CytomX Therapeutics Inc (CTMX) 2024 Q2 法說會逐字稿

Good afternoon, everyone thank you for standing by and welcome to the CytomX Therapeutics second quarter 2024 financial results call. Please be advised that today's call is being recorded.

下午好，大家感謝大家的支持，歡迎參加 CytomX Therapeutics 2024 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 will now hand the call over to your host for today, Chris Ogden, CytomX's Chief Financial Officer. Please go ahead.

現在我將把電話轉交給今天的主持人 CytomX 財務長 Chris Ogden。請繼續。

Thank you. Good afternoon and thank you for joining us. Before we begin, I'd 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.

謝謝。下午好，感謝您加入我們。在開始之前，我想提醒大家，在這次電話會議中，我們將做出前瞻性陳述，因為前瞻性陳述涉及未來，它們受到難以預測的固有不確定性和風險的影響，並且許多其中超出了我們的控制範圍。

Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. We undertake no obligations to update any forward-looking statements whether as a result of new information, future developments, or otherwise.

我們最近在 sec.gov 向 SEC 公開提交的文件中列出了重要的風險和不確定性。我們不承擔因新資訊、未來發展或其他原因而更新任何前瞻性陳述的義務。

Earlier this afternoon, we issued a press release that includes a summary of our second quarter 2024 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.

今天下午早些時候，我們發布了一份新聞稿，其中包括 2024 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以及已向 SEC 提交的相關資料。

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、本次電話會議錄音以及我們向 SEC 提交的文件可以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 the company's progress and pipeline before I cover the financials for the quarter and we open up the call for Q&A.

今天與我一起參加電話會議的是 CytomX 執行長兼董事長 Sean McCarthy 博士。在我介紹本季度的財務狀況並開始問答之前，肖恩將提供有關公司進展和管道的最新資訊。

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

這樣，我會將電話轉給肖恩。

Thanks, Chris, and good afternoon, everyone. We're delighted today to provide an update on our recent progress which includes the continued development of CX-904 and Phase I dose escalation and clinical study initiation for our newest wholly-owned programs, CX-2051 and CX-801.

謝謝克里斯，大家下午好。今天，我們很高興提供有關我們最新進展的最新信息，其中包括 CX-904 的持續開發和 I 期劑量遞增以及我們最新的全資項目 CX-2051 和 CX-801 的臨床研究啟動。

CytomX's PROBODY Therapeutic Platform encompasses more than a decade of innovation in antibody masking and conditional activation and it's designed to enable the clinical development of anti-cancer modalities directed against targets that would otherwise be undruggable or significantly limited by therapeutic window.

CytomX 的 PROBODY 治療平台包含十多年來在抗體遮蔽和條件活化方面的創新，旨在實現針對無法成藥或受到治療窗口顯著限制的標靶的抗癌模式的臨床開發。

CytomX currently has 15 active programs across our internal and partnered research and development activities, including three clinical-stage PROBODY therapeutics designed to address large patient populations.

CytomX 目前在我們的內部和合作研發活動中擁有 15 個活躍項目，其中包括三種旨在解決大量患者群體問題的臨床階段 PROBODY 療法。

Based on our continued strong execution, CytomX is currently very well positioned to build value and make a meaningful difference for cancer patients. Let me dive right in and start with CX-904, our masked PROBODY T-cell Engager targeting EGFR.

基於我們持續強大的執行力，CytomX 目前處於非常有利的位置，可以為癌症患者創造價值並產生有意義的改變。讓我直接從 CX-904 開始，這是我們針對 EGFR 的掩蔽 PROBODY T 細胞接合劑。

Last quarter, we announced positive initial Phase 1a clinical data for CX-904, which was an important first step in the clinical development of this program. EGFR is a very attractive target, given its broad expression across multiple tumor types and also its high level of clinical and commercial validation with multiple approved small molecule and antibody therapies.

上季度，我們宣布了 CX-904 積極的初始 1a 期臨床數據，這是該計畫臨床開發的重要第一步。EGFR 是一個非常有吸引力的靶點，因為它在多種腫瘤類型中廣泛表達，並且透過多種已批准的小分子和抗體療法進行了高水平的臨床和商業驗證。

CX-904 constitutes a novel therapeutic strategy that leverages EGFR as an address to direct T-cell mediated killing to tumor cells via CD3 binding. EGFR-CD3 has previously been considered an attractive, but undruggable target combination because of the widespread expression of EGFR in normal tissues.

