Summit Therapeutics Inc (SMMT) 2023 Q4 法說會逐字稿

Hello, everyone. First and foremost, we'd like to apologize for the delay of this event.

大家好。首先，我們對本次活動的延遲表示歉意。

Good morning, and welcome to Summit Fourth Quarter and Year End 2023 earnings call. All participants, all participants will be able to will be able to listen only until the question-and-answer portion of this call. We do not expect any technical difficulties today for worried However, in the event that we lose the webcast connection and we are unable to provide any updates, lease rate up to 10 minutes for resolution, please refer to the company's website for updates. Please note that today's call is being recorded. (Operator Instructios)

早安，歡迎參加 Summit 第四季和 2023 年底財報電話會議。所有參與者，所有參與者將能夠只能收聽本次通話的問答部分。我們預計今天不會出現任何技術困難，但如果我們失去網路廣播連線並且無法提供任何更新，租賃費率最多 10 分鐘即可解決，請參閱公司網站以獲取更新。請注意，今天的通話正在錄音。（操作員說明）

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

現在，我想將電話轉給 Summit Therapeutics 首席業務和策略長 Dave Gancarz。現在請您繼續。

Good morning, and thank you for joining us. Our press release was issued earlier this morning and is available on the homepage of our website. Our Forms 10K and S. three were also filed earlier this morning and are 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, w. w. w. dot SMMTTX. dot com.

早安，感謝您加入我們。我們的新聞稿於今天早上早些時候發布，可在我們網站的主頁上找到。我們的 10K 表格和 S.3 表格也在今天早上提交，可在我們的網站上取得。今天的電話會議同時進行網路直播，存檔重播也將於今天晚些時候在我們的網站上提供，w。 w。 w。點 SMMTTX。 .com。

Joining me on the call today is Bob Duggan our Chairman of the Board and Chief Executive Officer, Dr. Matthews on getting our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer, Oncor, Dan Gray, our Chief Financial Officer, and Dr. Allen Yang, our Chief Medical Officer.

今天與我一起參加電話會議的是我們的董事會主席兼執行長 Bob Duggan、Matthews 博士，我們的執行長兼總裁、我們的營運長 Manmeet Soni、Oncor、我們的財務長 Dan Gray 和楊艾倫博士，我們的首席醫療官。

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. Some and 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. 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.

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對我們今天可能提出的問題的一些答复可能會被視為基於我們當前預期的前瞻性聲明。有些人警告說，這些前瞻性陳述存在風險和不確定性，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。請參閱我們向 SEC 提交的文件，以了解有關這些風險和不確定性的資訊。除法律要求外，峰會不承擔更新這些前瞻性聲明的義務。

Following comments from Bob Mackie and Oncor, we will take questions.

根據 Bob Mackie 和 Oncor 的評論，我們將回答問題。

With that, I will turn the call over to Bob Thank you, Dave.

這樣，我會將電話轉給鮑勃，謝謝你，戴夫。

Good morning, everyone, and thank each of you for joining us today. I'd like to say a few words about our progress and what team Summit has accomplished that I will hand it over to Mickey to add more color and then offer will provide financial updates.

大家早安，謝謝你們今天加入我們。我想談談我們的進展以及 Summit 團隊所取得的成就，我將把它交給 Mickey 以添加更多色彩，然後提供財務更新。

It has been just one year since we closed on our partnership with cash so I'm very proud of the accomplishments and impressive progress team Summit has made in this period of time of initial mAb, our lead investigational compound and the only PD-1 VEGF bispecific antibody in Phase 3 in some U.S. territories continues to actively enroll two registrational Phase 3 trials in non-small cell lung cancer, our Harmoni and HARMONi-3 trials in Harmoni. We are looking at evidence I-Mab in combination with chemotherapy as a second-line treatment for non-small cell lung cancer patients with EGFR mutations with disease progression after receiving a third generation TKI in HARMONi-3. We are studying this I-Mab in combination with chemotherapy as first-line treatment for patients with squamous cell carcinoma of the lung in a head-to-head trial against the current standard of care we treated our first patient in the HeartMate three study, our second Phase 3 study in the fourth quarter of 2023. Combine the two populations represented by these two clinical trials account for approximately 120,000 patients in our licensed territories for whom evidence I-Mab could potentially offer a better treatment option team, so much conviction and our belief in our business, and that continues to drive our progress forward in our efforts to collapse time and reach critical milestones faster. We approach these efforts with the intent of helping patients improve quality of life, increase the potential duration of life and resolves serious medical need in line with somewhat strongly held mission statement. Mickey and I are appreciative and honored to be leading team Summit, where our accomplished leaders and team members have unparalleled track records for high-speed execution that delivers intended results. This experience and our expertise are foundational to achieving our goals for 2024 and beyond, continuing to execute on our Phase 3 clinical trials while expanding our clinical development plan.

