So can you remind us how you're tracking response rate underestimates? Should we just focus on the disease control rate, or you mentioned that they'll be ctDNA? Is there anything else?

那麼您能否提醒我們您如何追蹤低估的回覆率？我們應該只關注疾病控制率，還是你提到它們會是 ctDNA？還有別的嗎？

Yes, it's a good question. I mean, we certainly saw this with uveal melanoma. This even patients with both radiographic increase in size that benefit that survival benefit and long-term survival. We saw a few patients of those with brenetafusp in the cutaneous melanoma. We will, I think, continue to see that in the ovarian and the lung as well.

是的，這是一個好問題。我的意思是，我們確實在葡萄膜黑色素瘤中看到了這一點。這甚至使影像學上尺寸增大的患者受益於生存獲益和長期生存。我們看到一些患有皮膚黑色素瘤的布雷內塔福斯患者。我認為，我們將繼續在卵巢和肺部看到這一點。

I think the way that we're looking at how do you measure benefit, of course, is ctDNA which is a way to measure independence of radiographic, but also looking at treatment beyond progression because this is where the investigator sees the patient having a radiographic increase in size. But they feel the patient is benefiting. So we saw this early, this treatment beyond progression was and a good initial indicator.

我認為我們研究如何衡量獲益的方法當然是ctDNA，這是一種衡量放射學獨立性的方法，但也著眼於進展之外的治療，因為這是研究人員看到患者進行放射學檢查的地方。但他們認為患者正在受益。所以我們很早就看到了這一點，這種超越進展的治療是一個很好的初步指標。

Now, although we do see this TD benefit, we see very strikingly for KIMMTRAKs. We feel that with brenetafusp, disease control rate is an equally -- is a very good metric to predict PFS. And in fact my sense of the data is that although brenetafusp does have benefit in the TD, it has more disease control than KIMMTRAK does. But I think at the end of the day, of course survival will be the ultimate endpoint. I do feel PFS is still a good endpoint for brenetafusp. Mohammed, anything to add on that?

現在，儘管我們確實看到了 TD 的優勢，但我們對 KIMMTRAK 的看法非常引人注目。我們認為，對於 brenetafusp，疾病控制率同樣是預測 PFS 的一個非常好的指標。事實上，我對數據的感覺是，雖然 brenetafusp 確實在 TD 方面有好處，但它比 KIMMTRAK 具有更多的疾病控製作用。但我認為最終，生存當然是最終的終點。我確實認為 PFS 仍然是 brenetafusp 的一個很好的終點。穆罕默德，還有什麼要補充的嗎？

No. Thank you.

不。謝謝。

Okay, that's helpful. And I guess sort of sticking to the ovarian cancer topic, what's the distribution of PRAME compared to folate receptor? Is there like an overlap there. I guess I'm just trying to gauge, you know, if you I'd like to see any patients coming off of date you'll hear into this. Would there be any of those types of patients in the combo?

好的，這很有幫助。我想還是繼續討論卵巢癌的話題吧，與葉酸受體相比，PRAME 的分佈如何？那裡有重疊嗎？我想我只是想衡量，你知道，如果你想看到任何病人過時，你會聽到這一點。組合中會有這些類型的患者嗎？

Sure. Naureen, happy to address that. So for PRAME per se, it's very similar to -- in ovarian it's very similar to melanoma. It's around 80% to 90%. With regards to the folate receptor alpha for LFR, it's like between 35% and 40%.

當然。諾琳，很高興能解決這個問題。因此，對於 PRAME 本身來說，它與卵巢中的黑色素瘤非常相似。大約是80%到90%。至於 LFR 的葉酸受體 α，大約在 35% 到 40% 之間。

The exact overlap, I don't think we have that data. But there's probably some overlap, but you can derive sort of 30% to 40% for folate receptor and 80% to 90% is the prevalence for PRAME in ovarian.

確切的重疊，我認為我們沒有這些數據。但可能會有一些重疊，但您可以推導出葉酸受體的盛行率約為 30% 至 40%，卵巢中 PRAME 的盛行率約為 80% 至 90%。

I'd just add that what we've seen continually we saw in melanoma, BRAF mutant wild-type and in the -- and with the EGFR because we've looked at that mutation that's in lung that we see PRAME expression independent of whether there's a mutation or not. And so although, as Mohammad said, we don't have the exact overlap with folate receptor alpha.

