CytomX Therapeutics Inc (CTMX) 2022 Q4 法說會逐字稿

Good day, and thank you for standing by. Welcome to the CytomX Therapeutics Fourth Quarter 2022 Financial Results Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker for today, Chris Ogden. Please go ahead.

美好的一天，謝謝你的支持。歡迎來到 CytomX Therapeutics 2022年第四季度財務業績電話會議。 （操作員說明）請注意，今天的會議正在錄製中。現在，我想將會議交給您今天的發言人 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'll 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。由於前瞻性陳述與未來相關，因此它們受到難以預測的內在不確定性和風險的影響，其中許多是我們無法控制的。

Important risks and uncertainties are set forth in our most recent public filings 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.

我們最近在 sec.gov 上向 SEC 提交的公開文件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，無論是由於新信息、未來發展還是其他原因。

Earlier this afternoon, we issued a press release that includes a summary of our 2022 full-year financial results that highlights recent progress at CytomX. We encourage everyone to read today's press release and the associated materials, which include the 2022 10-K and 2021 amended 10-K, which has been filed today with the SEC.

今天下午早些時候，我們發布了一份新聞稿，其中包括我們 2022 年全年財務業績的摘要，重點介紹了 CytomX 的最新進展。我們鼓勵大家閱讀今天的新聞稿和相關材料，其中包括今天已提交給美國證券交易委員會的 2022 年 10-K 和 2021 年修訂後的 10-K。

Please also note that comments made in this call regarding the company's financials reflect restated financial statements, as outlined in our most recent SEC filings today. The adjusted financial statements reflect changes in the timing of certain revenue recognition in the years from 2019 to 2022.

另請注意，本次電話會議中就公司財務狀況發表的評論反映了我們今天向美國證券交易委員會提交的最新文件中概述的重述財務報表。調整後的財務報表反映了 2019 年至 2022 年某些收入確認時間的變化。

Additionally, the press release, a recording of this call and our SEC filings can be found under the Investors and News section of our website. With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide a business and pipeline update before I walk through the financials for 2022. With that, let me turn the call over to Sean.

此外，新聞稿、此次電話會議的錄音和我們向美國證券交易委員會提交的文件可以在我們網站的投資者和新聞部分找到。今天與我通話的是 CytomX 的首席執行官兼董事長 Sean McCarthy 博士。在我介紹 2022 年的財務報告之前，肖恩將提供業務和管道更新。有了這個，讓我把電話轉給肖恩。

Thanks, Chris, and good afternoon, everyone. Thanks for joining us for an update on recent progress at CytomX. On today's call, I'll provide an overview of the company's therapeutic pipeline, including status updates for our emerging programs, CX-904, CX-801 and CX-2051. I'll also cover recent developments within our CD71-targeting program and additional updates on our corporate partnerships.

謝謝，克里斯，大家下午好。感謝您加入我們了解 CytomX 的最新進展。在今天的電話會議上，我將概述公司的治療管道，包括我們新興項目 CX-904、CX-801 和 CX-2051 的狀態更新。我還將介紹我們的 CD71 靶向計劃的最新進展以及我們公司合作夥伴關係的其他更新。

At CytomX, we believe that as biologic anticancer therapies become more and more potent, the need for localizing empowered modalities such as antibody drug conjugates, T cell engagers and cytokines into cancer tissue becomes increasingly important as a way to improve therapeutic window. Indeed, we believe that localization will be the future of biologics.

在 CytomX，我們相信，隨著生物抗癌療法變得越來越有效，將抗體藥物偶聯物、T 細胞接合劑和細胞因子等授權模式定位到癌組織中的需求變得越來越重要，作為改善治療窗口的一種方式。事實上，我們相信本地化將是生物製劑的未來。

CytomX's vision is to transform lives with safer, more effective therapies. We aim to realize our vision for the benefit of patients by leveraging our Probody platform to create high-impact therapeutics that are localized to disease tissue, thereby reducing systemic toxicities and maximizing overall benefit.

CytomX 的願景是通過更安全、更有效的療法改變生活。我們的目標是通過利用我們的 Probody 平台創造針對疾病組織的高影響力療法，從而減少全身毒性並最大限度地提高整體效益，從而實現我們造福患者的願景。

2022 is an important year of transition for our company, in which we restructured and repositioned CytomX for future success by prioritizing our earlier-stage portfolio that incorporates learning from our experience with the first wave of Probody therapeutics that we pioneered and advanced into the clinic.

2022 年是我們公司轉型的重要一年，我們重組和重新定位了 CytomX，以通過優先考慮我們的早期產品組合來獲得未來的成功，這些產品組合結合了我們在第一波 Probody 療法方面的經驗，我們率先推出並推進了臨床。

Since our early years, CytomX has pursued a consistent strategy, focused on long-term company build around the Probody platform and maximizing impact for patients.

自我們早年以來，CytomX 一直奉行一致的戰略，專注於圍繞 Probody 平台的長期公司建設，並最大限度地提高對患者的影響。

Our substantial investments to date have allowed for a broad clinical evaluation of our platform, have resulted in a uniquely strong scientific foundation and a deep pipeline of therapeutic candidates positioned to deliver significant near- and long-term value.

迄今為止，我們的大量投資使我們能夠對我們的平台進行廣泛的臨床評估，從而形成了獨特而強大的科學基礎和深入的治療候選管道，這些候選藥物有望提供顯著的近期和長期價值。

We currently have more than 15 active Probody therapeutic programs, including 3 clinical-stage molecules, and we expect to file 2 new INDs for wholly-owned programs later this year. Additionally, through our collaborations, we have substantially extended the reach of our science.

我們目前有超過 15 個活躍的 Probody 治療項目，包括 3 個臨床階段分子，我們預計將在今年晚些時候為全資項目提交 2 個新的 IND。此外，通過我們的合作，我們大大擴展了我們科學的範圍。

CytomX entered 2023 with robust financial resources and funding into 2025, positioning the company to execute towards multiple milestones over the next 12 to 24 months.

CytomX 進入 2023 年，擁有強大的財務資源和進入 2025 年的資金，使公司能夠在未來 12 至 24 個月內實現多個里程碑。

Moving now to our pipeline. I'd like to start with T cell-engaging bispecifics, and our company is expanding efforts with this modality. T cell engagers hold tremendous promise for the treatment of solid tumors. However, the very potency of this modality can lead to widespread activation of the immune system, imposing constraints on therapeutic window.

現在轉到我們的管道。我想從 T 細胞接合雙特異性藥物開始，我們公司正在擴大這種方式的努力。 T 細胞接合器對實體瘤的治療具有巨大的前景。然而，這種方式的效力可能導致免疫系統的廣泛激活，從而對治療窗口施加限制。

Localization of the powerful anticancer activity of this class of drugs could unlock enormous potential for patients by enhancing therapeutic window. CytomX and our partners believe the Probody platform to be ideally suited to addressing this challenge.

