Summit Therapeutics Inc (SMMT) 2024 Q4 法說會逐字稿

Good morning, and welcome to Summit Therapeutics fourth quarter and year-end 2024 earnings and update Call. (Operator Instructions). Please note that today's call is being recorded. (Operator Instructions).

早安，歡迎參加 Summit Therapeutics 第四季和 2024 年年終收益和更新電話會議。（操作員指令）。請注意，今天的通話正在錄音。（操作員指令）。

At this time, I would like to turn the call over to Dave Gancarz, Summit Therapeutics' Chief Business and Strategy Officer. You may proceed.

現在，我想將電話轉給 Summit Therapeutics 的首席業務和策略長 Dave Gancarz。您可以繼續。

Good morning and thank you for joining us. Two press releases were issued earlier this morning and are available on the homepage of our website. Our Form 10-K was also filed earlier this morning and is available on our website. Today's call is being simultaneously webcast and an archived replay will also be made available later today on our website, www.smmttx.com.

早安，感謝您加入我們。今天早上已發布了兩份新聞稿，可在我們網站的主頁上查閱。我們的 10-K 表格也已於今天早上提交，並可在我們的網站上查閱。今天的電話會議將同時進行網路直播，存檔重播也將在今天稍後在我們的網站 www.smmttx.com 上提供。

Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer; Dr. Maky Zanganeh, our Chief Executive Officer and President; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; and Dr. Allen Yang, our Chief Medical Officer.

今天與我一起參加電話會議的還有我們的董事會主席兼首席執行官 Bob Duggan；我們的首席執行官兼總裁 Maky Zanganeh 博士； Manmeet Soni，我們的首席營運官兼首席財務官；以及我們的首席醫療官 Allen Yang 博士。

Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we may make today may be considered forward-looking statements based on our current expectations. Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements.

在我們開始電話會議的其餘部分之前，我想指出，我們的管理團隊所做的一些聲明以及我們今天可能提出的一些問題的回答可能被視為基於我們當前預期的前瞻性陳述。Summit 警告稱，這些前瞻性陳述受風險和不確定性的影響，可能導致實際結果與前瞻性陳述中所示的結果有重大差異。

Please refer to our SEC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements, except as required by law. Following comments from Bob, Maky and Manmeet, we will take questions. With that, I will turn the call over to Bob.

有關這些風險和不確定性的信息，請參閱我們的美國證券交易委員會 (SEC) 文件。除非法律要求，Summit 不承擔更新這些前瞻性聲明的義務。根據 Bob、Maky 和 ​​Manmeet 的評論，我們將回答問題。說完這些，我會把電話轉給鮑伯。

Thank you, Dave. Good morning, everyone, and thank you for joining us today. I am very pleased with recent accomplishments of Team Summit and the accelerating positive information and enthusiasm surrounding Ivonescimab, our lead investigational asset. In Q4 of last year and to date in 2025, we have reached several meaningful milestones around the development of Ivonescimab, importantly, with our partners in China as well as here in the US and western markets.

謝謝你，戴夫。大家早安，感謝大家今天加入我們。我對 Team Summit 最近的成就以及圍繞我們的主要研究資產 Ivonescimab 不斷增加的積極訊息和熱情感到非常高興。從去年第四季到 2025 年至今，我們在 Ivonescimab 的開發方面取得了幾個有意義的里程碑，重要的是，我們與中國以及美國和西方市場的合作夥伴一起取得了這些里程碑。

We continue to progress towards our mission of building an organization making a significant positive difference in serious unmet medical needs. Specifically, earlier today, we announced a clinical trial collaboration with Pfizer which will evaluate Ivonescimab in combination with multiple Pfizer antibody drug conjugates, or ADCs, in unique solid tumor settings. Rapidly developing novel mechanisms that go beyond what is currently available to patients and physicians is what we believe will make the most significant impact for those facing the greatest challenges from cancer to date.

我們將繼續朝著我們的使命邁進，建立一個能夠為尚未滿足的嚴重醫療需求帶來​​重大積極變化的組織。具體來說，今天早些時候，我們宣布與輝瑞公司進行一項臨床試驗合作，該合作將評估 Ivonescimab 與多種輝瑞抗體藥物偶聯物（ADC）在獨特實體瘤環境中的聯合應用。我們相信，快速開發超越患者和醫生目前可用方法的新機制將對那些迄今為止面臨癌症最大挑戰的人產生最重大的影響。

We believe this collaboration with Pfizer will accelerate the advancement of potentially landscape-changing therapeutic combinations, which intend to improve the standards of care for patients facing serious unmet needs. Clinical trials associated with this collaboration are expected to start by the middle of this year.

我們相信，與輝瑞的這項合作將加速可能改變格局的治療組合的進步，旨在提高面臨嚴重未滿足需求的患者的護理標準。與此合作相關的臨床試驗預計將於今年年中開始。

In October of last year, we completed enrollment in and received Fast Track designation for HARMONi, our global Phase III trial patients with EGFR mutated advanced non-small cell lung cancer who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor, or TKI. Top line data from Ivonescimab's first global registrational Phase III trial HARMONi is expected in mid-2025.

去年 10 月，我們完成了 HARMONi 的招募並獲得了快速通道資格，這是我們的全球 III 期試驗，試驗對象為患有 EGFR 突變的晚期非小細胞肺癌且在接受第三代 EGFR 酪氨酸激酶抑製劑或 TKI 治療後病情出現進展的患者。Ivonescimab 的首個全球註冊 III 期試驗 HARMONi 的頂線數據預計將於 2025 年中期公佈。

Additionally, in October of last year, we announced a steady amendment to the HARMONi-3 protocol expanding the study to include patients with both squamous and non-squamous histologies. With this amendment, HARMONi-3 is a multiregional registrational Phase III trial assessing Ivonescimab as first-line treatment for patients with metastatic non-small cell lung cancer with both squamous and non-squamous histologies.

此外，去年 10 月，我們宣布對 HARMONi-3 方案進行穩步修訂，將研究範圍擴大到包括鱗狀和非鱗狀組織學患者。經過此項修訂，HARMONi-3 是一項多區域註冊 III 期試驗，旨在評估 Ivonescimab 作為鱗狀和非鱗狀組織學轉移性非小細胞肺癌患者的一線治療。

Enrollment is ongoing globally for patients with tumors with squamous histology, and we have begun enrollment in patients in the United States with non-squamous tumors.

我們正在全球招募患有鱗狀組織學腫瘤的患者，並且已開始在美國招募患有非鱗狀腫瘤的患者。

HARMONi-3 now addresses a patient population 2x to 3x larger than prior to the amendment significant -- prior to the amendment, significantly expanding the numbers of patients with cancer that Ivonescimab can potentially help.

HARMONi-3 目前治療的患者數量比修訂前增加了 2 到 3 倍，大大擴大了 Ivonescimab 可能能夠幫助的癌症患者數量。

Towards the end of the year, we announced our third global Phase III trial, HARMONi-7, would be initiated in early 2025. Initial trial sites have begun activating in the United States and HARMONi-7 continues to progress as planned. As a reminder, HARMONi-7 is evaluating Ivonescimab monotherapy against Pembrolizumab monotherapy in first-line metastatic non-small cell lung cancer patients whose tumors have high PD-1, PD-L1 expression without actionable genomic alterations.

接近年底，我們宣布第三次全球 III 期試驗 HARMONi-7 將於 2025 年初啟動。初步試驗地點已在美國開始啟動，HARMONi-7 繼續按計畫進展。提醒一下，HARMONi-7 正在評估 Ivonescimab 單藥治療與 Pembrolizumab 單藥治療一線轉移性非小細胞肺癌患者的療效，這些患者的腫瘤具有高 PD-1、PD-L1 表達，且沒有可操作的基因組改變。

Maky will further discuss these accomplishments, including additional strides taken to drive our continued belief and what could be accomplished by Team Summit as well as our conviction in the potential of Ivonescimab in non-small cell lung cancer and very importantly, indications beyond lung cancer.

Maky 將進一步討論這些成就，包括為推動我們持續信念而採取的額外措施和 Team Summit 可以取得的成就，以及我們對 Ivonescimab 在非小細胞肺癌以及非常重要的肺癌以外適應症方面的潛力的信心。

We are a mission-driven organization with an overriding patient goal to improve quality of life, increased potential duration of life and resolve serious medical needs. We are the right team, and we believe we have the molecule in Ivonescimab to realize this goal.

我們是一個以使命為導向的組織，我們的首要目標是改善患者的生活品質、延長潛在壽命並解決嚴重的醫療需求。我們是一支合適的團隊，我們相信我們擁有 Ivonescimab 中的分子來實現這一目標。

With that, I will turn the call over to Maky for additional context and recent highlights for consideration. Maky?

接下來，我將把電話交給 Maky，讓他提供更多背景資訊和近期亮點以供考慮。瑪基？

Thank you, Bob, and good morning, everyone. As Bob said, I remain incredibly enthusiastic about the future of Summit and the possibilities of what can be accomplished with our lead candidate, Ivonescimab.

謝謝你，鮑勃，大家早安。正如鮑勃所說，我仍然對 Summit 的未來以及我們的主要候選藥物 Ivonescimab 所能取得的成就充滿熱情。

Before providing some additional detail and reviewing the current pipeline, I would like to touch on the clinical work that has been conducted with Ivonescimab and some of the interest and recognition received last year.