我想補充一點，我們在黑色素瘤、BRAF 突變野生型和 EGFR 中不斷觀察到的情況，因為我們觀察了肺部的突變，我們發現 PRAME 表現與是否存在無關是否有突變。因此，正如穆罕默德所說，我們與葉酸受體α並不完全重疊。

I suspect 90% of folate receptor alpha positive are going to be positive for PRAME, and I suspect 90% of folate receptor alpha negative are going to be. I suspect that, but we just don't have that data right now.

我懷疑 90% 的葉酸受體 α 陽性的人 PRAME 呈陽性，我懷疑 90% 的葉酸受體 α 陰性的人 PRAME 呈陽性。我對此表示懷疑，但我們現在沒有這些數據。

Thanks for taking my questions.

感謝您回答我的問題。

Ranjan Sharma, Goldman Sachs.

蘭詹·夏爾馬，高盛。

Hi. Thanks for taking my questions. So just going back to KIMMTRAK dynamics, and I just wanted to get your thoughts on how you see pricing evolving in the long term. I think your slide 10, where you laid out the increased patient opportunity with the additional indications. But just given the extent of that potential volume uplift you expect there to be some pressure on price, both in the US and in Europe?

你好。感謝您回答我的問題。回到 KIMMTRAK 動態，我只是想了解您對長期定價演變的看法。我認為您的投影片 10 中列出了增加的患者機會以及附加適應症。但考慮到潛在銷售成長的程度，您預期美國和歐洲的價格都會面臨一些壓力嗎？

And I guess related to your comments on Europe, if there is kind of downward pressure on price with these additional indications, do you think that a European launch would be viable for those? And then just to follow up, in ovarian cancer, do you expect to include folate receptor alpha positive patients in that trial as well?

我想與您對歐洲的評論有關，如果這些額外的跡象對價格造成某種下行壓力，您認為在歐洲推出這些產品是否可行？然後，為了跟進，在卵巢癌中，您是否希望將葉酸受體α陽性患者也納入該試驗中？

And then just one follow up on HIV, if I could where do you think dose could go? So I think at the minute, you said 300 is the upper level related to that, how high do you think you can dose?

然後只是對愛滋病毒進行一次跟進，如果可以的話，您認為劑量會去哪裡？所以我認為目前你說 300 是與此相關的上限，你認為你可以劑量多高？

Great. Thank you, Ranjan. And several questions. Maybe we'll start with the HIV and then we'll go from there to commercial.

偉大的。謝謝你，蘭詹。以及幾個問題。也許我們會從愛滋病毒開始，然後從那裡開始走向商業化。

So what's the HIV, if you remember, we showed at 15 micrograms were already seeing target engagement because we saw IL6. With our platform, you don't need to give a lot. With KIMMTRAK, that was in the 64 -- 68 microgram dose, we see a survival benefit. So we don't know how high we can go. We're going to go as high as needed. But we certainly know that you don't need to go up to milligram doses with our platform.

那麼什麼是 HIV，如果您還記得的話，我們在 15 微克濃度下就已經看到了目標參與，因為我們看到了 IL6。有了我們的平台，您不需要付出太多。使用 KIMMTRAK，劑量為 64 - 68 微克，我們看到了存活獲益。所以我們不知道我們能走多高。我們將根據需要達到盡可能高的高度。但我們當然知道您不需要使用我們的平台服用高達毫克的劑量。

In terms of the folate receptor alpha, we don't exclude prior folate receptor alpha. In fact, we have had a few patients who were -- who had prior ATC enrollment for our trial. Our approach, once, again, is not to replace brenetafusp. It's not to go head-to-head, which is why it's to add on to chemotherapy and so it's independent of the data.

就葉酸受體α而言，我們不排除先前的葉酸受體α。事實上，我們有一些患者之前已在 ATC 中登記參加我們的試驗。我們的方法再一次不是要取代 brenetafusp。這不是正面交鋒，這就是為什麼它要添加到化療中，因此它獨立於數據。

And Ralph, can you comment on the reimbursement just to reiterate here, I don't think we have any issues in the US, but it's mostly the EU. Go ahead, Ralph, please.

拉爾夫，您能否對報銷發表評論，在這裡重申一下，我認為我們在美國沒有任何問題，但主要是歐盟。繼續吧，拉爾夫，請。

Sure, happy to. So first of all, our pricing strategy really depends on the benefit that we see from the data, right? So it should bring benefits -- significant benefits to patients and society. That's how we price our further indication. To your question on the US and to Bahija's point, we have not seen any downward pressure in the US so far.

