CytomX Therapeutics Inc (CTMX) 2025 Q2 法說會逐字稿

Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics second-quarter 2025 financial results call. Please be advised that today's call is being recorded.

大家下午好。感謝您的支持。歡迎參加 CytomX Therapeutics 2025 年第二季財務業績電話會議。請注意，今天的通話正在錄音。

I would now like to hand the call over to your host for today, Chris Ogden, CytomX's Chief Financial Officer. Please go ahead.

現在我想將電話交給今天的主持人，CytomX 的財務長 Chris Ogden。請繼續。

Thank you. Good afternoon, and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov.

謝謝。下午好，感謝您加入我們。在我們開始之前，我想提醒大家，在這次電話會議中，我們將做出前瞻性的陳述。由於前瞻性陳述與未來有關，因此它們受制於難以預測的固有不確定性和風險，其中許多是我們無法控制的。我們最近向美國證券交易委員會 (SEC) 提交的公開文件 (sec.gov) 中列出了重要的風險和不確定性。

We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our second quarter 2025 financial results and highlights recent progress at CytomX. We encourage everyone to read today's press release and the associated materials, which have been filed with the SEC.

我們不承擔更新任何前瞻性聲明的義務，無論其是否出現新資訊、未來發展或其他原因。今天下午早些時候，我們發布了一份新聞稿，其中包括我們 2025 年第二季財務業績摘要，並重點介紹了 CytomX 的最新進展。我們鼓勵大家閱讀今天的新聞稿和相關資料，這些資料已提交給美國證券交易委員會。

Additionally, the press release, recording of this call and our SEC filings can be found under the Investors and News section of our website.

此外，新聞稿、本次電話會議的記錄以及我們向美國證券交易委員會提交的文件均可在我們網站的「投資者和新聞」部分找到。

With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter. We will then conclude with a Q&A session.

今天與我一起參加電話會議的是 CytomX 的執行長兼董事長 Sean McCarthy 博士。在我介紹本季度的財務狀況之前，肖恩將提供有關我們的管道和公司進展的最新資訊。然後我們將以問答環節結束。

With that, I'll now turn the call over to Sean.

說完這些，我現在將電話轉給肖恩。

Thanks, Chris, and good afternoon, everyone.

謝謝，克里斯，大家下午好。

We're thrilled to be here today to review our progress for the second quarter, highlighted by the exciting clinical data we announced in May for CX-2051, our PROBODY antibody drug conjugate targeting EpCAM, which we view as having significant potential in colorectal cancer and potentially many other tumor types. We're also making great progress with our second current clinical program, CX-801, that I'll come to a little later. I'll focus initially today on CX-2051 and our work in colorectal cancer, which I'll refer to from here on as CRC.

我們很高興今天在這裡回顧我們第二季度的進展，其中最突出的是我們在 5 月公佈的 CX-2051 令人興奮的臨床數據，CX-2051 是我們針對 EpCAM 的 PROBODY 抗體藥物偶聯物，我們認為它在結直腸癌和潛在的許多其他腫瘤類型中具有巨大的潛力。我們的第二個臨床計畫 CX-801 也取得了很大進展，稍後我會詳細介紹。我今天將首先重點介紹 CX-2051 和我們在結直腸癌方面的工作，從現在開始我將其稱為 CRC。

CRC remains one of the biggest unmet needs in oncology with approximately 1.9 million patients diagnosed per year on a global basis. This disease burden is expected to increase considerably over the next couple of decades to more than 3 million, and is currently the second leading cause of death by cancer worldwide. Despite many advances across many other cancer types in recent years, CRC has seen little impact from innovation over this period of time, resulting in current five-year survival rates in metastatic CRC of about 13%.

CRC 仍然是腫瘤學領域最大的未滿足需求之一，全球每年約有 190 萬名患者被診斷出患有 CRC。預計未來幾十年內，這種疾病的負擔將大幅增加，達到300多萬人，目前是全球第二大癌症死亡原因。儘管近年來許多其他癌症類型取得了許多進展，但 CRC 在此期間幾乎沒有受到創新的影響，導致轉移性 CRC 的當前五年存活率約為 13%。

New treatments like antibody drug conjugates are urgently needed to treat this cancer. In other solid tumor types, ADCs such as ENHERTU, TRODELVY and ELAHERE have made a big difference for patients, but ADCs have yet to break through in CRC, representing a major scientific, clinical and commercial opportunity. At CytomX, we have intentionally designed CX-2051 to address this opportunity, building on years of experience in how to optimally leverage our PROBODY technology for the maximum benefit of cancer patients.

迫切需要抗體藥物偶聯物等新療法來治療這種癌症。在其他實體腫瘤類型中，ENHERTU、TRODELVY 和 ELAHERE 等 ADC 已為患者帶來了巨大的改變，但 ADC 尚未在 CRC 領域取得突破，這代表著重大的科學、臨床和商業機會。在 CytomX，我們特意設計了 CX-2051 來抓住這一機遇，並基於多年的經驗，了解如何最佳地利用我們的 PROBODY 技術為癌症患者帶來最大益處。

Let me recap the key design elements of CX-2051. EpCAM is a very highly expressed target in CRC, making it very attractive for an ADC. The payload on CX-2051 is a topoisomerase-1 inhibitor, which is ideally matched to CRC, where the Topo-1 inhibitor, irinotecan, has been a core component of the standard of care for many years. And thirdly, critically, CX-2051 uses CytomX PROBODY masking technology to limit binding in normal tissues, something that has thwarted previous attempts to drug EpCAM.

