CytomX Therapeutics Inc (CTMX) 2024 Q3 法說會逐字稿

Good afternoon, everyone. Thank you for standing by. Welcome to CytomX Therapeutics third quarter, 2024 Financial results call. Please be advised that today's call is being recorded.

大家下午好。謝謝你的支持。歡迎參加 CytomX Therapeutics 2024 年第三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, Chief Financial Officer. Please go ahead.

我現在想將今天的電話轉交給主持人。Chris Ogden CytomX，財務長。請繼續。

Thank you. Good afternoon and thank you for joining us.

謝謝。下午好，感謝您加入我們。

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.

在我們開始之前。我想提醒大家，在這次電話會議中，我們將做出前瞻性陳述，因為前瞻性陳述與未來有關。

They are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside our control.

它們受到難以預測的固有不確定性和風險的影響，其中許多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 do not take no obligation to update any forward-looking statements whether as a result of new information, future developments or otherwise.

我們最近在 sec.gov 向美國證券交易委員會提交的公開文件中闡述了重要的風險和不確定性，我們沒有義務更新任何前瞻性聲明，無論是由於新資訊、未來發展或其他原因。

Earlier this afternoon, we issued a press release that includes a summary of our third quarter, 2024 financial results and highlights recent progress at atomic.

今天下午早些時候，我們發布了一份新聞稿，其中包括 2024 年第三季財務業績摘要，並重點介紹了atomic 的最新進展。

We encourage everyone to read today's press release and the associated materials which have been filed with the SEC. Additionally, the press release recording of this call and our sec filings can be found under the investors and news section of our website.

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。此外，本次電話會議的新聞稿記錄和我們的證券交易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 A. McCarthy CytomX is Chief Executive Officer and Chairman Sean will provide an update on our pipeline and company progress. Before I walk through the financials for the third quarter, we will then conclude with a Q&A session with that. I will now turn the call over to Sean.

今天與我一起參加電話會議的是 CytomX 執行長 Sean A. McCarthy 博士，董事長 Sean 將提供有關我們的產品線和公司進展的最新資訊。在介紹第三季的財務數據之前，我們將以問答環節結束。我現在會把電話轉給肖恩。

Thanks Chris and good afternoon, everyone.

謝謝克里斯，大家下午好。

As always, we are very pleased to be here today to provide an update on CytomX progress as we advance towards our vision of transforming lives with safer, more effective therapies.

一如既往，我們很高興今天能夠在這裡提供 CytomX 的最新進展，我們正在朝著透過更安全、更有效的療法改變生活的願景邁進。

Since our inception and the creation of the PROBODY therapeutic platform. We have been leaders in the field of masked conditionally activated biologics and our team has been working tirelessly to address areas of oncology with high unmet need, leveraging our multi-modality PROBODY platform.

自從我們成立和創建 PROBODY 治療平台以來。我們一直是蒙面條件活化生物製劑領域的領導者，我們的團隊一直在不懈地努力，利用我們的多模態 PROBODY 平台來解決需求未滿足的腫瘤學領域。

We have more than 15 active discovery and development programs across our internal and partnered research pipeline with 3 of these programs currently in phase 1 physical development CX-904 PROBODY T-cell engager targeted to EGFR and CD-3, CX-2051, an EpCAM directed PROBODY antibody drug conjugate and also CX-801 our PROBODY interferon Alpha-2b.

我們在內部和合作研究管道中擁有超過15 個積極的發現和開發項目，其中3 個項目目前處於第一階段物理開發階段CX-904 PROBODY T 細胞接合器，針對EGFR 和CD-3、CX-2051 、EpCAM定向 PROBODY 抗體藥物偶聯物以及 CX-801 我們的 PROBODY 幹擾素 Alpha-2b。

Each of these programs really stands on the shoulders of our broad platform and clinical experience to date with mass therapeutics. And we continue to push boundaries. In our quest to make the biggest difference we can for cancer patients.

這些項目中的每一個都真正建立在我們迄今為止大規模治療的廣泛平台和臨床經驗的基礎上。我們繼續突破界限。我們力求為癌症患者帶來最大的改變。

The site services pipeline is poised to deliver multiple clinical readouts in 2025 that will inform next steps for later phase clinical development and create significant value for shareholders.

該現場服務管道預計將在 2025 年提供多個臨床讀數，這將為後期臨床開發的後續步驟提供信息，並為股東創造巨大價值。

Now, moving to our pipeline updates for the quarter, I will start with our work in the T-cell engager space.

現在，轉向本季度的管道更新，我將從 T 細胞接合器領域的工作開始。

The field of T-cell engagers in solid tumors has seen meaningful advances over the past 1 to 2 years but there remains a scarcity of really good tumor targets for conventional unmasked T-cell engagers because of target expression in normal tissues.

實體瘤中的 T 細胞接合器領域在過去 1 至 2 年中取得了有意義的進展，但由於正常組織中的標靶表達，傳統未掩蔽的 T 細胞接合器仍然缺乏真正好的腫瘤標靶。

At CytomX, we are applying our PROBODY therapeutic platform to mask T-cell engagers directed against highly expressed solid tumor targets in order to maximize their activity in tumors and minimize systemic toxicities in normal tissues.

在 CytomX，我們正在應用 PROBODY 治療平台來掩蓋針對高表達實體瘤標靶的 T 細胞接合劑，以最大限度地提高它們在腫瘤中的活性並最大限度地減少正常組織中的全身毒性。

We are working on multiple T-cell engager programs including CX-904. Our mast PROBODY T-cell engager targeting EGFR and CD-3, which is partnered with Amgen in a global Co Development alliance.

我們正在進行多個 T 細胞參與計劃，包括 CX-904。我們的桅杆 PROBODY T 細胞接合器針對 EGFR 和 CD-3，與安進 (Amgen) 合作建立了全球共同開發聯盟。

EGFR is a well validated target in multiple cancer types. Nobody has yet been able to develop a T-cell engager against this target. So, we are breaking new ground with this program.