在提供更多細節和回顧目前的研發線之前，我想談談 Ivonescimab 開展的臨床工作以及去年獲得的一些關注和認可。

Since first entering the clinic with our partner, Akeso back in 2019, more than 2,300 patients have been treated in clinical trials with Ivonescimab. In 2024, alone, Ivonescimab was featured in 14 publications across seven tumor types and selected for five oral presentations at major medical conferences. Currently, between our partners at Akeso and our team at Summit, four Phase III trials have been completed enrollment, two of which are waiting top line data readout including the Summit sponsored HARMONi trial.

自 2019 年與我們的合作夥伴康方生物首次進入臨床以來，已有超過 2,300 名患者在臨床試驗中接受了 Ivonescimab 的治療。僅在 2024 年，Ivonescimab 就出現在 7 種腫瘤類型的 14 篇出版物中，並在 5 次主要醫學會議上被選為口頭報告。目前，我們在康方生物的合作夥伴和 Summit 的團隊已經完成了四項 III 期試驗的招募，其中兩項正在等待頂線數據讀數，其中包括 Summit 贊助的 HARMONi 試驗。

Five Phase III trials are currently ongoing, two of these are Summit sponsored drugs in first-line non-small cell lung cancer and three are Akeso sponsored trial studying Ivonescimab in head and neck, biliary tract, triple-negative breast cancers.

目前正在進行五項 III 期試驗，其中兩項是 Summit 贊助的一線非小細胞肺癌藥物，三項是康方生物贊助的試驗，研究 Ivonescimab 在頭頸部、膽道、三陰性乳癌中的應用。

Akeso has also announced its intention to start a clinical study in pancreatic cancer later this year. A significant amount of additional data is being generated in additional indications, including colorectal cancer, ovarian cancer, gastric cancer and hepatocellular carcinoma, in addition to more data to support the lung cancer program.

康方生物也宣布計劃於今年稍後啟動胰腺癌臨床研究。除了支持肺癌計畫的更多數據外，還在其他適應症方面產生了大量額外數據，包括大腸癌、卵巢癌、胃癌和肝細胞癌。

Turning specifically to the Summit sponsored pipeline, as Bob mentioned last quarter, HARMONi completed enrollment in the fourth quarter with top line data expected in mid-2025. This data is expected to contain data for both primary endpoints, progression-free survival and overall survival. HARMONi-3 was amended by significantly expanding the addressable patient population to include all frontline metastatic, non-small cell lung cancer patients without driver mutations by including patients with non-squamous tumors in addition to squamous tumors.

具體談到峰會贊助的管道，正如鮑勃上個季度提到的，HARMONi 在第四季度完成了註冊，預計在 2025 年中期會獲得頂線數據。預計該數據將包含兩個主要終點的數據，即無惡化存活期和總體存活期。HARMONi-3 經過修訂，顯著擴大了可尋址患者群體，除了鱗狀腫瘤患者外，還納入了非鱗狀腫瘤患者，將所有沒有驅動突變的一線轉移性非小細胞肺癌患者納入其中。

Squamous tumors represent approximately 25% to 30% of non-small cell lung cancer in the United States with non-squamous tumors representing a large proportion of the rest. A reminder, this trial includes patients with tumors that are PD-L1 negative, PD-L1 low expressing and PD-L1 high expressing.

在美國，鱗狀細胞腫瘤約佔非小細胞肺癌的 25% 至 30%，其餘大部分為非鱗狀腫瘤。提醒一下，該試驗包括 PD-L1 陰性、PD-L1 低表達和 PD-L1 高表達的腫瘤患者。

We announced our intention to initiate HARMONi-7 in early 2025, for which we have begun to activate clinical trial site in the United States. Later this year, we expect to announce additional details around expanding our clinical development plan around Ivonescimab, specifically beyond lung cancer.

我們宣布了在 2025 年初啟動 HARMONi-7 的計劃，並且已開始在美國啟動臨床試驗地點。今年晚些時候，我們預計將公佈有關擴大 Ivonescimab 臨床開發計劃的更多細節，特別是針對肺癌以外的領域。

After receiving interest for more than 75 investigator-sponsored trials in the most recent open window, we have approved over 30 ISTs today, which will either enhance our sponsored clinical development activities or can show signals in settings where Akeso has not yet had the opportunity to explore.

在最近的開放窗口中收到了超過 75 項研究者發起的試驗的興趣後，我們今天已經批准了 30 多項 IST，這要么將增強我們贊助的臨床開發活動，要么可以在康方生物尚未有機會探索的環境中顯示信號。

In 2024, we started our collaboration with MD Anderson, which now has studied that are activated and open for enrollment in Houston. We have committed $15 million to the collaboration to quickly discover additional opportunities for Ivonescimab, including several tumor things outside of its current development plan as well as the possibility of either buying biomarkers through additional research activities.

2024年，我們開始與MD Anderson 合作，目前研究已經在休士頓啟動並開放招生。我們承諾為該合作投入 1500 萬美元，以快速發現 Ivonescimab 的更多機會，包括其當前開發計劃之外的幾種腫瘤，以及透過額外的研究活動購買生物標誌物的可能性。

Finally, as we announced this morning, our clinical trial collaboration with Pfizer will look at Ivonescimab in combination with several Pfizer vedotin-based ADCs in multiple tumor types. As we seek to accelerate the development of Ivonescimab across non-small set lung cancer and other solid tumor setting, this collaboration will allow us to quickly advance beyond our promising late-stage development plan to evaluate Ivonescimab in combination with some of the most innovative ADCs provider.

最後，正如我們今天早上宣布的那樣，我們與輝瑞的臨床試驗合作將研究 Ivonescimab 與幾種基於輝瑞 vedotin 的 ADC 在多種腫瘤類型中的聯合應用。當我們尋求加速 Ivonescimab 在非小細胞肺癌和其他實體腫瘤領域的開發時，此次合作將使我們能夠快速超越我們有前景的後期開發計劃，以評估 Ivonescimab 與一些最具創新性的 ADC 提供者的結合。

Clinical trials as part of this collaboration are expected to start mid-2025. Pfizer will be responsible for the operations and costs associated with these trials, we will provide Ivonescimab and join the overseas study.

作為此次合作的一部分，臨床試驗預計將於 2025 年中期開始。輝瑞將負責這些試驗相關的營運和費用，我們將提供Ivonescimab並參與海外研究。

As a reminder for those new to the Summit story, Ivonescimab has significant lead in the clinical development of this global class of compound. Ivonescimab brings two highly validated targets together into one novel bispecific antibody that targets both PD-1 and VEGF.

對於那些剛了解 Summit 故事的人來說，Ivonescimab 在這一全球化合物類別的臨床開發中佔據重要領先地位。Ivonescimab 將兩個經過高度驗證的標靶結合在一起，形成一種新型雙特異性抗體，同時針對 PD-1 和 VEGF。

Next, I would like to review upcoming catalysts for this year and beyond. As we touch on a moment ago, we are expecting HARMONi top line data in mid-2025 which we expect will include both primary endpoints of progression-free survival and overall survival. This will be the first global Phase III clinical trial readout for Ivonescimab which provides a potential path to applying for marketing authorization in our territories, including potentially, the United States.

接下來，我想回顧一下今年及以後即將出現的催化劑。正如我們剛才提到的，我們預計 HARMONi 將在 2025 年中期獲得頂線數據，其中將包括無進展生存期和總體生存期這兩個主要終點。這將是 Ivonescimab 的首次全球 III 期臨床試驗讀數，為在我們的領土（包括美國）申請行銷授權提供了潛在途徑。

Secondly, we intend to expand our sponsored clinical development plan to go beyond non-small cell lung cancer in 2025 and 2026 in addition to continuing engagement with a rapidly increasing number of investigators seeking to conduct investigator-sponsored trial at various institutions across a large number of different tumor types. And you will see continual activating of additional ISTs in a variety of solid tumor settings.

其次，我們打算在 2025 年和 2026 年將我們贊助的臨床開發計劃擴展到非小細胞肺癌之外，此外還將繼續與越來越多的研究人員合作，尋求在各種機構針對大量不同腫瘤類型進行研究者贊助的試驗。您將會看到在各種實體腫瘤環境中持續啟動額外的 IST。

This is in addition to Akeso continuing its execution of its Phase III studies, including completing the enrollment of HARMONi-6 in frontline squamous non-small set lung cancer with Ivonescimab combined with chemo as well as continuing the enrollment of its Phase III biliary tract cancer, triple-negative breast cancer and head and neck cancer study.

除此之外，康方生物也持續執行其 III 期研究，包括完成 HARMONi-6 與 Ivonescimab 聯合化療治療一線鱗狀非小細胞肺癌的臨床試驗的招募，以及繼續進行其 III 期膽道癌、三陰性乳癌和頭頸癌研究的招募。

Over the course of this year, we will continue to seek clinical trial data readouts from Akeso in variety of tumor times. And finally, we expect to see more Phase III initiations from Akeso in non-small cell lung cancer and beyond, likely in indications in which Phase II data has been generated, which we touched on earlier. We are excited for the catalyst switch path ahead of us for convention and belief in the potential for Ivonescimab to improve patient lives for the better, remains strong and consistent.

