CytomX Therapeutics Inc (CTMX) 2024 Q4 法說會逐字稿

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

大家下午好。感謝您的支持。歡迎參加 CytomX Therapeutics 2024 年第四季和財務業績電話會議。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.

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

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

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

We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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

Earlier this afternoon, we issued a press release that includes a summary of our 2024 full-year financial results and highlight recent progress at CytomX. We encourage everyone to read today's press release and the associated materials, which have been filed with the SEC. Additionally, the press release recorded on this call and our SEC filings can be found under the Investors and News section of our website.

今天下午早些時候，我們發布了一份新聞稿，其中包括我們 2024 年全年財務表現摘要，並重點介紹了 CytomX 的最新進展。我們鼓勵大家閱讀今天的新聞稿和相關資料，這些資料已提交給美國證券交易委員會。此外，本次電話會議記錄的新聞稿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。

With me on the call today is Dr. Sean McCarthy, CytomX' Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I walk through the financials for 2024. We will then conclude with a Q&A session.

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 2024 年的財務狀況之前，肖恩將提供有關我們的管道和公司進展的最新資訊。然後我們將以問答環節結束。

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

說完這些，我現在將電話轉給肖恩。

Thanks, Chris, and good afternoon, everyone. We're very pleased to be here with you today to provide updates on our continued progress at CytomX towards our mission of urgently advancing our Probody therapeutic pipeline for the maximum benefit of cancer patients.

謝謝，克里斯，大家下午好。我們非常高興今天能在這裡與大家分享 CytomX 在實現我們的使命方面取得的持續進展，即緊急推進我們的 Probody 治療管線，為癌症患者帶來最大利益。

As a pioneer in the field of antibody masking and conditional activation, we continue to direct our powerful technology platform towards major unmet needs in oncology. We're seeing broad strategic interest in antibody masking and CytomX is uniquely positioned with expertise and capabilities to deliver novel masked therapeutics across multiple treatment modalities, including antibody drug conjugates, T cell engagers and cytokines. Our current clinical programs have been built on over a decade of scientific and clinical expertise and follow clear design principles aimed at optimally selecting the cancer type of interest, the tumor target, and the relevant effector function in order to deliver differentiated cancer therapies.

作為抗體掩蔽和條件活化領域的先驅，我們繼續將我們強大的技術平台用於滿足腫瘤學領域尚未滿足的主要需求。我們看到人們對抗體掩蔽的廣泛策略興趣，而 CytomX 憑藉其專業知識和能力在多種治療方式中提供新型掩蔽療法，包括抗體藥物偶聯物、T 細胞接合劑和細胞因子，擁有獨特的優勢。我們目前的臨床計畫建立在十多年的科學和臨床專業知識之上，遵循明確的設計原則，旨在最佳地選擇感興趣的癌症類型、腫瘤靶點和相關效應功能，以提供差異化的癌症治療方法。

2024 was a very productive year for us, including the advancement of two new programs into the clinic, CX-2051 and CX-801. In January 2025, we announced the prioritization of these programs and the streamlining of our organization, extending our cash runway to Q2 of 2026, supporting our ability to deliver upon key clinical milestones. We see our lead program, CX-2051 as a highly differentiated first-in-class ADC that is designed to address a large unmet need in colorectal cancer and build significant value for CytomX.

2024 年對我們來說是非常有成效的一年，包括將兩個新計畫 CX-2051 和 CX-801 推進到臨床階段。2025 年 1 月，我們宣布優先考慮這些項目並精簡組織結構，將現金流延長至 2026 年第二季度，以支持我們實現關鍵臨床里程碑的能力。我們將我們的領先項目 CX-2051 視為高度差異化的一流 ADC，旨在解決結直腸癌領域未滿足的大量需求並為 CytomX 創造巨大價值。

CX-801 is a mass version of interferon alpha with, we believe, broad potential as a next-generation targeted immunotherapy. 2025 promises to be an exciting year for CytomX, where we expect to generate initial clinical data for both CX-2051 and CX-801 that we believe could drive significant near-term value creation. I'd like to cover recent progress in our pipeline before handing over to Chris, who will review our financials.

CX-801 是乾擾素 α 的大規模版本，我們相信它作為下一代標靶免疫療法具有廣泛的潛力。 2025 年對 CytomX 來說將是令人興奮的一年，我們預計將為 CX-2051 和 CX-801 產生初步臨床數據，我們相信這可以推動近期的重大價值創造。在將工作交給克里斯（他將審查我們的財務狀況）之前，我想先介紹一下我們管道方面的最新進展。

I'll start with our lead program, CX-2051, our first-in-class masked ADC targeting epithelial cell adhesion molecule. We are the only organization to our knowledge, addressing this target in this unique way. EpCAM has been viewed as a high potential opportunity for many years due to its pan tumor expression and it's particularly high expression in colorectal cancer.