EGFR 是多種癌症類型中經過充分驗證的標靶。目前還沒有人能夠開發出針對該標靶的 T 細胞接合劑。因此，我們正在透過這個計劃開闢新天地。

CX-904 is designed with a single EGFR binding arm and a single CD-3 binding arm and both are masked in a protease dependent manner allowing for tumor activation.

CX-904 設計有單一 EGFR 結合臂和單一 CD-3 結合臂，兩者均以蛋白酶依賴性方式被掩蔽，允許腫瘤活化。

In May, this year, we shared a first look at safety and efficacy for this clinical program. Announcing positive Phase 1A dose escalation data from 35 patients that showed an emerging favorable safety profile and encouraging early signs of single aged anticancer activity at doses up to 10 mg.

今年五月，我們首次分享了這個臨床項目的安全性和有效性。宣布來自 35 名患者的 1A 期劑量遞增數據，顯示出良好的安全性，並在劑量高達 10 mg 時出現令人鼓舞的單齡抗癌活性的早期跡象。

Since our May. Data disclosure dose escalation has continued, and we have been focusing enrolment on patients with Pancreatic ductal adenocarcinoma, non-small cell lung cancer, head, and neck squamous cell carcinoma.

自從我們五月以來。數據揭露劑量持續增加，我們一直將招募重點放在胰臟導管腺癌、非小細胞肺癌、頭頸鱗狀細胞癌患者。

We are pleased to report that the 15 mg step dosing cohort has cleared. A maximum tolerated dose has not been reached for step dosing and escalation continues since the escalation is continuing. We do not expect any decision in 2024 regarding initiation of phase 1B, we continue to engage with our partner and gen regarding plans for CX-904. And we look forward to providing additional updates on the program next year, including potential phase one B initiation.

我們很高興地報告，15 毫克階梯劑量組已經清除。尚未達到分步給藥的最大耐受劑量，並且由於繼續增加而繼續增加。我們預計 2024 年不會就 1B 階段的啟動做出任何決定，我們將繼續與我們的合作夥伴和一代就 CX-904 計劃進行接觸。我們期待明年提供該計劃的更多更新，包括可能啟動的第一階段 B 階段。

I would like to turn now to CX-2051. Our wholly owned first in class antibody drug conjugate targeting epithelial cell adhesion molecule or EpCAM developing therapies targeting EpCAM has been a goal of cancer research and development since its first identification as a highly expressed colorectal cancer.

我現在想談談 CX-2051。我們全資擁有的一流抗體藥物偶聯物靶向上皮細胞黏附分子或 EpCAM 開發針對 EpCAM 的療法自首次被鑑定為高表達結直腸癌以來一直是癌症研究和開發的目標。

More than 40 years ago, EpCAM is a highly attractive drug target due to its high expression in many solid tuber types, including colorectal cancer, non-small cell lung cancer, ovarian cancer, triple negative, breast cancer, and gastric cancers.

40多年前，EpCAM因其在許多實體塊莖類型中高表達而成為極具吸引力的藥物靶點，包括結直腸癌、非小細胞肺癌、卵巢癌、三陰性癌、乳腺癌和胃癌。

EpCAM has been implicated in many aspects of cancer biology, including signal transduction cell proliferation and epithelial mesenchymal transition. And it is particularly highly expressed in colorectal cancer.

EpCAM 與癌症生物學的許多方面有關，包括訊號傳導細胞增殖和上皮間質轉化。它在結直腸癌中尤其高表達。

In fact, we estimate that more than 90% of CRC patients have high level EpCAM expression.

事實上，我們估計超過 90% 的 CRC 患者俱有高水平的 EpCAM 表現。

Furthermore, we know that if EpCAM can, can be engaged successfully and safely, it can lead to tumor responses in patients. As best demonstrated by the anti EpCAM toxin fusion of Auzam moot that elicited a 40% complete response rate in Non muscle invasive bladder cancer because of its systemic toxicity. Though this drug needed to be administered locally.

此外，我們知道，如果 EpCAM 能夠、能夠成功且安全地參與，它可以導致患者的腫瘤反應。Auzam moot 的抗 EpCAM 毒素融合蛋白因其全身毒性而在非肌肉浸潤性膀胱癌中獲得了 40% 的完全緩解率，這一點得到了最好的證明。雖然這種藥物需要局部給藥。

Similarly, the previously approved transpacific antibody catchy maxim was shown to be effective in the treatment of malignant ascites. But again, had to be locally administered.

同樣，先前批准的跨太平洋抗體朗朗上口的格言被證明可有效治療惡性腹水。但同樣，必須在當地進行管理。

Interest in EpCAM continues to be high across the industry. But why has it taken the field so long to develop a successful systemic anti EpCAM cancer therapeutic?

整個產業對 EpCAM 的興趣持續高漲。但為什麼該領域花了這麼長時間才開發出成功的系統性抗 EpCAM 癌症治療藥物呢？

The answer lies in normal tissue expression.

答案在於正常組織的表達。

EpCAM expression is in fact, relatively low on most normal tissues compared to its expression on cancer cells, but it does have particularly high expression in the normal gastrointestinal tract.

事實上，與癌細胞上的表現相比，EpCAM 在大多數正常組織中的表現相對較低，但它在正常胃腸道中的表現確實特別高。

This became problematic with first generation anti EpCAM antibodies that induced acute pancreatitis.

對於誘導急性胰臟炎的第一代抗 EpCAM 抗體來說，這就成為了一個問題。

Second generation approaches such as the EpCAM CD-3, T-cell engager soliom had even more severe toxicity including grade three and higher upper GI inflammatory diarrhea and acute elevation of liver enzymes at sub therapeutic doses.

