CytomX Therapeutics Inc (CTMX) 2025 Q1 法說會逐字稿

Good morning, everyone, and thank you for standing by. Welcome to the CytomX Therapeutics CX-2051 Phase 1 Interim Clinical Data Call. Please be advised that today's call is being recorded.

大家早安，謝謝大家的支持。歡迎參加 CytomX Therapeutics CX-2051 第 1 期中期臨床資料電話會議。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 morning, 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 filing with the SEC at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise.

謝謝。早安，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。我們不承擔更新任何前瞻性陳述的義務，無論由於新資訊、未來發展或其他原因。

Earlier today, we issued a press release that includes a summary of our first quarter 2025 financial results and highlights recent progress at CytomX. Additionally, this morning, we are excited to announce both positive interim Phase 1 data for CX-2051 in advanced colorectal cancer as well as a $100 million financing with a leading group of health care investors.

今天早些時候，我們發布了一份新聞稿，其中包括我們 2025 年第一季財務業績摘要，並重點介紹了 CytomX 的最新進展。此外，今天上午，我們很高興地宣布 CX-2051 在治療晚期結直腸癌方面取得了積極的第一階段中期數據，並且獲得了來自領先的醫療保健投資者集團的 1 億美元融資。

The focus of our call today will be the Phase 1 data for CX-2051. For details on the company's financial results and pipeline updates, we encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC. Additionally, the press releases, a recording of this call, and our SEC filings can be found under the Investors and News section of our website.

我們今天電話會議的重點是 CX-2051 的第一階段數據。有關公司財務業績和產品線更新的詳細信息，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 (SEC)。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 are Dr. Sean McCarthy, CytomX Chief Executive Officer and Chairman; and Dr. Yu-Waye Chu, CytomX Chief Medical Officer. Sean will provide introductory remarks regarding CX-2051's design and clinical strategy. Yu-Waye will then walk through the CX-2051 Phase 1 interim clinical results and next steps for the program. We will then wrap up with concluding remarks before we move to Q&A.

今天與我一起參加電話會議的還有 CytomX 執行長兼董事長 Sean McCarthy 博士；以及 CytomX 首席醫療官 Yu-Waye Chu 博士。Sean 將就 CX-2051 的設計和臨床策略提供介紹說明。隨後，Yu-Waye 將介紹 CX-2051 第一階段中期臨床結果以及該計劃的後續步驟。然後，我們將進行總結發言，然後進入問答環節。

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

現在，我將把電話交給肖恩 (Sean) 來致開場白。

Thanks, Chris. It's a real pleasure to be here today to share our exciting update on CX-2051. This is a transformational moment for CytomX. We believe we've really broken new ground in colorectal cancer with this novel antibody drug conjugate that has been uniquely enabled by the CytomX PROBODY therapeutic platform. The results we're sharing today represent the integration of years of learning about our technology and importantly, how to best direct it to the maximum benefit for cancer patients.

謝謝，克里斯。今天能夠在這裡與大家分享 CX-2051 的令人興奮的最新消息，我感到非常高興。對 CytomX 來說，這是一個轉型時刻。我們相信，這種由 CytomX PROBODY 治療平台獨特實現的新型抗體藥物偶聯物確實在結直腸癌治療領域開闢了新天地。我們今天分享的結果代表了我們多年來對科技的學習的整合，更重要的是，如何最好地引導它為癌症患者帶來最大的益處。

Before getting to CX-2051, we're, of course, delighted to have also announced today, as Chris just mentioned, $100 million financing with a top-tier syndicate of healthcare specialist investors. Their belief in CytomX truly underscores the importance of what we have achieved with 2051 and the potential of this product. This financing positions us extremely well to continue our determined and focused execution toward bringing transformational cancer therapies to patients.

在談到 CX-2051 之前，正如克里斯剛才提到的，我們今天當然很高興地宣布，我們與頂級醫療保健專家投資者集團合作獲得了 1 億美元的融資。他們對 CytomX 的信任真正凸顯了我們在 2051 上所取得的成就的重要性以及該產品的潛力。這筆融資將使我們處於非常有利的地位，能夠繼續堅定而專注地為患者帶來變革性的癌症治療方法。

Turning now to CX-2051. Colorectal cancer remains one of the biggest unmet needs in oncology today with approximately 1.9 million patients diagnosed each 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 cancer death worldwide.

現在轉向 CX-2051。大腸直腸癌仍然是當今腫瘤學中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大腸癌。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。

This is a significant global health problem. And despite many advances across many other cancer types in recent years, colorectal cancer has not seen very much impact at all from innovation over that period of time, resulting in a current 5-year survival rate in metastatic colorectal cancer of only 5 -- only 13%. The current -- this dire situation is unfortunately really underscored by just how inadequate options are for the treatment of late-stage CRC in the third and fourth-line settings or later. Current standard of care therapies have poor response rates and limited survival benefits. There is enormous room for improvement.

這是一個重大的全球健康問題。儘管近年來許多其他類型的癌症治療取得了許多進展，但大腸癌在這段時間內並沒有受到太大的創新影響，導致目前轉移性大腸直腸癌的 5 年存活率僅為 5 - 僅為 13%。不幸的是，目前這種嚴峻情況實際上因三線、四線或更晚的治療方案對晚期 CRC 的治療選擇不足而更加突出。目前的標準治療反應率較低，存活獲益有限。還有巨大的進步空間。

At CytomX, we've taken this challenge head on by designing a colorectal cancer targeting antibody drug conjugate, CX-2051. Antibody drug conjugates are transforming cancer care, making a really big impact in the treatment of many solid tumors, accruing benefits from many, many thousands of patients around the world. This class of differentiated targeted oncology therapeutics continues to build very substantial value.

在 CytomX，我們透過設計針對大腸直腸癌的抗體藥物偶聯物 CX-2051 迎接了這項挑戰。抗體藥物偶聯物正在改變癌症治療，對許多實體腫瘤的治療產生了巨大的影響，使世界各地成千上萬的患者受益。這類差異化的標靶腫瘤治療方法繼續創造非常巨大的價值。

ADCs have yet to break through, however, in colorectal cancer. Our goal is to transform colorectal cancer care with CX-2051, a first-in-class antibody drug conjugate that we have carefully designed to target a protein called EpCAM that is present at high levels in CRC.

然而，ADC 在大腸直腸癌治療領域尚未取得突破。我們的目標是利用 CX-2051 改變結直腸癌治療，CX-2051 是我們精心設計的首創抗體藥物偶聯物，用於靶向 CRC 中高水平存在的一種名為 EpCAM 的蛋白質。

We've been highly focused on running a Phase 1 clinical trial over the past year, entirely focused on CRC. This is a very tough cancer to treat, but we really wanted to do the killer experiment to see what CX-2051 can do for these patients.

在過去的一年裡，我們一直高度專注於進行第一階段臨床試驗，完全專注於 CRC。這是一種非常難治的癌症，但我們真的想做這項殺手級實驗，看看 CX-2051 能為這些患者帶來什麼。

Today, we are very excited to share positive Phase 1 clinical data for CX-2051. In our first 12 months in the clinic, we have demonstrated robust anticancer activity for CX-2051 in metastatic CRC with a 28% confirmed overall response rate, a 94% disease control rate, and 5.8 months of preliminary progression-free survival. This strong anticancer activity offers the potential to position CX-2051 as a new standard of care in late-line colorectal cancer.

今天，我們非常高興地分享 CX-2051 的積極 1 期臨床數據。在臨床的前 12 個月中，我們已證明 CX-2051 在轉移性 CRC 中具有強大的抗癌活性，確認的總體反應率為 28%，疾病控制率為 94%，初步無惡化存活期為 5.8 個月。這種強大的抗癌活性使得 CX-2051 有可能成為晚期大腸直腸癌治療的新標準。

Regarding safety, CX-2051 has shown a favorable safety profile to date, including no dose-limiting toxicities during dose escalation. We believe the safety profile we have seen to date in late-line CRC is strongly supportive of developing 2051 in earlier lines of therapy, including in combinations.