我將從我們的主導計畫 CX-2051 開始，這是我們的首創針對上皮細胞黏附分子的掩蔽 ADC。據我們所知，我們是唯一以這種獨特方式實現這一目標的組織。EpCAM 由於在全腫瘤中表達，特別是在結直腸癌中的表達較高，多年來一直被視為具有很高潛力的藥物。

However, EpCAM is also expressed at moderate to high levels in normal tissues which has prohibited the successful development of systemic therapeutics against this target. The strong evidence, though that EpCAM targeting with locally delivered approaches can achieve clinical anticancer activity, including the multi-specific antibody, Korjuny, that is currently being relaunched in the EU for the localized treatment of intraperitoneal malignant ascites.

然而，EpCAM 在正常組織中也以中等至高水平表達，這阻礙了針對該目標的系統療法的成功開發。有力的證據表明，透過局部給藥方法靶向 EpCAM 可以實現臨床抗癌活性，包括多特異性抗體 Korjuny，該藥物目前正在歐盟重新推出，用於局部治療腹膜內惡性腹水。

Despite success with localized therapies, however, prior systemic EpCAM-targeting strategies have not been able to reach therapeutically active drug levels in patients. And these include the T cell engager, solitomab, and other antibody approaches, which showed early promise but were unable to deliver a viable therapeutic window due to dose-limiting toxicities in the pancreas, liver and gastrointestinal tract.

儘管局部治療取得了成功，但先前的系統性 EpCAM 標靶策略仍無法在患者體內達到治療活性藥物水平。這些方法包括 T 細胞接合器、solitomab 和其他抗體方法，這些方法早期顯示出前景，但由於胰腺、肝臟和胃腸道的劑量限制性毒性而無法提供可行的治療窗口。

CX-2051 is a Probody ADC comprising a high-affinity EpCAM antibody with a peptide mask and a protease-cleavable mask linker that has been validated in prior clinical work by CytomX. In designing CX-2051, our goal is to mitigate potential on-target EpCAM toxicities and to localize CX-2051 preferentially to tumor tissue. Preclinically CX-2051 has shown a wide potential therapeutic index and potent anticancer activity in multiple EpCAM-expressing indications.

CX-2051 是一種 Probody ADC，包含高親和力 EpCAM 抗體、勝肽掩蔽和蛋白酶可裂解的掩蔽接頭，已在 CytomX 之前的臨床工作中得到驗證。在設計 CX-2051 時，我們的目標是減輕潛在的靶向 EpCAM 毒性並將 CX-2051 優先定位到腫瘤組織。臨床前研究表明，CX-2051 在多種 EpCAM 表達適應症中具有廣泛的潛在治療指數和強大的抗癌活性。

The payload on CX-2051, CAMP59, is a topoisomerase-1 inhibitor selected specifically to treat topo-1-sensitive tumors, and in particular, colorectal cancer. The topo-1 inhibitor irinotecan is, of course, a key component in the treatment of metastatic CRC in the first and second-line settings. And so it's well established that this cancer can respond well to this class of drug. The global unmet need in colorectal cancer is one of the most significant in oncology with more than 1.9 million new cases annually and limited new treatments emerging for patients over the last two decades.

CX-2051 上的有效載荷 CAMP59 是一種拓樸異構酶 1 抑制劑，專門用於治療拓樸異構酶 1 敏感腫瘤，尤其是大腸直腸癌。當然，拓樸異構酶 1 抑制劑伊立替康是第一線和第二線治療轉移性 CRC 的關鍵成分。因此可以充分證實，這種癌症對這類藥物有良好的反應。大腸直腸癌是全球未滿足的腫瘤治療需求之一，是腫瘤學中最顯著的疾病之一，每年新增病例超過 190 萬，而過去二十年中為患者出現的新型治療方法有限。

Unfortunately, there's also an increasing percentage of new CRC cases diagnosed as metastatic and a concerning trend of growing incidents in younger patient populations. First- and second-line treatment to metastatic CRC are still primarily based on systemic chemotherapy regimens that include irinotecan or oxaliplatin. In the later-line setting, patient options remain highly inadequate in patients that have generally had three or more prior lines of therapy, current standard of care only achieves low to mid-single-digit objective response rates and median progression-free survival of only two to four months.