第二代方法，例如 EpCAM CD-3、T 細胞接合器 soliom，具有更嚴重的毒性，包括三級及以上的上消化道炎性腹瀉以及亞治療劑量下肝酵素的急性升高。

So how can we unlock the potential of EpCAM with a systemic therapy.

那我們如何透過全身性治療來釋放 EpCAM 的潛力呢？

Well, let me list the key properties of CX-2051 that we believe make it a very attractive clinical candidate.

好吧，讓我列出 CX-2051 的關鍵特性，我們認為這些特性使其成為非常有吸引力的臨床候選藥物。

CX-2051 is a masked high affinity anti-antibody incorporating a [protac] cleavable linker that we have validated clinically. In other contexts, the cytotoxic payload cap-59 is a [Tobiis sos] one inhibitor well matched to cancer types where CM is highly expressed including CRC.

CX-2051 是一種掩蔽的高親和力抗抗體，包含我們已經過臨床驗證的 [protac] 可裂解接頭。在其他情況下，細胞毒性有效負載 cap-59 是一種 [Tobiis sos] one 抑制劑，與 CM 高表達的癌症類型（包括 CRC）非常匹配。

The C-59 payload has comparable preclinical antitumor efficacy to Daiichi's dire TAM both as a free payload and in the context of the [acam] binding ADC.

無論是作為免費有效負載還是在 [acam] 結合 ADC 的情況下，C-59 有效負載都具有與 Daiichi 可怕的 TAM 相當的臨床前抗腫瘤功效。

The payload antibody linker in CX 2051 has been optimized for bystander effect, which is believed to be an important contributor to ADC anticancer activity.

CX 2051 中的有效負載抗體連接器已針對旁觀者效應進行了最佳化，這被認為是 ADC 抗癌活性的重要貢獻者。

Furthermore, we have shown in preclinical models that CX-2051 is equivalent in activity to the unmasked ADC. But it is much better tolerated in terms of [GIOCS] CX-2051 also has shown antitumor activity in atic and resistant colorectal cancer models. A particularly important finding since we anticipate this drug will be used in the post atic anesthetic CytomX's advanced CX-2051 into the clinic in the second quarter of this year. In Metastatic CRC.

此外，我們在臨床前模型中表明，CX-2051 的活性與未屏蔽的 ADC 相當。但就 [GIOCS] 而言，它的耐受性要好得多，CX-2051 也在無性大腸直腸癌和抗藥性結直腸癌模型中顯示出抗腫瘤活性。這是一個特別重要的發現，因為我們預計該藥物將用於麻醉後麻醉劑 CytomX 的先進 CX-2051 在今年第二季度進入臨床。在轉移性大腸直腸癌。

Given the very high expression and substantial medical need in CRC, we are focusing dose escalation in this cancer type to initially assess safety, explore initial science of anti-cancer activity and determine optimal dose levels for further evaluation, EpCAM expression levels in the phase 1 study are being assessed retrospectively and are anticipated to be high in the majority of patients.

鑑於CRC 的高表達和巨大的醫療需求，我們將重點放在這種癌症類型的劑量遞增上，以初步評估安全性、探索抗癌活性的初步科學並確定進一步評估的最佳劑量水平、第一階段的EpCAM 表達水平研究正在進行回顧性評估，預計大多數患者的感染率較高。

And while for now, we are focused in CRC to gain initial experience with 2051 we see a broad opportunity to expand into several additional EpCAM positive tumor types. Once we have a preliminary assessment of safety and anti- tumor activity from this initial study.

雖然目前我們的重點是結直腸癌，以獲得 2051 年的初步經驗，但我們看到了擴展到其他幾種 EpCAM 陽性腫瘤類型的廣泛機會。一旦我們從這項初步研究中對安全性和抗腫瘤活性進行了初步評估。

I am very pleased to report excellent early progress in the phase one study of CX-2051. We are already enrolling the fifth dose escalation cohort just six months into the trial. And we have observed a favorable safety profile to CX-251 to date suggesting that masking is functioning as designed.

我很高興地向大家報告 CX-2051 一期研究的早期進展。試驗僅六個月後，我們就已經招募了第五個劑量遞增隊列。迄今為止，我們觀察到 CX-251 具有良好的安全性，顯示掩蔽功能按設計發揮作用。

It is still relatively early days. But we see this as a very promising start and we remain on track to provide an initial phase 1, an update in the first half of 2025 to hopefully set the stage for broad based development of this drug.

現在還處於相對早期的階段。但我們認為這是一個非常有希望的開始，我們仍有望提供初始第一階段，即 2025 年上半年的更新，希望為該藥物的廣泛開發奠定基礎。

With respect to the long-term opportunity for CX-251 we estimate that there are approximately 300,000 EpCAM positive addressable patients in the United States alone. So, this program represents a potentially transformational value creating opportunity.

關於 CX-251 的長期機會，我們估計光在美國就有約 30 萬名 EpCAM 陽性可尋址患者。因此，該計劃代表了一個潛在的變革性價值創造機會。

Moving now to our third clinical program, CX-801 our masked interferon alpha two B PROBODY cytokine interferon alpha is a well validated molecule that we view as overlooked in the field of oncology. Interferon has established single agent anticancer activity in multiple tumor types. And it has also demonstrated potential as a combination therapy with checkpoint inhibitors.

現在轉向我們的第三個臨床項目，CX-801，我們的掩蔽幹擾素 α 2 B PROBODY 細胞因子乾擾素 α 是一種經過充分驗證的分子，我們認為在腫瘤學領域被忽視。幹擾素已在多種腫瘤類型中建立了單一抗癌活性。它也顯示出與檢查點抑制劑合併治療的潛力。

The powerful ability of infer alpha to both directly kill tumor cells and drive antigen presentation makes it an ideal mechanism for combination with checkpoint inhibition potentially across a wide range of indications.