CX-904 構成了一種新穎的治療策略，利用 EGFR 作為地址，透過 CD3 結合指導 T 細胞介導的對腫瘤細胞的殺傷。由於 EGFR 在正常組織中廣泛表達，EGFR-CD3 以前被認為是一種有吸引力但不可成藥的目標組合。

In the absence of masking, we would expect an EGFR-CD3 bispecific to be severely toxic and undevelopable, likely with high rates of severe skin rash and cytokine release syndrome. By using the CytomX PROBODY platform to mask both EGFR and CD3 binding domains, however, we are opening a therapeutic window for this target combination and we've been very encouraged by our clinical findings reported to-date.

在沒有掩蔽的情況下，我們預期 EGFR-CD3 雙特異性抗體具有嚴重毒性且無法發育，可能會導致嚴重皮疹和細胞激素釋放症候群的高發生率。然而，透過使用 CytomX PROBODY 平台來掩蓋 EGFR 和 CD3 結合域，我們為該標靶組合打開了一個治療窗口，並且我們對迄今為止報告的臨床結果感到非常鼓舞。

In May, we were delighted to release positive initial Phase 1a dose escalation results for CX-904, achieving our early Phase 1 goals. In this first stage of release for CX-904, based on an April 16th, 2024 data cutoff, we reported on 35 heavily pre-treated patients with a median of four prior lines of therapy.

5 月，我們很高興發布 CX-904 的 1a 期初始劑量遞增結果，實現了我們早期的 1 期目標。在 CX-904 發布的第一階段，基於 2024 年 4 月 16 日的數據截止日期，我們報告了 35 名接受過深度治療的患者，他們之前接受過四線治療。

The initial safety profile of CX-904 looks very encouraging, specifically in step dosing cohorts up to a target dose of 10 milligrams. We did not see any cytokine release syndrome and across all 35 patients treated with non-step and step dosing schedules, we saw only one grade three rash.

CX-904 的初始安全性看起來非常令人鼓舞，特別是在高達 10 毫克目標劑量的逐步給藥組中。我們沒有發現任何細胞激素釋放綜合徵，並且在所有 35 名接受非階梯式和階梯式給藥方案治療的患者中，我們只看到了 1 例三級皮疹。

In common with certain other T-cell engagers, we observed some musculoskeletal events that were manageable, in part with tocilizumab prophylaxis. These early findings show that masking is effectively blunting CRS and other toxicities that would be expected for the corresponding unmasked EGFR-CD3 T-cell Engager.

與某些其他 T 細胞參與者一樣，我們觀察到一些肌肉骨骼事件是可以控制的，部分可以透過托珠單抗預防來控制。這些早期發現表明，掩蔽可有效減弱 CRS 和其他毒性，而這些毒性對於相應的未掩蔽的 EGFR-CD3 T 細胞接合器來說是預期的。

In the context of this emerging favorable safety profile, we also reported encouraging early signs of single agent anti-cancer activity for CX-904. In 26 efficacy-evaluable patients treated at doses above 750 micrograms, we observed eight measurable tumor reductions, including confirmed partial responses in two of six efficacy-evaluable patients with pancreatic ductal adenocarcinoma.

在這種新興的有利安全性背景下，我們也報告了 CX-904 單藥抗癌活性的令人鼓舞的早期跡象。在接受超過 750 微克劑量治療的 26 名可評估療效的患者中，我們觀察到 8 例可測量的腫瘤縮小，其中包括 6 名可評估療效的胰腺導管腺癌患者中的 2 名確診的部分緩解。

These initial findings are particularly encouraging because pancreatic cancer has not been shown historically to respond to immunotherapy or to EGFR antibodies. However, EGFR is expressed in more than 90% of pancreatic cancer patients, and our data suggests that CD3-mediated T-cell killing via EGFR binding can be effective in this cancer type.

這些初步發現特別令人鼓舞，因為歷史上尚未顯示胰臟癌對免疫療法或 EGFR 抗體有反應。然而，EGFR 在超過 90% 的胰腺癌患者中表達，我們的數據表明，CD3 介導的 EGFR 結合的 T 細胞殺傷可以有效治療這種癌症類型。

Moreover, there's also increasing evidence from others in the field that pancreatic cancer can be immune competent and mount a T-cell response. This is both based on progress with neoantigen vaccines and recent data from ASCO 2024 for a Claudin 18 CD3 T-cell Engager.