不幸的是，被診斷為轉移性的 CRC 新病例比例也在增加，而且年輕患者群體中發病率不斷上升的趨勢令人擔憂。轉移性 CRC 的第一線和第二線治療仍主要基於包括伊立替康或奧沙利鉑在內的全身化療方案。在後線治療中，對於通常接受過三種或更多種先前療法的患者，患者的選擇仍然非常不足，目前的標準治療僅能達到低到中等個位數的客觀反應率，中位無進展生存期僅為兩到四個月。

We advanced CX-2051 into the clinic in Q2 last year, and we have been pleased with the execution and enrollment in the study to date. We are currently focused in late-line CRC with enrolled patients generally having received at least three prior systemic therapies. Given the consistently high levels of EpCAM expression in CRC, we are not preselecting patients for EpCAM expression in our Phase 1 study or for disease characteristics such as KRAS mutational status or liver metastases.

我們在去年第二季將 CX-2051 推進至臨床，迄今為止我們對研究的執行和入組情況感到滿意。我們目前專注於晚期 CRC，入組患者通常已接受過至少三種全身性治療。鑑於 CRC 中 EpCAM 的表達水平始終較高，我們在第 1 階段研究中不會根據 EpCAM 表達或 KRAS 突變狀態或肝轉移等疾病特徵預先選擇患者。

In dose escalation thus far, we've been encouraged by the CX-2051 safety profile, having successfully dose escalated to levels that we predict based on preclinical modeling to be biologically active and that we're confident could not be achieved with an unmasked ADC. As we continue in dose escalation, our expectation is that the maximum tolerated dose of 2051 will be largely driven by the cytotoxic payload.

到目前為止，在劑量遞增方面，CX-2051 的安全性讓我們感到鼓舞，我們已成功將劑量遞增至我們根據臨床前模型預測的生物活性水平，並且我們相信這是無法透過未掩蔽的 ADC 實現的。隨著劑量不斷增加，我們預計 2051 的最大耐受劑量將主要由細胞毒性有效載荷決定。

Specifically, we will be fully characterizing the anticipated GI toxicities and cytopenias such as neutropenia and anemia that's are commonly associated with topo-1 inhibitors. We're currently evaluating the seventh dose level in our dose escalation, and we have also begun to selectively backfill at certain dose levels to gain additional experience with the drug. Overall, we believe our early clinical experience with CX-2051 is showing that this first-in-class ADC is performing as designed, underpinning its prioritization is the lead program for CytomX and our focus on bringing this therapy to patients as quickly as possible.

具體來說，我們將全面描述預期的胃腸道毒性和血球減少症，例如通常與拓樸異構酶-1 抑制劑相關的中性粒細胞減少症和貧血。我們目前正在評估劑量遞增中的第七個劑量水平，並且我們也已經開始選擇性地補充某些劑量水平，以獲得更多該藥物的經驗。總體而言，我們相信，我們對 CX-2051 的早期臨床經驗表明，這種一流的 ADC 性能符合設計，其優先地位是 CytomX 的領先計劃，而我們的重點是盡快將這種療法帶給患者。

We remain on track to provide initial Phase 1a data in CRC in the first half of 2025, and we expect to be in a position to define next steps for the program in the second half of the year.

我們仍有望在 2025 年上半年提供 CRC 的初始 1a 階段數據，並且我們預計將能夠在下半年確定該計劃的後續步驟。

Now moving to CX-801, our masked Probody interferon alpha-2b which is also making good early progress in Phase 1.

現在轉向 CX-801，我們的遮蔽 Probody 幹擾素 α-2b 在第 1 階段也取得了良好的早期進展。

Interferon alpha is a well-validated therapeutic and was one of the first immunotherapies to be approved for cancer treatment. Interferon has established single-agent anticancer activity in multiple tumor types, including renal cancer, bladder cancer, and melanoma. Over time, systemic interferon has fallen out of clinical use in oncology, primarily due to its poor tolerability arising from systemic toxicities. However, interferon alpha is a powerful driver of T cell activation and antigen presentation, making it an ideal combination agent with checkpoint inhibitors.