Infer α 具有直接殺死腫瘤細胞和驅動抗原呈現的強大能力，使其成為與檢查點抑制相結合的理想機制，可能適用於多種適應症。

CX-801 incorporates a dual masking strategy with a peptide mask, blocking the interferon domains and a steric FC mask which are designed to clamp down the activity of systemic interferon and significantly increase the therapeutic window.

CX-801採用了雙重掩蔽策略，包括勝肽掩蔽，阻斷幹擾素結構域和空間FC掩蔽，旨在抑制全身幹擾素的活性並顯著增加治療窗。

Our preclinical data for CX-801 demonstrates synergy with PD one inhibition both in terms of anti- tumor activity and activation of the tumor inflammatory microenvironment.

我們的 CX-801 臨床前數據表明，在抗腫瘤活性和腫瘤發炎微環境活化方面，CX-801 與 PD 1 抑制具有協同作用。

Moreover, we have also shown in animal models that systemic activity of our mass interferon is significantly reduced and overall tolerability is markedly improved compared to the unmasked side effects.

此外，我們在動物模型中也表明，與未掩蓋的副作用相比，我們的質量幹擾素的全身活性顯著降低，整體耐受性顯著改善。

We are excited to have recently initiated the phase one clinical study for CX-801 having dosed our first patient during the third quarter.

我們很高興最近啟動了 CX-801 的一期臨床研究，並在第三季度對我們的第一位患者進行了給藥。

Our initial goal for this program is to markedly improve on the clinical profile for a mass interferon and PD 1 inhibition in melanoma and CX-801 phase one dose escalation will primarily focus in this tumor type initially as monotherapy. Before moving into combination dose escalation with Keytruda, which we have access to through a collaboration supply group with Merck initial phase 18 data for CX-801 is anticipated in the second half of 2025.

我們該計劃的最初目標是顯著改善黑色素瘤中大規模幹擾素和 PD 1 抑制的臨床特徵，CX-801 一期劑量遞增將主要集中在這種腫瘤類型，最初作為單一療法。在與 Keytruda 進行聯合劑量遞增之前，我們可以透過與默克的合作供應小組獲得 CX-801 的初始 18 期數據，預計將於 2025 年下半年獲得。

So, with that, let me hand things back over to Chris to provide an update on our finances.

因此，讓我將事情交還給克里斯，以提供我們財務狀況的最新資訊。

Thank you, Sean. Echoing Sean sediments. We are in an exciting stage with our pipeline and as we move into next year, we plan to deliver important clinical updates that have the potential to deliver significant value creation for CytomX. And we will also further inform our highest priorities for capital allocation across the pipeline.

謝謝你，肖恩。迴響肖恩沉積物。我們的產品線正處於令人興奮的階段，隨著我們進入明年，我們計劃提供重要的臨床更新，這些更新有可能為 CytomX 創造巨大的價值。我們也將進一步告知我們整個管道中資本配置的最高優先事項。

With that context, we continue to remain disciplined in capital allocation with a focus on delivering against our clinical milestones in 2025.

在此背景下，我們將繼續嚴格資本配置，並專注於 2025 年實現臨床里程碑。

Now, with that, I am pleased to be able to share our third quarter 2024 financial results with everyone today.

現在，我很高興今天能夠與大家分享我們 2024 年第三季的財務表現。

As of September 30, 2024, we ended the quarter with $118 million in cash, cash equivalents and investments compared to $137 million in cash. At the end of the second quarter, we expect that our cash balance will continue to fund CytomX operations to the end of 2025.

截至 2024 年 9 月 30 日，本季結束時，我們的現金、現金等價物和投資為 1.18 億美元，而現金為 1.37 億美元。在第二季末，我們預計我們的現金餘額將繼續為 CytomX 的營運提供資金直到 2025 年底。

As always, our cash guidance does not assume any additional milestones from existing collaborations, or any new business development and we are active in this area.

像往常一樣，我們的現金指導不會假設現有合作或任何新業務開發中的任何額外里程碑，我們在這一領域很活躍。

Turning to revenue and operating expenses for the third quarter revenue was $33.4 million compared to $26.4 million in the third quarter of 2023. The higher revenue in the third quarter was driven primarily by research under our collaborations with Bristol Myers Squibb and Moderna operating expenses for the third quarter were $29.3 million.

就收入和營運支出而言，第三季收入為 3,340 萬美元，而 2023 年第三季收入為 2,640 萬美元。第三季營收的增加主要是由於我們與百時美施貴寶 (Bristol Myers Squibb) 合作進行的研究推動的，Moderna 第三季的營運費用為 2,930 萬美元。

An increase of $6.1 million compared to the third quarter of 2023. R&D expenses were $21.4 million for the third quarter of 2024 which was an increase of $4.9 million compared to the corresponding quarter in 2023.

與 2023 年第三季相比增加 610 萬美元。2024 年第三季的研發費用為 2,140 萬美元，比 2023 年同期增加了 490 萬美元。

This was primarily driven by increased clinical and manufacturing spend for CX-2051 as well as higher clinical spend for CX-904 G&A expenses increased by $1.1 million during the 3 months ended September 30, 2024, to $8 million compared to $6.8 million for the corresponding period in 2023.

這主要是由於CX-2051 的臨床和製造支出增加以及CX-904 的臨床支出增加，截至2024 年9 月30 日的三個月內，一般管理費用增加了110 萬美元，達到800 萬美元，而相應的680 萬美元2023年期間。

Operationally, we continue to make significant progress with Amgen, Ellis, BMS Moderna and Regeneron. With the majority of our partnered research currently focused on masked T-cell engagers year-to-date. We have received $10 million in pre-clinical milestones through our collaboration with Ellis and continue to receive R&D funding across a number of our partnerships.