這類藥物強大的抗癌活性的定位可以通過擴大治療窗口為患者釋放巨大的潛力。 CytomX 和我們的合作夥伴相信 Probody 平台非常適合應對這一挑戰。

Our lead program in this area is CX-904, a clinical-stage Probody T cell engager targeting EGFR and CD3, partnered with Amgen in a global co-development alliance. EGFR is a highly validated and broadly expressed cancer target, and we see a compelling opportunity to leverage this target to localize antitumor T cell responses, preferentially to the tumor microenvironment.

我們在這一領域的領先項目是 CX-904，這是一種針對 EGFR 和 CD3 的臨床階段 Probody T 細胞接合劑，與 Amgen 合作建立了全球共同開發聯盟。 EGFR 是一個經過高度驗證和廣泛表達的癌症靶點，我們看到了利用該靶點來定位抗腫瘤 T 細胞反應（優先針對腫瘤微環境）的絕佳機會。

Our published preclinical data showed that a localized bispecific EGFR-CD3 Probody has a widened therapeutic window compared to its unmarked counterpart. These preclinical data led to the advancement of CX-904, and we're now well underway with Phase I dose escalation.

我們發表的臨床前數據表明，與其未標記的對應物相比，局部雙特異性 EGFR-CD3 Probody 具有更寬的治療窗口。這些臨床前數據推動了 CX-904 的進步，我們現在正在順利進行 I 期劑量升級。

The Phase I study has advanced from initial single-patient cohorts into the 3 plus 3 phase of dose escalation. The primary goal of dose escalation for this drug candidate is to assess safety, and we aim to reach those levels and exposures by the end of 2023, at which we can start enrollment into backfill cohorts in certain EGFR-positive tumors.

I 期研究已從最初的單一患者隊列推進到劑量遞增的 3 加 3 階段。該候選藥物劑量遞增的主要目標是評估安全性，我們的目標是到 2023 年底達到這些水平和暴露水平，屆時我們可以開始招募某些 EGFR 陽性腫瘤的回填隊列。

Looking ahead to 2024, a key milestone on the horizon will be the selection of recommended Phase II dose and the potential decision to initiate Phase Ib expansion cohorts in EGFR-positive tumors. This decision will be taken in conjunction with our partner, Amgen.

展望 2024 年，地平線上的一個重要里程碑將是推薦的 II 期劑量的選擇，以及可能決定在 EGFR 陽性腫瘤中啟動 Ib 期擴展隊列。該決定將與我們的合作夥伴安進一起做出。

CytomX would then be responsible for the execution of expansion cohorts. And upon the conclusion of the expansion phase, Amgen will take over global development, with CytomX retaining certain co-funding, co-development and co-commercialization rights. We look forward to providing additional CX-904 updates as the program advances.

然後 CytomX 將負責擴展隊列的執行。擴張階段結束後，安進（Amgen）將接管全球開發工作，而 CytomX 將保留某些共同資助、共同開發和共同商業化的權利。隨著項目的推進，我們期待提供更多的 CX-904 更新。

Staying with T cell engagers, we were delighted that in January 2023, our partner, Astellas, nominated the first collaboration clinical candidate, triggering a $5 million milestone payment to CytomX.

與 T 細胞參與者一起，我們很高興在 2023 年 1 月，我們的合作夥伴 Astellas 提名了第一個合作臨床候選者，觸發了對 CytomX 的 500 萬美元里程碑付款。

CytomX and Astellas are also collaborating on additional T cell engagers, and CytomX is eligible to receive future preclinical, clinical and commercial milestones across these programs. We also retain the option to select U.S. development and commercial rights within the Astellas collaboration.

CytomX 和 Astellas 還在合作開發更多的 T 細胞參與者，CytomX 有資格在這些項目中獲得未來的臨床前、臨床和商業里程碑。我們還保留在 Astellas 合作中選擇美國開發和商業權利的選擇權。

Continuing with T cell bispecifics, in November 2022, CytomX entered a multi-target R&D collaboration with Regeneron to discover and develop new bispecific immunotherapies. Regeneron has considerable efforts in T cell bispecifics, and both companies see opportunities to broaden the reach of T cell engagers by utilizing the CytomX platform to localize these highly potent agents to tumor tissue, widening therapeutic window.

繼續 T 細胞雙特異性，2022 年 11 月，CytomX 與 Regeneron 進行了多靶點研發合作，以發現和開發新的雙特異性免疫療法。 Regeneron 在 T 細胞雙特異性藥物方面做出了相當大的努力，兩家公司都看到了通過利用 CytomX 平台將這些高效藥物定位到腫瘤組織、擴大治療窗口來擴大 T 細胞參與者範圍的機會。

This shared vision formed the basis of our discussions last year, leading to the deal we announced in November. Given Regeneron's acknowledged high bar for external innovation, this collaboration is yet another point of validation of CytomX's scientific and platform expertise.

這一共同願景構成了我們去年討論的基礎，促成了我們在 11 月宣布的交易。鑑於 Regeneron 公認的外部創新高標準，此次合作是對 CytomX 科學和平台專業知識的又一驗證點。

Moving now to our upcoming INDs for next-generation molecules, CX-2051 and CX-801. Starting with CX-2051, our conditionally active Probody ADC targeting EpCAM.

現在轉到我們即將推出的下一代分子 CX-2051 和 CX-801 的 IND。從 CX-2051 開始，我們的有條件激活的 Probody ADC 以 EpCAM 為目標。

EpCAM has been regarded as a high potential target for decades and has been clinically validated by others. But clinical activity has only been achieved with local administration. CX-2051 is tailored to optimize therapeutic index for EpCAM-expressing epithelial cancers by matching the target with payload mechanism of action and tumor sensitivity.

幾十年來，EpCAM 一直被視為一個高潛力目標，並已被其他人臨床驗證。但臨床活動僅通過地方管理實現。 CX-2051經過定制，可通過將靶標與有效載荷作用機制和腫瘤敏感性相匹配來優化表達 EpCAM 的上皮癌的治療指數。

We have optimized [marketing] proteases cleavability, and we have selected a [cancer-decent] derivative, the topoisomerase 1 inhibitor in the TCAM class, as the payload for this program and with a drug antibody ratio of 8.

我們優化了 [營銷] 蛋白酶的可切割性，我們選擇了一種 [抗癌] 衍生物，即 TCAM 類中的拓撲異構酶 1 抑製劑，作為該程序的有效載荷，藥物抗體比為 8。

The TCAM payload class has shown exciting clinical results with ADCs, including HER2 and Trodelvy, and we really think this payload is an optimal choice for this program. Although locally administered anti-EpCAM therapeutics have shown promise, efforts to generate systemic anti-EpCAM therapeutics have, to date, not been successful.

TCAM 有效載荷類已經顯示出令人興奮的 ADC 臨床結果，包括 HER2 和 Trodelvy，我們真的認為這種有效載荷是該項目的最佳選擇。儘管局部施用的抗 EpCAM 療法已顯示出希望，但迄今為止，產生全身性抗 EpCAM 療法的努力尚未成功。

CX-2051, however, when systemically administered, has demonstrated a wide predicted therapeutic index and strong preclinical activity in multiple preclinical models, including colorectal cancer. We anticipate filing an IND for this novel ADC in the second half of 2023.