此外，該領域其他人也有越來越多的證據表明，胰臟癌具有免疫能力並引發 T 細胞反應。這既基於新抗原疫苗的進展，也基於 ASCO 2024 的 Claudin 18 CD3 T 細胞接合器的最新數據。

In our view, our early CX-904 results in pancreatic cancer highlight exactly why CX-904 was designed, and they illustrate the power of antibody masking, opening a therapeutic window for an undruggable T-cell Engager target, and bringing a unique pharmacology to a cancer type of high incidence and significant unmet medical need.

我們認為，我們的早期CX-904 在胰腺癌中的結果準確地凸顯了CX-904 的設計原因，它們說明了抗體掩蔽的力量，為不可成藥的T 細胞Engager 靶點打開了治療窗口，並為癌症帶來了獨特的藥理學一種發病率高且醫療需求未滿足的癌症類型。

Indeed, pancreatic ductal adenocarcinoma is currently the third leading cause of cancer death in the U.S., and second-line treatments have response rates of less than 10% and only two to three months of progression pre-survival, leaving a major need for new therapies.

事實上，胰臟導管腺癌目前是美國癌症死亡的第三大原因，二線治療的緩解率低於 10%，且僅在生存前兩到三個月出現進展，因此迫切需要新療法。

We are now accelerating enrollment in pancreatic cancer to further explore this signal, and in parallel, we're prioritizing enrollment in head and neck and non-small cell lung cancers where we had not previously enrolled a meaningful number of patients in the initial dose escalation. We continue to enroll in multiple dose levels to further inform the selection of a recommended Phase 1b dose, or potentially doses.

我們現在正在加速胰腺癌的入組，以進一步探索這一信號，同時，我們正在優先考慮頭頸癌和非小細胞肺癌的入組，我們之前在初始劑量遞增中並未入組大量患者。我們繼續招募多個劑量水平，以進一步告知選擇建議的 1b 期劑量或潛在劑量。

Our principal goal for the second half of the year is to generate data to enable strategic dialogue with our global development partner, Amgen, regarding potential initiation of CX-904 Phase 1b expansions in select EGFR-expressing tumor types, and we expect to provide a CX-904 program update by the end of 2024.

我們下半年的主要目標是產生數據，以便與我們的全球開發合作夥伴安進 (Amgen) 進行策略對話，討論在選定的 EGFR 表達腫瘤類型中可能啟動 CX-904 1b 期擴展，我們希望提供CX -904計劃將於2024年底更新。

Turning now to CX-2051, our wholly-owned, first-in-class, EpCAM-directed PROBODY ADC. EpCAM, or epithelial cell adhesion molecule, is a high-potential oncology target with high cell surface expression in many solid tumor types, and that has been implicated in many aspects of cancer biology.

現在轉向 CX-2051，這是我們全資擁有的、一流的、EpCAM 導向的 PROBODY ADC。EpCAM（即上皮細胞黏附分子）是一種高潛力的腫瘤學靶點，在許多實體瘤類型中具有高細胞表面表達，並且與癌症生物學的許多方面有關。

Anti-EpCAM therapeutic strategies have previously been translated into clinical activity, but to date, clinical success has been limited to local administration because EpCAM is present in most normal epithelial tissues. Efforts to generate systemically-administered anti-EpCAM therapies have not been successful to-date due to toxicities in epithelial tissues, including in the gastrointestinal tract.

抗 EpCAM 治療策略先前已轉化為臨床活性，但迄今為止，臨床成功僅限於局部給藥，因為 EpCAM 存在於大多數正常上皮組織中。由於上皮組織（包括胃腸道）的毒性，迄今為止系統性抗 EpCAM 療法的努力尚未成功。

Our innovative drug candidate, CX-2051, is a masked ADC tailored to optimize the therapeutic window for EpCAM-expressing epithelial cancers by masking the antibody to reduce binding in normal tissues, but allowing activation in tumor tissue.

我們的創新候選藥物 CX-2051 是一種掩蔽 ADC，旨在透過掩蔽抗體以減少在正常組織中的結合，但允許在腫瘤組織中激活，從而優化表達 EpCAM 的上皮癌的治療窗口。

We have armed the antibody with a cytotoxic payload based on camptothecin, a [topoisomerase-1] inhibitor, which is a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets, leading, in recent years, to dramatic advances for patients.

我們為抗體配備了基於喜樹鹼（一種[拓撲異構酶-1]抑製劑）的細胞毒性有效負載，喜樹鹼是一類藥物，在ADC 背景下針對多個靶點顯示出強大的臨床抗癌活性，近年來，為患者帶來巨大的進步。

CX-2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, including colorectal cancer, and like EGFR, discussed previously in the context of CX-904, CX-2051 could also potentially address large patient populations, because EpCAM is highly expressed across many indications, including colorectal, lung, gastric, endometrial, pancreatic, and ovarian cancers.