在營運方面，我們繼續與 Amgen、Ellis、BMS Moderna 和 Regeneron 取得重大進展。今年迄今為止，我們的大部分合作研究目前都集中在蒙面 T 細胞參與者身上。透過與 Ellis 的合作，我們已獲得 1000 萬美元的臨床前里程碑資金，並繼續透過我們的多個合作夥伴獲得研發資金。

Additionally, we have the potential to earn additional milestones through our collaborations over the next year.

此外，我們有潛力透過明年的合作贏得更多里程碑。

Closing out our financial updates, we continue to be disciplined in capital allocation with financial resources to support key pipeline milestones which we expect could drive meaningful value for shareholders and inform later state development for the pipeline.

在完成我們的財務更新後，我們將繼續嚴格進行資本配置，並提供財務資源來支持關鍵的管道里程碑，我們預計這些里程碑可以為股東帶來有意義的價值，並為管道的後續國家發展提供信息。

With that. I will turn the call back to Sean for closing remarks.

就這樣。我將把電話轉回給肖恩，讓他發表結束語。

Thanks Chris and thank you everyone for joining us today. We are excited about the work we are doing at CytomX to advance our multimodality clinical pipeline towards value inflection in the near term. And we continue to push boundaries with our science.

感謝克里斯，也感謝大家今天加入我們。我們對 CytomX 所做的工作感到興奮，這些工作旨在推動我們的多模式臨床管道在短期內實現價值轉折點。我們繼續突破科學的界限。

The PROBODY platform and antibody masking in general is of high strategic interest in the industry. And we continue to be at the forefront of this field.

PROBODY 平台和抗體掩蔽總體上在業界具有很高的策略意義。我們繼續處於該領域的前沿。

Looking ahead to 2025 we are well positioned to deliver multiple clinical data readouts across the pipeline. And we remain focused on advancing CX-904 CX-2051 and CX-801 to clinical proof of concept and to rapidly advancing programs into later phase development where we can deliver meaningful and differentiated outcomes for patients.

展望 2025 年，我們已做好充分準備，能夠在整個管道中提供多種臨床數據讀數。我們仍然專注於將 CX-904、CX-2051 和 CX-801 推進到臨床概念驗證，並將專案快速推進到後期開發，以便為患者提供有意義和差異化的結果。

Furthermore, I would underscore that CytomX is and always has been built to deliver value over the near and long term. And we maintain our long-term perspective. We have deep expertise in the field of mass therapeutics across multiple modalities. Strong large pharma and biotech partnerships which position CytomX drive sustainable innovation over time to close out.

此外，我想強調的是，CytomX 始終是為了在短期和長期內提供價值而建構的。我們保持長遠的眼光。我們在多種模式的大眾治療領域擁有深厚的專業知識。強大的大型製藥和生物技術合作夥伴關係使 CytomX 隨著時間的推移推動永續創新。

As always, I want to thank sincerely the patients who join our studies, their families, our clinical investigators, and our team for continuing to drive our mission forward. And with that operator, let us go ahead and open up the call for Q&A.

一如既往，我要衷心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和我們的團隊，感謝他們繼續推動我們的使命向前發展。讓我們與該接線員一起開始問答環節。

Thank you. At this time, I would like to remind everyone in order to ask a question. (Operator Instructions) And your first question comes from the line of Joseph Catanzaro with Piper Sandler. Your line is open.

謝謝。這時我想提醒大家，以便提出一個問題。（操作員說明）您的第一個問題來自 Joseph Catanzaro 和 Piper Sandler 的線路。您的線路已開通。

Great. Thanks for taking the questions. Thanks for the update. So may maybe first one on the CX-904 update and, and timing around the phase 1B decision. And it sounds like that's contingent on finishing the dose escalation and optimization.

偉大的。感謝您提出問題。感謝您的更新。因此，可能是第一個關於 CX-904 更新的問題，以及圍繞 1B 階段決定的時間表。聽起來這取決於完成劑量遞增和優化。

I guess, you know, as we think about that, is, is there a like pre specified target dose that you are looking to achieve to achieve, is that a, hit the MTD, I guess, talk us through, how you are going about making the decision that you have identified the right dose, the right schedule there.

我想，你知道，正如我們所思考的那樣，是否有一個類似預先指定的目標劑量，你希望達到達到的目標劑量，是達到 MTD，我想，請告訴我們，你打算如何進行關於做出決定，您已經確定了正確的劑量，正確的時間表。

Yeah. Hi Joe. Thanks for the question. As you know, I mean, since we presented our first results on this program earlier this year, you know, we have been very pleased with the safety profile of 904 and as we have continued our work over the course of the year, we have continued to learn about that safety profile and, and as a result, been able to continue to successfully escalate.

是的。嗨喬。謝謝你的提問。如您所知，我的意思是，自從我們今年早些時候公佈了該計劃的第一個結果以來，您知道，我們對904 的安全狀況非常滿意，並且隨著我們在這一年中繼續我們的工作，我們已經繼續了解該安全狀況，並因此能夠繼續成功升級。

And, you know, we, we believe that it is important to continue to maximize dose for this, for this drug and, and keep going. You know, we know that we, I think we are all still learning in this field. I think generally that we, we do see those responses for T-cell engagers.

而且，你知道，我們相信，繼續最大限度地增加這種藥物的劑量並繼續下去是很重要的。你知道，我們知道我們，我認為我們都還在這個領域學習。我認為總的來說，我們確實看到了 T 細胞參與者的這些反應。

So we think it is in our interest and, you know, our partner's interest really continues dose escalation. And we are really pleased now to be at the next dose level up from 15, which we are, which we are actively enrolling. So, of course, the flip side of that is it means that it is going to take more time.