今年，我們將繼續向康方生物尋求各種腫瘤時期的臨床試驗數據讀數。最後，我們預期康方生物將在非小細胞肺癌及其他領域啟動更多 III 期臨床試驗，很可能是針對已生成 II 期數據的適應症，我們之前曾提到過這一點。我們對眼前的催化劑轉換路徑感到興奮，並相信 Ivonescimab 改善患者生活的潛力依然強勁且一致。

Now I would like to take a moment to review study design for our two ongoing global Phase III trials, HARMONi-3 and HARMONi-7. Here, we have the study design for HARMONi-3, HARMONi-3 is a randomized, double-blind, global Phase III clinical trial, evaluating Ivonescimab in combination with chemotherapy against pembro in combination with chemotherapy as first line treatment for patients with metastatic non-small cell lung cancer.

現在，我想花點時間回顧一下我們正在進行的兩項全球 III 期試驗 HARMONi-3 和 HARMONi-7 的研究設計。這裡，我們有針對 HARMONi-3 的研究設計，HARMONi-3 是一項隨機、雙盲、全球 III 期臨床試驗，評估 Ivonescimab 聯合化療對比 pembro 聯合化療作為轉移性非小細胞肺癌患者的一線治療。

This trial includes patients with squamous and non-squamous histologies with no activating genomic alterations regardless of PD-L1 expression, including high, low and negative PD-L1 expressing tumors. Dual primary endpoint for HARMONi-3 include progression-free survival and overall survival, and results will be stratified by squamous and non-squamous histology.

本試驗包括鱗狀和非鱗狀組織學患者，無論 PD-L1 表現如何，均無活化基因組改變，包括高、低和陰性 PD-L1 表達腫瘤。HARMONi-3 的雙重主要終點包括無惡化存活期和總體存活期，結果將以鱗狀和非鱗狀組織學分層。

Next, we have the study design for HARMONi-7. HARMONi-7 is randomized double-blind global Phase III clinical trial, evaluating Ivonescimab monotherapy against pembro monotherapy as first-line treatment for the metastatic non-small cell lung cancer patients with tumors with high PD-L1 expression.

接下來，我們有針對 HARMONi-7 的研究設計。HARMONi-7 是一項隨機雙盲全球 III 期臨床試驗，評估 Ivonescimab 單藥治療與 pembro 單藥治療對 PD-L1 高表達轉移性非小細胞肺癌患者的一線治療效果。

Dual primary endpoints for HARMONi-7 include progression-free survival, overall survival and results will be stratified by squamous and non-squamous histologies. As a reminder, our HARMONi-7 study shares similarity with Akeso sponsored HARMONi-2 Phase III trials which reported data last year, but specifically targeted the PD-L1 high expressing tumors consistent with the standard of care for monotherapy immunotherapy in the US and Europe.

HARMONi-7 的雙重主要終點包括無惡化存活期、整體存活期，結果將以鱗狀和非鱗狀組織學分層。提醒一下，我們的 HARMONi-7 研究與康方生物贊助的 HARMONi-2 III 期試驗有相似之處，該試驗去年報告了數據，但專門針對 PD-L1 高表達腫瘤，與美國和歐洲單一療法免疫治療的護理標準一致。

Turning to the market opportunity for Ivonescimab, the value proposition here is clear. Ivonescimab has the potential to be a platform blockbuster drug and is well positioned to make a significant impact across the treatment landscape of non-small cell lung cancer and beyond. Specifically in non-small cell lung cancer, there are a combined six announced or ongoing Phase III studies conducted by either Akeso or Summit.

談到 Ivonescimab 的市場機會，這裡的價值主張很明確。Ivonescimab 有可能成為平台重磅藥物，並有望對非小細胞肺癌及其他領域的治療產生重大影響。具體來說，在非小細胞肺癌領域，康方生物和 Summit 共宣布或正在進行六項 III 期研究。

Non-small cell lung cancer alone has an addressable market that could ultimately approach $20 billion for checkpoint inhibitors according to the third quarter research from the likes of TD Cowen and others, but this is just a start.

根據 TD Cowen 等公司第三季的研究，非小細胞肺癌領域的潛在市場最終可能達到 200 億美元的檢查點抑制劑市場，但這只是一個開始。

There are more than 50 indications where PD-1, PD-L1 or VEGF therapies have been approved. Ivonescimab will continue to be rapidly tested and developed beyond non-small cell lung cancer. Across all checkpoint inhibitors indications, the addressable market approached $90 billion globally in the next couple of years, according to IQVIA Research.

PD-1、PD-L1 或 VEGF 療法已獲批准用於 50 多種適應症。Ivonescimab 將繼續在非小細胞肺癌之外進行快速測試和開發。根據 IQVIA Research 的數據，在所有檢查點抑制劑適應症中，未來幾年全球潛在市場規模將接近 900 億美元。

However, this still excludes the full impact that Ivonescimab could have, where it has shown promising data in multiple tumor types, where checkpoint inhibitors have not been effective, including microsatellite stable colorectal cancer, PD-L1 low triple-negative breast cancer and EGFR mutant non-small cell lung cancer after targeted therapy.

然而，這仍然排除了 Ivonescimab 可能產生的全部影響，它已經在多種腫瘤類型中顯示出有希望的數據，而檢查點抑製劑在這些腫瘤類型中並沒有效果，包括微衛星穩定的結直腸癌、PD-L1 低的三陰性乳腺癌和 EGFR 突變的非小細胞肺癌在靶向治療後。

We are excited to continue to progress our development in non-small set lung cancer into '25. Additionally, data shared in 2024 showed that Ivonescimab has a market potential much larger than non-small set lung cancer and our current ongoing global Phase III clinical studies that we are sponsoring at Summit.

我們很高興能夠在 2025 年繼續推動非小細胞肺癌領域的研發。此外，2024 年分享的數據表明，Ivonescimab 的市場潛力遠大於非小細胞肺癌以及我們目前在 Summit 贊助的全球 III 期臨床研究。

There are multiple Phase II trials that have been conducted, providing encouraging data to continue to explore Ivonescimab and the opportunity to become a standard of care across several solid tumor settings, which we intend to continue to explore with a goal to improve the lives of as many patients as possible facing high unmet medical needs.

目前已進行了多項 II 期試驗，為繼續探索 Ivonescimab 提供了令人鼓舞的數據，並有機會成為多種實體瘤治療的標準，我們打算繼續探索，目標是改善盡可能多的面臨高度未滿足醫療需求的患者的生活。

I would also like to take the opportunity to thank most importantly, the patients in our clinical studies as well as our investigators, hospitals, including our collaborators at MD Anderson and our partner in China, Dr. Michel Shaw and the entire Akeso team, as we continue to pave the way for rapid development of Ivonescimab globally.

我還想藉此機會，最重要的是感謝我們臨床研究中的患者以及我們的研究人員、醫院，包括我們在 MD Anderson 的合作者和我們在中國的合作夥伴 Michel Shaw 博士以及整個康方團隊，我們將繼續為 Ivonescimab 在全球範圍內的快速發展鋪平道路。

And of course, the Summit team. As Bob and I look back on all of the many achievements over just the past two years, Team Summit has done a tremendous job across every department in making our goals a reality and appropriately condensing time when and where possible. We continue to look at opportunities to accelerate our timeline in bringing additional therapeutic options to patients with high unmet cancer needs.

當然還有 Summit 團隊。當鮑伯和我回顧過去兩年所取得的許多成就時，高峰會團隊在各部門都做了大量工作，使我們的目標成為現實，並儘可能地適當壓縮時間。我們將繼續尋找機會加快我們的時間表，為癌症治療需求尚未滿足的患者提供更多的治療選擇。

It is an honor and privilege to work with each member of Team Summit, and I would like to express my heartfelt thanks to everyone of our team members.

能夠與 Team Summit 的每位成員一起工作是我的榮幸，我謹向我們團隊的每位成員表示衷心的感謝。

With that update, I will now ask Manmeet provide details on our financial position and operations update.

有了該更新，我現在將要求 Manmeet 提供有關我們的財務狀況和營運更新的詳細資訊。

Thank you, Maky, and good morning, everyone. This morning, we issued our earnings release for the fourth quarter and year ended 2024. Today, in addition to providing you with an update on our cash position and operating expenses, I will also be providing an update on our progress on clinical trial enrollment on HARMONi-3, HARMONi-7, an update on tech transfer for manufacturing in our licensed territories.

謝謝你，Maky，大家早安。今天上午，我們發布了 2024 年第四季和全年的收益報告。今天，除了向您提供我們的現金狀況和營運費用的最新情況外，我還將提供有關 HARMONi-3、HARMONi-7 臨床試驗註冊進展的最新情況，以及在我們許可的地區進行製造的技術轉移的最新情況。

On the financial front, let me start with the cash position. We ended the year 2024 with a strong cash position of approximately $412 million. Let me remind you that we have paid off our debt in entirety and now we are debt free. With a strong cash position and zero debt, we are well positioned to continue to execute on our clinical trials.