CX-2051 已在多種臨床前模型（包括結直腸癌）中表現出廣泛的預測治療指數，並且與先前在CX-904 背景下討論的EGFR 一樣，CX-2051 也有可能解決大量患者群體的問題，因為EpCAM 在整個腫瘤中高度表達。

In April of this year, we treated our first patient in our Phase 1 dose escalation study of CX-2051, and we're now already enrolling into our third patient cohort. At this stage, enrollment is principally focused in colorectal cancer, where EpCAM expression is particularly high, and we're really looking forward to seeing what CX-2051 could do for patients. And based on this progress, we remain on track to share initial data for CX-2051 in the first half of 2025.

今年 4 月，我們在 CX-2051 的 1 期劑量遞增研究中治療了第一位患者，現在我們已經將其納入第三個患者群。現階段，入組主要集中在 EpCAM 表達特別高的大腸癌中，我們非常期待看到 CX-2051 能為患者帶來什麼。基於這項進展，我們仍預計在 2025 年上半年分享 CX-2051 的初始數據。

Now turning to our third clinical program, CX-801, which is our dually masked interferon alpha 2B PROBODY cytokines. We're excited about CX-801 as a foundational immuno-oncology agent with potential for activity across multiple tumor types, including those that are insensitive to current immuno-oncology therapies. Interferon is a compelling and differentiated opportunity for a masked cytokine for two key reasons.

現在轉向我們的第三個臨床項目 CX-801，這是我們的雙重掩蔽幹擾素 α 2B PROBODY 細胞因子。我們對 CX-801 作為一種基礎免疫腫瘤藥物感到興奮，它具有跨多種腫瘤類型的活性潛力，包括那些對目前免疫腫瘤治療不敏感的腫瘤類型。對於隱藏的細胞激素來說，幹擾素是一個令人信服且差異化的機會，有兩個關鍵原因。

First, the biology of interferon is unique in that it has been shown to directly kill tumor cells, and interferon also increases adjutant presentation to activate T cells, making it an ideal mechanism for combination with checkpoint inhibition.

首先，幹擾素的生物學獨特之處在於它已被證明可以直接殺死腫瘤細胞，並且幹擾素還可以增加佐劑呈現以激活T細胞，使其成為與檢查點抑制相結合的理想機制。

Secondly, as a previously approved cancer therapy, interferon has a high level of prior clinical validation, including as both a localized therapy and systemically when combined with PD-1. The use of interferon at its broader development as a systemic therapy has been limited, however, due to systemic toxicities.

其次，作為先前批准的癌症治療方法，幹擾素具有高水平的先前臨床驗證，包括作為局部治療以及與 PD-1 聯合使用時的全身性治療。然而，由於全身毒性，幹擾素作為全身性治療的廣泛發展受到限制。

Our pre-clinical data for CX-801, most recently presented at SITC 2023, demonstrates synergy for our masked interferon alpha with PD-1 inhibition, both in terms of anti-tumor activity and activation of the tumor inflammatory microenvironment.

我們最近在 SITC 2023 上發表的 CX-801 臨床前數據證明了我們的掩蔽幹擾素 α 與 PD-1 抑制的協同作用，無論是在抗腫瘤活性還是活化腫瘤發炎微環境方面。

Moreover, we've also shown that systemic activity of our masked interferon is significantly reduced and overall tolerability is markedly improved compared to the unmasked cytokine in animal models.

此外，我們還表明，與動物模型中未掩蔽的細胞因子相比，我們的掩蔽幹擾素的全身活性顯著降低，整體耐受性顯著提高。

Our Phase 1 dose escalation study is now open and our first clinical site has been activated. This study will evaluate safety and signs of clinical activity for CX-801 as a monotherapy and in combination with Keytruda under a collaboration and supply agreement that we recently executed with Merck. We anticipate initial data for CX-801 in the second half of 2025.

我們的一期劑量遞增研究現已開放，我們的第一個臨床中心已經啟動。這項研究將評估 CX-801 作為單一療法以及根據我們最近與默克公司簽署的合作和供應協議與 Keytruda 聯合使用的安全性和臨床活性跡象。我們預計 CX-801 的初始數據將於 2025 年下半年提供。

On the collaboration front, we continue to have more than 10 ongoing research programs with our partners, which include Amgen, Astellas, BMS, Moderna and Regeneron, with the majority of our partnered research currently focused in masked T-cell Engagers.