所以我們認為這符合我們的利益，而且你知道，我們合作夥伴的利益確實在繼續劑量遞增。我們現在真的很高興能夠從 15 劑量水平上升到下一個劑量水平，我們正在積極招募這一劑量水平。當然，另一方面，這意味著這將需要更多時間。

That is sometimes the way it goes t cell engagers in general. We are, we are all learning are tending to take more time rather than less, but we have got to make sure we do the right experiments.

有時這就是 T 細胞接合者的一般情況。我們，我們所有人的學習都傾向於花費更多的時間而不是更少的時間，但我們必須確保我們做了正確的實驗。

Great that is helpful if I could ask maybe one quick follow up on CX-2051. It is great to see the dose escalation moving along nicely wondering if you could say where dose level 5 falls within the number of planned dose levels and whether dose level 5 is, you know, within the expected therapeutic window or, or maybe there's still a ways to go there just trying to maybe start to think about the first half 25 update.

太棒了，如果我能詢問有關 CX-2051 的快速跟進，這會很有幫助。很高興看到劑量逐步增加，很好地想知道您是否可以說劑量水平 5 在計劃劑量水平的數量範圍內，以及劑量水平 5 是否在預期的治療窗口內，或者也許仍然存在去那裡的方法只是試試也許開始思考25更新的前半部。

Yeah. So again, great question. So, as I said, we are, we are, we are very pleased with the early progress with 2051. You quickly having moved into cohort five. This is obviously quite an experimental therapeutic, you know, cam being the target a mass ADC with an actually a novel payload count 59.

是的。再說一遍，很好的問題。因此，正如我所說，我們對 2051 年的早期進展感到非常滿意。你很快就進入了第五組。這顯然是一種相當實驗性的治療方法，你知道，目標是一個質量 ADC，實際上新的有效負載數為 59。

This is the first experience with this payload in the clinic. So, you know, we will learn as we go in terms of how the clinical data matches up to our models predicted range for safety and efficacy.

這是診所首次使用這種有效載荷。因此，您知道，我們將持續了解臨床數據如何與我們的模型預測的安全性和有效性範圍相符。

What I so what I can, what I can say is that compared to our modelling, we are at, we believe we are at doses where an unmasked ADC would be very likely to show the kinds of GI toxicities that have been seen with other unmasked cm strategies in the past. So, we, so we are pleased with where we are, but it is still relatively early days and we will, have more to say in the first half of next year.

我所能說的是，與我們的模型相比，我們相信，我們所處的劑量是，未掩蔽的 ADC 很可能會表現出其他未掩蔽的 ADC 所出現的胃腸道毒性。 。所以，我們對我們的現狀感到滿意，但現在還處於相對早期的階段，我們將在明年上半年有更多的話要說。

Okay, great. That is all helpful. Thanks for taking my questions.

好的，太好了。這都是有幫助的。感謝您回答我的問題。

Next question comes from the line of Liam Chang with Jeffrey. Your line is open.

下一個問題來自 Liam Chang 和 Jeffrey 的對話。您的線路已開通。

Great. Thank you for taking our questions. This is Leon Cheung for Roger. So, I guess for us, we have a question about 904. So, regarding the phase 1B decision, so just wonder, you know, I believe the Pancreatic was the first ahead of the, in terms of enrolment. So where are we remind us? Where are we for the enrolment of the non-small cell line? And the head and neck.

偉大的。感謝您接受我們的提問。這是羅傑的張立昂。所以，我想對我們來說，我們有一個關於 904 的問題。因此，關於 1B 階段的決定，我想知道，就入組而言，我相信胰臟是第一個領先的。那我們在哪裡提醒我們呢？非小細胞系的註冊工作在哪裡？還有頭部和頸部。

And also, when you make the decision for phase 1B, will you also report the data, or you report it separately at a medical conference or like a company event? Thank you.

另外，當你做出 1B 階段的決定時，你會同時報告數據嗎？謝謝。

Great. Thanks. Thanks for the questions. So, with regards to enrolment, as we mentioned, we have continued over the course of this year to obviously enroll in pancreatic where we reported our first single agent activity earlier this year. And we have continued to well increased, I guess emphasis on enrolment in head and neck and lung cancer. Since that may update in the may update, we had just a handful of patients in those two indications.

偉大的。謝謝。感謝您的提問。因此，就入組而言，正如我們所提到的，我們在今年繼續明顯地入組胰腺領域，我們在今年早些時候報告了我們的第一個單藥活動。我想我們繼續大幅增加頭頸癌和肺癌的入學率。由於這可能會在五月更新中更新，因此我們只有少數患有這兩種適應症的患者。

So, you know, enrolment has progressed well over the course of the year, we have been enrolling at the previously cleared doses of five and 10 mg. Now that we have 15 cleared, we will enroll at that dose and also continue to escalate to the next dose level. So that is where we are in terms of tumor types, in terms of data and decision.

所以，你知道，這一年的入組進展順利，我們一直在以之前明確的 5 毫克和 10 毫克劑量進行入組。現在我們已經批准了 15 例，我們將按照該劑量進行註冊，並繼續升級到下一個劑量等級。這就是我們在腫瘤類型、數據和決策上的位置。

This is of course, you know, a program in close collaboration with and we are we continue to be very, very focused on, on the and relationship on building a data package to share with them when the time is right to discuss next steps, which would be ideally the move from phase 1A to phase 1B and the data should be anticipated on the other side of that potential decision sometime later in 2025.

當然，您知道，這是一個與我們密切合作的計劃，我們將繼續非常非常關注建立資料包的關係，以便在適當的時候討論下一步，與他們共享，理想情況下，這將是從1A 階段轉向1B 階段，並且應該在2025 年晚些時候的某個時候在該潛在決定的另一邊預期數據。

Got it, Thanks.

明白了，謝謝。

You are welcome.

不客氣。

And your next question comes from the line of the, the route with PMO capital markets. Your line is open.