在財務方面，讓我先從現金狀況開始。截至 2024 年年底，我們的現金狀況強勁，約 4.12 億美元。讓我提醒你，我們已經全部還清了債務，現在我們沒有債務了。憑藉強大的現金狀況和零債務，我們有能力繼續進行臨床試驗。

Turning to operating expenses, I will be providing details to both GAAP and non-GAAP numbers. You can refer to our press release issued this morning for a reconciliation of GAAP to non-GAAP financial measures. Just to remind you, non-GAAP expenses exclude stock-based compensation expense. Our GAAP R&D expense during the full year 2024 were $150.8 million compared to $59.4 million for the previous year.

談到營運費用，我將提供 GAAP 和非 GAAP 數字的詳細資訊。您可以參考我們今天早上發布的新聞稿，以了解 GAAP 與非 GAAP 財務指標的對帳。需要提醒您的是，非公認會計準則費用不包括股票薪資費用。我們 2024 年全年的 GAAP 研發費用為 1.508 億美元，而前一年為 5,940 萬美元。

And non-GAAP R&D expenses were $134.8 million during the full year 2024 compared to $55 million for the previous year. The increase in the R&D expenses reflect the expansion of our clinical trials related to Ivonescimab.

2024 年全年非 GAAP 研發費用為 1.348 億美元，而前一年為 5,500 萬美元。研發費用的增加反映了我們與 Ivonescimab 相關的臨床試驗的擴大。

Our acquired in-process R&D expenses during the year 2024 were $15 million compared to $520.9 million for the previous year. To remind, acquired in-process R&D expenses for the year 2023 which were $520.9 million were related to the upfront payments made to Akeso for the licensing agreement. And $50 million expense in the year 2024 is related to the amendment of the licensing agreement with Akeso to include Latin America, Middle East and Africa regions into our license territory.

我們在 2024 年獲得的在研研發費用為 1,500 萬美元，而前一年為 5.209 億美元。需要提醒的是，2023 年收購的在研研發費用為 5.209 億美元，與支付給康方生物的授權協議預付款有關。2024 年的 5,000 萬美元支出與修改與康方生物的授權協議有關，將拉丁美洲、中東和非洲地區納入我們的授權區域。

Our GAAP G&A expenses during the full year 2024 were $60.5 million compared to $30.3 million for the previous year. And non-GAAP G&A expenses were $25.5 million during the full year 2024 compared to $20.6 million for the prior year.

我們 2024 年全年的 GAAP G&A 費用為 6,050 萬美元，而前一年為 3,030 萬美元。2024 年全年非公認會計準則一般及行政費用為 2,550 萬美元，而前一年為 2,060 萬美元。

Our GAAP G&A expenses primarily increased due to an increase in the stock-based compensation charges related to achievement of certain conditions on performance milestones, which vested during 2024. Overall, our non-GAAP expenses during the full year 2024 were $175.3 million compared to $596.5 million previous year.

我們的 GAAP G&A 費用增加主要是由於與實現某些績效里程碑條件相關的股票薪酬費用增加，這些費用於 2024 年歸屬。整體而言，我們 2024 年全年的非 GAAP 支出為 1.753 億美元，而前一年為 5.965 億美元。

The decrease in non-GAAP operating expenses was primarily related to the decrease in acquired and in-process R&D expenses, as mentioned earlier, which were offset by the increase in R&D expenses due to the expansion of clinical studies and development costs related to Ivonescimab.

非公認會計準則營業費用的減少主要與前文提到的收購和在研研發費用的減少有關，但這一減少被因擴大臨床研究和與 Ivonescimab 相關的開發成本而導致的研發費用的增加所抵消。

To remind that last quarter, we announced that we plan to expand HARMONi-3 study to include non-squamous patients in addition to the squamous patients. I'm very pleased that our Summit Team was able to activate non-squamous arm in a record time, and we recently started enrolling patients for non-squamous in the United States.

提醒一下，上個季度，我們宣布計劃擴大 HARMONi-3 研究，除了鱗狀患者外，還將非鱗狀患者納入其中。我很高興我們的 Summit 團隊能夠在創紀錄的時間內啟動非鱗狀細胞癌治療組，並且我們最近開始在美國招募非鱗狀細胞癌患者。

We expect to start activating sites to enroll non-squamous patients in other regions during the second quarter of 2025. We continue to enroll squamous patients in all the territories. Additionally, during last quarter, we had given guidance that we will initiate our newly announced pembro trial HARMONi-7 in frontline non-small cell lung cancer or PD-1 high patients in early 2025.

我們預計將於 2025 年第二季開始在其他地區啟動站點招募非鱗狀患者。我們將繼續在所有地區招募鱗狀細胞癌患者。此外，上個季度我們曾給予指導，將於 2025 年初啟動我們新宣布的針對一線非小細胞肺癌或 PD-1 高患者的 pembro 試驗 HARMONi-7。

A head of our schedule, Team Summit has already begun to activate sites in the United States. We expect to initiate activating sites in the other regions during this quarter of 2025.

比我們的計劃提前，Team Summit 已經開始在美國啟動站點。我們預計將於 2025 年本季在其他地區啟動啟動站點。

Turning to tech transfer for manufacturing, we continue to make progress in transferring relevant know-how to third parties to establish additional supply sources in our licensed territory. And with that, I will hand it back over to Dave. Dave?

在製造技術轉移方面，我們繼續在將相關技術轉移給第三方以在我們的許可區域內建立額外的供應源方面取得進展。說完這些，我就把權力還給戴夫。戴夫？

Thank you, Bob, Maky and Manmeet. We will now see if there are any questions that we can help -- that our team can help answer. Kate, if you could please open up the line for questions.

謝謝你，Bob、Maky 和 ​​Manmeet。我們現在將看看是否有任何問題我們可以幫助解決—我們的團隊可以幫助解答。凱特，請您打開熱線來回答問題。

(Operator Instructions).

（操作員指令）。

Yigal Nochomovitz, Citigroup.

花旗集團的 Yigal Nochomovitz。

Obviously, we're getting a lot of inbounds on HARMONi-2 and Akeso has provided some comments on the timing of the OS. If you could help us understand what you believe to be the timing for the HARMONi-2 OS. And given the fact that it may be approved in China as early as the third quarter of this year for the second indication for frontline, what is the potential or is there any expectation that we could see glimpse of some early OS data in that China label?

顯然，我們收到了很多有關 HARMONi-2 的訊息，而 Akeso 也對作業系統的時間安排提出了一些評論。如果您能幫助我們了解您認為 HARMONi-2 OS 的時機。鑑於它可能最早在今年第三季在中國獲得批准用於第二線治療，我們是否有可能或是否有期望在該中國標籤中看到一些早期的 OS 數據？

Thanks, Yigal. This is Dave. So I appreciate the question, and I know there's a bit of commentary with respect to HARMONi-2. As our partners at Akeso have mentioned, they expect to reach the number of events required for their interim analysis by the end of year 2025. We ultimately don't have more information on that front other than continuing partnership with Akeso. But at this point, there's been nothing new on that front with respect to any additional information. But appreciate the question.

謝謝，伊加爾。這是戴夫。我很感謝這個問題，而且我知道關於 HARMONi-2 有一些評論。正如我們在康方生物的合作夥伴所提到的，他們預計到 2025 年底將達到中期分析所需的事件數量。除了繼續與康方生物合作外，我們在這方面沒有更多相關資訊。但目前為止，這方面還沒有任何新的補充資料。但我很感謝你提出這個問題。

Okay. No worries. And then on the second-line EGFR, the HARMONi trial, I think Maky mentioned, you will have the OS data in the top line readout. What is your understanding as to whether you need that to be only a trend or actually hit on set that significant in order to be in a good position for approval in the US?

好的。不用擔心。然後在第二線 EGFR、HARMONi 試驗中，我認為 Maky 提到過，您將在頂行讀數中獲得 OS 數據。您認為，是否需要這只是一種趨勢，還是實際上達到瞭如此重要的程度，才能在美國獲得批准？

Yes, Yigal. This is Allen Yang. Thanks for the question. So I think there's two things. I think we, of course, would want to hit OS and be statistically significant. However, if you look at the precedent of previous approvals in this space, they have not required OS for PFS has been adequate.

是的，伊加爾。我是艾倫楊。謝謝你的提問。所以我認為有兩件事。我認為，我們當然希望達到 OS 並具有統計意義。然而，如果你看一下該領域以前的批准先例，你會發現他們並沒有要求 PFS 的 OS 就足夠了。

Okay. And then I know Manmeet just mentioned that you're starting to add the patients for non-squamous in the second quarter for HARMONi-3. Is there any possibility you could provide even a rough guideline as to the timing for the top line readout for HARMONi-3. And if you can't do that, anything you can say around HARMONi-6, given that's possibly helpful in terms of the read-through to HARMONi-3.

好的。然後我知道 Manmeet 剛剛提到，您將在第二季度開始為 HARMONi-3 添加非鱗狀患者。您能否提供關於 HARMONi-3 頂線讀數時間的粗略指導？如果您做不到這一點，您可以就 HARMONi-6 發表任何評論，因為這可能有助於理解 HARMONi-3。

Yigal, this is Manmeet. You heard it correct, right? We have just initiated our sites in US, and we have started enrolling for US the non-squamous arm. It's too early to give clarity on the completion of the enrollment until we complete all the sites and other territories, which is obviously in Europe and other regions, which we plan to initiate. We would be able to provide once all those sites are activated, and we have a quarter or two of the run rate, then we will have clarity in our time lines over there.