讓我回顧一下 CX-2051 的關鍵設計元素。EpCAM 是 CRC 中表現非常高的靶點，因此對於 ADC 來說非常有吸引力。CX-2051 上的有效載荷是拓撲異構酶 1 抑製劑，它與 CRC 完美匹配，其中 Topo-1 抑製劑伊立替康多年來一直是標準治療的核心成分。第三，至關重要的是，CX-2051 使用 CytomX PROBODY 掩蔽技術來限制正常組織中的結合，這項技術阻礙了先前對 EpCAM 進行藥物治療的嘗試。

Our initial experience with CX-2051 in the clinic announced in May is very encouraging. We have focused our Phase 1 clinical evaluation exclusively in CRC with the goal of delivering clear clinical proof of concept in this high area of unmet need. I'd like to briefly recap the CX-2051 initial Phase 1 data from May.

我們在 5 月宣布的 CX-2051 臨床初步體驗非常令人鼓舞。我們將第一階段臨床評估的重點完全放在 CRC 上，目的是在這個尚未滿足需求的領域提供明確的臨床概念驗證。我想簡單回顧一下 5 月 CX-2051 第一階段的初步數據。

For context, CX-2051 has initially been studied in a fifth-line CRC patient population where approved standard of care therapies are typically associated with 1% to 2% response rates and progression-free survival of only two to three months. In comparison to these benchmarks, CX-2051 has demonstrated robust clinical activity with a 28% confirmed overall response rate, 94% disease control, and 5.8 months of preliminary progression-free survival in the first 18 efficacy evaluable patients at relevant dose levels.

具體來說，CX-2051 最初是在五線 CRC 患者群體中進行研究的，該群體中批准的標準治療通常具有 1% 至 2% 的反應率，無進展生存期僅為兩到三個月。與這些基準相比，CX-2051 已表現出強勁的臨床活性，在相關劑量水平下，前 18 名可評估療效的患者中確認的總體反應率為 28%，疾病控制率為 94%，初步無進展生存期為 5.8 個月。

We're also encouraged to have observed clinical activity, including confirmed objective responses across a relatively wide range of doses. Our initial data has also validated that EpCAM expression is abundant in late-line CRC with every evaluable patient having high target levels. This is important because it suggests that CX-2051 may broadly address CRC and may not require patient selection, potentially a significant commercial advantage.

我們也很高興地觀察到臨床活動，包括在相對較寬的劑量範圍內確認的客觀反應。我們的初步數據也證實，EpCAM 在晚期 CRC 中表達豐富，並且每個可評估的患者都具有較高的目標水平。這很重要，因為它表明 CX-2051 可能廣泛解決 CRC 問題，並且可能不需要患者選擇，這可能是一個顯著的商業優勢。

Furthermore, our CX-2051 masking strategy has succeeded in avoiding classic EpCAM toxicities such as pancreatitis that have impeded the successful development of drugs against this target previously. In terms of next steps, we have initiated dose expansions at doses of 7.2, 8.6 and 10 milligrams per kilogram administered every three weeks, and we are targeting enrollment of approximately 20 patients at each dose level.

此外，我們的 CX-2051 掩蔽策略成功避免了經典的 EpCAM 毒性，例如胰臟炎，這些毒性之前阻礙了針對該標靶的藥物的成功開發。就下一步而言，我們已經開始每三週注射 7.2、8.6 和 10 毫克/公斤的劑量進行劑量擴展，我們的目標是在每個劑量水平招募大約 20 名患者。

Enrollment is going well, and we remain on track for an updated data set from a total of about 70 patients in Q1 2026. Our goals for the dose expansions are to more fully characterize the dose response of CX-2051, both in terms of clinical activity and safety with the goal to inform dose selection for Phase 2.

招募工作進展順利，我們預計在 2026 年第一季獲得總共約 70 名患者的更新資料集。我們進行劑量擴展的目標是更全面地描述 CX-2051 的劑量反應，包括臨床活性和安全性，以便為第 2 階段的劑量選擇提供資訊。

In terms of safety, the most common adverse events in the interim Phase 1 data were diarrhea, nausea, vomiting and anemia. In the expansion phase, we're paying particular attention to management of diarrhea using prophylactic medications, and we'll continue to iterate and refine our AE management strategies to best position CX-2051 for Phase 2 and beyond.

在安全性方面，第一階段中期數據中最常見的不良事件是腹瀉、噁心、嘔吐和貧血。在擴展階段，我們特別注意使用預防性藥物治療腹瀉，並且我們將繼續迭代和完善我們的 AE 管理策略，以使 CX-2051 在第 2 階段及以後處於最佳位置。

In parallel to enrolling the expansion cohorts, we are in the process of developing our Phase 2 strategy in late-line CRC and planning for potential initiation during the first half of 2026. While detailed next steps will, of course, be data dependent, our current view is that the next study would likely evaluate CX-2051 monotherapy in fourth-line CRC based on the high unmet need, the potential speed to market and the multibillion-dollar market opportunity we see in this treatment setting.

在招募擴展隊列的同時，我們正在製定後期 CRC 的第二階段策略，並計劃在 2026 年上半年啟動。當然，下一步的具體措施將取決於數據，但我們目前的觀點是，下一項研究可能會根據未滿足的巨大需求、潛在的上市速度以及我們在此治療環境中看到的數十億美元的市場機會，評估 CX-2051 在四線 CRC 治療中的單一療法。

Looking out to the longer term, CX-2051 is also anticipated to have potential in earlier lines of CRC therapy and ultimately may be positioned, we believe, to replace irinotecan as a foundational component of CRC treatment. In support of this strategy, we anticipate starting combination studies in CRC in 2026.