當然，很高興。首先，我們的定價策略實際上取決於我們從數據中看到的好處，對吧？所以它應該帶來好處——為患者和社會帶來巨大的好處。這就是我們對進一步指示進行定價的方式。至於你提到的美國問題，以及巴希賈的觀點，到目前為止，我們沒有看到美國出現任何下行壓力。

In fact I expect that if the data is good in cutaneous, given that these are settings of high unmet need and with small patient populations that we would not have to erode the price significantly in the US.

事實上，我預計，如果皮膚方面的數據良好，考慮到這些地區的需求未滿足，而且患者人數較少，我們就不必大幅降低美國的價格。

On the other hand in Europe, you have a good question in terms of price erosion. And I think it's too soon to tell. We need data for us to decide whether we'll be launching in Europe or not although it is a very tough market access environment. Frankly, one of the toughest I've seen through all my years of working with Europe.

另一方面，在歐洲，價格侵蝕是一個很好的問題。我認為現在下結論還為時過早。我們需要數據來決定是否在歐洲推出，儘管這是一個非常艱難的市場准入環境。坦白說，這是我多年來在歐洲工作中遇到的最艱難的事情之一。

Ethan Markowski, Needham & Company.

伊森‧馬科夫斯基，李約瑟公司。

This is Ethan on for Gil. Thank you for taking our questions. I think most of them have been answered thus far, but just wondering -- so I know endometrial is not one of the focused indications for PRAME. But wondering if you plan on going into a similar strategy there where moving any combination in earlier lines like you're planning to do in non-small cell lung cancer and ovarian.

這是伊森替吉爾代言。感謝您接受我們的提問。我認為到目前為止，大多數問題都已得到解答，但只是想知道 - 所以我知道子宮內膜並不是 PRAME 的重點適應症之一。但想知道您是否計劃採取類似​​的策略，在早期的生產線中移動任何組合，就像您計劃在非小細胞肺癌和卵巢癌中所做的那樣。

And then for KIMMTRAK, you talked about the difficult reimbursement in Europe. Will growth there really be mostly driven by just adding additional countries or do you think that those dynamics are likely to change over time?

然後對於 KIMMTRAK，您談到了歐洲的報銷困難。那裡的成長真的主要是透過增加更多國家來推動的嗎？

Thank you, Ethan. Mohammad, you could take the first two are Ralph, maybe on Europe.

謝謝你，伊森。穆罕默德，你可以認為前兩個是拉爾夫，也許是在歐洲。

Thanks, Ethan, for the question. I think you know, as David mentioned, the focus has been on ovarian, melanoma and lung for now. So the endometrial data that we're generating. it's really on in monotherapy with some of the chemotherapies that are used in late line. And right now, we don't have current plans to explore endometrial in earlier lines until we actually generate data in the late lines to guide.

謝謝伊森提出的問題。我想你知道，正如大衛所提到的，目前的焦點是卵巢癌、黑色素瘤和肺癌。我們正在產生的子宮內膜數據。它確實在單一療法中與後期使用的一些化療一起發揮作用。目前，我們目前沒有計劃在早期線中探索子宮內膜，直到我們真正在後期線中產生數據來指導。

Ralph?

拉爾夫？

Sure. So the there is, in fact, a very tough environment in Europe as we've been discussing. However, we've had a lot of successes when it comes to reimbursement. So we've had nine launches in the first half of the year.

當然。事實上，正如我們一直在討論的那樣，歐洲的環境非常艱難。然而，我們在報銷方面取得了許多成功。今年上半年我們已經發布了九次產品。

And we expect some of that marginal growth will come from further additional launches because we're currently in negotiations with several countries. In addition to that. I mean, obviously, we're very well penetrated. The team has been doing a great job in Europe. So really, it's the launches driving the next level of growth.

我們預計部分邊際成長將來自進一步的額外發布，因為我們目前正在與多個國家進行談判。除此之外。我的意思是，顯然，我們的滲透力非常好。該團隊在歐洲表現出色。事實上，正是產品的推出推動了新一輪的成長。

At this time, I'd like to hand the call back to Bahija Jallal for closing comments.

此時，我想將電話轉回 Bahija Jallal 以徵求結束意見。

Thank you, operator. So once again, I just want to thank you for your patience, first of all, and continued trust and commitment. We'll now close the call. Thank you.

謝謝你，接線生。首先，我想再次感謝您的耐心以及持續的信任和承諾。我們現在將結束通話。謝謝。

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

謝謝。今天的電話會議到此結束。我們感謝您的參與。此時您可以斷開線路。並享受剩下的一天。