你的下一個問題來自於 PMO 資本市場的路線。您的線路已開通。

Great. Thanks for taking a question. Just another one in CX-904. As you are thinking about you know, sort of potential phase one B just across, you know, pancreatic or the other tumor types. Would these be monotherapy studies or maybe studies in combination with standard of care, particularly in like head and neck or, or non-small cell lung cancer. If and, and how you thought about that? Be great. Thank you.

偉大的。感謝您提出問題。CX-904 中的另一款。正如您所想，您知道，潛在的 B 期可能跨越胰腺或其他腫瘤類型。這些是單一療法研究，還是與標準護理相結合的研究，特別是在頭頸癌或非小細胞肺癌方面。如果是的話，你是怎麼想的？棒極了。謝謝。

Yeah, hi. So, thanks. We are very focused on monotherapy at the moment and that is very consistent with the goals of our partner. Not to say that we are not giving consideration to combination strategies obviously on a, on an indication-by-indication basis. But right now, we remain at least in the phase one, a setting, of course, principally focused on, on monotherapy as to whether there will be any combination component of potential future phase one B. That is something that we do, we do plan to talk to our partner about, but as yet we have no defined plans for.

是的，嗨。所以，謝謝。目前我們非常專注於單一療法，這與我們合作夥伴的目標非常一致。並不是說我們沒有明顯地在逐個適應症的基礎上考慮組合策略。但現在，我們至少仍處於第一階段，當然，主要集中在單一療法上，以確定未來潛在的第一階段 B 是否會有任何組合成分。我們的合作夥伴討論，但到目前為止我們還沒有明確的計劃。

Thank you.

謝謝。

You're welcome.

不客氣。

Your next question comes from the line of Anupam Rama with JP Morgan. Your line is open.

你的下一個問題來自 Anupam Rama 與摩根大通的對話。您的線路已開通。

Hey, guys, thanks so much for taking the question just wondering if we could, I could get one in on CX-2015. I know that you -- retrospectively if you looked at cm expression levels and they are high in the phase one study, is it fair to assume moving forward that you will be enrolling only high cam expressing patients or will you be taking all comers? Thanks so much.

嘿，夥計們，非常感謝您提出這個問題，只是想知道我們是否可以，我可以參與 CX-2015。我知道，如果您回顧 cm 表達水平，並且在第一階段研究中它們很高，那麼假設您將只招募高 cam 表達患者還是會吸收所有患者，這是否公平？非常感謝。

Yeah, no problem. That is a really good question. So, in CRC, as I mentioned, it is, the cancer type where EpCAM was first described long time ago and it was first identified there as a function of its really, really high expression.

是的，沒問題。這是一個非常好的問題。因此，正如我所提到的，在結直腸癌中，EpCAM 是很久以前首次描述的癌症類型，並且因其非常非常高的表達而首次被識別出來。

And, you know, we have, done work with our own, our own assay that we have developed here at CytomX to confirm that in our hands, more than 90% of metastatic CRC patients have, have high level [cm] expression. And so, II I do not think, you know, and we will, validate that as we continue to look at the retrospective analysis in this ongoing study.

而且，您知道，我們已經在 CytomX 開發了我們自己的檢測方法，以確認在我們手中，超過 90% 的轉移性 CRC 患者俱有高水平 [cm] 表達。因此，我認為，你知道，當我們繼續研究這項正在進行的研究中的回顧性分析時，我們將驗證這一點。

But I do not expect that on a go forward basis. In CRC, we would need to select the target. You know, for, that tumor type, if you look across other tumor types, one of the great things about EpCAM is it is expressed on so many cancers, you know, also at high level. But in some like, you know, lung cancer, it is high in, you know, 60%- 70% of patients that compares to gastric cancer, similar kinds of kinds of levels.

但我並不期望這種情況會持續下去。在 CRC 中，我們需要選擇目標。你知道，對於這種腫瘤類型，如果你看看其他腫瘤類型，EpCAM 的偉大之處之一就是它在許多癌症中表達，而且表達水平也很高。但在某些肺癌等疾病中，與胃癌相比，60% - 70% 的患者的發生率較高，處於類似的水平。

And in some tumor types like bladder prostate pancreatic, it is a little bit lower. And so, you know, we, we have developed, we think a very good assay, a good, a great IHC assay that will enable us in some of those other tumor types to potentially select for patients if we need to. And we will cross that bridge when we come through it, come to it.

在某些腫瘤類型中，例如膀胱前列腺胰腺，它要低一些。所以，你知道，我們開發了一種非常好的檢測方法，一種很好的、很棒的IHC 檢測方法，如果需要的話，這將使我們能夠在其他一些腫瘤類型中潛在地選擇患者。當我們走過那座橋時，我們就會跨過那座橋，來到它的前方。

I think another key point here though is that if you, if you aggregate across tumor types for EpCAM expression, there are hundreds of thousands of patients to be treated with a drug like this and we do see 2051 in the long run, you know, for that reason, having potential, you know, pan tumor potential a little bit like we have seen with there to.

我認為這裡的另一個關鍵點是，如果你匯總不同腫瘤類型的 EpCAM 表達，就會有數十萬患者接受此類藥物的治療，從長遠來看，我們確實會看到 2051 年，你知道，出於這個原因，具有潛力，你知道，全腫瘤潛力有點像我們在那裡看到的那樣。

Again, if you would like to ask a question (Operator Instructions). Your next question comes from the line of Mitchell Kapoor with HC Wainwright. Your line is open.

再次，如果您想問問題（操作員說明）。你的下一個問題來自米切爾·卡普爾 (Mitchell Kapoor) 和 HC Wainwright 的對話。您的線路已開通。

Good afternoon. This is Dayal on for Mitch. Thanks for taking our questions. Kind of on the idea of FCOM EpCAM expression and we were talking about the different tumor types. Are there any tumor types that you think are particularly vulnerable to the bystander effect?