從長遠來看，CX-2051 預計在早期 CRC 治療中也具有潛力，我們相信最終可能取代伊立替康成為 CRC 治療的基礎組成部分。為了支持這項策略，我們預計將於 2026 年開始在 CRC 進行組合研究。

Now turning to CX-801, our masked interferon alpha-2b program that we're developing in combination with the PD-1 inhibitor, KEYTRUDA. Interferon alpha is a powerful immune system modulator with known anticancer activity across multiple tumor types, including renal cancer, bladder cancer and melanoma. But it's fallen out of clinical use in oncology due to its poor tolerability.

現在談談 CX-801，這是我們與 PD-1 抑制劑 KEYTRUDA 共同開發的掩蔽幹擾素 α-2b 計畫。幹擾素α是一種強大的免疫系統調節劑，已知對多種腫瘤類型具有抗癌活性，包括腎臟癌、膀胱癌和黑色素瘤。但由於耐受性差，它已不再在腫瘤臨床中使用。

We designed CX-801 to really clamp down on the undesired broad systemic activity of interferon and localized activity to the tumor microenvironment. In May of 2025, during Q2, we dosed the first patient in the combination arm of our Phase 1 study with KEYTRUDA. This study is focused in metastatic melanoma, and we're targeting initial data for the combination in 2026.

我們設計 CX-801 是為了真正抑制干擾素不良的廣泛全身活性和腫瘤微環境的局部活性。2025 年 5 月，即第二季度，我們為 KEYTRUDA 第一階段研究的聯合治療組中的第一位患者進行了給藥。這項研究的重點是轉移性黑色素瘤，我們的目標是在 2026 年獲得該組合的初步數據。

In the fourth quarter of this year, we anticipate providing a first look at translational data for monotherapy CX-801 impaired tumor biopsies and specifically how it's modulating the tumor microenvironment, including potential upregulation of interferon stimulated genes like PD-L1. Positive early results here would provide evidence that the mechanism of action is working as designed, underpinning our rationale for the KEYTRUDA combination and supporting our vision of turning cold tumors hot with this novel immunotherapy.

今年第四季度，我們預計將首次提供單一療法 CX-801 受損腫瘤活檢的轉換數據，特別是它如何調節腫瘤微環境，包括幹擾素刺激基因（如 PD-L1）的潛在上調。早期的積極結果將提供證據，證明作用機制正在按設計發揮作用，鞏固了我們對 KEYTRUDA 組合的理論基礎，並支持我們利用這種新型免疫療法將冷腫瘤轉變為熱腫瘤的願景。

We look forward to providing this initial CX-801 translational update in Q4 this year.

我們期待在今年第四季提供此初始 CX-801 轉換更新。

With that, let me turn the call over to Chris for updates on our finances.

說完這些，讓我把電話轉給克里斯，詢問我們的財務狀況的最新情況。

Thank you, Sean. Echoing Sean's earlier comments, the second quarter was important as we presented initial CX-2051 Phase 1 data that informed clear next steps for the program. From a capital formation standpoint, we are pleased to have completed a $100 million follow-on offering with a top-tier group of shareholders, further underscoring CX-2051's potential.

謝謝你，肖恩。與肖恩之前的評論相呼應，第二季度非常重要，因為我們提供了初步的 CX-2051 第一階段數據，為該計劃的後續步驟提供了明確的信息。從資本形成的角度來看，我們很高興與頂級股東完成了 1 億美元的後續發行，這進一步凸顯了 CX-2051 的潛力。

Following the execution of the financing, CytomX is in a strong financial position with projected cash runway to the second quarter of 2027. Of note, our cash guidance does not assume any additional milestones from existing collaborations or any new business development. Outside of CX-2051, we will continue to employ a focused capital allocation approach, including for CX-801, where we are aiming to deliver initial proof of concept in combination with KEYTRUDA in melanoma.

融資完成後，CytomX 的財務狀況良好，預計現金流量將持續到 2027 年第二季。值得注意的是，我們的現金指引並不假設現有合作或任何新業務發展能帶來任何額外的里程碑。除了 CX-2051 之外，我們將繼續採用集中的資本配置方法，包括對於 CX-801，我們的目標是將其與 KEYTRUDA 結合用於治療黑色素瘤，提供初步的概念驗證。

In terms of our research collaborations, we continue to view partnering as a capital-efficient way to extend the reach of our technology and drive increased long-term value. A key current focus in our collaborations is T-cell engagers, where, for example, we have momentum with partners, Regeneron and Astellas and have the potential to earn milestones over the next one to two years.

在我們的研究合作方面，我們繼續將合作視為一種資本高效的方式，以擴大我們的技術覆蓋範圍並提高長期價值。我們目前合作的一個重點是 T 細胞抑制劑，例如，我們與合作夥伴 Regeneron 和 Astellas 合作勢頭強勁，並有可能在未來一到兩年內取得里程碑式的進展。

With that, I'll walk through our second quarter financial results. As of June 30, 2025, we ended the quarter with $158.1 million in cash, cash equivalents and investments versus $79.9 million in cash at the end of the first quarter of 2025. Total revenue was $18.7 million compared to $25.1 million in the second quarter of 2024. The lower revenue was driven by the completion of our performance obligations in the BMS and Amgen collaborations as well as decreased activity with Moderna.