距離我們以現金結束合作關係僅一年時間，因此我對 Summit 團隊在此期間在初始 mAb、我們的主要研究化合物和唯一的 PD-1 VEGF 方面取得的成就和令人印象深刻的進展感到非常自豪雙特異性抗體在美國一些地區的3 期試驗繼續積極招募兩項針對非小細胞肺癌的註冊3 期試驗，即我們在Harmoni 進行的Harmoni 試驗和HARMONi-3 試驗。我們正在研究 I-Mab 聯合化療作為二線治療用於接受 HARMONi-3 第三代 TKI 後出現疾病進展的 EGFR 突變非小細胞肺癌患者的證據。我們正在一項頭對頭試驗中研究這種 I-Mab 與化療相結合，作為肺鱗狀細胞癌患者的一線治療，與我們在 HeartMate 3 研究中治療第一位患者的當前護理標準相比，我們將於2023 年第四季進行第二次3 期研究。將這兩項臨床試驗所代表的兩個人群相結合，在我們的許可地區約有120,000 名患者，證據顯示I-Mab 可能會為他們提供更好的治療選擇團隊，我們對我們的業務充滿信心和信念，這將繼續推動我們的業務發展。我們在縮短時間並更快地達到關鍵里程碑的努力中取得進展。我們進行這些工作的目的是幫助患者提高生活質量，延長潛在的生命週期，並根據堅定的使命宣言解決嚴重的醫療需求。米奇和我很感激也很榮幸能夠領導團隊高峰會，我們卓有成效的領導者和團隊成員在高速執行方面擁有無與倫比的記錄，能夠實現預期的結果。這些經驗和我們的專業知識是實現 2024 年及以後目標的基礎，繼續執行我們的 3 期臨床試驗，同時擴大我們的臨床開發計劃。

With that, I would like to turn it over to Mickey to provide additional context for our accomplishments and next steps.

至此，我想將其交給米奇，為我們的成就和後續步驟提供更多背景資訊。

Thank you, Bob, and good morning, everyone. As Bob discussed, I remain incredibly enthusiastic about our new CMO and its potential. This rate of team Summit and the accomplishments we have made just one year into our partnership with Aircastle across the globe. Over 1,006 of 1,600 patients have now been treated with Avonex sema. Currently a case is conducting or participating in 19 clinical trials evaluating our new CMO, four of which are in Phase 3 and seven trials are evaluating our Seamap in solid tumor settings beyond non-small cell lung cancer. We are fortunate to have such a strong partnership and ongoing collaboration with AK., so including the ability to leverage data generated for Ivernia sema across multiple solid tumors studies in support of some its own clinical development in our licensed territories, the US, Canada, Europe and Japan, and turning specifically to some its own Phase 3 trials. Active enrollment continues in Harmoni and Harmoni tree. As a reminder, Harmoni, our fast to market approach is in non-small cell lung cancer patients with EGFR mutations to have progressed following a third-generation TKI such as osimertinib. We intend to complete enrollment in this trial in the second half of 2024. Our Harmoni two trial is seeking a front-line treatment indication for patients with squamous non-small cell lung cancer. This head to head trial is designed to compare obinutuzumab plus chemotherapy against the current standard of care pembrolizumab plus chemotherapy. We continue to progress as well as collapse time in order to achieve our aggressive but realistic goals for Ivernia Seamap to ultimately improve up and existing treatment options so there are many lung cancer patients with serious ongoing unmet need, our conviction and belief in the potential of Ionis Sema and our decision to quickly pursue two registrational Phase 3 trials has come in part from data generated from Phase 2 clinical trials conducted by a castle. These data evaluating of Anetumab plus chemotherapy in multiple lung cancer settings, eight K. one one two two oh one was updated by a case or last month, notably in patients with first line advanced or metastatic squamous non-small cell lung cancer without actionable genomic alterations in a Phase 2 population supporting our Harmoni treat trial at 24 months, overall survival rate of 64.8% was observed. Median overall survival has not yet been reached after a median follow-up time of 21 months. Furthermore, in patients with advanced or metastatic non-small cell lung cancer with tumors positive for EGFR mutations and having progressed following an EGFRTKI., the Phase 2 trial cohort supporting our Harmoni trial in median overall survival of 22.5 months was observed in both settings. I want to see MAP has had an acceptable safety profile in the Phase 2 clinical trial. We believe that this study data is very promising. Also when considering the current standard of care in this patient population and the Phase 2 data supports our decision to directly move forward in both of our Phase 3 clinical trials.