然而，CX-2051 在全身給藥時，已在多種臨床前模型（包括結直腸癌）中顯示出廣泛的預測治療指數和強大的臨床前活性。我們預計在 2023 年下半年為這種新型 ADC 提交 IND。

Turning now to CX-801, our duly-masked interferon alpha-2b, the lead program within our broad efforts in the cytokine field. We believe there's enormous potential to harness the powerful anticancer activity of cytokines by using our localization strategies to direct their activity towards tumor tissue and away from systemic immune system activation.

現在轉向 CX-801，我們經過適當掩蔽的干擾素 alpha-2b，它是我們在細胞因子領域廣泛努力中的領先項目。我們相信，通過使用我們的定位策略將細胞因子的活性引導至腫瘤組織並遠離全身免疫系統激活，利用細胞因子強大的抗癌活性具有巨大的潛力。

Interferon alpha-2b is an improved immunotherapeutic that has demonstrated clinical activity in multiple cancer types and, we believe, provides a potentially superior approach to activating antitumor immune responses than cytokines such as IL-2, IL-12 and IL-15.

干擾素 alpha-2b 是一種改進的免疫療法，已在多種癌症類型中顯示出臨床活性，我們相信，它提供了一種比 IL-2、IL-12 和 IL-15 等細胞因子更可能激活抗腫瘤免疫反應的方法。

Interferon alpha stimulates antigen-presenting cells to activate cytotoxic T cells and combines effectively with checkpoint inhibition, offering tremendous potential to unlock checkpoint refractory and/or resistant cancers.

干擾素 α 刺激抗原呈遞細胞激活細胞毒性 T 細胞，並與檢查點抑制有效結合，提供解鎖檢查點難治性和/或耐藥性癌症的巨大潛力。

Interferon alpha also has direct tumor cell-killing activity, providing a dual mechanism of action. However, the powerful anticancer activity of interferon alpha has thus far been difficult to harness due to its systemic toxicity.

干擾素 α 還具有直接的腫瘤細胞殺傷活性，提供雙重作用機制。然而，由於其全身毒性，迄今為止難以利用乾擾素 α 的強大抗癌活性。

In data presented at SITC 2022, we demonstrated that CX-801 has a wide therapeutic index and an enhanced tolerability profile compared to unmasked interferon. Our data have highlighted CX-801's preferential activity in the tumor microenvironment as well as the potential for synergistic effects when combined with checkpoint inhibitors.

在 SITC 2022 上提供的數據中，我們證明與未掩蔽的干擾素相比，CX-801 具有廣泛的治療指數和增強的耐受性。我們的數據突出了 CX-801 在腫瘤微環境中的優先活性以及與檢查點抑製劑聯合使用時產生協同效應的潛力。

We believe CX-801 has the potential to become a unique centerpiece of combination therapy for a wide range of tumor types, and we aim to rapidly advance this potentially best-in-class program towards clinical evaluation with an IND filing targeted for the second half of 2023.

我們相信 CX-801 有潛力成為多種腫瘤類型聯合治療的獨特核心，我們的目標是通過下半年的 IND 申請，快速推進這一可能一流的項目進行臨床評估2023 年。

Let me turn now to our CD71 program. At CytomX, we have had a long-standing interest in leveraging the unique molecular properties of CD71, the transferrin receptor, as an anticancer target. Our goal is to use our Probody platform to open a therapeutic window for this high-potential but previously undruggable target.

現在讓我轉向我們的 CD71 程序。在 CytomX，我們長期以來一直有興趣利用 CD71（轉鐵蛋白受體）的獨特分子特性作為抗癌靶標。我們的目標是使用我們的 Probody 平台為這個具有高潛力但以前無法下藥的目標打開一個治療窗口。

And as such, we have developed an antibody drug conjugate to CD71 that we call CX-2029. We partnered the program with AbbVie in an alliance that dates back to 2016, and that was focused on the advancement of CX-2029 into IND-enabling and clinical studies.

因此，我們開發了一種針對 CD71 的抗體藥物偶聯物，我們稱之為 CX-2029。早在 2016 年，我們就與 AbbVie 建立了合作夥伴關係，重點是將 CX-2029 推進到 IND 支持和臨床研究中。

Under the collaboration agreement, CytomX was responsible for early development up to the completion of cohort expansions and with AbbVie being responsible for later-stage development.

根據合作協議，CytomX 負責早期開發直至隊列擴展完成，AbbVie 負責後期開發。

We've made substantial progress since this alliance started. And in January this year, we announced updated results from the cohort expansions, which included encouraging clinical activity in unselected heavily pretreated patients with tumors of squamous histologies, including a 21% confirmed response rate in squamous esophageal cancer.

自該聯盟成立以來，我們取得了實質性進展。今年 1 月，我們公佈了隊列擴展的最新結果，其中包括鼓勵在未經選擇的經過大量預處理的鱗狀組織腫瘤患者中開展臨床活動，包括 21% 的鱗狀食管癌確診緩解率。

Grade 3 anemia remains the most common treatment-related adverse event. Strategies for management of anemia have included transfusions, dose delays and dose reductions. And patients who have responded to CX-2029, have been actively managed through the use of anemia mitigation measures.

3 級貧血仍然是最常見的治療相關不良事件。貧血的管理策略包括輸血、劑量延遲和劑量減少。對 CX-2029 有反應的患者已通過使用貧血緩解措施得到積極管理。

Our January data update for CX-2029 essentially marks the conclusion of CytomX's responsibilities for execution of the clinical program within the AbbVie alliance, and the data has been under evaluation at AbbVie in recent months.

我們 1 月份的 CX-2029 數據更新實質上標誌著 CytomX 在艾伯維聯盟內執行臨床計劃的責任的結束，最近幾個月艾伯維一直在評估這些數據。

AbbVie informed us on March 21 that they do not plan to advance CX-2029 into further clinical studies for strategic portfolio reasons, and the alliance will conclude. CytomX regains full rights to CD71 and has an exclusive option to reacquire full rights to CX-2029, and these discussions are underway.

艾伯維（AbbVie）於 3 月 21 日通知我們，出於戰略組合原因，他們不打算將 CX-2029 推進進一步的臨床研究，該聯盟將結束。 CytomX 重新獲得 CD71 的全部權利，並擁有重新獲得 CX-2029 全部權利的獨家選擇權，這些討論正在進行中。

While we're disappointed with AbbVie's decision, in our work to date on CD71, we have pushed new scientific boundaries and demonstrated for the first time that targeting CD71 with an antibody drug conjugate can lead to tumor shrinkage in late-stage cancer patients.

雖然我們對 AbbVie 的決定感到失望，但在我們迄今為止關於 CD71 的工作中，我們已經突破了新的科學界限，並首次證明用抗體藥物偶聯物靶向 CD71 可以導致晚期癌症患者的腫瘤縮小。

Going forward, CytomX will be evaluating next steps for CX-2029 while also continuing to pursue next-generation strategies to targeting CD71. We would like to thank AbbVie for their partnership in helping us bring CX-2029 and our CD71 program to this stage in its development.