關於安全性，CX-2051 迄今已顯示出良好的安全性，包括劑量增加期間沒有劑量限制性毒性。我們相信，迄今為止我們在晚期 CRC 中看到的安全性特徵強烈支持在早期治療（包括聯合治療）中開發 2051。

Furthermore, our masking strategy has succeeded in avoiding classic EpCAM toxicities that have impeded the successful development of drugs against this target before. Additionally, we can say with some confidence that EpCAM has the potential to be a pan-CRC target since we have validated that the target is indeed present at high levels in all patients we have tested. Taken together, we see this as a very strong start to the CX-2051 development program.

此外，我們的掩蔽策略成功避免了經典的 EpCAM 毒性，這種毒性之前曾阻礙針對該靶點的藥物的成功開發。此外，我們可以相當有信心地說，EpCAM 有可能成為泛 CRC 目標，因為我們已經驗證了該目標在我們測試的所有患者中確實存在高水平。總的來說，我們認為這是 CX-2051 開發計畫的一個好開始。

Before I hand over to Wayne to walk through our exciting results, I'd like to make a few comments on the molecular design of CX-2051 and our Phase 1 clinical strategy. First of all, a few words on the target. EpCAM, or epithelial cell adhesion molecule, we really believe is an ideal CRC target enabled by the CytomX PROBODY platform.

在讓韋恩介紹我們令人興奮的結果之前，我想對 CX-2051 的分子設計和我們的第一階段臨床策略發表一些評論。首先，簡單談一下目標。我們堅信 EpCAM（上皮細胞黏附分子）是 CytomX PROBODY 平台實現的理想 CRC 標靶。

EpCAM has high and uniform expression across colorectal cancer. And you can see here an immunohistochemistry image of a patient actually in our Phase 1 clinical trial showing just how high EpCAM expression is in this cancer type. In fact, this patient has a maximum score -- a score of 300 by this assay.

EpCAM 在結直腸癌中具有較高且均勻的表達。您可以在這裡看到我們第一階段臨床試驗中一名患者的免疫組織化學影像，該影像顯示了這種癌症類型中 EpCAM 的表達有多高。事實上，根據本次檢測，該患者獲得了最高分——300 分。

Now the challenge with EpCAM in the past has been its expression in normal tissues, and this has limited drug development due to toxicities that have emerged, including acute pancreatitis. So we have developed and designed CX-2051 as a first-in-class EpCAM-targeting antibody drug conjugate. And we really believe with this molecule, we have the right target, the right payload and the right tumor type. And it's really how these three design elements come together that underscore the progress that we are sharing today with this really exciting program.

過去 EpCAM 面臨的挑戰是它在正常組織中的表達，而由於出現的毒性（包括急性胰臟炎），這限制了藥物開發。因此，我們開發並設計了 CX-2051 作為一流的針對 EpCAM 的抗體藥物偶聯物。我們確實相信，透過這種分子，我們找到了正確的目標、正確的有效載荷和正確的腫瘤類型。這三個設計元素的結合確實凸顯了我們今天分享的這個令人興奮的計劃的進展。

So 2051 is based on a high-affinity anti-EpCAM monoclonal antibody that we have masked using our proprietary PROBODY therapeutic platform. And the masking is designed to reduce EpCAM binding in normal tissues. The masks, however, are removed specifically and selectively within tumor tissue by tumor-associated proteases, resulting in anticancer activity within the tumor.

因此，2051 基於高親和力抗 EpCAM 單株抗體，我們使用專有的 PROBODY 治療平台對其進行了掩蓋。而這種掩蔽的目的是減少正常組織中的 EpCAM 結合。然而，腫瘤相關蛋白酶會在腫瘤組織內特異性地、選擇性地去除這些掩模，進而在腫瘤內產生抗癌活性。

We have empowered this masked antibody with the topoisomerase-1 inhibitor, CAMP59, which is a cytotoxic payload designed to kill cancer cells. The payload is linked to the antibody through a cleavable peptide linker optimized for what we call bystander effect, which is the ability of the drug to kill neighboring cancer cells. The drug antibody ratio for CX-2051 is 8.

我們利用拓樸異構酶 1 抑制劑 CAMP59 增強了這種掩蔽抗體，CAMP59 是一種旨在殺死癌細胞的細胞毒性有效載荷。有效載荷透過可裂解的勝肽連接體與抗體相連，該連接體針對我們所說的旁觀者效應進行了優化，即藥物殺死鄰近癌細胞的能力。CX-2051的藥物抗體比率為8。

Moving now to our clinical strategy. We commenced this Phase 1 study just about one year ago, and we really have made terrific progress. We began dose escalation at the dose of 2.4 mg/kg administered every three weeks, and we have escalated through seven dose levels to date. The focus of today's update will be the first five dose levels, where we have 25 safety-evaluable patients across the doses of 2.4 to 10 mg/kg. We have 23 safety evaluable patients at the doses of 7.2, 8.6, and 10 mg/kg. And these three doses, we have already started to expand based on the exciting results we have already seen with 2051.

現在轉到我們的臨床策略。我們大約一年前開始了第一階段的研究，並且確實取得了巨大的進展。我們開始以每三週 2.4 mg/kg 的劑量增加劑量，迄今為止我們已經增加了七個劑量水平。今天更新的重點是前五個劑量水平，我們有 25 名安全性可評估的患者，劑量範圍為 2.4 至 10 mg/kg。我們有 23 位安全性可評估的患者，劑量分別為 7.2、8.6 和 10 mg/kg。根據 2051 年已經看到的令人興奮的結果，我們已經開始擴大這三種劑量的治療範圍。

We have 18 efficacy-evaluable patients across these three dose levels. And we do anticipate once these expansions are completed towards the end of this year, that our recommended Phase 2 doses will come from among this broad dose range.

我們有 18 位可評估這三個劑量水平療效的患者。我們確實預計，一旦這些擴展在今年年底完成，我們建議的第二階段劑量將來自這個廣泛的劑量範圍。

I should also say that in this clinical study, every patient enrolled was a metastatic CRC patient. We didn't enroll any patients with any other tumor types. So this has been a highly focused study. And we did not select for EpCAM expression because of our expectation that the target will be highly expressed in all patients enrolled, and Wayne will update you on that in just a moment.

我還應該說，在這項臨床研究中，每位入選的患者都是轉移性 CRC 患者。我們沒有招募任何其他腫瘤類型的患者。所以這是一項高度集中的研究。我們沒有選擇 EpCAM 表達，因為我們預計該目標在所有入組患者中都會高度表達，Wayne 稍後會向您更新這種情況。

So it's been a really strong year of execution, and I'll now hand over to Wayne to talk through our findings so far.

所以這是執行力非常強勁的一年，現在我將把時間交給韋恩來介紹我們迄今為止的發現。

Thanks, Sean. So as Sean mentioned, we've exclusively focused enrollment of this study in patients with metastatic colorectal cancer or CRC. So summarized here are the key baseline characteristics of this patient population. As is typical for a Phase 1 trial, this represents a very heavily pretreated advanced CRC population, essentially a median fifth-line patient population as evidenced by the median number of prior lines of cancer therapy of 4.

謝謝，肖恩。正如肖恩所提到的，我們專門針對轉移性大腸直腸癌或 CRC 患者進行這項研究。這裡總結了該患者群體的關鍵基線特徵。正如 I 期試驗的典型情況一樣，這代表了接受過大量預先治療的晚期 CRC 患者群體，本質上是中位數五線患者群體，這可以從先前癌症治療的中位數為 4 線看出。

Relevant to the mechanism of action of 2051 as a topoisomerase-1 inhibitor, it is important to note that as is expected for this late-line population of CRC patients, all received prior irinotecan. And in many cases, patients received multiple lines of irinotecan containing therapy.