謝謝你，鮑勃，大家早安。正如鮑伯所討論的，我對我們的新行銷長及其潛力仍然充滿熱情。團隊高峰會的速度以及我們與 Aircastle 在全球範圍內合作僅一年以來所取得的成就。1,600 名患者中已有超過 1,006 名患者接受了 Avonex sema 治療。目前，一個案例正在進行或參與評估我們新 CMO 的 19 項臨床試驗，其中 4 項處於 3 期，7 項試驗正在評估我們的 Seamap 在非小細胞肺癌以外的實體瘤環境中的應用。我們很幸運能夠與 AK. 建立如此強大的合作夥伴關係並持續合作，因此能夠利用 Ivernia sema 在多項實體瘤研究中產生的數據來支持其在我們的許可地區（美國、加拿大、歐洲和日本，並專門轉向一些自己的第三階段試驗。Harmoni 和 Harmoni 樹中的積極註冊仍在繼續。Harmoni 提醒您，我們的快速上市方法是針對具有 EGFR 突變的非小細胞肺癌患者，這些患者在使用奧希替尼等第三代 TKI 後病情有所進展。我們計劃在 2024 年下半年完成試驗的註冊。我們的 Harmoni 兩項試驗正在尋找鱗狀非小細胞肺癌患者的第一線治療適應症。這項頭對頭試驗旨在將 obinutuzumab 加化療與目前的護理標準 pembrolizumab 加化療進行比較。我們繼續進步並縮短時間，以實現 Ivernia Seamap 積極但現實的目標，最終改善現有的治療方案，因此有許多肺癌患者的嚴重持續未得到滿足的需求，我們堅信和相信 Ivernia Seamap 的潛力Ionis Sema 和我們快速進行兩項註冊3 期試驗的決定部分來自於一座城堡進行的2 期臨床試驗所產生的數據。這些評估Anetumab 聯合化療在多種肺癌環境中的數據，8 K.一一二二哦一已由病例或上個月更新，特別是在沒有可操作基因組的一線晚期或轉移性鱗狀非小細胞肺癌患者中支持 Harmoni 治療試驗的第 2 期族群在 24 個月時發生了變化，觀察到總存活率為 64.8%。中位追蹤時間為 21 個月後，尚未達到中位總存活期。此外，在患有EGFR 突變且腫瘤呈陽性且在EGFRRTKI 後病情進展的晚期或轉移性非小細胞肺癌患者中，支持Harmoni 試驗的2 期試驗隊列在兩種情況下均觀察到中位總生存期為22.5 個月。我希望看到 MAP 在 2 期臨床試驗中具有可接受的安全性。我們相信這項研究數據非常有希望。此外，考慮到該患者群體目前的護理標準，2 期數據支持我們直接推進兩項 3 期臨床試驗的決定。

Slide 5, please. I would also like to spend a moment to remind everyone of the differentiated mechanism of action for hypoglycemia.

請幻燈片 5。我還想花點時間提醒大家低血糖的差異化作用機制。

To start, I want to see my brings two highly validated mechanism in oncology together into one novel molecule targeting both PD-1 and BJ. And as Bob mentioned earlier, we are the only Phase 3 PD. one VEGF bispecific in our licensed territories, making it the most clinically advanced compound of its kind in the US, Canada, Europe and Japan. What differentiates I panitumumab in its intention of design is a concept known as corporative binding specifically in the presence of each of the binding of Avon is earmarked to be the one in vitro increases by 18 fold in the presence of PD-1. We have affinity increases by over fourfold and when I say, maps cooperating binding qualities lead to the potential to steer more drug to the tumor and tumor microenvironment. The area around the tumor where high higher levels of PD-1 and reach of our Express and comparatively less drug, we believe is steered towards normal healthy tissue.

首先，我希望看到我將腫瘤學中兩種經過高度驗證的機制結合到一種針對 PD-1 和 BJ 的新型分子。正如鮑伯之前提到的，我們是唯一的第 3 階段 PD。在我們許可的地區，它是一種 VEGF 雙特異性化合物，使其成為美國、加拿大、歐洲和日本同類化合物中臨床最先進的化合物。帕尼單抗在設計意圖上的不同之處在於一個稱為協同結合的概念，特別是在存在 PD-1 的情況下，Avon 的每一種結合都被指定為在體外增加 18 倍。我們的親和力增加了四倍以上，當我說時，圖譜協同結合質量導致有可能將更多藥物引導至腫瘤和腫瘤微環境。我們相信，腫瘤周圍區域的 PD-1 水平較高，我們的 Express 和相對較少的藥物能夠到達該區域，這些區域會流向正常的健康組織。

On Slide 6, you can see in addition, because of the increased presence of PD-1 and rejects in the tumor microenvironment. There is not only increased affinity, but also increased advocacy because we do have is expressed as a dimer. There is an opportunity to bind multiple avenues of our compounds to this VEGF dimers in the tumor microenvironment as what we believe I wouldn't assume a corporative binding goes further than the sequential administration of an anti-PD-1 and anti-VEGF therapy. Our goal is to improve upon previously established efficacy standards. In addition to side effects and safety profile associated with these two targets, we believe I have on this map has the potential to achieve this.