展望未來，CytomX 將評估 CX-2029 的後續步驟，同時繼續追求針對 CD71 的下一代戰略。我們要感謝 AbbVie 的合作夥伴關係，幫助我們將 CX-2029 和我們的 CD71 計劃帶到了開發的這個階段。

I'd like to now briefly update on our collaborative work with Bristol Myers Squibb and Moderna. Our alliance with BMS has continued to make progress, and I would like to take a few minutes to cover the latest updates on the CTLA-4 program.

我現在想簡要介紹一下我們與 Bristol Myers Squibb 和 Moderna 的合作工作。我們與 BMS 的聯盟不斷取得進展，我想花幾分鐘時間介紹 CTLA-4 計劃的最新更新。

We have worked with BMS on 2 CTLA-4 Probody approaches. The first is a Probody version of ipilimumab that's called 249. We're also working with BMS on a Probody version of their nonfucosylated anti-CTLA-4 antibody, designed to be a more potent version of ipi. This Probody, named 288, is designed to be a safer, more effective version of the nonfucosylated ipi.

我們與 BMS 合作開發了 2 種 CTLA-4 Probody 方法。第一個是 ipilimumab 的 Probody 版本，稱為 249。我們還與 BMS 合作開發其非岩藻糖基化抗 CTLA-4 抗體的 Probody 版本，旨在成為更有效的 ipi 版本。這個名為 288 的 Probody 旨在成為更安全、更有效的非岩藻糖基化 ipi 版本。

At their earnings call a few weeks ago, BMS announced their prioritization and advancement of the nonfucosylated Probody 288, which is now the leading edge of their next-generation CTLA-4 program.

在幾週前的財報電話會議上，BMS 宣布了他們對非岩藻糖基化 Probody 288 的優先排序和推進，該產品現在是他們下一代 CTLA-4 計劃的前沿。

At SITC in 2022, BMS presented Phase I data on 218, which is the nonfucosylated antibody that underlies 288, showing intriguing activity, including in microsatellite-stable colorectal cancer. The 288 probody is being advanced to Phase II, and we look forward to future updates from BMS.

在 2022 年的 SITC 上，BMS 展示了 218 的 I 期數據，218 是 288 的基礎非岩藻糖基化抗體，顯示出有趣的活性，包括在微衛星穩定的結直腸癌中。 288 probody 正在推進到 II 期，我們期待 BMS 的未來更新。

Lastly, I'd like to reemphasize our most recent collaboration with Moderna, which highlights CytomX's continued innovation, breadth and pioneering efforts in the field of conditional activation and also our continued ability to leverage partnering as a financing vehicle for our company.

最後，我想再次強調我們最近與 Moderna 的合作，這突出了 CytomX 在條件激活領域的持續創新、廣度和開拓性努力，以及我們繼續利用合作夥伴作為我們公司的融資工具的能力。

We're excited to have already kicked off this collaboration, which brings together 2 leading platforms to research and develop mRNA-encoded conditionally-activated biologics.

我們很高興已經開始這項合作，它匯集了兩個領先的平台來研究和開發 mRNA 編碼的條件激活生物製劑。

CytomX and Moderna share a vision of investing at the intersection of biology and technology to transform the lives of patients in oncology and also in non-oncology therapeutic areas, and we look forward to doing great things together.

CytomX 和 Moderna 有著共同的願景，即投資於生物學和技術的交叉領域，以改變腫瘤學和非腫瘤學治療領域患者的生活，我們期待共同做出偉大的事情。

Let me now turn the call over to Chris to provide you with a financial overview for the quarter.

現在讓我把電話轉給克里斯，為您提供本季度的財務概覽。

Thank you, Sean. I'm pleased to be able to share an update on our 2022 financial results with you today. CytomX entered 2023 with a strong balance sheet, with $194 million in cash, cash equivalents and investments as of December 31, 2022, which we project will fund the operations of the company into 2025.

謝謝你，肖恩。我很高興今天能夠與您分享我們 2022 年財務業績的最新情況。 CytomX 以強勁的資產負債表進入 2023 年，截至 2022 年 12 月 31 日擁有 1.94 億美元的現金、現金等價物和投資，我們預計這些資金將為公司運營到 2025 年提供資金。

This amount includes the upfront payment received as part of the Regeneron collaboration, but does not include the upfront payment of $35 million received in Q1 2023 from Moderna.

該金額包括作為再生元合作的一部分收到的預付款，但不包括 2023 年第一季度從 Moderna 收到的 3500 萬美元預付款。

We continue to operate from a position of financial strength, and our recent collaborations continue to highlight CytomX's ability to leverage its differentiated science to bring capital into the company and build long-term value.

我們繼續在財務實力的基礎上運營，我們最近的合作繼續突出了 CytomX 利用其差異化科學為公司帶來資本並建立長期價值的能力。

Moving to the financials for the full year 2022. I would like to note that my comments regarding the financial statements refer to our most recent SEC filings, which include restated financial information from 2019 to 2022 as a result of a change in our revenue recognition accounting method for certain collaboration agreements.

轉向 2022 年全年的財務狀況。我想指出，我對財務報表的評論是指我們最近提交給美國證券交易委員會的文件，其中包括由於我們的收入確認會計發生變化而重述的 2019 年至 2022 年的財務信息某些合作協議的方法。

The restatement impacts the timing of certain revenue recognition and does not impact total revenue that will be recognized for each collaboration. Also, the restatement has no impact on the company's current cash position or cash flows.

重述會影響某些收入確認的時間，但不會影響將為每次合作確認的總收入。此外，重述對公司當前的現金狀況或現金流量沒有影響。

Revenue in 2022 was $53.2 million compared to $37.3 million in 2021, driven by higher estimated percentages of completion for research and development programs in the company's collaborations with AbbVie and Bristol Myers Squibb.

2022 年的收入為 5320 萬美元，而 2021 年為 3730 萬美元，這是由於公司與 AbbVie 和 Bristol Myers Squibb 合作的研發項目的估計完成百分比更高。

R&D expenses decreased by $2.5 million to $111.6 million in 2022. The decrease was primarily due to lower clinical trials and lab contract services, partially offset by $5.3 million of restructuring expenses. G&A expenses increased $3.6 million in 2022 to $42.8 million, driven primarily by $2.4 million of restructuring expenses.

2022 年研發費用減少 250 萬美元至 1.116 億美元。減少的主要原因是臨床試驗和實驗室合同服務減少，部分被 530 萬美元的重組費用所抵消。 G&A 費用在 2022 年增加了 360 萬美元，達到 4280 萬美元，這主要是由於 240 萬美元的重組費用。

Overall, full year 2022 expenses related to the company's restructuring, which was announced in July of 2022, were $7.7 million. The restructuring is substantially complete as of the end of 2022. With that, I'll turn the call back to Sean.

總體而言，與公司於 2022 年 7 月宣布的重組相關的 2022 年全年支出為 770 萬美元。截至 2022 年底，重組已基本完成。有了這個，我會把電話轉回給肖恩。

Thanks, Chris. In summary, CytomX has begun 2023 with strong execution across the pipeline and with considerable momentum. This will continue to be a year of focused execution by the company across our partnered and wholly-owned pipeline. .