與 2051 作為拓樸異構酶 1 抑制劑的作用機制相關，值得注意的是，正如預期的那樣，對於這群晚期 CRC 患者，所有患者都曾接受過伊立替康治療。在許多情況下，患者接受了多線含有伊立替康的治療。

Other key baseline characteristics that have been known to affect therapeutic selection and therapeutic outcomes of agents used in colorectal cancer include liver metastases and KRAS mutation status, which are observed in the majority of these patients.

已知會影響大腸直腸癌治療選擇和藥物治療結果的其他關鍵基線特徵包括肝轉移和 KRAS 突變狀態，這些特徵在大多數患者中都有觀察到。

Finally, virtually all patients were microsatellite stable -- had microsatellite stable disease, indicating that these patients are not -- have tumors that are responsive to immune checkpoint therapy.

最後，幾乎所有患者都是微衛星穩定的 - 患有微衛星穩定疾病，這表明這些患者沒有對免疫檢查點療法有反應的腫瘤。

Shown here is the waterfall plot, illustrating the objective responses in patients enrolled at the three relevant doses of 7.2 to 10 mg/kg. Among the 18 efficacy-evaluable patients, a total of five or 28% had a confirmed partial response by RECIST 1.1 criteria. And this included three of seven efficacy-evaluable patients at the 10-mg/kg dose level. You can see the depth of the responses in the waterfall plot, including on patient who had a 100% reduction in measurable target lesions.

這裡顯示的是瀑布圖，說明了接受 7.2 至 10 mg/kg 三種相關劑量治療的患者的客觀反應。在 18 名可評估療效的患者中，共有 5 名（28%）患者根據 RECIST 1.1 標準確認為部分緩解。其中包括 10 mg/kg 劑量水平的七名可評估療效的患者中的三名。您可以在瀑布圖中看到反應的深度，包括可測量目標病灶減少 100% 的患者。

I'll turn your attention to the table at the bottom of the waterfall plot, which indicates the specific baseline characteristics for each of these patients. And you can see that 2051 had activity in patients who had many lines of prior systemic therapy. Antitumor activity was observed in patients with KRAS wild-type tumors as well as KRAS-mutated tumors. And importantly, activity of 2051 was observed in patients whose disease has spread to other organs, specifically the liver.

我將請您注意瀑布圖底部的表格，該表格顯示了每位患者的特定基線特徵。您可以看到，2051 對接受過多種全身性治療的患者有療效。在患有 KRAS 野生型腫瘤和 KRAS 突變型腫瘤的患者中均觀察到了抗腫瘤活性。重要的是，在疾病擴散到其他器官（特別是肝臟）的患者中觀察到了 2051 的活性。

Finally, and importantly, as Sean mentioned, supporting the hypothesis of high and uniform levels of EpCAM expression in CRC, we tested baseline tumor biopsy for EpCAM expression using H-score, which captures the proportion and the intensity of EpCAM expression in --tumor cells. And as you can see, all tumors that have been evaluated had near maximal H-scores, supporting the fact that 2051 is a therapy that will not require patient selection based on EpCAM expression.

最後，重要的是，正如 Sean 所提到的，為了支持 CRC 中 EpCAM 表達水平高且均勻的假設，我們使用 H 分數測試了基線腫瘤活檢中的 EpCAM 表達，H 分數可以捕獲腫瘤細胞中 EpCAM 表達的比例和強度。如您所見，所有經過評估的腫瘤均具有接近最大值的 H 分數，證明了 2051 是一種不需要根據 EpCAM 表達來選擇患者的療法。

The spider plot on the next slide shows the evolution of antitumor responses over time. And I wanted to highlight two important observations. First, in addition to the confirmed partial responses, you can see in multiple examples of continuing evolution of antitumor activity over time, exemplified by patients who had a stable disease response assessment at the first tumor assessment, but with continued treatment with 2051 had conversion of that stable disease to a RECIST partial response.

下一張投影片上的蜘蛛圖顯示了抗腫瘤反應隨時間的演變。我想強調兩個重要的觀察。首先，除了已確認的部分反應外，您還可以看到抗腫瘤活性隨時間不斷演變的多個例子，例如，患者在第一次腫瘤評估時具有穩定的疾病反應評估，但繼續接受 2051 治療後，穩定疾病轉變為 RECIST 部分反應。

The second important observation is the disease control. In addition to virtually all patients, 17 out of 18 efficacy-evaluable patients with disease control, which is RECIST stable disease or better, this disease control was durable. There were no examples of patients with rapid disease progression following an initial assessment showing either stable disease or an objective response. And this durability of disease control is highlighted by the individual patient treated at the 7.2 mg/kg dose level who is able to maintain that disease control in excess of nine months on therapy.

第二個重要的觀察是疾病控制。除了幾乎所有患者外，18 名可評估療效的患者中有 17 名的疾病控制達到 RECIST 穩定疾病或更好，這種疾病控制是持久的。沒有發現患者在初步評估顯示病情穩定或客觀反應後病情迅速進展的例子。接受 7.2 mg/kg 劑量水平治療的個別患者凸顯了這種疾病控制的持久性，該患者能夠在治療後超過九個月維持疾病控制。

So, when you take into account the objective responses and the durability of disease control, this has allowed a preliminary estimate of the median progression-free survival of 5.8 months. 10 of the 18 patients who are efficacy-evaluable continue on 2051 treatment, including three of the five patients who had a confirmed partial response who continue on treatment.

因此，當考慮到客觀反應和疾病控制的持久性時，可以初步估計中位無惡化存活期為 5.8 個月。 18 名可評估療效的患者中有 10 名繼續接受 2051 治療，其中包括 5 名確認有部分緩解並繼續接受治療的患者中的 3 名。

Importantly, there were no discontinuations for ongoing treatment-related adverse events. And while some patients had dose delays and/or reductions for the management of adverse event, this has not precluded patients continuing to derive clinical benefit from 2051 nor has it prevented patients from continuing 2051 treatment.

重要的是，沒有因持續的治療相關不良事件而停止治療。雖然有些患者為了應對不良事件而延遲和/或減少劑量，但這並不妨礙患者繼續從 2051 中獲得臨床益處，也沒有阻止患者繼續接受 2051 治療。

I wanted to highlight an example of the activity that we've been observing with 2051 in this case study. This is a 46-year-old male with metastatic CRC, KRAS wild-type microsatellite stable disease. And as is typical for patients with metastatic colorectal cancer, there are multiple lesions in multiple locations outside of the GI tract. Specifically, for this patient, there were metastatic lesions in the lung, the lymph node, and as you can see by the example CT scans, multiple lesions in the liver. This patient received three prior therapy, and this represents the typical course of treatment for metastatic colorectal cancer comprised of combinations of monoclonal antibody and systemic chemotherapy.

我想強調我們在這個案例研究中觀察到的 2051 活動的一個例子。這是一名 46 歲的男性，患有轉移性 CRC、KRAS 野生型微衛星穩定疾病。對於轉移性大腸直腸癌患者來說，其胃腸道外的多個位置存在多處病變。具體來說，對於該患者，肺部、淋巴結中存在轉移性病變，並且從示例 CT 掃描中可以看出，肝臟中存在多處病變。該患者之前接受過三種治療，這是轉移性大腸直腸癌的典型治療過程，包括單株抗體和全身性化療的組合。

And the last line of prior treatment was combinations of bevacizumab and Lonsurf. The patient came on study, was treated with 2051 at a dose of 7.2 mg/kg every three weeks. The patient tolerated 2051 extremely well. And as you can see by the CT scans on the right, at the first tumor assessment, the patient had a significant reduction in tumor burden, corresponding to a near 50% reduction in burden that corresponds to a partial response by RECIST criteria.