在投影片 6 上，您也可以看到，由於腫瘤微環境中 PD-1 和排斥的存在增加。不僅親和力增加，宣傳力度也增加，因為我們確實以二聚體的形式表達。我們的化合物有機會透過多種途徑與腫瘤微環境中的 VEGF 二聚體結合，因為我們相信我不會認為聯合結合比抗 PD-1 和抗 VEGF 療法的順序給藥更進一步。我們的目標是改進先前製定的功效標準。除了與這兩個目標相關的副作用和安全性之外，我們相信我在這張地圖上有潛力實現這一目標。

Moving to Slide 7. Looking at meaningful near term catalysts for Avon and sema, we are expecting multiple events to occur in 2020 for next quarter. There are two key milestones expected from randomized Phase 3 clinical trials in China from our partners at Acacia data from the Chinese patients enrolled in AK. one one two three oh one, a large portion of which represent the Chinese patients included in the modified intent to treat population of our multi-regional study, also known as Harmoni was submitted to the Chinese regulatory authority, the CDE. last year, specifically seeking marketing approval in China. A decision is expected in the second quarter of this year from the CD. We also expect that it has always provide a data read out of the top line results of their Phase 3 trial at this time. Additionally, a case or has an interim analysis planned for next quarter for each study comparing Ivernia sema to pembrolizumab in a monotherapy setting for first line advanced lung cancer patients harboring tumors with positive PDL. one expression referred to as AK. one one two three or three. This head-to-head trial against pembrolizumab is a major milestone for Ivernia Sema, both in differentiating our initial remark from a PD-1 antibody as well as illustrating the potential of its novel mechanism of action that simply does not exist in oncology therapeutics today, given the direct implications of the AK. one one two three oh one results on our Harmoni study as well as the potential ability to compare Ionis Seamap pembrolizumab in a one one, two, three or three. We believe these events will be pivotal moment drivers in IONA's SIMOPS development globally. As mentioned earlier, we also plan to complete enrollment in the Harmoni study in the second half of this year, providing momentum towards a submission for Ivernia Seamap in our licensed territories. While non-small cell lung cancer indication represent our initial development plans for opening remarks, we will continue to expand our clinical program, Harmoni and HARMONi-3 represent the first step in our strategy, and we believe our new CMO has potential in both additional non-small cell lung cancer indications and in other solid tumors. In addition, to progressing our internal development program. We appreciate the high level of enthusiasm we are hearing from key opinion leaders and other physician leaders for what I've only seen map can do to make significant positive difference in and outside of lung cancer, we continue to receive and are considering multiple inquiries for potential investigator-sponsored trials or IC programs. We expect to share additional information later in 2024.

轉到投影片 7。考慮到雅芳和 sema 的近期有意義的催化劑，我們預計 2020 年下個季度將發生多項事件。我們的合作夥伴 Acacia 數據來自 AK 入組的中國患者，預計在中國進行的隨機 3 期臨床試驗將實現兩個關鍵里程碑。一一二三哦一，其中很大一部分代表了我們的多區域研究（也稱為 Harmoni）修改後的治療意圖人群中的中國患者，該研究已提交給中國監管機構 CDE。去年，專門尋求在中國的營銷批准。裁談會預計將在今年第二季做出決定。我們也預期它此時始終會提供從第三階段試驗的頂線結果中讀出的數據。此外，計劃在下個季度對每項研究進行一個病例或中期分析，比較 Ivernia sema 與 pembrolizumab 在單一療法中治療 PDL 陽性腫瘤的一線晚期肺癌患者的情況。一種表達方式稱為 AK。一一二三或三。這項針對pembrolizumab 的頭對頭試驗是Ivernia Sema 的一個重要里程碑，既區分了我們最初的評論與PD-1 抗體，也說明了其新穎作用機制的潛力，而這種作用機制在當今的腫瘤治療中根本不存在，考慮到 AK 的直接影響。我們 Harmoni 研究的一一二三哦一結果，以及在一一、二、三或三中比較 Ionis Seamap pembrolizumab 的潛在能力。我們相信這些事件將成為 IONA SIMOPS 全球發展的關鍵動力。如前所述，我們還計劃在今年下半年完成 Harmoni 研究的註冊，為在我們許可的地區提交 Ivernia Seamap 提供動力。雖然非小細胞肺癌適應症代表了我們開場白的初步開發計劃，但我們將繼續擴大我們的臨床項目，Harmoni 和HARMONi-3 代表了我們策略的第一步，我們相信我們的新CMO 在這兩個方面都有潛力非小細胞肺癌適應症和其他實體腫瘤。此外，也推動我們的內部發展計劃。我們感謝關鍵意見領袖和其他醫生領袖對我所看到的地圖可以在肺癌內外產生顯著積極影響的高度熱情，我們繼續收到並正在考慮針對以下問題的多次詢問：潛在的研究者資助的試驗或IC 項目。我們預計在 2024 年稍後分享更多資訊。