午安.這是米奇的達亞爾。感謝您回答我們的問題。有點關於 FCOM EpCAM 表現的想法，我們正在討論不同的腫瘤類型。您認為有哪些腫瘤類型特別容易受到旁觀者效應的影響？

Like, are there any biological rationale for that? And are there any specific tumor types with lower her two expression that might be less validated for an ADC approach but have higher EpCAM expression and somewhat higher unmet need. That might make it a cancer of interest.

例如，這有什麼生物學原理嗎？是否有任何特定的腫瘤類型具有較低的 her 兩種表達，這些腫瘤類型對於 ADC 方法的驗證可能較少，但具有較高的 EpCAM 表達和較高的未滿足需求。這可能使它成為一種令人感興趣的癌症。

Well, I would say the main way we think about that in the context of this drug candidate is really in the design of the, of the payload and the linker itself. So those of you who have followed CytomX for, for a while may, may recall that we actually we had a prior version of a net CM, ADC which we had conjugated to a matanza payload. But we would always been really interested in, this expression in CRC and how to develop a drug that was more tailored to that tumor type just because of the unbelievably high expression of the target.

嗯，我想說的是，在這種候選藥物的背景下，我們思考的主要方式實際上是有效負載和連接器本身的設計。因此，那些關注 CytomX 一段時間的人可能還記得，我們​​實際上有一個早期版本的網絡 CM、ADC，我們已將其與 matanza 有效負載結合在一起。但我們一直對結直腸癌中的這種表現以及如何開發一種更適合該腫瘤類型的藥物感興趣，因為該標靶的表達令人難以置信。

And that is what led to our selection of the cap-59 payload is a tool one inhibitor because as a, tool one inhibitor, it is indicated for the treatment of [T] and sensitive tumors like CRC. So we have been very deliberate in the design of this drug in terms of selecting payload to match level of target in areas of higher met need, including CRC, but not limited to CRC, also including lung, both squamous and adeno, ovarian, gastric as I have mentioned.

這就是我們選擇 cap-59 有效負載是工具一抑制劑的原因，因為作為工具一抑制劑，它適用於治療 [T] 和敏感腫瘤（如結直腸癌）。因此，我們在設計該藥物時經過深思熟慮，選擇有效負載以匹配更高滿足需求領域的標靶水平，包括結直腸癌，但不限於結直腸癌，還包括肺、鱗狀和腺癌、卵巢、胃正如我所提到的。

And many other tumors besides with regards to bystander effect, the linker, the trine linker that is in this ADC is also optimized for bystander effect.

許多其他腫瘤除了旁觀者效應之外，此 ADC 中的連接體、三重連接體也針對旁觀者效應進行了最佳化。

And bystander effect can be particularly effective in the presence of high levels of target where ADC will bind target and in the extracellular environment release payload.

在存在高水平標靶的情況下，旁觀者效應尤其有效，其中 ADC 將結合標靶並在細胞外環境中釋放有效負載。

So, so you know, we just feel like the overall design of, we took our time to really get this one optimized and we feel like the overall design of 2051 the payload, the cleavable trial a linker, of course, the antibody mask and the protease cleavable linker and the selection of EpCAM as a very high potential previously clinically validated target really gives us, you know, the highest probability of technical success with this drug relative to the other ADC that we put in the clinic in the past.

所以，所以你知道，我們只是覺得整體設計，我們花了時間真正優化了這個設計，我們覺得2051有效負載、可裂解試驗、連接器的整體設計，當然還有抗體掩模和蛋白酶可切割連接體以及選擇EpCAM 作為先前經過臨床驗證的非常高潛力的靶標，確實為我們提供了相對於我們過去投入臨床的其他ADC 而言，該藥物獲得技術成功的最高可能性。

Awesome. And if I could ask just for a little bit more color on the 904-program update, that was expected by year end. Has that been delayed or did the lack of ma maximum tolerated dose complicate that? And if so, when can we expect the next data release for phase 1A with 904? Thank you.

驚人的。如果我能要求對 904 程序更新提供更多的信息，預計會在年底完成。這是否被推遲了，或者缺乏最大耐受劑量是否使情況變得複雜？如果是這樣，我們什麼時候可以期待 904 的 1A 階段的下一個資料發布？謝謝。

Yeah. So, we consider today's call really this, this is the update on 904.

是的。所以，我們認為今天的電話會議確實是這樣，這是 904 的更新。

And you know, we are now and as we have said, this is very much a function of continued dose escalation. I wanted to make sure that we really fully explore dose intensity for 904 in the clinic.

你知道，正如我們所說，這在很大程度上是劑量持續增加的結果。我想確保我們在臨床上真正充分探索 904 的劑量強度。

So that, that means that the next update on this program will be next year. And what we are laser focused on is our alignment with Amgen as we continue to collect data and work with them as we move into next year on potential next steps.

因此，這意味著該計劃的下一次更新將是明年。我們重點關注的是與安進的合作，我們將繼續收集數據並與他們合作，邁入明年潛在的後續步驟。

Thank you so much for the answers.

非常感謝您的回答。

You are welcome.

不客氣。

Thank you. I am not showing any further questions in the queue.

謝謝。我不會在隊列中顯示任何其他問題。

I would now like to turn the call back to Dr. Sean McCarthy, Chairman and CEO for closing works.

現在我想將電話轉回董事長兼執行長肖恩麥卡錫博士來結束工作。

Well, thanks everyone for tuning in today. We are really excited about progress through 2024 at CytomX and we look forward to providing additional updates as we move into 2025. So, thank you all for your time.

好的，感謝大家今天的收看。我們對 CytomX 在 2024 年取得的進展感到非常興奮，並期待在進入 2025 年時提供更多更新。謝謝大家抽出寶貴的時間。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。