最後一種先前的治療方法是貝伐單抗和 Lonsurf 的組合。該患者接受研究，每三週接受一次 2051 治療，劑量為 7.2 mg/kg。患者對 2051 的耐受性非常好。從右側的 CT 掃描結果可以看出，在第一次腫瘤評估時，患者的腫瘤負擔顯著減少，相當於負擔減少了近 50%，符合 RECIST 標準的部分反應。

In addition to the measurable lesions as indicated by the green arrow, the patient also had noticeable reductions in multiple liver metastatic lesions as indicated by the blue arrows. Importantly, in addition to the radiographic response of 2051 against patients' metastatic cancer, the patient also had significant clinical improvement, highlighted by the discontinuation of multiple medications for the management of cancer-related pain. This patient was able to maintain its partial response through six months of treatment. And this example nevertheless highlights the fact that the patient derived significant clinical benefit where otherwise the patient would have received worse clinical benefit with standard of care therapies.

除了綠色箭頭所示的可測量病灶外，患者肝臟多處轉移性病灶也明顯減少，如藍色箭頭所示。重要的是，除了 2051 對患者轉移性癌症的放射學反應外，患者的臨床症狀也有顯著改善，尤其突出的是停止服用多種治療癌症相關疼痛的藥物。經過六個月的治療，該患者仍能維持部分反應。儘管如此，這個例子還是強調了這樣一個事實：患者獲得了顯著的臨床益處，否則患者接受標準護理療法所獲得的臨床益處會更差。

Turning our attention to safety. This is a table of the treatment-related adverse events observed in more than 1 patient. And as Sean mentioned earlier, previous efforts to develop systemically administered EpCAM-directed anticancer therapies have been extremely limited by the evolution of dose-limiting toxicities in the absence of compelling efficacy.

將我們的注意力轉向安全。這是在 1 名以上患者中觀察到的治療相關不良事件的表格。正如 Sean 之前提到的，先前開發系統性給藥 EpCAM 導向抗癌療法的努力因缺乏令人信服的療效而受到劑量限制性毒性的極大限制。

So, in that context, I want to mention multiple observations on this table. First, what is notable by its absence are, number one, there were no dose-limiting toxicities observed on this trial to date. Number two, there were no Grade 4 or 5 treatment-related adverse events. And number three, some of the key dose-limiting toxicities, specifically severe pancreatitis that have hampered the development of other therapies were not observed in this study.

因此，在這種情況下，我想提及關於此表的多項觀察結果。首先，值得注意的是，迄今為止，在這次試驗中沒有觀察到劑量限制性毒性。第二，沒有發生 4 級或 5 級治療相關不良事件。第三，一些關鍵的劑量限制性毒性，特別是阻礙其他療法發展的嚴重胰臟炎在本研究中並未觀察到。

Overall, the AE profile of 2051 is manageable and reversible. If you look at the hematologic adverse events of anemia and neutropenia, these have primarily been laboratory in nature, and there were no significant clinical sequela such as febrile neutropenia or sepsis observed on the study. And with respect to non-hematologic adverse events, the profile is consistent with that of other topoisomerase inhibitors and that the most frequently observed adverse events were gastrointestinal in nature, including diarrhea and nausea.

整體而言，2051 年的 AE 概況是可控且可逆的。如果你觀察貧血和嗜中性球減少症的血液學不良事件，這些主要是實驗室性質的，並且在研究中沒有觀察到發燒性嗜中性球減少症或敗血症等顯著的臨床後遺症。至於非血液學不良事件，其情況與其他拓樸異構酶抑制劑一致，最常見的不良事件是胃腸道不良事件，包括腹瀉和噁心。

Nevertheless, again, these AEs were generally manageable and reversible and this overall profile combined with the compelling efficacy that we discussed earlier, clearly indicates the presence of a robust therapeutic index.

儘管如此，這些不良事件通常是可控且可逆的，並且這種總體情況與我們之前討論過的令人信服的療效相結合，清楚地表明了存在強大的治療指數。

Few words on PK. We continue to evaluate pharmacokinetics and shown here is a summary of interim analysis of Cycle 1 PK. Overall, CX-2051 is behaving as expected for an antibody drug conjugate. Importantly, the rate of payload deconjugation was low and in line with other Topo I inhibitor ADCs, as you can see by the low levels of the free linker payload. In addition, CX-2051 remained masked in circulation as evidenced by the superimposable PK curves for intact 2051 and total 2051, which represent masked and masked and unmasked 2051, respectively. The half-life of 2051 is approximately six days. And based on this early analysis of Cycle 1 PK, 2051 showed dose linearity with respect to both AUC and Cmax.

關於PK，簡單說幾句。我們繼續評估藥物動力學，這裡顯示的是第 1 週期 PK 的中期分析摘要。整體而言，CX-2051 作為抗體藥物偶聯物的表現符合預期。重要的是，有效載荷解偶聯的速率很低並且與其他 Topo I 抑制劑 ADC 一致，正如您可以從自由連接體有效載荷的低水平看到的那樣。此外，完整 2051 和總 2051 的疊加 PK 曲線證明 CX-2051 在流通中仍處於掩蔽狀態，完整 2051 和總 2051 分別代表掩蔽的 2051 和掩蔽且未掩蔽的 2051。2051的半衰期約為六天。根據第 1 週期 PK 的早期分析，2051 顯示 AUC 和 Cmax 的劑量線性。

So when you take the clinical data together with respect to safety and with the efficacy and then compare what we've observed with 2051 with other standard of care therapies in late-line metastatic CRC, it is already evident based on this early data set that with respect to key efficacy-based endpoints, including objective response rate, disease control rate and Median PFS that 2051 compares very favorably to the standard of care, and we have potentially -- potential to establish 2051 as the new standard of care in the late-line CRC setting.

因此，當您將安全性和療效方面的臨床數據放在一起，然後將我們在 2051 中觀察到的情況與晚期轉移性 CRC 中的其他標準治療方法進行比較時，根據這一早期數據集已經可以明顯看出，就關鍵的基於療效的終點而言，包括客觀反應率、疾病控制率和中位 PFS，2051 與標準治療方法相比將非常有利 205 2051 與標準 CRC環境中的新治療方法。

As the data continue to mature with respect to the number of patients and longer follow-up, we are optimistic that this efficacy endpoints will continue to be maintained, if not improved.

隨著患者數量和長期追蹤數據的不斷成熟，我們樂觀地認為，這種療效終點將繼續保持，甚至有所改善。

As far as our plans going forward, as Sean mentioned, we continue to expand at the relevant dose levels of 7.2, 8.6 and 10 mg/kg, we are expanding each of the three dose levels to a total of 20 patients, such that by the time of Q1 2026, we will have a robust data set across these three dose levels corresponding to approximately a total of 70 patients of Phase 1 data that we will update. Furthermore, the data from these dose expansions will be the basis of a go-forward plan regarding Phase 2 design, which we also anticipate to initiate in the first half of 2026.

就我們未來的計劃而言，正如 Sean 所提到的，我們將繼續擴大 7.2、8.6 和 10 mg/kg 的相關劑量水平，我們將把這三個劑量水平分別擴大到總共 20 名患者，這樣到 2026 年第一季度，我們將擁有涵蓋這三個劑量水平的強大數據集，相當於我們將第 70 名患者的第 70 名患者的數據集。此外，這些劑量擴展的數據將成為第 2 階段設計前進計畫的基礎，我們預計該計畫也將在 2026 年上半年啟動。

So with that, I will turn it back to Sean for concluding remarks.

因此，我將把話題交還給肖恩，請他做總結發言。

Great. Thanks, Wayne. Well, based on this really exciting data that we're absolutely thrilled to share with you all today, I believe we can say that CX-2051 is functioning exactly as we have designed it. We've broken new ground for EpCAM and colorectal cancer with our masking strategy, unlocking EpCAM as a viable therapeutic target for systemic anticancer therapy for the first time. This is a highly differentiated program and very consistent with our overall philosophy at CytomX over the years of making a difference by being different.