在合作方面，我們繼續與安進(Amgen)、安斯泰來(Astellas)、百時美施貴寶(BMS)、Moderna 和再生元(Regeneron) 等合作夥伴開展10 多個正在進行的研究項目，目前我們的合作研究大多集中在掩蔽T 細胞接合器上。

To date in 2024, we've already achieved $10 million in pre-clinical milestones through our collaboration with Astellas and across our collaborations we have the potential to earn additional milestones over the next 12 to 18 months and beyond.

迄今為止，到2024 年，我們已經透過與安斯泰來的合作實現了1000 萬美元的臨床前里程碑，並且透過我們的合作，我們有可能在未來12 至18 個月甚至更長時間內獲得更多里程碑。

CytomX also retains significant U.S. commercial rights and certain partnerships, including with Astellas for a select number of programs and with Amgen as part of our global development alliance on CX-904. And partnering continues to be a cornerstone of our business strategy.

CytomX 也保留重要的美國商業權利和某些合作夥伴關係，包括與安斯泰來 (Astellas) 合作進行一些選定的項目，以及與安進 (Amgen) 作為我們 CX-904 全球開發聯盟的一部分。合作仍然是我們業務策略的基石。

Before handing over to Chris to cover financials, let me first congratulate him on his promotion to Chief Financial Officer. We're really excited to have Chris's cross-functional leadership and strategic finance experience in this key role. And my colleagues and I look forward to continuing to partner with Chris as we build value in CytomX over the near and long term.

在交給克里斯負責財務之前，讓我先祝賀他晉升為財務長。我們非常高興克里斯的跨職能領導和策略財務經驗能夠擔任這一關鍵角色。我和我的同事期待繼續與 Chris 合作，在近期和長期內為 CytomX 創造價值。

With that, let me hand over to Chris to provide an update on our finances.

接下來，讓我請克里斯提供有關我們財務狀況的最新資訊。

Thank you, Sean. It is a privilege to be part of the CytomX team and I look forward to helping lead the company towards multiple new treatment options for our patients over the long term. Now, turning to the second quarter results, I am pleased to be able to share an update on our financials with everyone today.

謝謝你，肖恩。能夠成為 CytomX 團隊的一員是我的榮幸，我期待著幫助領導公司為我們的患者長期提供多種新的治療選擇。現在，談到第二季的業績，我很高興今天能夠與大家分享我們財務狀況的最新情況。

CytomX finished the second quarter of 2024 with $137 million in cash, cash equivalents and investments versus $150 million in cash at the end of the first quarter of 2024. We expect our cash balance will fund the operations of the company to the end of 2025.

截至 2024 年第二季末，CytomX 的現金、現金等價物和投資為 1.37 億美元，而 2024 年第一季末的現金為 1.5 億美元。我們預計我們的現金餘額將為公司的營運提供資金直至 2025 年底。

Also, as a reminder, this cash guidance does not assume any additional milestones from existing collaborations or any new business development. Operationally, we continue to be focused on controlling cost and discipline capital allocation, investing behind the clinical progression of our lead pipeline programs.

此外，提醒一下，本現金指引並未假設現有合作或任何新業務開發中出現任何額外里程碑。在營運方面，我們繼續專注於控製成本和紀律資本分配，投資於我們領先管道專案的臨床進度。

Now, moving on to revenue and operating expenses for the quarter. For the second quarter of 2024, revenue was $25.1 million compared to $24.7 million in the second quarter of 2023. Operating expenses for the second quarter were $33.6 million.

現在，我們來看看本季的收入和營運支出。2024 年第二季的營收為 2,510 萬美元，而 2023 年第二季的營收為 2,470 萬美元。第二季營運費用為 3,360 萬美元。

R&D expenses were $25.2 million in the second quarter of 2024, an increase of $4.5 million versus Q2 2023, driven by investments in our clinical pipeline. G&A expenses increased by $1 million during the three months ended June 30th, 2024 to $8.4 million compared to $7.4 million for the corresponding period in 2023.

2024 年第二季的研發費用為 2,520 萬美元，比 2023 年第二季增加了 450 萬美元，這得益於我們對臨床管道的投資。截至 2024 年 6 月 30 日的三個月內，一般管理費用增加了 100 萬美元，達到 840 萬美元，而 2023 年同期為 740 萬美元。

Overall, our prudent financial management of the company and focused capital allocation has resulted in continued balance sheet strength and positions us to deliver meaningful value through our pipeline over the next 12 to 18 months and in the long-term.