Finally, to capitalize on and expand our reach with physicians from KOLs and academic leaders to community physicians and local caregivers. Seeing so many cancer patients we are participating in a few upcoming conferences. There will be at the slide targeted therapies for lung cancer or TTLC. meeting later this week in Santa Monica, California In addition, we plan to participate in a small European Lung Cancer Congress 2020 for next month in Prague where we have submitted along with our partners at.

最後，利用並擴大我們與醫生的影響力，從 KOL 和學術領袖到社區醫生和當地護理人員。看到這麼多癌症患者，我們正在參加一些即將舉行的會議。幻燈片上將有針對肺癌或 TTLC 的標靶治療。本週稍晚在加州聖莫尼卡舉行會議 此外，我們計劃參加下個月在布拉格舉行的 2020 年小型歐洲肺癌大會，我們已與合作夥伴一起在該大會上提交了資料。

Okay.

好的。

So multiple abstracts for presentation on Ivernia sema. We intend to educate and activate as many physicians as possible regarding Ivernia Seamap and its potential as we ramp up Phase 3 clinical trials in the United States, Europe, Canada and Japan.

在 Ivernia sema 上展示了多個摘要。隨著我們在美國、歐洲、加拿大和日本加強 3 期臨床試驗，我們打算對盡可能多的醫生進行有關 Ivernia Seamap 及其潛力的教育和活化。

With that update, I will now ask our Ankur to provide details on our financial position and outlook.

隨著這項更新，我現在將要求我們的 Ankur 提供有關我們財務狀況和前景的詳細資訊。

Thank you, Maggie and Bob and good morning, everyone. Echoing the sentiment, we're very pleased with the speed of execution of team Summit and our partners at Puma co-sell in the development of Avanex amounts seem Moving to slide 8, I'll give you an update on some its cash position, the extended cash runway guidance, Andy and the P&L. We have a strong cash position with $186 million in cash and investments as of end of year 2023. This position provides us a strong ability to continue our investments in the development of either Nassib. In addition, we have taken steps to extend our cash runway going into the first quarter of 2025. As you may recall, our previous guidance for cash runway was going into September of 2024. As we announced earlier, we have amended the $100 million note to extend the maturity date to April first, 2025 and the future interest payments will also be paid at maturity. This extension, coupled with our strong cash position, provides funding to make significant progress in the development of NSMA. as well as covering some of the key milestones that Maggie spoke about.

謝謝瑪姬和鮑勃，大家早安。與這種情緒相呼應的是，我們對Summit 團隊的執行速度以及我們在Puma 的合作夥伴共同銷售Avanex 金額的開發感到非常滿意。轉到幻燈片8，我將向您提供有關其現金狀況的最新訊息，擴展現金跑道指導、安迪和損益表。截至 2023 年底，我們擁有雄厚的現金狀況，現金和投資為 1.86 億美元。這一地位使我們有強大的能力繼續投資 Nassib 的開發。此外，我們也採取措施將現金跑道延長至 2025 年第一季。您可能還記得，我們​​先前的現金跑道指引將持續到 2024 年 9 月。正如我們先前宣布的，我們修改了 1 億美元票據，將到期日延長至 2025 年 4 月 1 日，未來的利息也將在到期時支付。此次延期，加上我們強大的現金狀況，為 NSMA 的發展取得重大進展提供了資金。以及瑪姬談到的一些關鍵里程碑。

Going to the P&L, I will speak about non-GAAP OpEx, which excludes stock-based compensation, in-process R&D and certain impairment charges. You can refer to our press release for reconciliation of GAAP to non-GAAP financial measures during the fourth quarter of 2023, our non-GAAP operating expenses were $27.7 million aligned with the company's focus. The majority of our spending is towards research and development, which is $22.4 million for the quarter on a non-GAAP basis and is focused towards clinical development of IV and SMM, including the clinical trials, the technology transfer and people costs and the G&A spend of $5.3 million for the quarter on a non-GAAP basis represents all the functions that provide infrastructure and support for this development.