接下來，我將介紹我們第二季的財務表現。截至 2025 年 6 月 30 日，本季末我們的現金、現金等價物和投資為 1.581 億美元，而 2025 年第一季末的現金為 7,990 萬美元。總收入為 1870 萬美元，而 2024 年第二季為 2510 萬美元。收入下降的原因是，我們完成了與 BMS 和 Amgen 合作中的履約義務，以及與 Moderna 合作的活動減少。

Operating expenses for the second quarter were $19.9 million compared to $33.6 million in the second quarter of 2024. R&D expenses were $13.3 million during the second quarter, representing a decrease of $11.9 million versus the second quarter of 2024.

第二季的營運費用為 1,990 萬美元，而 2024 年第二季的營運費用為 3,360 萬美元。第二季研發費用為 1,330 萬美元，較 2024 年第二季減少 1,190 萬美元。

General and administrative expenses also decreased by $1.8 million during the three months ending June 30, 2025, to $6.6 million compared to $8.4 million for the corresponding period in 2024, driven by lower personnel costs and lower legal and patent expenses.

截至 2025 年 6 月 30 日的三個月內，一般及行政開支也減少了 180 萬美元，至 660 萬美元，而 2024 年同期為 840 萬美元，這主要是由於人員成本降低以及法律和專利開支減少。

Overall, we will continue to maintain a disciplined data-driven capital allocation approach in order to advance the most promising opportunities in our pipeline.

總體而言，我們將繼續保持嚴謹的數據驅動資本配置方法，以推進我們通路中最有前景的機會。

With that, I'll turn the call back to Sean for closing remarks.

說完這些，我會把電話轉回給肖恩，請他做最後發言。

Thanks, Chris, and thanks, everyone, for joining us today. CytomX made tremendous progress during Q2, and we look forward to the second half as we set our sights on 2026 and in particular, next steps for the CX-2051 program. With EpCAM, we believe we have unlocked a new approach to the treatment of late-stage CRC, leveraging our proprietary platform technology and prior experience with masked ADCs.

謝謝克里斯，也謝謝大家今天加入我們。CytomX 在第二季度取得了巨大進展，我們期待下半年，因為我們將目光投向了 2026 年，特別是 CX-2051 計劃的下一步。利用 EpCAM，我們相信我們已經開闢了一種治療晚期 CRC 的新方法，利用我們專有的平台技術和先前使用掩蔽 ADC 的經驗。

We view CX-2051 as a first-in-class and highly differentiated asset with broad scope for value creation. Based on the interim Phase 1 dose escalation results disclosed to date, we see a clear path forward to develop CX-2051 in late-line CRC, and we plan to execute against this opportunity as our top near-term priority. We're excited to see Phase 1 results in Q1 of 2026, together with our next steps for the program.

我們認為 CX-2051 是一流的、高度差異化的資產，具有廣泛的價值創造空間。根據迄今為止披露的 I 期中期劑量遞增結果，我們看到了在晚期 CRC 中開發 CX-2051 的明確道路，並且我們計劃抓住這一機會作為我們近期的首要任務。我們很高興看到 2026 年第一季的第一階段成果以及該計劃的下一步進展。

Regarding CX-801, we're executing a similarly focused strategy to CX-2051 in melanoma in order to generate proof of concept for the KEYTRUDA combination. Positive data here would reestablish interferon as a potential new centerpiece of combination immunotherapy with broad potential across many immunologically cold tumors or for patients who become refractory to checkpoint inhibition. We look forward to advancing CX-801 towards this vision.

關於 CX-801，我們正在對黑色素瘤執行與 CX-2051 類似的重點策略，以便為 KEYTRUDA 組合產生概念證明。這裡的積極數據將重新確立幹擾素作為聯合免疫療法的潛在新核心的地位，對許多免疫冷腫瘤或對檢查點抑制產生抗藥性的患者俱有廣泛的潛力。我們期待 CX-801 朝著這個願景邁進。

Before I wrap up today's call, I want to sincerely thank and honor the patients who joined our studies, their families, our clinical investigators and our dedicated team here at CytomX. Your collective contributions are responsible for our advancements, and we're grateful for your help in getting us to where we are today.

在結束今天的電話會議之前，我想真誠地感謝和敬意加入我們研究的患者、他們的家人、我們的臨床研究人員以及 CytomX 的專業團隊。你們的集體貢獻促成了我們的進步，我們感謝你們的幫助，使我們達到了今天的水平。

With that, operator, please go ahead and open up the call for Q&A.

接線員，請繼續打開電話進行問答。

(Operator Instructions) Edward Tenthoff, Piper Sandler.

（操作員指示）Edward Tenthoff，Piper Sandler。

Congrats on all the progress here. So my question has to do with the potential to move into earlier lines of colorectal therapy. What's going into those decisions? And how do you envision sort of announcing those trials?

恭喜你在這裡取得的所有進展。所以我的問題與進入早期結直腸治療的可能性有關。這些決定是基於什麼做出的？您打算如何宣布這些試驗？

Ted, thanks for the question. So as I mentioned, first of all -- first and foremost, we're super focused on executing towards the late-line opportunity. We see a terrific opportunity there to move really quickly in fourth line. Coming into the earlier lines, obviously, is a key -- will be a key focus for us over time to really broaden the opportunity. That will require combination studies to assess the doses that we ultimately select for the Phase 2 for the monotherapy in the context of certain combinations to come into -- well, into third line and then, of course, into second line, where the vision would be to replace irinotecan.