偉大的。謝謝，韋恩。好吧，基於我們今天非常高興與大家分享的這些令人興奮的數據，我相信我們可以說 CX-2051 的運作完全按照我們的設計進行。我們透過掩蔽策略為 EpCAM 和結直腸癌開闢了新天地，首次將 EpCAM 揭示為全身抗癌治療的可行治療標靶。這是一個高度差異化的計劃，與 CytomX 多年來透過與眾不同來創造差異的整體理念非常一致。

Looking ahead, we see a very broad development opportunity for CX-2051. We will be highly focused on advancing 2051 in late-line CRC towards approval as rapidly as we can -- as fast as we can. We see tremendous opportunities to advance the drug in the third-line or later setting based on these groundbreaking results that we've shared today.

展望未來，我們看到CX-2051非常廣闊的發展機會。我們將高度集中精力，盡快推進 2051 年後期 CRC 的批准。根據我們今天分享的這些突破性成果，我們看到了在三線或更晚的治療中推進藥物的巨大機會。

As I mentioned earlier, the current standard of care and as Wayne just reviewed, the current standard of care in the late-line setting is highly inadequate, and we believe we've got something really valuable that can make a big difference for patients.

正如我之前提到的，目前的護理標準以及韋恩剛才回顧的，後期環境中的當前護理標準嚴重不足，我們相信我們已經獲得了一些真正有價值的東西，可以為患者帶來巨大的改變。

In addition to the late-line setting, of course, we see enormous opportunities to bring CX-2051 forward in the treatment paradigm for colorectal cancer. Indeed, our vision for 2051 has always been based on using a Topo I payload that we could bring it to earlier lines, potentially replacing irinotecan in earlier line regimens and perhaps even more broadly replacing chemotherapy in the treatment and management of earlier line CRC. So this drug has, we believe, transformational potential based on this early look at our Phase 1 data showing just how effectively the drug is performing in the metastatic CRC setting.

當然，除了後期治療之外，我們還看到了將 CX-2051 應用於大腸直腸癌治療模式的巨大機會。事實上，我們對 2051 年的願景始終是基於使用 Topo I 有效載荷，我們可以將其應用於早期治療，有可能在早期治療方案中取代伊立替康，甚至可能更廣泛地取代化療在早期 CRC 的治療和管理中的作用。因此，根據我們第一階段的早期數據顯示該藥物在轉移性 CRC 環境中的有效性，我們相信這種藥物具有轉化潛力。

We, of course are also we also note that in having done the CRC experiment, in a way, we've done the hardest experiment first. EpCAM is not only very highly expressed in colorectal cancer, but it is an antigen that is present on most solid tumors at high levels. This presents a very large opportunity for expanding the 2051 program into multiple other solid tumors over time. And we really believe that in addition to being a pan-CRC target, this is a potential pan-tumor target with tremendous value creation opportunities for CytomX over time.

當然，我們也注意到，在進行 CRC 實驗時，在某種程度上，我們首先做了最困難的實驗。EpCAM 不僅在結腸直腸癌中表現非常高，而且它是一種在大多數實體腫瘤中高水平存在的抗原。這為 2051 計劃隨著時間的推移擴展到多種其他實體腫瘤提供了巨大的機會。我們確實相信，除了作為泛 CRC 目標之外，這也是一個潛在的泛腫瘤目標，隨著時間的推移，它將為 CytomX 帶來巨大的價值創造機會。

So to summarize, again, we are super excited about this first look at 2051. We have shown today clinical proof of concept for EpCAM targeting TOPO I ADC. And this really is a big landmark for CytomX and the pinnacle achievement for our technology platform to date. This first-in-class antibody drug conjugate represents a multibillion-dollar annual sales opportunity on a global basis, and that's in late-line CRC alone. Our top priority is to advance now towards the potential first approval in late-stage metastatic colorectal cancer while also advancing in parallel into combination regimens to bring 2051 earlier in the treatment paradigm, while starting to explore additional opportunities for this exciting drug.

總而言之，我們對 2051 的首次亮相感到非常興奮。今天，我們已經展示了針對 TOPO I ADC 的 EpCAM 的臨床概念驗證。這對 CytomX 來說確實是一個重要的里程碑，也是我們技術平台迄今的巔峰成就。這種一流的抗體藥物偶聯物在全球範圍內代表著每年數十億美元的銷售機會，而且僅在後期 CRC 領域。我們的首要任務是現在推進晚期轉移性結直腸癌的潛在首次批准，同時同步推進聯合治療方案，使 2051 更早地成為治療範例，同時開始探索這種令人興奮的藥物的更多機會。

Now before opening up to questions, I want to recognize and sincerely thank the patients who join our studies, their families, our clinical investigators, and our highly dedicated team at CytomX, including present and past employees. This team has been through many ups and downs, but to a person has stayed laser-focused on execution for the benefit of patients. I want to also thank our Board of Directors for their continued belief and support and also our investors, including the new investors that we're welcoming to the company in today's financing.

現在，在開始提問之前，我想先感謝並真誠感謝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 高度敬業的團隊，包括現在和過去的員工。這個團隊經歷了許多起起落落，但對於一個人來說，他們始終專注於為患者謀福利。我還要感謝董事會對我們的持續信任和支持，也感謝我們的投資者，包括我們在今天的融資中歡迎加入公司的新投資者。

At CytomX, we've never been more committed to our vision, mission and values, and we look forward to great things to come.

在 CytomX，我們從未像現在這樣致力於我們的願景、使命和價值觀，我們期待未來的偉大成就。

So, with that, operator, let's go ahead and open up the call for Q&A.

那麼，接線員，讓我們繼續進行問答環節。

(Operator Instructions) Roger Song, Jefferies.

（操作員指示）Roger Song，Jefferies。

Excellent. Congrats for the data, really impressive. A couple from us. So the number one is you have a very high disease control and then also very meaningful -- partial response patients. Just curious about what do you see for those patients different between the stable disease versus responders in terms of the baseline, maybe the response from the prior lines? That's the first part of the question. Second part, how likely this antitumor activity will deepen over time given you have 10 of 18 patients still tumor ongoing?

出色的。恭喜獲得這些數據，真的令人印象深刻。我們中的一對夫婦。因此，首先，您的疾病控制率非常高，其次，也是非常有意義的—部分反應患者。我只是好奇，就基線而言，您認為病情穩定的患者與有反應的患者之間有什麼不同，也許是來自先前治療線的反應？這是問題的第一部分。第二部分，考慮到 18 名患者中有 10 名腫瘤仍在持續發展，這種抗腫瘤活性隨著時間的推移會加深的可能性有多大？

Yes. Thanks, Roger, for the questions. So look, we're absolutely delighted with the overall profile of 2051 after this first year of work in the clinic. The disease control rate is indeed impressive. We believe the response rate across this dose range that we're advancing into expansions is also impressive in this very difficult-to-treat tumor type.

是的。謝謝羅傑提出的問題。所以，看，經過第一年的臨床工作，我們對 2051 年的整體情況感到非常滿意。疾病控制率確實令人印象深刻。我們相信，對於這種極難治療的腫瘤類型，我們正在擴展的劑量範圍內的反應率也令人印象深刻。

In terms of patient characteristics that could determine response versus stable disease, I think that's something we'll continue to look at, but we just think this overall level of activity in an unselected patient population, not just unselected for EpCAM, but also unselected for other clinical characteristics like KRAS mutation or liver metastases is just really impressive and quite frankly, surpassing our expectations.

至於可以決定療效與病情穩定的患者特徵，我想這是我們將繼續關注的，但我們認為，在未經選擇的患者群體中，這種總體活動水平，不僅僅是未經 EpCAM 選擇，而且未經 KRAS 突變或肝轉移等其他臨床特徵選擇，確實令人印象深刻，坦率地說，超出了我們的預期。

In terms of improvement over time, I think on that point, I'm sure Waye would say the same that we would point to the emerging preliminary progression-free survival, where we see 5.8 months so far. There is, of course, a confidence interval on that. This is an early data set, but we do have many patients still on study as of the data cutoff, and we have good reason to believe that that PFS number will improve over time.