謝謝，克里斯。總之，CytomX 以強大的執行力和可觀的勢頭開啟了 2023 年。今年將繼續是公司在我們的合作夥伴和全資擁有的渠道中重點執行的一年。 .

Our progress with CX-904, taken together with our exciting collaborative efforts with Regeneron and Astellas, positions the company with significant ongoing efforts in T cell engagers and an opportunity to make an important impact in one of the most promising areas of oncology R&D.

我們在 CX-904 方面取得的進展，加上我們與 Regeneron 和 Astellas 的激動人心的合作努力，使公司在 T 細胞參與者方面不斷做出重大努力，並有機會在最有前途的腫瘤研發領域之一產生重要影響。

We also continue to invest in cancer immunotherapy strategies through our work on CX-801, our conditionally-active interferon alpha, which is on track for IND filing this year. As we assess potential next steps for the CX-2029 asset and our CD71 program more broadly, we're also excited to advance our latest ADC, CX-2051, targeting EpCAM, towards IND filing.

我們還通過 CX-801（我們的條件活性干擾素 α）的工作繼續投資於癌症免疫治療策略，該藥物有望在今年提交 IND 申請。在我們更廣泛地評估 CX-2029 資產和我們的 CD71 計劃的潛在後續步驟時，我們也很高興將我們最新的 ADC CX-2051（針對 EpCAM）推進到 IND 備案。

The translational cycle of bench to bedside to bench has continued to teach us where the highest-impact applications of our technology lie for the benefit of people with cancer, and we remain strongly committed to our patients.

從工作台到床邊再到工作台的轉化循環繼續告訴我們，我們的技術最有影響力的應用是為了癌症患者的利益，我們仍然堅定地致力於為我們的患者服務。

I would like to extend my sincere thanks to the CytomX team for their ongoing dedication and commitment to our vision and mission. Operator, let's now open the call up for Q&A.

我要衷心感謝 CytomX 團隊對我們的願景和使命的持續奉獻和承諾。接線員，現在讓我們打開問答環節。

(Operator Instructions) The first question we have is coming from Roger Song of Jefferies.

（操作員說明）我們的第一個問題來自 Jefferies 的 Roger Song。

A couple of questions from us, maybe start from the 904. Sean, you mentioned you potentially will go through the dose escalation by the end of this year and move in to the expansion next year. So can you just give us some kind of comment around what should we expect to see in terms of the data update from that program? And what are the key criteria for you to move into the tumor-specific expansion?

我們有幾個問題，也許從 904 開始。肖恩，你提到你可能會在今年年底前完成劑量升級，並在明年進入擴展階段。那麼，您能否就該程序的數據更新方面我們應該期望看到的內容給我們一些評論？您進入腫瘤特異性擴增的關鍵標準是什麼？

Yes, Roger, thanks for the question. So as I mentioned, we're pleased with the progress in the early program for 904. And the goal of the dose escalation that we're engaged in right now is really to assess safety of this very novel T cell engager.

是的，羅傑，謝謝你的提問。所以正如我提到的，我們對 904 早期計劃的進展感到滿意。我們現在正在進行的劑量升級的目標實際上是評估這種非常新穎的 T 細胞接合器的安全性。

And we do believe we're on track to -- or our goal is to reach doses by the end of the year that should enable us to start backfilling cohorts as it's fairly common in early Phase I.

我們確實相信我們正在走上正軌——或者我們的目標是在今年年底達到劑量，這應該使我們能夠開始回填隊列，因為這在第一階段的早期相當普遍。

With an agent like this really, like any T cell engager, the step-wise dose escalation, these are highly potent molecules. And the selection of doses to move forward, I think these days, we need to be even more thoughtful about this, given FDA's guidance with Optimus and how to think about MTD, how to think about RP2D.

使用這樣的試劑，就像任何 T 細胞接合器一樣，逐步增加劑量，這些都是非常有效的分子。以及向前推進的劑量選擇，我認為這些天，我們需要更加深思熟慮，鑑於 FDA 對 Optimus 的指導以及如何考慮 MTD，如何考慮 RP2D。

So we're going to be thoughtful here. And we're not ready to guide to when we'll have data, but we are making good progress.

所以我們要在這裡深思熟慮。我們還沒有準備好指導何時獲得數據，但我們正在取得良好進展。

Okay, that's fair. And then so in terms of your upcoming R&D for 801 and 2051, can you just let us know what the status of the IND-enabling studies are in terms of the [CMC] and [paths] that you are doing? And also, what are the initial indications for those two, the potential INDs?

好吧，這很公平。然後就您即將進行的 801 和 2051 研發而言，您能否讓我們知道 IND 支持研究在您正在進行的 [CMC] 和 [路徑] 方面的狀態？而且，這兩個潛在的 IND 的初步跡像是什麼？

Yes, thanks for the question. So very excited about these 2 new INDs. As I've mentioned, they have broad potential across multiple tumor types. And as you mentioned, Roger, the team is very busy right now with IND-enabling activities for both of these programs.

是的，謝謝你的提問。對這兩個新的 IND 感到非常興奮。正如我所提到的，它們在多種腫瘤類型中具有廣泛的潛力。正如你提到的，羅傑，團隊現在非常忙於為這兩個項目開展 IND 支持活動。

We're pleased with the progress. We're on track with manufacturing steps, with toxicology programs. And everything remains on track for our guidance for these INDs being filed this year.

我們對進展感到滿意。我們正在按照製造步驟和毒理學計劃走上正軌。對於我們今年提交的這些 IND 的指導，一切都按計劃進行。

In terms of tumor types, let's take EpCAM first. One of the things we love about this target is just how broadly expressed it is on epithelial tumors. I did call out CRC in my comments a few moments ago, as this is the tumor type where EpCAM is the most highly expressed, is very highly expressed in CRC.

在腫瘤類型方面，我們先來看EpCAM。我們喜歡這個靶標的其中一個原因是它在上皮腫瘤上的廣泛表達。剛才我在評論中確實提到了 CRC，因為這是 EpCAM 表達最高的腫瘤類型，在 CRC 中表達非常高。

And that's one of the reasons that we've selected the [counterpiece] in payload, which we think is well matched to that tumor type, given the high target expression as well. But there are many other tumor types that we could potentially move into, including pancreatic, ovarian, to name just two. So many, many different areas to go. We'll be guided by what we see in Phase I, of course.

這就是我們在有效載荷中選擇 [counterpiece] 的原因之一，我們認為它與該腫瘤類型非常匹配，因為目標表達也很高。但是還有許多其他類型的腫瘤我們有可能進入，包括胰腺癌、卵巢癌，僅舉兩個例子。這麼多，許多不同的領域去。當然，我們將以我們在第一階段看到的內容為指導。

With regards to 801, interferon has been approved in several tumor types in the past. We already know it's an active drug, it's an approved drug. Our strategy there with 801, given the potency of interferon alpha as an immunotherapy, is to work in the area of increasing antitumor immunity, turning colder tumors into warmer tumors, turning warmer tumors into hot tumors.