伊加爾，我是 Manmeet。你聽得沒錯吧？我們剛剛在美國啟動了我們的網站，並且已經開始為美國招募非鱗狀細胞癌患者。在我們完成所有站點和其他地區（顯然是在歐洲和其他地區，我們計劃啟動）之前，現在就明確完成招生還為時過早。一旦所有這些站點都啟動，我們就能提供服務，並且我們的運行率達到四分之一或二分之一，然後我們就能清楚地了解那裡的時間表。

Related to HARMONi-6, you're also correct, right, that trial has been completed enrollment, which was fully in China in the squamous arm and what I believe as for the guidance from Akeso, that should read out sometime in the middle to end of this year. We don't have visibility into any more details further than that.

關於 HARMONi-6，您說得也對，該試驗已經完成招募，該試驗完全在中國的鱗狀細胞癌組中進行，我相信康方生物的指導意見應該會在今年年中到年末的某個時候公佈。我們無法了解進一步的更多細節。

And then last quick one, I would be remiss if I didn't ask you about the news in on the Pfizer collab. Anything you could say there in terms of additional details, which of the vedotin ADCs, what tumor types? How big would these early studies be? And things of that nature?

最後，如果我不問您有關輝瑞合作的消息，那我就太失職了。您能提供更多細節嗎，例如哪種 vedotin ADC 適用於哪些腫瘤類型？這些早期研究的規模有多大？還有類似的事情嗎？

Yes. Thanks, Yigal, this is Dave. I really appreciate the interest there. I think -- so what we've said this morning, multiple ADCs from Pfizer, we plan to go into multiple solid tumor settings and expanding that beyond just non-small cell lung cancer, obviously. We haven't given specifics in terms of which ones just yet, but they are likely to be Phase Ib2 level trail at this point. We need -- these are the first combinations that we'll do with Ivonescimab in these specific ADCs. So normal course operations there. But we'll give additional details as we get close up.

是的。謝謝，伊加爾，我是戴夫。我真的很感激大家的關注。我認為——正如我們今天早上所說的，我們計劃將輝瑞的多種 ADC 應用於多種實體瘤環境，並將其擴展到非小細胞肺癌之外。我們還沒有給出具體細節，但目前它們很可能是階段 Ib2 等級的試驗。我們需要——這些是我們與 Ivonescimab 在這些特定 ADC 中進行的首次組合。所以那裡的課程運作正常。但當我們進一步了解後，我們會提供更多細節。

But we are very excited to get moving here. And I think as we've mentioned before, this is one of the strategic advantages that we feel we have in terms of the opportunity to combine Ivonescimab with a number of different products from a number of different organizations, pharmas and biotechs. And so this is one of the first steps in terms of moving forward from that perspective, but we will be giving additional details as we continue to get closer to the beginnings of these trials, which are expected in the middle of this year, so short term from that perspective.

但我們非常高興能夠搬到這裡。我認為，正如我們之前提到的，這是我們認為的戰略優勢之一，即有機會將 Ivonescimab 與來自許多不同組織、製藥公司和生物技術公司的多種不同產品相結合。因此，從這個角度來看，這是向前邁出的第一步，但隨著這些試驗的開始，我們將提供更多細節，預計試驗將在今年年中開始，所以從這個角度來看是短期的。

Brad Canino, Stifel.

布拉德‧卡尼諾 (Brad Canino)，Stifel。

In the Pfizer ADC collaboration, do you think about this more from the perspective of providing further therapeutic enhancement beyond the KEYNOTE-189 benchmark or more from the perspective of bringing Ivonescimab outside of lung with a better probability of success?

在輝瑞 ADC 合作中，您是否更多地從提供超越 KEYNOTE-189 基準的進一步治療增強的角度來考慮這一點，還是更多地從將 Ivonescimab 帶到肺部之外並提高成功率的角度來考慮這一點？

Brad, thanks for the question. Both, but probably the latter more. So clearly, ADCs are going to be important across solid tumor oncology. I think the data in lung cancer is interesting but the data outside of lung cancer has been stronger. And I think the fact that multiple ADCs is involved in this is important.

布拉德，謝謝你的提問。兩者都有，但可能後者更多。顯然，ADC 在實體腫瘤學中將發揮重要作用。我認為肺癌的數據很有趣，但肺癌以外的數據更有力。我認為多個 ADC 參與其中這一事實很重要。

And maybe just a quick follow-up on that. In lung specifically, as I look at the Pfizer pipeline of ADCs. Can I check your confidence level in integrin beta-6 for an ADC target over TROP-2 where obviously, competitors have frontline Phase III reading out this year?

也許只是對此進行快速跟進。具體來說，在肺部，當我查看輝瑞公司的 ADC 管道時。我可以檢查一下您對 ADC 標靶整合素 β-6 優於 TROP-2 的信心水平嗎？顯然，競爭對手今年已經有了前線 III 期數據？

Yes. So I appreciate the question, Brad. And I think we'll be in a better position to give a little bit more details as we get closer to launching the Phase Ib2 clinical trials. But at this point, we're not really getting into the specifics just yet in terms of the design as we want to allow for this trial to get up in the activation portion and then ultimately get up and running.

是的。所以我很感謝你提出這個問題，布拉德。我認為，隨著 Ib2 期臨床試驗的啟動，我們將能夠更好地提供更多細節。但目前，我們還沒有真正深入設計的細節，因為我們希望讓這次試驗在激活部分啟動，然後最終啟動並運行。

Brad, for what it's worth, it's an important question. We wish we can answer it, but we can't do it yet.

布拉德，不管怎樣，這是一個重要的問題。我們希望能夠回答這個問題，但目前我們還無法做到。

Maybe last for me. With the HARMONi EGFR data coming midyear, how do you plan to show the data to investors to demonstrate that there's comparable efficacy and safety and its effect in Western patients relative to Akesa's China patients?

或許對我來說是最後一次。HARMONi EGFR 數據將於年中公佈，您計劃如何向投資者展示這些數據，以證明其對西方患者與阿康薩的中國患者俱有相當的療效和安全性？

Thanks, Brad. Yes, I mean, I think that is going to be a key component. I think we and especially Allen, have been talking about this for over the course of the past year or so. One of the key components we'll be showing, the comparability of the data, to your point, both efficacy and safety in the eastern and western population.

謝謝，布拉德。是的，我的意思是，我認為這將是一個關鍵組成部分。我想我們，特別是艾倫，在過去一年左右的時間裡一直在談論這個問題。我們將要展示的關鍵要素之一是資料的可比性，正如您所說，即東西方人群的功效和安全性。

So while we haven't explicably described the ways in which we will show this. We'll obviously have presentations at major medical conferences. And this, the granularity will be there so that, that data can be interpreted.

因此，雖然我們還沒有明確描述我們將如何展示這一點。我們顯然會在大型醫學會議上進行演講。而且，粒度將會存在，以便可以解釋資料。

Kelly Shi, Jefferies.

Kelly Shi，傑富瑞集團。

Congrats on the progress. Maybe a couple of questions, how many trials, global trial design. So regarding the following assumptions on both PFS and OS, should we assume it is designed based on the total of 420 patients, but not a subgroup of ex-China patients?

恭喜你取得進展。也許有幾個問題，需要多少次試驗，全球試驗設計。那麼，關於 PFS 和 OS 的以下假設，我們是否應該假設它是基於總共 420 名患者而不是中國以外患者的一個亞組設計的？

Yes. Kelly, this is Allen Yang. Yes, it is a primary analysis of the total study population. Of course, as Brad alluded to, that there will be looks at the regional differences. We've had discussions on this from a regulatory standpoint about how the data analyzed and presented. But then, of course, during the analysis and during the review process, they could always ask for additional studies as well.

是的。凱利，我是艾倫楊。是的，這是對總體研究人群的初步分析。當然，正如布拉德所暗示的，我們會關注地區差異。我們從監管的角度討論如何分析和呈現數據。但是，當然，在分析和審查過程中，他們也可以隨時要求進行額外的研究。

Okay. And you guided a midyear for the data disclosure. I just want to confirm, this is referring to like June, July or actually could be like the entire Q2, Q3 time frame?

好的。您為資料揭露制定了年中計畫。我只是想確認一下，這是指六月、七月，還是實際上可能是整個第二季、第三季的時間範圍？

Yes, I appreciate the question, Kelly. I think we're probably a little bit broader on that and more in the Q2, Q3 timeline. But obviously, as we get closer to that, we'll be letting people know.

是的，我很感謝你的提問，凱利。我認為我們可能會對此進行更廣泛的討論，並且更多地關注第二季和第三季的時間軸。但顯然，隨著我們越來越接近這個目標，我們會讓人們知道。

Okay. Terrific. And one more on Pfizer collaboration. So regarding EV in bladder cancer, just curious, is there like a possibility to add some combo arm to the ongoing or the initiating Phase III trials running by Pfizer? Or should we expect more like early phase trials.