泰德，謝謝你的提問。正如我首先提到的——首先，我們非常注重抓住後期機會。我們看到了在第四線快速前進的絕佳機會。顯然，進入早期階段是關鍵——隨著時間的推移，這將成為我們真正拓寬機會的重點。這將需要進行組合研究來評估我們最終選擇的用於第二階段單一療法的劑量，在某些組合的背景下進入第三線，然後當然進入第二線，其願景是取代伊立替康。

So one, clear opportunity there in terms of combinations, given the extent of its use in treatment of CRC is to evaluate the combination with bevacizumab. And that's something that we're looking at carefully. And we will be doing -- I'm pretty sure in the future, we need to obviously round out the Phase 1 study and select our doses.

因此，考慮到其在 CRC 治療中的應用範圍，就組合而言，一個明顯的機會是評估與貝伐單抗的組合。我們正在仔細研究這個問題。我們將會這樣做——我很確定在未來，我們顯然需要完成第一階段的研究並選擇我們的劑量。

Nabeel Nissar, Jefferies.

傑富瑞的納比爾‧尼薩爾 (Nabeel Nissar)。

This is Nabeel on for Roger. Thanks for the updates. Quick question regarding the rationale for value creation of EpCAM beyond CRC. Are we approaching this with partnerships? And what is the strategy? Are we looking for a particular TAM? Or is there a particular tumor indication that would fit better with your technology?

這是納比爾 (Nabeel) 代替羅傑 (Roger) 上場。感謝您的更新。關於 CRC 之外 EpCAM 價值創造的理由的快速問題。我們是否透過合作的方式來實現這一目標？那麼策略是什麼呢？我們正在尋找特定的 TAM 嗎？或者是否有特定的腫瘤適應症更適合您的技術？

Thanks for the question. It's a terrific opportunity to broaden the 2051 development program outside of CRC. We do, of course, currently have our hands rather full with the scope and scale of the opportunity in colorectal alone. But just to restate, EpCAM is expressed in most solid tumors and in many of them at high levels.

謝謝你的提問。這是在 CRC 之外拓展 2051 發展計畫的絕佳機會。當然，目前我們確實已經忙得不可開交，尤其是在大腸癌領域，機會的範圍和規模都非常大。但需要重申的是，EpCAM 在大多數實體腫瘤中都有表達，並且在許多實體腫瘤中表達量較高。

So for example, lung, pancreatic, gastric, endometrial breast cancer. So there's an enormous opportunity here now that we have initial proof of concept in colorectal. So it is the kind of drug or the kind of profile of drug that over time, could very well benefit from a partnership.

例如肺癌、胰臟癌、胃癌、子宮內膜癌、乳癌。因此，現在我們在結直腸領域已經有了初步的概念證明，這是一個巨大的機會。因此，隨著時間的推移，這種藥物或這種藥物的特徵很可能會從合作中受益。

We'll get there when the time is right. As I've said many times on these calls, we'll do the right deal or right deals at the right time. But that could certainly make sense in the future for value creation. But again, right now, over the next few months, I think it's important for us to be laser focused on really building value initially through the CRC opportunity.

時機合適時我們就會到達那裡。正如我在電話中多次說過的那樣，我們會在正確的時間達成正確的交易。但這對於未來的價值創造肯定是有意義的。但是，現在，在接下來的幾個月裡，我認為對我們來說重要的是要集中精力透過 CRC 機會真正地創造價值。

Matt Biegler, Opco.

馬特·比格勒（Matt Biegler），Opco。

What do you think is the bar for accelerated approval in CRC right now, assuming you do go forward with like a monotherapy fourth line? I think obviously, like the rule of thumb that the buy side loves to point to is a 30% ORR, but we've recently seen an ESMO working group come out advocating as low as 20%, I think, like given how poor salvage therapies work in this setting. So I'm just kind of curious if you had any thoughts on that or whether you think ORR is even the most relevant outcome versus PFS or OS or something like that?

假設您確實繼續推進單一療法第四線治療，您認為目前 CRC 加速審批的標準是什麼？我認為，顯然，買方喜歡指出的經驗法則是 30% ORR，但我們最近看到 ESMO 工作組提出將 ORR 降低至 20%，我想，這是考慮到在這種情況下挽救療法的效果很差。所以我只是有點好奇您對此有什麼想法，或者您認為 ORR 是與 PFS 或 OS 或類似的東西相比最相關的結果？

Yes. Thanks, Matt. Great question. And of course, an exceedingly difficult one to answer at the moment. But given the activity that we've seen so far and the performance of 2051 in this area of such enormous unmet medical need, we, of course, have to be thinking about strategies that could lead to an accelerated approval.

是的。謝謝，馬特。好問題。當然，這個問題目前很難回答。但考慮到我們迄今為止所看到的活動以及 2051 在如此巨大的未滿足醫療需求領域的表現，我們當然必須考慮可能導致加速批准的策略。

We want to get this drug to patients as quickly as we possibly can. That said, there are two major considerations as we develop that strategy. One, there's not precedent for accelerated approval in the CRC setting based on ORR, as you know, that would be breaking new ground. More typically, we're looking at a patient population in a clinical setting where we're relying on PFS and of course, ultimately OS endpoints.