總體而言，我們對公司審慎的財務管理和集中的資本配置導致資產負債表持續強勁，並使我們能夠在未來 12 至 18 個月以及長期內透過我們的管道創造有意義的價值。

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

現在，我將把電話轉回給肖恩，讓他作結束語。

Thanks, Chris, and thanks everyone for joining us today. CytomX has continued to make excellent progress throughout 2024, but we believe the company outlook is very compelling as we drive forward with our multi-modality PROBODY therapeutic pipeline.

謝謝克里斯，也謝謝大家今天加入我們。CytomX 在 2024 年繼續取得出色進展，但我們相信，隨著我們推進多模式 PROBODY 治療管道，公司前景非常引人注目。

Our current pipeline reflects broad investments over time and deep learning as a leading innovator in the field of antibody masking and conditional activation. Our progress with CX-904 positions CytomX at the forefront of the exciting field of T-cell engages for solid tumors, and we, like many others, see this area as being on the cusp of breakthroughs for patients.

我們目前的產品線反映了作為抗體掩蔽和條件活化領域領先創新者的長期投資和深度學習。我們在 CX-904 方面取得的進展使 CytomX 處於令人興奮的 T 細胞治療實體瘤領域的前沿，我們和許多其他人一樣，認為這一領域正處於患者突破的風口浪尖。

CytomX continues to prosecute a multi-modality strategy with each of CX-904, CX-2051, and CX-801 being well-positioned for new clinical data sets over the next 18 months. Moreover, masking strategies, as exemplified by the PROBODY therapeutic platform, are growing strategic interest in the biopharma R&D area, and CytomX remains a recognized leader having created this field.

CytomX 持續推行多模式策略，CX-904、CX-2051 和 CX-801 均已為未來 18 個月內的新臨床資料集做好準備。此外，以 PROBODY 治療平台為代表的掩蔽策略在生物製藥研發領域的策略興趣與日俱增，而 CytomX 仍然是創建該領域的公認領導者。

In conclusion here at CytomX, we remain highly committed and focused on creating innovative treatments for people living with cancer, and we believe our PROBODY pipeline has the potential to deliver safer, more effective therapies.

總而言之，在 CytomX，我們仍然高度致力於並專注於為癌症患者創造創新的治療方法，我們相信我們的 PROBODY 管道有潛力提供更安全、更有效的治療方法。

I want to sincerely thank the patients who join our studies, their families, and our team for helping to drive our mission forward, and with that, Operator, let's go ahead and open up the call for Q&A.

我要真誠地感謝加入我們研究的患者、他們的家人以及我們的團隊，感謝他們幫助推動我們的使命向前發展，因此，操作員，讓我們繼續進行問答徵集。

(Operator Instructions)

（操作員說明）

Darout from BMO Capital Markets.

來自 BMO 資本市場的 Darout。

Great. Thanks for taking the question. Just a quick one on CX-904. You know if you've had any more insights into sort of the correlation between efficacy and EGFR expression and what could be driving the activity that you're seeing in pancreatic cancer? And maybe just remind us for CX-904, can you discuss sort of the venue if you've kind of given some thoughts into sort of the venue where you'll be presenting this update by year end? Thanks.

偉大的。感謝您提出問題。簡單介紹一下 CX-904。您知道您是否對療效和 EGFR 表現之間的相關性以及是什麼驅動了您在胰臟癌中看到的活性有更多的了解？也許只是提醒我們 CX-904，如果您對年底前發布此更新的地點有一些想法，您能討論一下地點嗎？謝謝。

Yes, thanks for the questions. So we're considering to look at EGFR and how it relates to activity for 904. As we've mentioned, pancreatic cancer, like many others, expresses EGFR.

是的，謝謝您的提問。因此，我們正在考慮研究 EGFR 及其與 904 活性的關係。正如我們所提到的，胰臟癌與許多其他癌症一樣表達 EGFR。

More than 90% of pancreatic ductal adenocarcinoma expresses EGFR, so that clearly relates to the activity that we're seeing, we were thinking, in that tumor type. As to specific correlations between target level and response, I think that remains to be determined.

超過 90% 的胰腺導管腺癌表達 EGFR，因此這顯然與我們在該腫瘤類型中看到的、我們正在思考的活性有關。至於目標水平和反應之間的具體相關性，我認為還有待確定。

And I would also say that, of course, for T-cell engagers, if we look at historical data from other programs, from other organizations, these agents are quite different to functional blocking antibodies. In that we wouldn't necessarily expect to require too much antigen to drive responses, but I think this is something we're still learning both for 904 and in the field of T-cell Engagers more broadly.