談到損益表，我將談論非 GAAP 營運支出，其中不包括基於股票的薪酬、正在進行的研發和某些減損費用。您可以參閱我們的新聞稿，了解 2023 年第四季 GAAP 與非 GAAP 財務指標的調節，我們的非 GAAP 營運費用為 2770 萬美元，與公司的重點一致。我們的大部分支出用於研發，按非 GAAP 計算，本季支出為 2,240 萬美元，重點是 IV 和 SMM 的臨床開發，包括臨床試驗、技術轉移和人員成本以及 G&A 支出按非公認會計準則計算，本季的530 萬美元代表了為這一發展提供基礎設施和支援的所有職能部門。

So in summary, we're excited about the potential of Fibernet I-Mab and have made a lot of progress in its in its development during 2023. We have a strong cash position and we have extended our cash runway going into 2025. And with that, I will hand it back over to Dave.

總而言之，我們對 Fibernet I-Mab 的潛力感到興奮，並在 2023 年的開發中取得了巨大進展。我們擁有強大的現金狀況，我們已將現金跑道延長至 2025 年。有了這個，我會把它交還給戴夫。

Thank you, Bob. Mackie and Oncor. We can now transition to see if there are any questions that we can help answer. Operator, if you could please open the line for questions.

謝謝你，鮑伯。麥基和昂科爾。我們現在可以過渡一下，看看是否有任何我們可以幫助回答的問題。接線員，如果可以的話，請撥打電話提問。

I'm opening the floor for the Q&A question. (Operator Instructions)

我現在開始問答問題。（操作員說明）

Brad Canino, Stifel.

布拉德·卡尼諾，斯蒂菲爾。

Hi, good morning and thank you for the updates. And having me Andrew Hall and I just wanted to get your thoughts on how to best interpret the upcoming Chinese regulatory action on. I have an estimate for EGFR mutant lung, in particular in relation to your ongoing Harmoni study and I'm asking in light of some of the differences between the two studies, thinking about the third-generation TKIs pretreatment requirements and then your study also adding the co-primary of survival. Thank you.

你好，早安，謝謝你的更新。我和安德魯霍爾只是想聽聽大家對如何最好地解讀中國即將採取的監管行動的看法。我對 EGFR 突變肺有一個估計，特別是與您正在進行的 Harmoni 研究有關，我根據兩項研究之間的一些差異進行詢問，考慮第三代 TKI 預處理要求，然後您的研究還添加了生存的共同首要因素。謝謝。

Thank you, Brad. I'll hand that question to Fibra.

謝謝你，布拉德。我會把這個問題交給 Fibra。

Thanks for the question. This is owning the Chief Medical Officer. So I think you should view it positively. The fact that as you know, the Chinese version of the Harmoni study enrolled 320 patients, approximately 300,000 patients, of which about 50 of them received a first or second generation TKIs, which is still considered standard of care in China.

謝謝你的提問。這是首席醫療官的擁有者。所以我認為你應該積極地看待它。事實上，如你所知，Harmoni 研究的中國版招募了 320 名患者，約 30 萬名患者，其中約 50 人接受了第一代或第二代 TKI，這在中國仍被視為標準治療。

And we will be using 270 patients so that there are approximately 270 patients. So that data of which only received a third-generation TKI or received a third-generation TKIs such as osimertinib somewhere along the course of their treatment. And that represents about 85% of the data. So I think the data should correlate pretty well for the global study. Now, remember, we're adding 150 patients from North America and Europe to that, and you know, I'm not aware of any treatment differences between Chinese and U.S. patients. In addition, I think the key question is, is there any difference of receiving a first or second generation TKIs prior to receiving a third-generation or receiving a third generation to guy on the impact of chemo immunotherapy. And the answer is I'm not aware of any such data. I don't think that data exists.

我們將使用 270 名患者，因此大約有 270 名患者。因此，這些數據僅接受了第三代 TKI 或在治療過程中的某個地方接受了第三代 TKI，例如奧希替尼。這代表了大約 85% 的數據。所以我認為這些數據對於全球研究來說應該要有很好的相關性。現在，請記住，我們將 150 名來自北美和歐洲的患者添加到其中，而且您知道，我不知道中國和美國患者之間有任何治療差異。此外，我認為關鍵問題是，在接受第三代或第三代 TKI 之前接受第一代或第二代 TKI 對化療免疫治療的影響是否有任何差異。答案是我不知道任何此類數據。我認為該數據不存在。

And then I think the last question you asked was around PFS and OS X and so PFS seems to track pretty well with U.S. That's why it's used as a surrogate endpoint as often, especially in patients with sort of survival periods. So the shortest survival period, the more likely that PFS will progress of corporate and retail, but it is an unknown at this time. And so the fact that we have co-primary endpoints is a little bit different than the case of study.

然後我認為您問的最後一個問題是關於PFS 和OS X 的，因此PFS 似乎與美國的追蹤情況相當好，這就是為什麼它經常被用作替代終點，尤其是在有某種生存期的患者中。所以生存期越短，企業和零售的PFS進步的可能性就越大，但目前還是一個未知數。因此，我們擁有共同主要終點的事實與研究案例略有不同。

Thanks for the question, Brett.