就隨著時間的推移而改善而言，我認為在這一點上，我相信 Waye 也會說同樣的話，我們會指出新出現的初步無進展生存期，到目前為止我們看到的是 5.8 個月。當然，這有一個信賴區間。這是一個早期數據集，但截至數據截止時，我們確實有許多患者仍在接受研究，我們有充分的理由相信 PFS 數字會隨著時間的推移而提高。

Great. If I may just add one more question related to the next step. This is late line, you say you will move this forward as quickly as possible. Can you just -- what is the current development strategy in terms of the pivotal, the endpoint and then also how you will move into this earlier line with some early work along with the later line?

偉大的。如果我可以再增加一個與下一步相關的問題。這是很晚才說的，你說你會盡快推進這件事。您能否－就關鍵點和終點而言，當前的發展策略是什麼？然後，您將如何透過一些早期工作以及後期工作進入這個早期領域？

Yes. Thanks again, Roger. Obviously, we've got a lot of work to do in now thinking through the mid- and late-stage development strategy for CX-2051 based on this very strong start. We are right now highly focused on generating data from the three expansion cohorts. We expect to have that data in Q1 of 2026. We will be discussing towards the end of this year. We expect with the regulatory authorities to ask and answer that exact question as to what is the optimal path forward for Phase 2, potentially Phase 2/3 to get this drug to patients who need it as quickly as possible. We do -- we will, of course, be exploring the fastest possible routes to the market in the context of the current regulatory landscape, but these will be data-driven decisions, including generating additional data beginning in 2026 in the combination setting to enable -- to start to enable bringing the drug into earlier lines of therapy.

是的。再次感謝你，羅傑。顯然，基於這一非常強勁的開端，我們現在還有很多工作要做，以思考 CX-2051 的中後期開發策略。我們現在高度專注於從三個擴展隊列中產生數據。我們預計將在 2026 年第一季取得該數據。我們將在今年年底進行討論。我們期望監管機構能夠提出並回答這個確切的問題，即第 2 階段，甚至可能是第 2/3 階段的最佳前進路徑是什麼，以便盡快將這種藥物送到需要的患者手中。當然，我們會在當前監管環境下探索最快的上市途徑，但這些將是由數據驅動的決策，包括從 2026 年開始在組合環境中產生更多數據，以便開始將藥物納入早期治療領域。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Just two quick ones for me. Just in the adverse events that you saw, the serious adverse events that you saw in five patients, can you give us a little color on how these are managed by dose reduction or dose holiday? And then I know that the Phase 1 update is expected in the first quarter of 2026. Are there any plans on presenting the data at a scientific or medical forum between now and the next data update?

我只想簡單說兩句話。就您所看到的不良事件，即您在五名患者身上看到的嚴重不良事件而言，您能否向我們稍微介紹一下如何透過減少劑量或停藥來控制這些事件？然後我知道第一階段更新預計將於 2026 年第一季進行。從現在到下次數據更新之間，是否有計劃在科學或醫學論壇上展示這些數據？

Yes. Thanks, Anupam. Let me just make a high-level comment on the AE SAE profile as reported today. I think as Waye mentioned, our initial sense of the safety profile of 2051 is that we have a great start here with a safety profile that is, we think, very encouraging and supportive of moving into earlier lines of therapy in potential combinations. The SAEs reported today are consistent with the overall adverse event profile. And we're not at liberty right now to really dig in patient by patient, as I'm sure you'll understand.

是的。謝謝，Anupam。我只想對今天報導的 AE SAE 概況發表一個高層次的評論。我認為，正如 Waye 所提到的，我們對 2051 的安全性的初步感覺是，我們在這裡有一個很好的開端，我們認為它的安全性非常令人鼓舞，並且支持進入潛在組合的早期治療階段。今天報告的嚴重不良事件與整體不良事件概況一致。我現在還不能真正深入研究每個病人的情況，我相信你會理解的。

In terms of presenting at a major medical meeting, the next update from CytomX right now is planned for Q1 of 2026. That will be data from the expansions. We would expect it to be about a 70-plus patient update, including 60 patients across the dose levels of 7.2, 8.6 and 10 mg/kg, and we have not yet decided exactly the venue to present or share that data. That will come over time.

就出席大型醫學會議而言，CytomX 目前的下一次更新計劃於 2026 年第一季進行。那將是來自擴充的數據。我們預計這將是一份關於 70 多名患者的最新消息，其中包括 60 名劑量水平為 7.2、8.6 和 10 mg/kg 的患者，我們尚未決定展示或分享該數據的具體地點。這需要時間。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

Just I guess, further questions just around the potential Phase 2, that's going to be a registrational study. Just if you've had discussions around accelerated development or breakthrough designations. And then, if this, I guess, the ability to include prophylactic strategies for -- to help reduce GI toxicities. And then I guess the other follow-up around that is just around the comparator arm, whether it's a single-arm study, kind of how you're thinking about that Phase 2?

我猜，進一步的問題只是關於潛在的第二階段，這將是一項註冊研究。就像您已經討論過加速開發或突破性指定一樣。然後，我想，如果能夠採取預防策略，就能夠幫助減少胃腸道毒性。然後我想圍繞這個問題的另一個後續行動是圍繞對照組，無論它是否是單組研究，您如何看待第二階段的研究？

Thanks, Peter. Let me address a couple of those questions, and then I'll hand over to Yu-Waye to make a few comments on prophylaxis on the GI side. So obviously, with this level of activity that we're seeing in this very late-line patient population, it does -- it should open avenues for moving quickly in mid- and late-stage development. Way too early to say exactly what they will be, but we will be discussing with the regulatory authorities to make sure we can move forward in the most expeditious way possible. We have not yet had dialogue with FDA. We believe that the expansion data across these three active dose levels will be, of course, important and very useful in those discussions at the right time.

謝謝，彼得。讓我先回答其中幾個問題，然後我會讓 Yu-Waye 對胃腸道方面的預防發表一些評論。因此，顯然，我們看到這一晚期患者群體表現出如此高的活動水平，這為中後期開發的快速推進開闢了道路。現在說具體是什麼還為時過早，但我們將與監管機構進行討論，以確保我們能夠以最快捷的方式推進。我們尚未與 FDA 進行對話。我們相信，這三個活性劑量水平的擴展數據在適當的時候的討論中當然會非常重要且非常有用。

In terms of comparator arm, I mean, obviously, moving into the next stage of development, we're mindful of a number of things in the regulatory environment. We are exploring multiple doses, of course, to -- with Project Optimus very much in mind. And we do see tremendous opportunities for demonstrating the full power and potential of 2051 by potentially comparing it to one or more of the current standards of care in the third and fourth-line setting, where I think we all agree there is substantial room for improvement in CRC.

就比較組而言，我的意思是，顯然，進入下一發展階段，我們會注意監管環境中的許多事情。當然，我們正在探索多種劑量——非常重視 Optimus 項目。我們確實看到了巨大的機會，可以透過將 2051 與第三線和第四線環境中的一個或多個當前護理標準進行比較來展示 2051 的全部威力和潛力，我認為我們都同意 CRC 有很大的改進空間。

Just one comment on the overall tox profile before I hand over to Wayne on the prophylaxis side. Again, we're really encouraged by the AE profile of 2051. I want to underscore that this is the first in-human study for this payload, CAMP59. This is a novel camptothecin -based topoisomerase 1 inhibitor that we licensed from ImmunoGen. And we're very pleased with how this linker and payload is functioning.