關於 801，干擾素過去已被批准用於多種腫瘤類型。我們已經知道它是一種活性藥物，是一種已獲批准的藥物。鑑於乾擾素 α 作為免疫療法的效力，我們對 801 的策略是在提高抗腫瘤免疫力、將較冷的腫瘤轉變為較熱的腫瘤、將較熱的腫瘤轉變為較熱的腫瘤方面發揮作用。

And there will be several opportunities to pursue there. But again, we'll be guided by the Phase I dose escalation data once we get that up and running.

並且會有很多機會在那裡追求。但同樣，一旦我們啟動並運行，我們將以 I 期劑量遞增數據為指導。

Great. Maybe just one last question, and I will hop back on the queue, is for the CD71. Since you are regaining the rights for this target and potentially for the entire 2029, so you talk about the next generation for CD71, and we know the anemia is on target kind of for -- probably the finding you have been observing.

偉大的。也許只有最後一個問題，我會跳回到隊列中，是關於 CD71 的。由於您正在重新獲得該目標的權利，並有可能在整個 2029 年重新獲得權利，因此您談到了 CD71 的下一代，我們知道貧血是針對目標的——可能是您一直在觀察的發現。

So can you just let us know what are the key strategies for the next generation? And how you're going to apply from the learning from the previous clinical data to the next generation?

那麼您能否讓我們知道下一代的關鍵戰略是什麼？您將如何從以前的臨床數據中學到的知識應用到下一代？

Yes, thanks. Great question. And so with regard to -- let's maybe start with the 2029 data, so just to give, I guess, our holistic view of the drug.

對了謝謝。很好的問題。因此，關於——讓我們從 2029 年的數據開始，我想只是為了給出我們對藥物的整體看法。

We have an active drug. This is an ADC, a very novel ADC that has shown antitumor activity in several tumor types and most recently, this really intriguing signal in squamous esophageal.

我們有一種活性藥物。這是一種 ADC，一種非常新穎的 ADC，已在多種腫瘤類型中顯示出抗腫瘤活性，最近，在鱗狀食管中顯示出這種非常有趣的信號。

We've learned more about anemia over the last year or so. We still have more work to do to further understand how to potentially manage and mitigate anemia if we were to move 2029 forward ourselves, assuming that, that was something that we ultimately decide to do.

在過去一年左右的時間裡，我們對貧血有了更多的了解。如果我們自己將 2029 年提前，我們還有更多工作要做，以進一步了解如何潛在地管理和減輕貧血，假設那是我們最終決定做的事情。

So I think we've learned a lot with 2029 over the last couple of years. There is a therapeutic window for the drug. I think it's fair to say that we believe with next gen, we could broaden that therapeutic window.

所以我認為我們在過去幾年中從 2029 年學到了很多東西。該藥物有一個治療窗口。我認為可以公平地說，我們相信有了下一代，我們可以擴大治療窗口。

And different ways to do that would be to increase the antitumor activity, find ways to decrease the incidence of anemia, and we have several ideas as how to do that. And I would anticipate we'll have more to say about this science as we go through the year.

不同的方法是增加抗腫瘤活性，找到降低貧血發生率的方法，我們有幾個關於如何做到這一點的想法。我預計，隨著這一年的過去，我們將對這門科學有更多話要說。

And our next question is coming from Mara Goldstein of Mizuho Group.

我們的下一個問題來自瑞穗集團的 Mara Goldstein。

So just maybe to clarify a little bit on CX-2029, you have rights to CD71, but you would then have to acquire the CX-2029 molecule if you chose to do that. Is that correct?

因此，也許需要澄清一下 CX-2029，您擁有 CD71 的權利，但如果您選擇這樣做，則必須獲得 CX-2029 分子。那是對的嗎？

That's right, Mara, yes. So the target -- the program broadly, as far as the target is concerned, reverts to CytomX. 2029 as a Phase II asset, we have an exclusive right to negotiate full rights back from AbbVie. And those discussions have been initiated.

是的，瑪拉，是的。因此，就目標而言，目標——從廣義上講，該程序將恢復為 CytomX。 2029年作為二期資產，我們擁有從 AbbVie 談判收回全部權利的獨家權利。這些討論已經啟動。

Okay, and -- Okay, fair enough. And then under the AbbVie -- the original AbbVie agreement, they had chosen a second target a couple of years ago. Is that still ongoing or is that also no longer active?

好吧，而且——好吧，很公平。然後根據 AbbVie——最初的 AbbVie 協議，他們在幾年前選擇了第二個目標。那是仍在進行中還是不再活躍？

Yes. So we had two separate collaborations that were initiated at the same time with AbbVie. One was the CD71 R&D agreement and the other was a research discovery agreement. And that's the collaboration under which a couple of additional targets for ADCs were selected. And that agreement is also coming to a conclusion as well.

是的。因此，我們與 AbbVie 同時發起了兩項獨立的合作。一個是 CD71 研發協議，另一個是研究發現協議。這就是為 ADC 選擇了幾個額外目標的合作。該協議也即將達成。

Okay, fair enough. And then I wanted to ask on the Moderna collaboration. I certainly understand it's at an early stage.

好吧，很公平。然後我想問一下與 Moderna 的合作。我當然知道它處於早期階段。

But can you talk to us a little bit about the sort of visibility from your perspective in terms of what you may or may not be able to speak to, particularly as it relates to where the benchmarks are for CytomX to, A, participate not just financially but also potentially clinically?

但是，您能否從您的角度談談您可能會或可能不會說的內容的可見性，特別是因為它涉及到 CytomX 的基准在哪裡，A，參與，而不僅僅是在經濟上但也可能在臨床上？

Well, the -- just -- again, to reiterate just how excited we are about the science that we're doing with Moderna that we've just kicked off. So just to recap, the goal of the alliance is to leverage their mRNA platform to encode and express conditionally-activated biologics in oncology and non-oncology.

好吧，再次重申，我們對剛剛開始的 Moderna 所做的科學感到多麼興奮。回顧一下，該聯盟的目標是利用他們的 mRNA 平台來編碼和表達腫瘤學和非腫瘤學中的條件激活生物製劑。

We're not ready to disclose additional details of the research program at this point. But the collaboration is structured such that we are responsible for certain discovery and lead [optimization] efforts, and Moderna will be responsible for development and commercialization, with milestones and royalties coming to CytomX.

我們目前不准備透露研究計劃的更多細節。但合作的結構使得我們負責某些發現和領導[優化]工作，而 Moderna 將負責開發和商業化，里程碑和版稅將交給 CytomX。

And so we do not expect to be involved in the development activities with Moderna, unlike, for example, the relationships with AbbVie or even Amgen on 904. This is, in some ways, a more traditional discovery relationship, in which Moderna will be conducting the development of the programs as they mature and move forward.

因此，我們不希望參與與 Moderna 的開發活動，這與與 AbbVie 甚至 Amgen 在 904 上的關係不同。在某些方面，這是一種更傳統的發現關係，Moderna 將在其中進行隨著程序的成熟和前進，程序的開發。

Our next question will be coming from Peter Lawson of Barclays.