當然，我還要說，對於 T 細胞參與者來說，如果我們查看其他項目、其他組織的歷史數據，這些藥物與功能性阻斷抗體有很大不同。我們不一定期望需要太多抗原來驅動反應，但我認為這是我們仍在為 904 和更廣泛的 T 細胞接合器領域學習的東西。

In terms of the next update, so yes, as we mentioned, we're planning on an update by the end of the year. That could take the form of a strategic update in terms of next steps for the program with actual data that underpins that strategic update, which will, of course, include dialogue with Amgen. With that data coming at a future date at a venue to be determined. So no additional color on that at this time.

就下一次更新而言，是的，正如我們所提到的，我們計劃在今年年底前進行更新。這可以採取策略性更新的形式，即該計劃的後續步驟，並使用支援該戰略更新的實際數據，當然，其中包括與安進的對話。這些數據將在未來某個日期在待確定的地點發布。所以目前沒有額外的顏色。

Great! Thank you.

偉大的！謝謝。

Malcolm Kuno from JPM

摩根大通的馬爾科姆·庫諾

Hi, thank you for taking the question. And this is Malcolm A. Kuno. So, you've talked about the CX-904 update at the end of the year? How should we think about the size of maybe the data that we may receive? And then given that you saw it as signaled earlier this year. How are you thinking about prioritizing indications?

您好，感謝您提出問題。這是馬爾科姆·A·庫諾。那麼，您談到了年底的 CX-904 更新嗎？我們應該如何考慮我們可能收到的數據的大小？然後考慮到你看到了今年早些時候發出的信號。您如何考慮適應症的優先順序？

Yeah, thanks, Malcolm. So again, with regard to our goal for an update by the end of this year, our overriding focus in the second half of 2024 is to generate additional data to facilitate strategic dialogue with our partner Amgen regarding potential next steps for the program. And the obvious next step, if the data supports it, of course, is to move from Phase 1a to Phase 1b.

是的，謝謝，馬爾科姆。因此，關於我們在今年年底之前進行更新的目標，我們在 2024 年下半年的首要任務是產生更多數據，以促進與我們的合作夥伴安進就該計劃可能的後續步驟進行戰略對話。當然，如果數據支持的話，下一步顯然是從階段 1a 轉向階段 1b。

So, we're currently enrolling, of course, additional patients in pancreatic cancer to continue to more fully explore that promising initial signal. And so I would say that, as we reach the end of 2024, I would hope that we'd have a reasonable number of patients enrolled in pancreatic to have a much better sense of the overall profile of the activity of the drug in that tumor type.

當然，我們目前正在招募更多的胰臟癌患者，以繼續更全面地探索這個有希望的初始訊號。因此，我想說，當我們到達 2024 年底時，我希望我們能夠有合理數量的胰臟患者入組，以便更好地了解該藥物在該腫瘤中的活性的總體情況類型。

We're also prioritizing enrollment in head and neck and also in non-small cell lung. And in those two indications, we've really enrolled very few patients when we gave the update in May. And so, there, we're looking to enroll additional patients to really look for an additional signal in those two tumor types.

我們也優先考慮頭頸部以及非小細胞肺的入組。在這兩個適應症中，當我們在 5 月發布更新資訊時，我們實際上招募了很少的患者。因此，我們希望招募更多患者來真正尋找這兩種腫瘤類型中的額外訊號。

And that would be our goal by the end of this year as well. So, and again, just to be clear in terms of our overriding objective, generate data, meet with Amgen, have that strategic dialogue, define Phase 1b strategy. Again, should the data support that? And most likely give a strategic update on the program by the end of the year with the data that underpins that update, more likely than not being presented at a venue TBD in 2025.

這也是我們今年底的目標。所以，再一次，為了明確我們的首要目標，產生數據，與安進會面，進行戰略對話，定義 1b 階段戰略。再說一遍，數據應該支持這一點嗎？很可能會在今年年底前對該計劃進行戰略更新，並提供支持該更新的數據，很可能會在 2025 年在某個地點（待定）進行展示。

Great. Thank you so much.

偉大的。太感謝了。

You're very welcome.

非常不客氣。

(Operator Instructions)

（操作員說明）

Mitchell Kapoor from H.C. Wainwright.

H.C. 米切爾·卡普爾溫賴特。

Good afternoon, this is Dan on for Mitch. Thanks for taking our questions and congratulations on the promotion, Chris.

下午好，我是丹為米奇發言。克里斯，感謝您回答我們的問題並祝賀您晉升。

Thank you.