好的。了不起。還有一個關於輝瑞合作的問題。因此，關於膀胱癌中的 EV，我只是好奇，是否有可能在輝瑞正在進行或啟動的 III 期試驗中添加一些組合療法？或者我們應該期待更多類似早期階段的試驗。

Yes. I don't think we've disclosed anything. We're exploring every opportunity to move as quickly as possible. We haven't said anything about EV specifically, but we believe that EV is important in bladder cancer. And yes, more to come.

是的。我認為我們沒有透露任何資訊。我們正在探索一切機會，以盡快採取行動。我們沒有具體談論 EV，但我們相信 EV 對膀胱癌很重要。是的，接下來還會有更多。

Yes. We're excited to give you a little bit more details in the upcoming couple of months.

是的。我們很高興在接下來的幾個月為您提供更多詳細資訊。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

This is Sadia Rahman on for Mohit. Congrats on all the progress over the year. So I wanted to ask on the Pfizer collaboration. Curious how you're thinking about the overlapping toxicities with VEGF and inhibition and vedotin-based ADCs, and how this could differ from combinations with ADCs using topoisomerase summary payloads?

這是 Sadia Rahman 代替 Mohit 上場。恭喜你一年來的所有進步。所以我想問一下有關輝瑞合作的情況。好奇您如何看待 VEGF 與抑制和基於 vedotin 的 ADC 的重疊毒性，以及這與使用拓撲異構酶摘要有效載荷的 ADC 組合有何不同？

Yes, I appreciate the question there. I think part of -- if I take a step back, one of the things that we've expressed more broadly, is that we want to be able to take Ivonescimab and combine it with the best available treatments on a tumor-by-tumor level, right? And so part of what we will be doing is doing safety run-ins with any combination in which we combine with Ivonescimab, and that will be the same here.

是的，我很感謝你提出這個問題。我認為部分原因——如果我退一步來說，我們更廣泛地表達的事情之一是，我們希望能夠採用 Ivonescimab 並將其與腫瘤水平上最好的可用治療方法相結合，對嗎？因此，我們將要做的工作之一是對與 Ivonescimab 結合的任何組合進行安全性測試，這裡也是一樣的。

So I don't think we're in a position to commentate specifically on each of the different types of ADCs, whether it be MMAE base, whether it be topoisomerase base. We've seen data historically, whether it be in combination with immunotherapy like pembrolizumab in some of these ADCs whether it would be, again, MMAE-based or topoisomerase base.

因此，我認為我們無法具體評論每種不同類型的 ADC，無論是 MMAE 鹼基，還是拓撲異構酶鹼基。我們已經看到了歷史數據，無論它是否與某些 ADC 中的 pembrolizumab 等免疫療法相結合，無論它是否再次基於 MMAE 或拓撲異構酶基礎。

But at this point, we're excited about the profile that's been shown to date for Ivonescimab. We're very aware of the profile to date for many of the progressing ADCs. And I think that's where we're going to take the opportunity to do rational step-by-step combinations, and then we'll take that to the next step as we see the data.

但目前，我們對 Ivonescimab 迄今為止所展現的情況感到非常興奮。我們非常了解許多正在取得進展的 ADC 的最新情況。我認為這就是我們要藉此機會進行合理的逐步組合的地方，然後根據看到的數據，我們將進入下一步。

Yes. And I would just add there's emerging data in combination with pembrolizumab that these types of ADC combinations are feasible, and we have good safety data comparing Ivonescimab to pembrolizumab. So we don't expect any additions or surprises in the combinations.

是的。我想補充的是，有新數據表明，與 pembrolizumab 聯合使用時，這些類型的 ADC 組合是可行的，而且我們有良好的安全性數據來比較 Ivonescimab 和 pembrolizumab。因此，我們並不期待組合中出現任何新增內容或意外情況。

Got it. And then on the upcoming readout this year in EGFR mutant lung cancer, I think you said the majority of those patients are coming from the China HARMONi study, and the majority of those patients received the first or second-gen TKI before getting a third-gen TKI.

知道了。然後，關於今年即將發布的 EGFR 突變型肺癌數據，我認為您說過，這些患者中的大多數來自中國 HARMONi 研究，並且大多數患者在接受第三代 TKI 治療之前都接受了第一代或第二代 TKI 治療。

Would all of the patients recruited into the HARMONi study receive only a third-gen TKI in that first-line setting? And can you talk about how -- about any differences in those populations that we could expect in terms of time from diagnosis or survival after that third-gen TKI, and whether that could result in any differences in efficacy when looking at the next line of treatment?

參與 HARMONi 研究的所有患者是否都會在一線治療中僅接受第三代 TKI 治療？您能否談談我們可以預期這些族群在診斷時間或使用第三代 TKI 後的生存時間方面存在哪些差異，以及這是否會導致在下一輪治療中療效存在任何差異？

Yes, Sadia, just to be clear, the majority of patients in HARMONi A did receive a third-generation TKI as part of the standard of care, and those patients will be included. Whether they received a first or second generation before receiving a third generation, they would still be eligible. And in terms of differences and responses in those that got first or second versus third generation and where they got them, that's outlined in The Lancet publication by Zhang, et all., and we didn't expect any differences.

是的，Sadia，需要明確的是，HARMONi A 中的大多數患者確實接受了第三代 TKI 作為標準治療的一部分，這些患者也將被納入其中。無論他們在獲得第三代之前獲得第一代還是第二代，他們仍然有資格。至於接種第一代或第二代疫苗與接種第三代疫苗的患者的差異和反應以及接種地點，張等人在《柳葉刀》雜誌上發表的文章中對此進行了概述，我們預計不會有任何差異。

Okay. And then maybe one more on the HARMONi-2 trial and your global trial. So the to separation on the PFS curve in HARMONi-2 happened very early on. Can you talk about what you would expect for the global study since it adds on chemo combination? Just trying to understand how much the curves could shift and how that could affect timing of when you hit on PFS relative to when HARMONi-2 hit on PFS?

好的。然後也許還會有關於 HARMONi-2 試驗和全球試驗的討論。因此，HARMONi-2 中的 PFS 曲線的分離發生得很早。由於這項全球研究增加了化療組合，您能談談您對它有何期望嗎？只是想了解曲線可以移動多少，以及這會如何影響您擊中 PFS 的時間（相對於 HARMONi-2 擊中 PFS 的時間）？

Yes. I think we've put out a decent amount of data with respect to AK112-201, which was the Phase II, which looked at Ivonescimab plus chemotherapy in multiple settings, including both squamous and non-squamous in the frontline setting. That's probably the earliest or best rather in terms of an early thought process with respect to what we would see from data with Ivonescimab plus chemo, and comparing that against the historical benchmarks that you would see from trial such as KEYNOTE-189, KEYNOTE-407, et cetera.

是的。我認為我們已經發布了有關 AK112-201 的大量數據，該研究處於第二階段，研究了 Ivonescimab 聯合化療在多種環境下的效果，包括一線環境下的鱗狀細胞癌和非鱗狀細胞癌。就我們從 Ivonescimab 聯合化療的數據中看到的結果而言，這可能是最早或最好的早期思考過程，並將其與您從 KEYNOTE-189、KEYNOTE-407 等試驗中看到的歷史基準進行比較。

So I think that's probably -- those are probably the landmarks that I would look at from an early read in terms of what's publicly available. And then obviously, as we get continuing data, including HARMONi-6 from our partners at Akeso in the squamous front-line setting, those will be additional inputs that we'll provide more color.

所以我認為這很可能是——就公開內容而言，這些可能是我從早期閱讀中看到的里程碑。然後顯然，隨著我們獲得持續的數據，包括來自康方生物合作夥伴在鱗狀前線環境中的 HARMONi-6 數據，這些將是我們提供更多顏色的額外意見。

Mitchell Kapoor, H.C. Wainwright.

米切爾·卡普爾，H.C.溫賴特。

Congrats on this deal. Just can we just talk about kind of when you were searching for a BD transaction like this, can you just talk about what you were looking for before you came to this arrangement with Pfizer. And now that this deal is on the table, do you foresee additional BD opportunities or does this kind of preclude those for a while?

祝賀這筆交易成功。我們能否談談您在尋找這樣的 BD 交易時的情況，您能否談談在與輝瑞達成此協議之前您在尋找什麼。現在這筆交易已經擺在桌面上，您是否預見了更多的 BD 機會，或者這是否會暫時阻礙這些機會？

And could you just talk about if you expect future business development to be in the pursuit of combination similarly like this? And importantly, if there are any particular BD opportunities that you're not considering?

您能否談談，您是否預期未來的業務發展也會追求類似的組合？重要的是，是否存在您尚未考慮的特定 BD 機會？

Yes. Thanks for the question, Mitchell. I think if I, again, take a step back here. I think one of the things that we have talked about is the strategic advantage for Summit and Ivonescimab is that we don't have that pipeline internally that we're kind of almost committed to combining with and will almost force through combinations as much as possible to try to keep internal synergies.

是的。謝謝你的提問，米切爾。我想如果我在這裡再次退一步。我認為我們討論過的事情之一是 Summit 和 Ivonescimab 的戰略優勢，即我們內部沒有那種幾乎致力於結合的管道，並且幾乎會盡可能地強制進行組合，以保持內部協同效應。

And so in general, our approach will to look out and say, what are the best therapies, what are the standards of care across each of the different solid tumor settings and to the extent that Ivonescimab plus one of those whether antibodies or small molecules make sense, then that will be an opportunity where Ivonescimab can combine there.