我們的下一個問題將來自巴克萊銀行的彼得勞森。

This is actually -- this is Alex on for Peter. I just had two quick questions on the BMS collaboration. The first one is, can you comment or remind us the key differences that you saw in Phase I for the 218 molecule compared to the data we've seen for the 249 molecule?

這實際上是——這是 Alex 替 Peter 做的。我剛剛有兩個關於 BMS 協作的快速問題。第一個是，你能評論或提醒我們你在第一階段看到的 218 分子與我們看到的 249 分子數據相比的主要區別嗎？

Yes, happy to comment on that. So it does take a bit of time to sort of cover the various moving parts here, so just bear with me for a second, just without we are all on the same page.

是的，很高興對此發表評論。因此，在這裡涵蓋各種活動部分確實需要一些時間，所以請耐心等待一秒鐘，只是我們都在同一頁上。

So 249 is the Probody version of ipi. The 218 is the nonfucosylated antibody, which is BMS' antibody. And then there's 288, which is the Probody version of 218, the nonfucosylated.

所以249是ipi的Probody版本。 218是非岩藻糖基化抗體，是BMS的抗體。然後是 288，它是 218 的 Probody 版本，是非岩藻糖基化的。

So the clinical data that BMS has presented previously relates to, as you rightly point out, 249 Phase I study and also the 218 Phase I study. No data has yet been presented for 288, which is a nonfucosylated Probody.

因此，正如您正確指出的那樣，BMS 之前提供的臨床數據與 249 I 期研究以及 218 I 期研究相關。尚未提供 288 的數據，它是一種非岩藻糖基化的 Probody。

I would say that the key learnings from the Phase I work on 249 and 218 are as follows: With the Probody 249, the Probody version of ipi, the dose escalation was able to achieve really very high levels of the mass ipi. So they achieved 30, 3-0, mg per kg of monotherapy and 15 mg per kg in combination with full-dose nivo.

我想說的是，從 249 和 218 的第一階段工作中學到的主要知識如下：使用 Probody 249，ipi 的 Probody 版本，劑量增加能夠達到非常高的質量 ipi 水平。因此，他們實現了 30、3-0、mg/kg 的單一療法和 15mg/kg 與全劑量 nivo 的組合。

And you can see how -- and I think this is pretty consistent with the work we've done over the years in the clinic that the masking shifts the dose response curve for toxicity, so they can get to higher levels and still have a well-tolerated drug.

你可以看到 - 我認為這與我們多年來在診所所做的工作非常一致，即掩蔽改變了毒性的劑量反應曲線，因此他們可以達到更高的水平並且仍然有很好的效果- 耐受藥物。

The other aspect of the Phase I data, and this was really the update last year at ESMO, clear evidence of clinical activity for 249 demonstrated in that poster presentation, including a response in MSS-stable CRC, which was highlighted as a case study.

I 期數據的另一方面，這實際上是去年 ESMO 的更新，海報展示中展示了 249 臨床活動的明確證據，包括在 MSS 穩定的 CRC 中的反應，這是作為案例研究突出顯示的。

The 218 poster was important, I think, for several reasons, demonstrated again that 218, the nonfucosylated ipi, is clinically active. Again, a case study was put forward in MSS CRC, which is an area where we're seeing a lot of progress by others, including [HNS] with their Fc-enhanced CTLA-4.

218 海報很重要，我認為，出於多種原因，它再次證明了 218（非岩藻糖基化的 ipi）具有臨床活性。同樣，在 MSS CRC 中提出了一個案例研究，這是一個我們看到其他人取得很多進展的領域，包括 [HNS] 及其 Fc 增強 CTLA-4。

The other noteworthy data from the 218 poster is that this drug, you can see how it's a lot more potent. It's designed to be more potent than ipi, and nonfucosylation leads to a more potent drug. And that meant that the doses administered are substantially lower than for ipi alone. So I think that's kind of an interesting take home.

218 海報中另一個值得注意的數據是這種藥物，你可以看到它的藥效如何。它被設計成比 ipi 更有效，非岩藻糖基化導致更有效的藥物。這意味著施用的劑量大大低於單獨的 ipi。所以我認為這是一種有趣的帶回家。

And the prioritization of 288, the masked version of that 218, I would think has the potential to evaluate higher doses of the nonfucosylated in masked form. So we don't have a lot of visibility at this point in what BMS' Phase II strategy will be for 288. But those are just a few thoughts from the data that's been presented thus far.

而 288 的優先級，即 218 的掩蔽版本，我認為有可能評估更高劑量的掩蔽形式的非岩藻糖基化。因此，目前我們對 BMS 的 288 階段 II 期戰略的了解不多。但這只是迄今為止提供的數據中的一些想法。

Okay, great. That makes a lot of sense. And then, yes, just I was also curious if you have any visibility in terms of -- or should we assume that the current ongoing studies with the 249 will sort of stop enrolling patients and -- going forward? And that's it.

好的，太好了。這很有意義。然後，是的，我也很好奇你是否有任何可見性——或者我們是否應該假設目前正在進行的 249 研究將停止招募患者，並且——繼續前進？就是這樣。

You're welcome.

不客氣。

Our next question will be coming from Mitchell Kapoor of H.C. Wainwright.

我們的下一個問題將來自 H.C. 的 Mitchell Kapoor。溫賴特。

Just wanted to ask about CX-2029 and a little bit more on the discussions to reacquire the rights. What does that entail? And then secondly, what is the -- what do you think the ability to more effectively treat esophageal cancers versus other cancers suggests about the profile and the mechanism of the drug with respect to the target?

只是想詢問有關 CX-2029 的問題，以及更多關於重新獲得權利的討論。這意味著什麼？其次，您認為與其他癌症相比，更有效地治療食管癌的能力表明藥物相對於靶標的概況和機制是什麼？

Yes. Thanks for the questions, Mitch. I can't really comment on the 2029 negotiation for obvious reasons at this point other than to say that those discussions have been initiated, and there's a process laid out in the contract that we negotiated some years ago for how to go about that. So we'll see where it all goes.

是的。謝謝你的問題，米奇。出於顯而易見的原因，目前我無法真正評論 2029 年的談判，只能說這些討論已經啟動，並且我們幾年前談判的合同中規定了一個流程來解決這個問題。因此，我們將看看它的去向。

With regards to esophageal, it is really interesting to us, the signal that we've seen there. One of the intriguing features of esophageal that relates to the target is published data from others, showing or suggesting that CD71 is amplified in certain squamous esophageal tumors.

關於食道，我們真的很感興趣，我們在那裡看到的信號。與目標相關的食管的一個有趣特徵是來自其他人的已發表數據，顯示或暗示 CD71 在某些鱗狀食管腫瘤中被擴增。

So one could certainly imagine that there's a relationship between target level or more specifically target amplification and clinical activity. And that is something that we're aggressively pursuing as to figure out whether there's a potential patient selection strategy there.