在我將預防方面的工作交給 Wayne 之前，我只想對整體毒性概況發表一點評論。再次，我們對 2051 年的 AE 概況感到非常鼓舞。我想強調的是，這是針對該有效載荷 CAMP59 進行的首次人體研究。這是我們獲得 ImmunoGen 許可的新型喜樹鹼類拓樸異構酶 1 抑制劑。我們對這個連結器和有效載荷的運作情況非常滿意。

And when we look at the AE profile overall, it looks to us very much like other TOPO I inhibitors. And we would have expected with our masking working as well as it is to prevent EpCAM toxicities like pancreatitis, we would have expected that the principal AEs would come from the payload because, of course, we're not masking the payload.

當我們從整體上看 AE 概況時，它看起來非常類似於其他 TOPO I 抑制劑。我們本來預計，由於我們的掩蔽作用能夠有效預防胰臟炎等 EpCAM 毒性，我們本來預計主要的 AE 將來自有效載荷，因為當然，我們沒有掩蔽有效載荷。

So with that, I'll hand over to Waye to talk about, of course, that does leave us with some GI tox to manage, but we have a very good plan.

因此，我會把時間交給 Waye 來談論，當然，這確實給我們留下了一些需要處理一些胃腸道毒素的問題，但我們有一個非常好的計劃。

So, regarding the GI tox, as we continue to get more experience with 2051, we continue to optimize our AE management strategy. And so a lot of -- actually, all of the data that we presented today are just reflections of earlier efforts to manage tox.

因此，關於胃腸道毒性，隨著我們在 2051 方面不斷獲得更多經驗，我們將繼續優化我們的 AE 管理策略。因此，實際上，我們今天提供的所有數據都只是早期控制毒性努力的反映。

But specific to the question of prophylaxis for diarrhea, we have implemented the use of prophylactic medications, specifically prophylactic loperamide or -- to prevent the onset and -- prevent the onset of severe diarrhea. This was only recently implemented. So a lot of the data that we showed today was actually in all patients were in patients who are not prophylaxis with loperamide. And as you probably are aware, the experience of prophylactic loperamide was explored with other ADCs, namely TRODELVY -- in the context of a clinical trial where they were able to demonstrate a notable reduction in the incidence of Grade 3 diarrhea with loperamide prophylaxis.

但具體到預防腹瀉的問題，我們已經實施了預防性藥物的使用，特別是預防性洛哌丁胺或—以防止嚴重腹瀉的發生。這項措施最近才得以實施。因此，我們今天展示的大量數據實際上來自所有未使用洛哌丁胺進行預防治療的患者。您可能已經知道，預防性洛哌丁胺的使用經驗已與其他 ADC（即 TRODELVY）進行了探討——在臨床試驗中，他們能夠證明使用洛哌丁胺預防可顯著降低 3 級腹瀉的發生率。

So moving forward, we will implement similar strategies for patients coming on the 2051 study. So our expectation, and we're very optimistic that those rates of diarrhea will change and change for the better.

因此，展望未來，我們將為 2051 年研究中的患者實施類似的策略。因此，我們非常樂觀地預期腹瀉的發生率將會發生變化，而且會變得更好。

(Operator Instructions) Robert Driscoll, Wedbush.

（操作員指示）羅伯特·德里斯科爾，韋德布什。

Just a couple of questions from us. We're seeing very high expression of EpCAM here in late-line patients. Is there kind of evidence for similarly kind of high and robust expression of EpCAM in earlier-stage patients, just as you think you go into -- as you go to those earlier lines next year, potentially? And then anything about the biology of EpCAM you think may be particularly attractive here in colorectal cancer, and then potentially in other solid tumors?

我們只想問幾個問題。我們發現晚期患者中 EpCAM 的表達非常高。是否有證據表明早期患者中 EpCAM 的表達同樣高且強勁，就像您認為的那樣——就像您明年進入那些早期階段一樣？那麼，您認為 EpCAM 的生物學特性在結直腸癌以及其它實體腫瘤中可能特別有吸引力嗎？

Robert, thanks for the question. So, EpCAM was first described quite some time ago as a CRC antigen. So it's been well established for decades actually to be a CRC target, and it is expressed on -- throughout the natural history of the disease. So we feel confident about bringing EpCAM earlier in the treatment paradigm based on target expression and other aspects that we've discussed today.

羅伯特，謝謝你的提問。因此，EpCAM 很久以前就被首次描述為 CRC 抗原。因此，幾十年來它實際上已被證實是 CRC 的目標，並且它在整個疾病的自然史中都有表現。因此，根據目標表達和我們今天討論的其他方面，我們有信心將 EpCAM 更早地引入治療範式中。

In terms of the biology of EpCAM, although it's been around a long time, its actual biological function is still not well characterized. And we haven't really focused on that as anything that relates to the design of 2051. We this completes so -- so, there's so much outcome on on CRC tumor cells that we've always thought of it as an address to target with this ADC.

就 EpCAM 的生物學而言，儘管它已經存在很長時間了，但其實際生物學功能仍未得到很好的描述。我們還沒有真正關注與 2051 年設計相關的任何事情。我們完成了這一點 — — 因此，CRC 腫瘤細胞有如此多的結果，我們一直認為它是該 ADC 的目標位址。

And just to put that in context, the expression level of EpCAM in CRC is similar to HER2 in breast cancer. So now we can't rule out that there's some biology here that blocking EpCAM is contributing to this really exciting clinical activity that we're seeing, but it's never been something that we've relied on or needed to invoke actually for the drug to work.

就此而言，CRC 中的 EpCAM 表現水準與乳癌中的 HER2 相似。所以現在我們不能排除存在一些生物學原理，阻斷 EpCAM 有助於我們看到這種非常令人興奮的臨床活動，但我們從來都不是依賴或需要真正調用來使藥物發揮作用的東西。

Got it. Thanks. And maybe just one more. In terms of the doses selected go forward, any plans to go higher in dosing, just kind of given that emerging signal of maybe a higher response in the 10 mg/kg dose?

知道了。謝謝。也許還剩一個。就所選的劑量而言，是否有計劃提高劑量，只是考慮到 10 mg/kg 劑量可能產生更高反應的新訊號？

Yes. Thanks. I'll start by saying we're already pretty excited about the response rate that we have across these three dose levels. And in this patient population, it really is, we think, a really significant achievement. We have escalated, as I mentioned in my presentation, to -- through seven dose levels to date in the clinical study. We do anticipate that although we haven't seen any dose-limiting toxicities in the execution of the study to date, but we do anticipate that at these upper dose levels, we will find our maximum assessed dose.

是的。謝謝。首先我想說的是，我們對這三個劑量等級的反應率感到非常興奮。我們認為，對於這群患者來說，這確實是一項非常重大的成就。正如我在演講中提到的那樣，迄今為止，我們在臨床研究中的劑量增加到七個劑量水平。我們確實預計，儘管迄今為止我們在研究執行中尚未看到任何劑量限制性毒性，但我們確實預計在這些較高劑量水平下，我們將找到最大評估劑量。

So we're not currently expanding those dose levels. We will present data from them when we present the overall update on the expansions in Q1 of 2026. But right now, we feel like the dose range that we're expanding, 7.2, 8.6 and 10 gives us a lot of room to maneuver.

所以我們目前不會擴大這些劑量水平。當我們在 2026 年第一季發布擴張的整體更新時，我們將提供其中的數據。但現在，我們覺得我們正在擴大的劑量範圍，7.2、8.6 和 10 給了我們很大的迴旋餘地。

(Operator Instructions) Mitchell Kapoor, H.C. Wainwright.

（操作員指示）Mitchell Kapoor，H.C.溫賴特。

This is Dan on for Mitchell. Thanks for taking our questions and congratulations on the data. So this data appears to be a very clear indicator that the PROBODY masking technology is at work, especially Slide 20. Why do you believe your PROBODY masking work most optimally with the EpCAM strategy versus with prior strategies in the past? And is there anything that's being done to enhance the PROBODY platform to where future pipeline candidates may have better odds of success? And I'd like to ask a follow-up, if I could.