謝謝。

I apologize if my questions are redundant. You're welcome. I hopped from another call. We were wondering, given the context of the positive responses you've demonstrated in pancreatic cancer, what response rate or duration of response would be considered meaningful in future updates?

如果我的問題是多餘的，我深表歉意。不客氣。我從另一個電話跳了出來。我們想知道，考慮到您在胰臟癌中表現出的正面反應，什麼反應率或反應持續時間在未來的更新中被認為是有意義的？

Yes, so regarding, again, thanks for the question. Regarding pancreatic, I think we're all aware of just how the dearth of therapies available for patients out the front line. And in the second-line setting, you're seeing activity of principally chemo regimens with single digit response rates.

是的，所以再次感謝您的提問。關於胰臟疾病，我想我們都知道第一線患者可用的治療方法非常缺乏。在二線治療中，您會看到主要是化療方案的活性，其反應率為個位數。

So these are patients that are in tough shape, very few options. And quite frankly, we think that bar is quite low, unfortunately, given the current state of treatment of pancreatic cancer. So that's one of the many reasons that we've been really excited about this initial signal in pancreatic that we're in the midst of firming up with additional enrollment as we move into the second half of the year.

因此，這些患者的情況很艱難，選擇很少。坦白說，不幸的是，考慮到目前胰臟癌的治療狀況，我們認為這個標準相當低。因此，這就是我們對胰臟中的這一初步訊號感到非常興奮的眾多原因之一，即隨著進入今年下半年，我們正在透過額外的招募來鞏固這一訊號。

Awesome. If I could ask a follow-up, do you expect to see any tolerability differences with 2051 given the variability in IHC EpCAM expression?

驚人的。如果我可以詢問後續情況，考慮到 IHC EpCAM 表現的變異性，您是否期望看到與 2051 的耐受性差異？

I'm sorry, could you repeat the question?

抱歉，您能重複這個問題嗎？

Do you expect to see tolerability differences with CX-2051 given the variability in an IHC EpCAM expression and the difference in EpCAM expression between individuals?

鑑於 IHC EpCAM 表現的變異性以及個體間 EpCAM 表現的差異，您是否預期會看到 CX-2051 的耐受性差異？

Well, we're obviously very early in our clinical exploration of 2051. We're very pleased to have, in a very short order, already have navigated into the third cohort in the Phase 1 dose escalation. And we're on track for initial data in first half of next year. EpCAM is, to us, a highly attractive target as it for a long time because of just how high its expression is in so many tumor types. And its expression is actually pretty consistent, particularly in colorectal, where we're focusing enrollment in Phase 1.

嗯，我們對 2051 年的臨床探索顯然還處於早期階段。我們很高興在很短的時間內就已經進入第一階段劑量遞增的第三組。我們預計在明年上半年獲得初步數據。對我們來說，EpCAM 長期以來一直是一個極具吸引力的靶點，因為它在多種腫瘤類型中的表現非常高。它的表達實際上非常一致，特別是在結直腸癌中，我們將重點放在第一階段的招募上。

In CRC, EpCAM is expressed at IC3 plus in the majority of patients. And that's actually allowing us to not need to select patients for enrollment in the Phase 1 study. So in terms of the expression in normal tissues, there's a fair amount of EpCAM in normal tissues, particularly also in the GI tract. It can be heterogeneous, but I think we'll have to see how that plays out in the clinic. But so far so good as we're into our third cohort.

在 CRC 中，大多數患者的 EpCAM 表達為 IC3+。這實際上使我們無需選擇患者參加第一階段研究。因此，就正常組織中的表現而言，正常組織中有相當數量的 EpCAM，特別是在胃腸道中。它可能是異質的，但我認為我們必須看看它在臨床上的表現如何。但到目前為止，我們已經進入了第三批。

Awesome! Thank you so much.

驚人的！太感謝了。

You're welcome.

不客氣。

Thank you. If no further questions in the queue. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

謝謝。如果隊列中沒有其他問題。現在我想請主席兼執行長 Sean McCarthy 博士致閉幕詞。

Thanks very much, and thanks, everyone, for tuning in today. We're really excited about the progress we've made so far this year at CytomX and we're looking forward to a busy second half and to reporting on additional progress as the year as the year goes on so far, have a great rest of the day.

非常感謝，也感謝大家今天的收聽。我們對今年迄今為止在 CytomX 取得的進展感到非常興奮，我們期待著忙碌的下半年，並隨著今年的進展報告更多進展，好好休息當天。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect, and everyone have a great day.

感謝您參加今天的會議。這確實結束了該程式。您現在可以斷開連接，祝大家有個愉快的一天。