謝謝你的提問，布雷特。

Great. Thank you very much.

偉大的。非常感謝。

Hartaj Singh from Oppenheimer.

來自奧本海默的哈塔吉·辛格。

Great.

偉大的。

Thank you, Tom, and thanks for the question. I've just got a couple one is your head to head study against pembro and chemo combo against non-small cell lung cancer. Can you just talk a little bit about what's the differentiation driving this demand and then maybe a little bit more into and I guess what's the hurdle or is it just the study on which pembro chemo combo data proved? Just how to think about the hurdle that that you're looking to either be equal to or surpass? And I just got a quick follow-up.

謝謝你，湯姆，也謝謝你提出這個問題。我剛剛得到了兩項針對 pembro 和化療組合治療非小細胞肺癌的頭對頭研究。您能否簡單談談推動這一需求的差異化是什麼，然後可能再深入探討一下，我猜障礙是什麼，或者只是對 pembro 化療組合數據證明的研究？只是如何考慮您希望達到或超越的障礙？我剛剛得到了快速跟進。

Thanks, Hartaj. So I think I heard two questions there. One, the differentiation between pembro, the standard of care. And I've been at I-Mab with respect to our HARMONi-3 study and then what that what other hurdle we may have in HARMONi-3 study or what the standard of care of what we need to be in that particular study is.

謝謝，哈塔傑。所以我想我在那裡聽到了兩個問題。一、pembro的區別，護理標準。我一直在 I-Mab 參與我們的 HARMONi-3 研究，然後我們在 HARMONi-3 研究中可能遇到什麼其他障礙，或者我們在該特定研究中需要達到的護理標準是什麼。

So again, I'll hand that question to Alan.

再次，我會把這個問題交給艾倫。

Akash, thanks for the question. So I'll answer the second part first.

阿卡什，謝謝你的提問。那我先回答第二部分。

Well, let me just review the two studies. As Mackey mentioned earlier, there's the Harmoni study, which is our fast-to-market site about with Brad's question in the second line EGFR mutant population, the HARMONi-3 study, which is sort of the first frontline study in squamous non-small cell lung cancer.

好吧，讓我回顧一下這兩項研究。正如 Mackey 先前提到的，Harmoni 研究是我們的快速上市網站，涉及 Brad 在二線 EGFR 突變族群中提出的問題，HARMONi-3 研究是鱗狀非小細胞肺癌的第一個一線研究細胞肺癌。

The second question about the benchmark is pretty easy it's the KEYNOTE 47 study, right? So this is where Merck got approval for pembrolizumab in a similar population. There are sort of expansion studies that look at the Chinese population so you can look those studies up to get the proper benchmark in terms of what distinguishes I've in SMA, it's a very clean study of five and SMS chemotherapy. And then pembro using the same chemotherapy and that pembro chemotherapy was before oh seven study based on the 47 study. So I think there's a couple of ways that are different right so I've in SMA from the simplest way to think about it has digest component to it. So if you think about the two targets independently pembro or PD-1 and the second one is that, Jeff. And so we have that VEGF component. And so we think that that adds sort of value to patients and important for patients. And then there's the opportunity that we think accentuates not only the VEGF but also the PDY. And so you can sort of distinguish that. And looking at that data, it will be very interesting to look at the data of both BI, PD-1, PD-L1 status, you know, are how much are we beating in the high PD-L1 expressors, which is part of the PD. one component, how much are we bidding in the lower PD-L1 expression, which is the that just compound, I would say some other bispecifics that target like take PD-1 and CTLA-4 are concentrating on the non expressing we're going to go after all of those.

關於基準的第二個問題很簡單，就是 KEYNOTE 47 研究，對吧？這就是默克公司在類似人群中批准派姆單抗的原因。有一些針對中國人群的擴展研究，因此您可以查閱這些研究，以獲得正確的基準，以了解我在 SMA 方面的獨特之處，這是一項針對五種化療和 SMS 化療的非常乾淨的研究。然後 pembro 使用相同的化療，而 pembro 化療是在 7 項研究之前基於 47 項研究進行的。所以我認為有幾種不同的方法，所以我從最簡單的角度考慮 SMA，它具有消化成分。所以，如果你獨立地考慮兩個目標 pembro 或 PD-1，第二個就是那個，傑夫。所以我們就有了 VEGF 成分。因此，我們認為這為患者增加了某種價值，並且對患者很重要。我們認為，還有一個機會，不僅可以強調 VEGF，還可以強調 PDY。所以你可以區分這一點。看看這些數據，看看 BI、PD-1、PD-L1 狀態的數據會非常有趣，你知道，我們在高 PD-L1 表達者中的表現是多少，這是警察局。一個成分，我們在較低的 PD-L1 表達中出價多少，這就是唯一的化合物，我想說一些其他針對 PD-1 和 CTLA-4 的雙特異性藥物專注於我們要進行的非表達去追求所有這些。