因此，總的來說，我們的方法是尋找並說出最佳治療方法是什麼，在每種不同的實體腫瘤環境中的護理標準是什麼，以及 Ivonescimab 加上其中一種抗體或小分子是否有意義的程度，那麼這將是 Ivonescimab 可以結合的機會。

So I would say, as a whole, we don't believe there's a single ADC platform that individually is the only way to move forward, but we do believe that multiple companies have multiple different types of ADCs, whether it be topoisomerase base, whether it be MMAE base, whether it's switching up the antibodies in different settings. Obviously, there's a number of, for example, TROP-2 ADCs with different antibodies. So what we can do is really exploit different combinations of Ivonescimab plus X, Y or Z, ADC, antibody small molecule.

因此我想說，總的來說，我們不認為單一的 ADC 平台是前進的唯一途徑，但我們確實相信多家公司擁有多種不同類型的 ADC，無論是拓樸異構酶鹼基，還是 MMAE 鹼基，還是在不同環境下切換抗體。顯然，存在許多具有不同抗體的 TROP-2 ADC。因此，我們可以做的是真正利用 Ivonescimab 加 X、Y 或 Z、ADC、抗體小分子的不同組合。

So we're not really giving guidance in terms of what we plan to do X additional collaborations like this or whatnot. But in general, we certainly feel well position for is that we will take Ivonescimab and look to combine it with the best possible alternative, if you will, out there from a standard of care perspective to bring the most potential value to Ivonescimab and ultimately help patients in any way that we can there.

因此，我們實際上並沒有就我們計劃開展哪些此類額外合作或諸如此類的事情提供指導。但總的來說，我們當然覺得最好的選擇是，我們將採用 Ivonescimab，並尋求將其與最佳替代方案相結合，從標準護理的角度為 Ivonescimab 帶來最大的潛在價值，並最終以任何我們能做到的方式幫助患者。

Yes, Mitch, and this is Allen Yang. I would just say we just want to pursue the best science to help patients, right? And so I think there was a lot of interest in combining with pembro in terms of combination therapies with different immunotherapies and different other agents. And based on the HARMONi-2 data, as we had suspected that now companies are interested in sort of pairing with Ivonescimab, and that's where the puck is going.

是的，米奇，這是艾倫楊。我只想說我們只是想追求最好的科學來幫助患者，對嗎？因此，我認為，就與不同的免疫療法和其他不同的藥物的聯合療法而言，人們對與派姆單抗的結合非常感興趣。根據 HARMONi-2 數據，正如我們所懷疑的那樣，現在各公司對與 Ivonescimab 的配對很感興趣，這就是冰球的發展方向。

Okay. Great. And just to clarify the last point, are there anything, any particular BD opportunities that you're not open to at this juncture?

好的。偉大的。為了澄清最後一點，目前是否存在任何您不願意接受的特定 BD 機會？

No, I wouldn't say that there's specific things we're not open to. I think it's more about what is possible with Ivonescimab.

不，我不會說我們不接受某些具體的事情。我認為這更多的是關於 Ivonescimab 的可能性。

Yes. And I would just add, if there was some clear safety issue or something like that, but we have not seen that signal yet. So we're pretty excited that we have a lot of opportunity.

是的。我想補充一點，如果存在一些明顯的安全問題或類似問題，但我們還沒有看到這種訊號。因此，我們很高興我們擁有如此多的機會。

Sorry, Mitch. This is Manmeet. And I would just clarify, I guess, to answer your question very specifically, this transaction with Pfizer doesn't preclude us to do any other regional or any partnerships or any other activities?

對不起，米奇。這是 Manmeet。我想澄清的是，為了非常具體地回答您的問題，與輝瑞的這筆交易並不妨礙我們進行任何其他區域或任何合作或任何其他活動？

Very helpful. And the last one for me, just on the first-line trials. Can you talk about a little bit more about the HARMONi-3 enrollment? I know you briefly touched on that, but does HARMONi-7 site activation compete for patients for the PD-L1 high enrollment for HARMONi-3 at all?

非常有幫助。對我來說，這是最後一個，僅涉及一線試驗。您能否再多談談有關 HARMONi-3 註冊的情況？我知道您簡要地提到了這一點，但是 HARMONi-7 位點激活是否會爭奪 HARMONi-3 的 PD-L1 高入組率患者？

Yes, Mitch, this is Manmeet, again. Yes. Obviously, there is a segment of patients, right, PD-1 high patients, which will be covered in our HARMONi-3 also, right? So there is some sort of that, but as you know, we have much ahead in our schedule on HARMONi-3 activations and there will be not a full overlap of the sites, right, as compared to HARMONi-7.

是的，米奇，我又是 Manmeet。是的。顯然，有一部分患者，對吧，PD-1 高患者，也將在我們的 HARMONi-3 中得到覆蓋，對吧？所以有某種情況，但正如你所知，我們在 HARMONi-3 激活計劃上已經提前了很多，與 HARMONi-7 相比，站點不會完全重疊。

So we have just taken HARMONi-7 initiation in the last few weeks, and HARMONi-3 is already enrolling, right, our patients. So there will be -- obviously, there is an overlap, but we don't expect there is a competition because of the new sites which we are planning to add in HARMONi-7.

因此，我們在過去幾週剛剛啟動了 HARMONi-7 計劃，而 HARMONi-3 計劃也已開始招募我們的患者。因此顯然會有重疊，但我們預計不會出現競爭，因為我們計劃在 HARMONi-7 中添加新站點。

Congrats again on this collaboration.

再次恭喜這次合作。

Asthika Goonewardene, Truits Securities.

Asthika Goonewardene，Truits 證券。

Congrats on the progress as well. I wanted to dig into HARMONi-3 a little bit, please. Will the primary statistical analysis for that study, are you doing the primary analysis on the combined non-squamous plus squamous population? Or will you do it more in a step-wise manner kind of looking at the squamous and non-squamous subgroups individually first and then look at the overall population?

也祝賀你的進展。我想稍微深入了解一下 HARMONi-3。研究的主要統計分析是否針對非鱗狀細胞癌和鱗狀細胞癌的合併族群進行主要分析？或者您會採取逐步的方式，先分別研究鱗狀和非鱗狀亞群，然後再研究總體人群？

I ask it because I believe the BioNTech study is structured more like the latter. I'm curious to know if you take a different approach if so, why you prefer your method?

我之所以會問這個問題，是因為我相信 BioNTech 研究的結構更像後者。我很好奇，如果您採取了不同的方法，如果是的話，為什麼您更喜歡您的方法？

This Allen. Yes, so it is -- our plan is to do a primary analysis of the combined population, and we believe that, that was the best way to bring this product to patients as fast as possible from an operational perspective. Of course, there is always data and ongoing data coming out, the HARMONi-6 will be informative as well, but our current plan is to do a combined analysis.

這個艾倫。是的，我們的計劃是對合併後的人群進行初步分析，我們相信，從營運角度來看，這是盡快將產品帶給患者的最佳方式。當然，總會有數據和持續的數據出來，HARMONi-6 也會提供信息，但我們目前的計劃是進行綜合分析。

Got it. Thanks, Allen. Have you discussed with the FDA anyway to accelerate a filing with HARMONi-3. I'm wondering if you're seeing a strong PFS signal, is there -- have you talked to the FDA about maybe doing an accelerated filing based on that.

知道了。謝謝，艾倫。您是否與 FDA 討論過如何加快 HARMONi-3 的申請。我想知道您是否看到了強烈的 PFS 訊號，您是否與 FDA 討論過基於此進行加速備案的可能性。

Of course, we want to bring this to patients as fast as possible and we've had several discussions with them on this study, but I can't disclose our discussions at this time.

當然，我們希望盡快將這項技術帶給患者，並且我們已經就這項研究與他們進行了多次討論，但我目前無法透露我們的討論內容。

Got it. Okay. And then on the Pfizer collaboration, do you feel Ivonescimab would be -- could better leverage the immunogenic cell death versus PD-1? Or is the rationale behind this deal, mainly about layering on the classical anti-angiogenic pressure in addition to PD-1 with the ADC?

知道了。好的。那麼，關於與輝瑞的合作，您是否認為 Ivonescimab 可以更好地利用免疫原性細胞死亡而不是 PD-1？或者這筆交易背後的原理主要是關於除了 PD-1 之外，還要在 ADC 上疊加經典的抗血管生成壓力？

Yes, Asthika, great question. We could talk a lot about that. But with that said, part of it is empiric. We know that both of these drugs are -- a lot of these drugs are active in different tumor types and then you clearly want to add those efficacies. Whether there will be some synergistic effect through to the immune system for the profile? Would it be different from pembro's sort of additive or synergistic effect, we think all of those are actually possible, and we're looking forward to these combinations, but yes, it's very interesting.