我們希望盡快將這種藥物送到患者手中。話雖如此，我們在製定該策略時有兩個主要考慮因素。首先，如你所知，在 CRC 設定中沒有基於 ORR 加速批准的先例，這將是一個新突破。更典型的是，我們在臨床環境中觀察患者群體，我們依賴 PFS，當然還有最終的 OS 終點。

That said, the scope of the unmet need, the nature of the unmet need here is so high and our activity is so encouraging that we are considering it, and we will, at the right time, have discussions with FDA. The second thing, of course, is just the overall regulatory uncertainty at the moment, which none of us can ignore. But just to reiterate, of course, we're all aligned here and wanting to get this drug to patients by the fastest possible means.

也就是說，未滿足需求的範圍和性質如此之高，而且我們的活動如此令人鼓舞，因此我們正在考慮它，並且我們將在適當的時候與 FDA 進行討論。第二件事當然是目前整體監管的不確定性，這是我們任何人都無法忽視的。但當然，我再次重申，我們都一致希望以最快的方式將這種藥物送到患者手中。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

So on the preliminary 801 monotherapy data here in the fourth quarter, what are you looking for that might give you confidence in sort of the combination potential of this product with KEYTRUDA and melanoma? And I guess, any thoughts on any risks of overlapping tox that you're going to be monitoring for?

那麼，根據第四季度的初步 801 種單一療法數據，您正在尋找什麼可以讓您對該產品與 KEYTRUDA 和黑色素瘤的結合潛力充滿信心？我想，您對要監測的重疊毒性風險有何看法？

Anupam, great question. I'm happy to talk about 801 a little bit more. So first of all, there's actually a very good precedent for -- mechanistically for PD-1, specifically KEYTRUDA and interferon alpha-2b having very powerful combination activity in melanoma. That's been shown by Merck in a somewhat earlier setting -- patient setting than we're currently working in.

Anupam，好問題。我很高興能再多談 801。首先，從機制上來說，PD-1 實際上有一個很好的先例，特別是 KEYTRUDA 和乾擾素 α-2b 在黑色素瘤中具有非常強大的組合活性。默克公司在比我們目前研究的更早的患者環境中已經證明了這一點。

But nonetheless, they showed robust activity, but it was limited by significant incidence of Grade 3 adverse events of various kinds, particularly immune adverse events. So we do know that this combination can be very effective in melanoma as a starting point. In terms of the progression of our development plan for 801, we're being very deliberate about it. We have escalated through several cohorts already of monotherapy just in a handful of patients to get initial experience with the drug.

但儘管如此，它們表現出了強勁的活性，但卻受到各種 3 級不良事件（尤其是免疫不良事件）發生率的限制。因此，我們確實知道，這種組合對於黑色素瘤的治療非常有效。就 801 發展計畫的進展而言，我們正在非常慎重地考慮。我們已經對少數患者進行了多組單一療法試驗，以獲得該藥物的初步經驗。

In that escalation, we've reported previously, we've already exceeded the clinically approved dose and clinically utilized dose of interferon alpha. So we've already made progress, which is consistent with masking showing an overall tolerability benefit. Most importantly, though, that initial experience with just a few monotherapy patients ungated our ability to start the combination, which we did during Q2, as we just mentioned.

在那次升級中，我們之前曾報告過，我們已經超過了乾擾素α的臨床批准劑量和臨床使用劑量。因此我們已經取得了進展，這與掩蔽顯示出的整體耐受性優勢是一致的。但最重要的是，最初僅對少數單一療法患者進行治療的經驗限制了我們開始聯合治療的能力，正如我們剛才提到的，我們在第二季度就已經開始聯合治療了。

And that really is the drug here. So we see the drug ultimately as being 801 plus KEYTRUDA, and we're now going to aggressively enroll that arm of the study, and that data will be reported next year. So the safety and efficacy data from the combination will come in 2026.

這確實是藥物。因此，我們認為該藥物最終將是 801 加上 KEYTRUDA，我們現在將積極招募該研究部分，並將於明年報告相關數據。因此，該組合的安全性和有效性數據將於 2026 年公佈。

In the meantime, with this handful of monotherapy patients that we've treated, we have been studying and we'll continue to study a series of paired tumor biopsies to interrogate the immune tumor microenvironment to look at how in the microenvironment, the unmasked interferon is modulating immune cells and also inducing what we would expect it to do, which is to induce interferon regulated genes, which include PD-L1, which really underscores the rationale for the combination with a checkpoint inhibitor like KEYTRUDA.

同時，對於我們治療過的少數單藥治療患者，我們一直在研究並將繼續研究一系列配對腫瘤活檢，以探究免疫腫瘤微環境，觀察在微環境中，未被掩蓋的干擾素如何調節免疫細胞，並誘導我們期望它做的事情，即誘導幹擾素調節基因，其中包括 PD-L1，這真正強調了與 KEYTRUDA 等檢查點抑製劑聯合使用的理由。

So the data that we're planning to share in Q4 will be from a handful of patients. It will be biopsy data initially. We're not expecting in this initial small number of patients to have any kind of initial ORR assessment. It's going to be translational data, but very important and hopefully very informative data that shows us that at the molecular level, the drug is behaving as we've designed it.

因此，我們計劃在第四季度分享的數據將來自少數患者。最初它將是活檢數據。我們並不期望對這少數最初的患者進行任何類型的初步 ORR 評估。這將是轉化數據，但非常重要，並且希望是非常有用的資料，它向我們表明在分子層面上，藥物的行為與我們設計的一致。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

I apologize if this has been asked, I joined late. On the EpCAM ADC, so we got the Phase 1 update in Q1. Kind of just if you could talk through the size of the data set we see and the scope of it, and kind of if we should expect to see durability and also biomarker data.