So the last component to think about is that we know that Avastin was trying to be developed in this space. And then after Phase 2, they halted development. There was a concern about bleeding risks early on. And therefore, I think lung cancer patients in the squamous setting never really fully realize the potential of anti-VEGF. And we believe that the safety profile demonstrated to date in the Phase 2 as well as large large database is supportive of developing a bad Jeff that has been attached to PD-1 with cooperative binding in this space. So there's a number of different aspects where we think we can have an advantage.

因此，最後一個要考慮的因素是我們知道阿瓦斯丁正試圖在這個領域進行發展。第二階段之後，他們停止了開發。人們很早就擔心出血風險。因此，我認為鱗狀細胞肺癌患者從未真正完全意識到抗 VEGF 的潛力。我們相信，迄今為止在第 2 階段中展示的安全性概況以及大型資料庫支援開發一個已附加到 PD-1 並在該空間中具有合作性綁定的壞 Jeff。因此，我們認為我們可以在許多不同的方面擁有優勢。

Puts your follow-up question, Hartaj Yes, great. And thank you so much that. So that's really good. Good detail on, you know, if we if you can just kind of give us what is the next sort of clinical and regulatory staff for Harmoni and HARMONi-3, I know I'm going to make a little bit into the future, but just not looking for guidance, but just kind of a rough cadence of events there?

請提出您的後續問題，Hartaj 是的，太好了。非常感謝你。所以這真的很好。很好的細節，你知道，如果你能給我們 Harmoni 和 HARMONi-3 的下一代臨床和監管人員是什麼樣的，我知道我會為未來做出一些貢獻，但是只是不尋求指導，而只是尋找事件的大致節奏？

Thank you.

謝謝。

Around HARMONi-3, I don't think we've disclosed it. So I'll turn to Dave, but I'll just say that you can sort of calculate enrollment based on the KEYNOTE 47. I think that's the key benchmark. And you know, it's what's interesting, Hartaj is the squamous non-small cell lung cancer population or that space has become a lot less crowded recently. So I think that will give us a lot of freedom to operate. I don't know, Dave, if you want to add anything to our disclosures Thanks, Alan.

關於 HARMONi-3，我認為我們還沒有披露過。因此，我將求助於 Dave，但我只想說，您可以根據 KEYNOTE 47 來計算入學人數。我認為這是關鍵的基準。你知道，有趣的是，Hartaj 是鱗狀非小細胞肺癌群體，或者說這個空間最近變得不那麼擁擠了。所以我認為這會給我們很大的操作自由。我不知道，戴夫，您是否想在我們的披露中添加任何內容，謝謝，艾倫。

So at this point, what we have disclosed is that the Harmoni study is we plan to complete enrollment in the second half of 2020 for the second half of this year. We haven't given further guidance with respect to the regulatory process there, except that we have our co-primary endpoints from a Harmoni free perspective. We just began enrollment in the fourth quarter of 2023. And we've yet to give the guidance in terms of when that will complete. But we're currently enrolling and are excited about moving quickly in that space setting as well.

所以目前我們透露的是Harmoni研究是我們計畫在2020年下半年完成今年下半年的入組。我們沒有就那裡的監管流程提供進一步的指導，除了我們從 Harmoni free 的角度來看我們的共同主要終點。我們於 2023 年第四季剛開始招生。我們還沒有給出何時完成的指導。但我們目前正在招募，並且對於在該空間環境中快速行動感到興奮。

Well, thank you, everyone. Thanks for the updates.

嗯，謝謝大家。感謝您的更新。

Don't have any raised hands right now. So I'd now like to hand back over to to Dave again, guys. Thank you.

現在沒有人舉手。所以我現在想再次將任務交回給戴夫，夥計們。謝謝。

I just want to thank everyone for attending our call and your continued interest in Summit. An archived version of this webcast will be available later today on our website, w. w. w. dot SMTTX. dot com. I want to thank everyone again and enjoy the rest of your day. Thank you.

我只想感謝大家參加我們的電話會議以及對高峰會的持續關注。該網路廣播的存檔版本將於今天晚些時候在我們的網站上提供，w。 w。 w。點 SMTTX。 .com。我想再次感謝大家並祝大家有個愉快的一天。謝謝。

Yes, thank you so much for attending today's session. Have a wonderful day.

是的，非常感謝您參加今天的會議。祝你有美好的一天。

I mean, I mean, no, yes.

我的意思是，我的意思是，不，是的。