因此，人們當然可以想像目標水平或更具體的目標放大與臨床活動之間存在關係。這是我們正在積極追求的事情，以確定那裡是否存在潛在的患者選擇策略。

Speaking in general terms, of course, given the high incidence of anemia that we have with this drug, but also given its clinical activity, if we elect to move the drug forward in esophageal, let's say, obviously, we'd be wanting to do everything we can to select patients in our favor to increase the likelihood of response and also, of course, continue to work to find ways to manage and mitigate anemia to give the drug its best chance of future success.

一般而言，當然，考慮到我們使用這種藥物時貧血的高發病率，但也考慮到它的臨床活性，如果我們選擇在食道中推進藥物，比方說，很明顯，我們想要盡我們所能選擇對我們有利的患者，以增加反應的可能性，當然，還要繼續努力尋找控制和減輕貧血的方法，為藥物提供未來成功的最佳機會。

So that's something that we're actively looking at that relates directly to the target.

所以這是我們正在積極研究的與目標直接相關的事情。

Our next question will be coming from Anupam Rama of JPMorgan.

我們的下一個問題將來自摩根大通的 Anupam Rama。

This is actually Malcolm Kuno on for Anupam. Just one quick question. So given that some of your collaborations involve cost sharing agreements, what should we assume as being baked into your cash runway?

這實際上是 Anupam 的 Malcolm Kuno。只是一個簡單的問題。因此，鑑於你們的一些合作涉及成本分攤協議，我們應該假設什麼被納入你們的現金跑道？

I'll pass that one over to Chris.

我會把那個交給克里斯。

Yes. Malcolm, just to reiterate what we've communicated on cash runway in the prepared remarks, so we reported $194 million of cash at the end of the year. As I mentioned, that does not include the Moderna upfront payment of $35 million received in Q1 of 2023 nor the Astellas milestone that we achieved of $5 million in January of this year.

是的。馬爾科姆，只是重申我們在準備好的發言中在現金跑道上傳達的內容，所以我們在年底報告了 1.94 億美元的現金。正如我所提到的，這不包括 Moderna 在 2023 年第一季度收到的 3500 萬美元預付款，也不包括我們在今年 1 月實現的 500 萬美元 Astellas 里程碑。

In terms of color on the guidance, we don't go into specifics on exactly what's assumed. From an overall capital allocation and resourcing perspective, we communicated in the summer of last year the focus on CX-904 and the next-generation pipeline. So of course, capital will be allocated to those programs as appropriate. But beyond that, we're not giving any additional color.

就指南中的顏色而言，我們不會詳細說明假設的具體內容。從整體資本配置和資源配置的角度來看，我們在去年夏天傳達了對 CX-904 和下一代管線的關注。因此，當然，資金將酌情分配給這些項目。但除此之外，我們不會提供任何額外的顏色。

Just one quick addition there in terms of the deal structures. As we mentioned in the comments earlier, the -- both the AbbVie and Amgen alliances have been structured in a way that we -- without we had, I guess, now we're obviously concluding that relationship that we had with Amgen, we have the opportunity to invest in later-stage development.

就交易結構而言，這裡只是一個快速的補充。正如我們在之前的評論中提到的那樣，艾伯維和安進聯盟的結構方式是我們 - 沒有我們，我想，現在我們顯然正在結束與安進的關係，我們有投資後期開發的機會。

But that's quite a bit further down the road. So as Chris mentioned, current financials and guidance is really focused on advancing the earlier-stage programs to key near-term [milestones].

但這還有很長的路要走。因此，正如克里斯提到的那樣，當前的財務和指導實際上側重於將早期項目推進到關鍵的近期[里程碑]。

That makes sense.

這就說得通了。

Next question is coming from Etzer Darout of BMO.

下一個問題來自 BMO 的 Etzer Darout。

Just wanted -- a clarifying question on the Probody program from BMS. Just sort of whether or not 249 is ongoing and advancing? Is this just sort of a leapfrog of 288 or is that the only program that BMS plans to move forward? I guess that's question one.

只是想要 - 一個關於 BMS Probody 程序的澄清問題。只是關於 249 是否正在進行和推進？這只是 288 的一次跨越，還是 BMS 計劃推進的唯一計劃？我想這是第一個問題。

And then if you could maybe speak to sort of maybe the safety tolerability differences potentially between 218, the antibody from Bristol and the ipi sort of AE profile, which we now know are fairly notorious, if you could maybe talk a little bit about that as well.

然後，如果你能談談 218、來自布里斯托爾的抗體和 ipi 類 AE 概況之間可能存在的安全耐受性差異，我們現在知道這是相當臭名昭著的，如果你能談談這個作為出色地。

Yes. Thanks, Etzer. Obviously, questions, I think, will probably be more compressively answered by our partner, BMS. But let me just make a couple of brief comments.

是的。謝謝，埃澤。顯然，我認為我們的合作夥伴 BMS 可能會更緊湊地回答問題。但是，讓我簡單地發表幾點評論。

So first of all, with regard to the 288 leapfrog as you put it, they have been pretty clear that they have prioritized 288 over the other programs, and the advancement from Phase I to Phase II reflects that.

所以首先，關於你所說的 288 跨越，他們非常清楚他們將 288 優先於其他計劃，從第一階段到第二階段的進展反映了這一點。

I think if one looks at the broad landscape of CTLA-4 next-gens that are being pursued by various parties, there is a move towards more potent versions of anti-CTLA-4 antibodies using strategies like Fc enhancement or in the case of BMS, nonfucosylation, which are functionally very similar.

我認為，如果看看各方正在追求的下一代 CTLA-4 的廣闊前景，就會發現使用 Fc 增強或 BMS 等策略向更有效版本的抗 CTLA-4 抗體邁進, 非岩藻糖基化，它們在功能上非常相似。

So their decision, I think, looking at it from the standpoint of the outside world and the way the field is evolving, makes sense to us.

因此，我認為，從外部世界的角度和該領域的發展方式來看，他們的決定對我們來說是有意義的。

With regard to safety of 218, again, I think the question would be much better answered by our partner. I would just observe from the data that we've seen in their presentations that 218, as I mentioned earlier, is a more potent antibody, when one thinks about engagement of the target, the target biology. It is less well tolerated.

關於 218 的安全性，我認為我們的合作夥伴會更好地回答這個問題。我只是從我們在他們的演示文稿中看到的數據觀察到，正如我之前提到的，當人們考慮參與目標、目標生物學時，218 是一種更有效的抗體。它的耐受性較差。

I think the profile though of adverse events that are seen, are similar. So I don't -- I'm not aware of anything that's particularly unique with the Fc enhanced, but we'd have to study the data a bit more closely.

我認為所見不良事件的概況是相似的。所以我不知道 - 我不知道 Fc 增強有什麼特別獨特的地方，但我們必須更仔細地研究數據。

Yes, and the goal of the Probody, of course, is to open that therapeutic window, and that's why we're encouraged that they prioritized 288.

是的，當然，Probody 的目標是打開那個治療窗口，這就是為什麼我們鼓勵他們優先考慮 288。

That concludes today's Q&A session as well as conclude today's conference call. Thank you all for joining. You may disconnect, and have a good evening.

今天的問答環節到此結束，今天的電話會議也到此結束。謝謝大家的加入。你可以斷開連接，祝你有個愉快的夜晚。