如果有人問到這個問題，我很抱歉，因為我加入晚了。在 EpCAM ADC 上，我們在第一季獲得了第一階段的更新。如果您可以談談我們看到的資料集的大小和範圍，以及我們是否應該看到耐用性和生物標記資料。

Yes. Thanks, Peter. Thanks for giving me the opportunity to recap some of our earlier comments on the call. It's very important. So as we said, we're super focused on generating this next data set for 2051. We anticipate that in Q1 2026, we'll have 70 and maybe a few more patients have experience with the drug compared to the update, the initial disclosure in May, which was 25 safety evaluable patients and 18 efficacy evaluable.

是的。謝謝，彼得。感謝您給我機會回顧我們之前在電話會議上發表的一些評論。這非常重要。正如我們所說，我們非常專注於產生 2051 年的下一組資料集。我們預計，到 2026 年第一季度，我們將有 70 名甚至更多的患者使用該藥物，而 5 月首次披露的數據為 25 名可進行安全性評估的患者和 18 名可進行療效評估的患者。

So by the time we get to Q1, that data set should be quite a bit larger and predominantly across three dose levels, 7.2, 8.6 and 10 mg per kg. Each of which were doses that we saw clinical activity for in that initial disclosure, right? So by then, yes, we would expect to have reasonable follow-up on the majority of those patients.

因此，當我們進入 Q1 時，該數據集應該會大得多，並且主要涵蓋三個劑量水平，即每公斤 7.2、8.6 和 10 毫克。我們在最初的披露中看到的每種劑量都有臨床活性，對嗎？所以到那時，是的，我們希望對大多數患者進行合理的追蹤。

And the other element of that update will be integration of that data into our go-forward plan for Phase 2. So that's our current plan is that the Q1 update will be a rounded out Phase 1 data set plus our strategy for moving forward into Phase 2. That's the current plan.

更新的另一個要素是將這些數據整合到我們第二階段的推進計畫中。因此，我們目前的計劃是，第一季的更新將是一個完整的第一階段資料集加上我們進入第二階段的策略。這是目前的計劃。

And that Phase 2, would that have a randomized component to it?

那麼第二階段是否會有隨機成分呢？

I think that's most likely. Yes, we're still obviously collecting data from the Phase 1. So no decisions made yet, but we are of the general view that the next study would be randomized to a component or components of current standard of care in the fourth line where, unfortunately, for patients today, the bar is very low.

我認為這很有可能。是的，我們顯然仍在收集第一階段的數據。因此尚未做出決定，但我們普遍認為，下一項研究將隨機分配到第四線當前護理標準的一個或多個組成部分，不幸的是，對於今天的患者來說，標準非常低。

So we think that 2051 is very well positioned against those comparators. And we'll also be thinking through in the context of Project Optimus and also, of course, based on the full Phase 1 data set that we analyzed later this year and into Q1, whether that's a one dose of 2051 or maybe two, that remains to be decided.

因此，我們認為 2051 與這些比較對象相比處於非常有利的地位。我們還將根據 Optimus 計劃的背景下進行思考，當然，也會根據我們在今年稍後和第一季度分析的完整第一階段數據集，確定 2051 年接種一劑還是兩劑，這還有待決定。

Mitchell Kapoor, H.C. Wainwright.

米切爾·卡普爾、H.C. 溫賴特。

You mentioned that there's quite a low bar for 2051. That makes a lot of sense. But thinking about what triggers a go/no-go move into the Phase 2 and fourth line as a monotherapy, can you just speak to what we should be looking for that would be indicative of a positive outcome that would immediately trigger looking to move into Phase 2?

您提到 2051 年的標準相當低。這很有道理。但是，考慮到什麼因素會觸發單一療法進入第 2 階段和第 4 線，您能否談談我們應該尋找什麼來表明可以立即觸發進入第 2 階段的積極結果？

Yes. Mitch, thanks for the question. Well, again, just to recap our experience with the first 18 efficacy evaluable patients where across the three dose levels of 7.2, 8.6 and 10, we saw a confirmed ORR of 28%. So I think we all agree that that's very exciting and would set up a very clear go-forward decision into the fourth-line study.

是的。米奇，謝謝你的提問。好吧，再次回顧我們對前 18 名可評估療效患者的經驗，在 7.2、8.6 和 10 三個劑量水平下，我們看到確認的 ORR 為 28%。所以我認為我們都同意這是非常令人興奮的，並且將為第四線研究做出非常明確的前進決定。

Number doesn't, of course, need to be as high as that to go forward. I don't think we're going to put a number on it today, but we've got a lot of room to maneuver, we think, with the data that we've already presented with CX-2051 as our data continues to mature.

當然，數字不需要這麼高才能繼續前進。我認為我們今天不會給出一個數字，但我們認為，隨著我們數據的不斷成熟，憑藉我們已經提供的 CX-2051 數據，我們還有很大的迴旋餘地。

Okay, great. And just one more on the CRC combos in earlier lines, would you potentially advance multiple combinations? And have any plans been discussed with the FDA on the combination strategy so far?

好的，太好了。關於之前幾行中的 CRC 組合，還有一點，您是否有可能推進多種組合？到目前為止，是否與 FDA 討論過聯合策略的計劃？

Multiple combinations are certainly on the table. We need to be mindful of our resources at this point in time. And as I mentioned, the place to start most likely would be the combination with bev. We have yet to have significant conversations with FDA relating to few go-forward study design. That will come, of course, as our Phase 1 data continues to mature.