是的，Asthika，這個問題問得很好。我們可以就此進行很多討論。但話雖如此，其中一部分是經驗性的。我們知道這兩種藥物——許多藥物對不同類型的腫瘤都有活性，然後你顯然想增加這些功效。該特性是否會對免疫系統產生一些綜效？它是否會與派姆的附加或協同作用有所不同，我們認為所有這些實際上都是可能的，我們期待這些組合，但確實，這非常有趣。

Ren Benjamin, Citizens JMP.

任本傑明（Ren Benjamin），公民 JMP。

Congratulations on all the progress. With HARMONi-3 and 7 kind of off to the races, can we talk a little bit about the next solid tumor indications you plan to invest in? And you've got some -- we had some ongoing study data reported last year. Can you talk a little bit about when we might see some updated results from those studies?

祝賀你取得的所有進展。隨著 HARMONi-3 和 7 的推出，我們可以談談您計劃投資的下一個實體瘤適應症嗎？您已經獲得了一些——我們去年報告了一些正在進行的研究數據。您能否談談我們何時可以看到這些研究的最新結果？

And I guess just as a sticking with this theme, I guess, broadly, do you kind of strategically follow Akeso based on their data, their solid tumor data and kind of do global studies based on what they reported? Or do you kind of broaden exposure and go after indications that maybe they're not addressing.

我想，只要堅持這個主題，我想，從廣義上講，您是否會根據康方生物的數據、實體腫瘤數據，從戰略上跟踪康方生物，並根據他們的報告進行全球研究？或者您是否會擴大曝光範圍並尋找他們可能尚未解決的跡象。

Sure, Ren. Thanks very much for the question. In reality, everything that you mentioned resonates, right? And so if you think about the last part of your question, which is do you follow Akeso or do you look to branch out, as Maky talked about, part of our MD Anderson collaboration looks to accomplish parts of that as well as our IST program.

當然，Ren。非常感謝您的提問。事實上，您提到的一切都會引起共鳴，對嗎？因此，如果您思考問題的最後一部分，即您是否會關注康方生物，還是會尋求拓展業務，正如 Maky 談到的，我們與 MD Anderson 合作的一部分旨在實現其中的部分目標以及我們的 IST 計劃。

If you look at some of the Phase II data generated by our partners at Akeso, which were released over the course of last year, whether it be BTC, colorectal cancer, head and neck cancer, and triple-negative breast cancer. There are some promising efficacy in that Phase II data.

如果你看一下我們在康方生物的合作夥伴產生的一些 II 期數據，這些數據是在去年發布的，無論是 BTC、大腸癌、頭頸癌還是三陰性乳癌。第二階段的數據顯示出一些有希望的療效。

There are also additional indications that have been explored in Phase II data hasn't yet been fully disclosed from that perspective, which gives us opportunities. And then obviously, we can run additional signal seeking or Phase II studies as well, whether on our own or through things like the collaboration the clinical trial collaboration with Pfizer here, which we'll look to do that as well.

從這個角度來看，第二階段的數據中還存在一些尚未完全披露的額外跡象，這給了我們機會。然後顯然，我們也可以進行額外的訊號搜尋或 II 期研究，無論是我們自己進行還是透過與輝瑞公司合作進行臨床試驗，我們也希望這樣做。

So as a whole, we've -- as Maky mentioned in her comments earlier, we're very keen to in addition to the significant work being done in non-small cell lung cancer look beyond lung cancer as well, and that's part of our '25-'26 development plan.

因此，總的來說，正如 Maky 在先前的評論中提到的那樣，除了在非小細胞肺癌領域所做的重要工作之外，我們還非常熱衷於研究肺癌以外的領域，這是我們 25-26 年發展計劃的一部分。

No, Ren. I was just going to add. So we haven't disclosed it, we're in the midst of multiple regulatory discussions around that. I would just say that we have been thinking about this for a long time, so we did this exercise even before the HARMONi-2 data read out shortly after the deal was done, looking at all the prior checkpoint inhibitor approvals, looking at all the angiogenic -- anti-angiogenic approvals.

不，任。我只是想補充一下。所以我們還沒有披露這一點，我們正處於圍繞這一問題的多項監管討論之中。我只想說，我們已經考慮這個問題很長時間了，所以我們甚至在交易完成後不久讀取 HARMONi-2 數據之前就做了這個練習，查看了所有之前的檢查點抑製劑批准，查看了所有血管生成 - 抗血管生成的批准。

Looking at we think the population size would be, what the comparator arm would be, and then you layer on top of that the Phase II data coming out from Akeso that all goes into the calculus of how we make those decisions and hopefully, we'll be able to disclose some exciting opportunities soon.

我們認為人口規模會是多少，比較組會是什麼，然後在此基礎上疊加來自康方生物的第二階段數據，所有這些都將用於我們做出這些決定的計算，希望我們能夠很快披露一些令人興奮的機會。

Outside of the opportunities, could we expect updated results from any of those studies or do you feel like they're largely concluded and it really, it's about the Phase III studies that are up and running.

除了這些機會之外，我們是否可以期待從這些研究中得到更新的結果，或者您是否覺得它們基本上已經結束，而這實際上與正在進行的第三階段研究有關。

Yes. Ren, this is Manmeet. You will continue to hear more updates as we progress on those all the studies which we had given some initial top line data earlier in the last year. But I would also mention that, right, colorectal cancer, right, where we are pretty excited. And we have just recently partnered with Akeso also on the Phase II study, which we have begin to activate over here on our side, and that would be the first one, which is -- which you would hear more details in next coming quarters.

是的。任，我是曼米特。隨著我們在所有這些研究上取得進展，您將繼續聽到更多更新，我們在去年早些時候提供了一些初步的頂線數據。但我還要提到，對，對，大腸癌，我們對此非常興奮。我們最近也與康方生物合作進行了第二階段研究，我們已經開始啟動這項研究，這將是第一項研究，您將在接下來的幾個季度中聽到更多詳細資訊。

Excellent. Okay. And just one last one for us. I think ct.gov said that there are three active sites for HARMONi-7. Can you talk a little bit about how many sites globally you expect to have on board by, call it, by the end of 2025 and for both HARMONi-3 and HARMONi-7.

出色的。好的。對我們來說，還有最後一個問題。我認為 ct.gov 說過 HARMONi-7 有三個活躍網站。您能否談談預計到 2025 年底全球將有多少個站點加入 HARMONi-3 和 HARMONi-7 計畫？

Ren, this is Manmeet, again. I think we don't give the specific number, but on the sites which we activate because we go into multiple regions, right, this is a global multi-regional study, but I would expect by end of 2025, almost -- most of the sites are like 100% -- near to 100% of the site should be activated.

任，我是 Manmeet，再次向你問好。我認為我們沒有給出具體的數字，但是在我們激活的站點上，因為我們進入了多個地區，這是一項全球多區域研究，但我預計到 2025 年底，幾乎 - 大多數站點都像 100％ - 接近 100％ 的站點應該被激活。

I will now turn the call back to Dave Gancarz for closing remarks.

現在我將把電話轉回給 Dave Gancarz 進行結束語。

Thanks very much, and I'd like to hand it over to Bob Duggan just for a couple of remarks before we close.

非常感謝，在結束之前，我想把它交給鮑勃·杜根 (Bob Duggan) 發表幾點評論。

Yes. I just want to weigh in on the question business development. Business development has a couple of arms. One is develop optimized ivo and make it the best product monotherapy, combination therapy that the world has -- can get from us and our partner, Akeso. And we're daily looking at that and evaluating that, there's plenty of room to go, as you see with the trials that we're entering into.

是的。我只是想就業務發展議題發表一下看法。業務發展有幾個面向。一是開發優化的ivo，使其成為世界上最好的產品單一療法、聯合療法——可以從我們和我們的合作夥伴康方生物中獲得。我們每天都在觀察和評估這一點，正如你所看到的，我們正在進行的試驗表明，我們還有很大的發展空間。

The second aspect of business development is what's the timing of gaining markets, additional market space, additional market opportunity and then how much share can you get? And how do you go about doing that? And that's also a major part of business development. So we're very active on two footprints: Pfizer is footprint one, how do we optimize the product.

業務發展的第二個面向是什麼時候獲得市場、額外的市場空間、額外的市場機會，然後你能獲得多少份額？那您打算怎麼做呢？這也是業務發展的一個重要部分。因此，我們在兩個足跡上非常活躍：輝瑞是足跡一，我們如何優化產品。

Other activities, we're constantly working on those here also. I just want to make clear that Pfizer is not the beginning and end of business development at Summit. Not that it isn't for most of you, but even for some of you.

其他活動，我們也在不斷進行。我只是想明確表示，輝瑞並不是 Summit 業務發展的起點和終點。這並不是說對你們大多數人來說不是這樣，甚至對你們中的某些人來說也是如此。

So back over to Dave.

現在回到戴夫。

Really appreciate it, Bob. Thanks very much. And I want to thank everyone for attending today's earnings call. An archived version of the webcast will be available later on our website, www.smmttx.com. Thank you very much for your participation, and we hope you enjoy the rest of your day. Thank you.

真的很感激，鮑伯。非常感謝。我要感謝大家參加今天的財報電話會議。網路廣播的存檔版本稍後將在我們的網站 www.smmttx.com 上提供。非常感謝您的參與，我們希望您度過愉快的一天。謝謝。

Bye-bye.

再見。