這是丹 (Dan) 代替米切爾 (Mitchell)。感謝您回答我們的問題，並對數據表示祝賀。因此，這些數據似乎非常清楚地表明 PROBODY 掩蔽技術正在發揮作用，尤其是幻燈片 20。為什麼您認為與過去的策略相比，您的 PROBODY 遮蔽與 EpCAM 策略配合效果最佳？是否有任何措施可以增強 PROBODY 平台，從而使未來的候選人有更高的成功幾率？如果可以的話，我想問一個後續問題。

Yes. Thanks, Dan. That's a terrific question. And this data is obviously super exciting and it absolutely is showing the power of our PROBODY therapeutic masking platform. And many of you will be aware, of course, that CytomX is the company that really originated the whole concept of antibody masking to increase therapeutic index.

是的。謝謝，丹。這是一個非常好的問題。這些數據顯然非常令人興奮，它絕對展示了我們的 PROBODY 治療掩蔽平台的強大功能。當然，你們中的許多人都會知道，CytomX 是真正首創抗體掩蔽以提高治療指數的整個概念的公司。

In terms of why it's working so well on this target, I've kind of always believed most of you will know that our platform has always worked. We've been in the clinic with multiple programs. We've shown a lot of really interesting clinical results over the years. I think we've come to the view that it's all about where you direct the power of the technology. And in this particular case, we have come to learn that -- and I think what we've really got right is the combination of the tumor type of interest and the clinical problem that we're trying to solve, the target, which, of course, is CRC, at least initially, the target, which is EpCAM and the effector mechanism, which in this case is the cytotoxic payload, the TOPO I inhibitor CAMP59. I think you've got to get all three of those things right, and I think we have to really nail it.

至於為什麼它能如此有效地實現這一目標，我一直相信大多數人都會知道我們的平台一直在發揮作用。我們在診所開展過多個專案。多年來，我們已經展示了許多非常有趣的臨床結果。我認為我們已經達成了這樣的觀點：一切都取決於如何引導科技的力量。在這個特殊的案例中，我們了解到——我認為我們真正正確的是將感興趣的腫瘤類型和我們試圖解決的臨床問題結合起來，目標當然是 CRC，至少在最初是，目標是 EpCAM 和效應機制，在這個案例中是細胞毒性有效載荷，即 TOPO I 抑製劑 CAMP59。我認為你必須把這三件事都做好，而且我認為我們必須真正做到這一點。

In terms of the underlying technology, the protease cleavable substrate and the masking strategy, which is a peptide masking strategy that we've always employed and continue to employ. This is a strategy that has been validated previously in our previous clinical work. So we're not surprised to see it doing so well in the clinic. It's worked before. It's just in this case, we really think we've got that combination of the tumor, the target, and the effector, we've got it right, and that's just really exciting.

就底層技術而言，蛋白酶可裂解底物和掩蔽策略是我們一直採用並將繼續採用的勝肽掩蔽策略。這是我們之前的臨床工作中已經驗證過的策略。因此，我們對它在臨床上取得如此好的表現並不感到驚訝。它以前曾經起作用。只是在這種情況下，我們真的認為我們已經獲得了腫瘤、目標和效應器的組合，我們得到了正確的結果，這真的令人興奮。

And of course, that opens up now many new opportunities to go back and design the next generation of PROBODY therapeutic candidates across our pipeline as we build the company for the long term. But thanks for the question. It's a terrific question.

當然，這為我們在公司長遠建設過程中重新設計下一代 PROBODY 治療候選藥物提供了許多新的機會。但感謝您的提問。這是一個非常棒的問題。

Yes, excellent answer. Thank you. And thinking about on the PR for the pan-tumor Phase 1b study expected in 2026, do you intend on registering as a basket study? Or are you thinking of targeting those indications piecemeal? And given the exceptional levels of EpCAM expression in CRC versus other solid tumors, which they still have high levels but CRC is the highest, would you lean towards identifying high EpCAM positive patients in the other solid tumors? Or are you thinking of going in an agnostic approach there? Thank you.

是的，非常好的答案。謝謝。考慮到預計在 2026 年進行的全腫瘤 1b 期研究的 PR，您是否打算註冊為籃子研究？還是您考慮逐步地針對這些跡象？並且考慮到 CRC 中 EpCAM 表達水平與其他實體腫瘤相比非常高，雖然其他實體腫瘤的 EpCAM 表達水平仍然很高，但 CRC 的 EpCAM 表達水平最高，您是否傾向於識別其他實體腫瘤中 EpCAM 陽性率高的患者？或者您正在考慮採取不可知論的方法？謝謝。

Yes. Well, clearly, a lot of ground to explore with 2051 across so many tumor types where there continues to be so much unmet medical need. So we are working through our strategy for moving into those additional cancer types at the moment.

是的。顯然，2051 年有很多領域需要探索，涉及如此多的腫瘤類型，並且仍有大量未滿足的醫療需求。因此，我們目前正在製定策略來治療其他類型的癌症。

We've been -- as I mentioned, we've been really, really focused on CRC for the last year, and that's been very intentional, and we really wanted to do, as I said, in a way, kind of the hardest experiment first to really put this drug through its paces. Now that it's delivering, it opens up a multitude of opportunities across other cancer types. And the specific design of that Phase 1b study, if that's what we call it, as a basket or looking in a more targeted way at specific tumor types is something we continue to discuss internally.

正如我所提到的，我們在過去一年中一直非常非常專注於 CRC，這是有目的性的，而且我們真的想做，正如我所說的，在某種程度上，最艱難的實驗，首先真正檢驗這種藥物的療效。如今，該療法已取得顯著成效，為治療其他類型的癌症開闢了大量機會。我們正在內部繼續討論該 1b 期研究的具體設計（如果我們這樣稱呼它的話），將其作為一個籃子或以更有針對性的方式研究特定腫瘤類型。

In terms of selection of patients, again, it's one of the great features of CRC is we don't have to select patients. We don't think we're going to need to. And we think ultimately, commercially, that's going to be a huge advantage for 2051 as we get this drug to the market. But we have a terrific IHC assay. You've seen some of the results in this study. We showed one of our patients in our presentation today. And it may be helpful to select patients in these other tumor types. But I would say we're also early in -- very early actually in understanding any relationship between target level and response. We don't actually know how much target is necessary. So there's just a lot more to be learned about this drug and obviously, a ton of potential. But thanks for the question.

在患者選擇方面，CRC 的一大特點就是我們不必選擇患者。我們認為我們不需要這麼做。我們認為，從商業角度來看，當我們在 2051 年將這種藥物推向市場時，這將是一個巨大的優勢。但我們有優秀的 IHC 檢測方法。您已經看到了這項研究的一些結果。我們在今天的演示中展示了我們的一位患者。這可能對選擇其他類型的腫瘤患者有所幫助。但我想說，我們還處於早期階段——實際上非常早期地了解目標水平和反應之間的關係。我們其實並不知道需要多少目標。因此，關於這種藥物，我們還有很多東西需要了解，而且顯然它具有巨大的潛力。但感謝您的提問。

(Operator Instructions) I'm not showing any further questions in the queue at this time. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

（操作員指示）我目前不會在隊列中顯示任何其他問題。現在，我想將發言權交還給董事長兼執行長肖恩·麥卡錫博士，請他作最後發言。

Well, thanks, everyone, for joining us today. It's obviously a very exciting day for all of us here at CytomX and a very important day for cancer patients. So thank you for your time, and we look forward to keeping you updated on our progress in the future.

好吧，感謝大家今天加入我們。顯然，對於 CytomX 的所有人來說，這是一個非常令人興奮的日子，對於癌症患者來說，這也是一個非常重要的日子。感謝您抽出時間，我們期待未來向您通報我們的進展。

This concludes today's conference call. Thank you for participating. You may now disconnect.

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。