當然，還有多種組合可供選擇。此時我們需要注意我們的資源。正如我所提到的，最有可能的起點是與 bev 的組合。我們尚未與 FDA 就一些前瞻性研究設計進行重要對話。當然，隨著我們第一階段資料的不斷成熟，這將會發生。

Mayank Mamtani, B. Riley.

Mayank Mamtani，B. Riley。

This is [Jeff] from B. Riley for Mayank. My first question is given that CX-2051's Grade 3 diarrhea rates exceeded those of other Topo-1 inhibitor ADCs. Will you explore alternative mitigation strategies such as specific protease inhibitors or microbial modulation rather than relying solely on loperamide?

我是 Mayank 的 B. Riley 的 [Jeff]。我的第一個問題是，鑑於 CX-2051 的 3 級腹瀉發生率超過了其他 Topo-1 抑制劑 ADC。您是否會探索替代緩解策略，例如特定的蛋白酶抑制劑或微生物調節，而不是僅依賴洛哌丁胺？

My second question is how much median follow-up are you expecting to have at 1Q update? And are you planning to present data at ASCO GI in January 2026?

我的第二個問題是，您預計第一季更新時的平均跟進次數是多少？您是否計劃在 2026 年 1 月的 ASCO GI 上展示資料？

Great. Thanks for the questions. So taking the first one relating to diarrhea. Yes, so as I mentioned on the call, that is one of the AEs that we're most focused on in this Phase 1 study. We've learned a lot about it in the context of the data that we initially disclosed. Just to recap what we're doing, as we've discussed before. In the earlier part of this study, of course, as we wanted to understand the overall AE profile of this drug, we have not implemented any prophylactic measures for management of diarrhea.

偉大的。感謝您的提問。因此，首先討論與腹瀉有關的問題。是的，正如我在電話中提到的，這是我們在第一階段研究中最多關注的不良事件之一。我們在最初披露的數據背景下對此了解了很多。正如我們之前討論過的，只是回顧一下我們正在做的事情。當然，在本研究的早期階段，由於我們想了解這種藥物的整體不良反應情況，因此我們沒有實施任何預防腹瀉的措施。

But we did earlier this year around the March time -- March, April time frame around the time that we were beginning to gear up some of these expansion studies. And so we continue to be focused on the use of loperamide as a prophylactic measure. We're going to learn a lot about that as we continue to execute on the expansions.

但我們在今年早些時候，也就是三月、四月左右就開始著手進行一些擴展研究。因此，我們繼續專注於使用洛哌丁胺作為預防措施。隨著我們繼續執行擴張，我們將學到很多關於這方面的知識。

And in terms of the incidence of Grade 3 diarrhea in the study, about 20%. I want to remind everyone that in the early days of irinotecan development, that number was closer to 30% to 40%. And we do know that Topo-1 inhibitors in the context of ADCs can also induce significant levels of Grade 3 and higher diarrhea. So it's something we need to understand more about, something we need to manage. We're really exploring loperamide as a starting point.

而就研究中3級腹瀉的發生率而言，約為20%。我想提醒大家，在伊立替康開發初期，這個數字接近30％到40％。我們確實知道，ADC 中的 Topo-1 抑制劑也能誘發顯著水平的 3 級及更高級別的腹瀉。所以這是我們需要更多了解的事情，也是我們需要管理的事情。我們確實在探索洛哌丁胺作為起點。

Your question on protease inhibitors, I think is an interesting one. At this point, that will be very exploratory, and we don't really have any evidence right now that protease biology is playing any role in the AE profile. So that may be something for future exploration. But thanks for the question. I think you had two more questions in terms of median follow-up.

我認為您關於蛋白酶抑制劑的問題很有趣。目前，這將是非常具有探索性的，我們現在還沒有任何證據表明蛋白酶生物學在 AE 概況中發揮任何作用。所以這可能是未來值得探索的事。但感謝您的提問。我認為您在中位追蹤方面還有兩個問題。

I guess there, what I would say is that, as I mentioned earlier, enrollment of the expansions has gone well. We're midway through 2025. So by the time we get to Q2 -- sorry, Q1 of next year, we'll have a pretty decent follow-up, we think, on the majority of these patients. So I can't give you a number. The study is still in progress.

我想說的是，正如我之前提到的，擴展的招生進展順利。我們已經到了 2025 年的一半。因此，到我們進入第二季度（抱歉，是明年第一季）時，我們認為我們將對大多數患者進行相當不錯的跟踪。所以我無法給你一個數字。該研究仍在進行中。

And of course, I can't comment on the ASCO GI 2026. We will plan to keep all of our options open in terms of where and exactly when we present data as is customary. But thanks for the questions.

當然，我無法評論 ASCO GI 2026。我們將按照慣例，在資料呈現地點和時間方面保留所有選項。但感謝您的提問。

Ladies and gentlemen, I'm showing no further questions in the queue. I would now like to turn the call back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

女士們、先生們，隊列中沒有其他問題了。現在，我想將電話轉回給董事長兼執行長肖恩·麥卡錫博士，請他致最後一次演講。

Thanks, everyone, for joining us today. It's been a pleasure to recap our tremendous progress during Q2 of 2025. We look forward to providing additional updates as we move through the second half of the year. So enjoy the rest of your day.

感謝大家今天加入我們。我很高興回顧我們在 2025 年第二季的巨大進步。我們期待在今年下半年提供更多更新。所以享受你剩下的時間吧。

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。