幹擾素α是一種經過充分驗證的治療方法，也是第一批獲準用於癌症治療的免疫療法之一。幹擾素已在多種腫瘤類型中建立了單一藥物抗癌活性，包括腎癌、膀胱癌和黑色素瘤。隨著時間的推移，全身性幹擾素已不再用於腫瘤臨床治療，主要是因為其全身性毒性導致耐受性較差。然而，幹擾素α是T細胞活化和抗原呈現的強大驅動力，使其成為與檢查點抑制劑的理想聯合用藥。

Similarly to EpCAM, it's been shown recently that localized interferon alpha-2b can be very effective as an anticancer therapy. Specifically, the recently approved gene therapy, Adstiladrin, encoding interferon alpha-2b achieved a 51% complete response rate in patients with bladder cancer, reaffirming that this potent cytokine can indeed achieve robust antitumor responses in patients.

與 EpCAM 類似，最近的研究顯示局部幹擾素 α-2b 可作為非常有效的抗癌療法。具體來說，最近批准的基因療法 Adstiladrin（編碼幹擾素 α-2b）在膀胱癌患者中實現了 51% 的完全緩解率，再次證明了這種強效細胞因子確實可以在患者中實現強大的抗腫瘤反應。

It's also been showing that interferon can potentiate the clinical effects of PD-1 inhibition including a Merck sponsored study, demonstrating a 60% response rate with KEYTRUDA in combination with KEYTRUDA in combination with interferon alpha-2b in advanced PD-1 naive melanoma. This combination was not further developed, however, due to grade 3 or higher adverse events occurring at approximately 50% of patients.

研究還表明幹擾素可以增強 PD-1 抑制的臨床效果，其中包括默克公司贊助的一項研究，該研究表明，對於晚期 PD-1 初治黑色素瘤，KEYTRUDA 聯合 KEYTRUDA 和乾擾素 α-2b 聯合治療的反應率為 60%。然而，由於大約 50% 的患者出現 3 級或更高級別的不良事件，因此該組合尚未進一步開發。

801 is designed to harness the proven power of interferon alpha-2b by reducing systemic activity and localizing therapeutic activity to the tumor microenvironment. We initiated our Phase 1/2 escalation study of CX-801 in the third quarter of 2024, focused in the advanced metastatic melanoma setting. We've made very good progress to date in the study, and we're currently enrolling the fourth monotherapy dose escalation cohort.

801 旨在透過降低全身活性並將治療活性定位到腫瘤微環境來利用乾擾素 α-2b 的已證實功效。我們在 2024 年第三季啟動了 CX-801 的 1/2 期升級研究，專注於晚期轉移性黑色素瘤。到目前為止，我們的研究取得了非常好的進展，目前正在招募第四組單一療法劑量遞增隊列。

Importantly, as of the third dose level, we had already achieved doses that surpassed the approved dose of unmasked interferon alpha-2b SYLATRON. Our translational science program for CX-801 is multifaceted and includes systemic and intratumoral analysis of PD biomarkers that will give us insight into molecular performance of the drug candidate, and we hope the induction of an inflammatory tumor microenvironment conducive to PD-1 combination therapy.

重要的是，從第三個劑量水平開始，我們已經達到了超過未掩蔽幹擾素 α-2b SYLATRON 的批准劑量。我們針對 CX-801 的轉化科學計劃是多方面的，包括對 PD 生物標記的系統性和腫瘤內分析，這將使我們深入了解候選藥物的分子性能，我們希望誘導有利於 PD-1 聯合治療的炎症腫瘤微環境。

Our goal is to present initial Phase 1a translational data for 801 in the second half of this year. Based on our progress to date, we also anticipate initiation of combination therapy with KEYTRUDA in 2025 under the collaboration and supply agreement we secured with Merck last year. Overall, we believe CX-801 is well positioned to demonstrate clinical proof of concept in advanced melanoma where the unmet need remains very high.

我們的目標是在今年下半年展示 8​​01 的初始 1a 期轉換數據。根據迄今為止的進展，我們還預計根據去年與默克達成的合作和供應協議，將於 2025 年開始與 KEYTRUDA 進行聯合治療。總體而言，我們相信 CX-801 完全有能力證明晚期黑色素瘤的臨床概念，因為疾病的未滿足需求仍然很高。

Longer term, we see CX-801 as a foundational combination agent which can potentially address the large population of cancer patients who do not respond to checkpoint inhibitors or who are refractory to immunotherapy. Turning now to our research collaborations.

從長遠來看，我們將 CX-801 視為一種基礎組合藥物，它可以潛在地解決對檢查點抑制劑沒有反應或對免疫療法有抵抗力的大量癌症患者的問題。現在談談我們的研究合作。

Our partnerships continue to be very important to us in 2024 and remain so in 2025. I'm very pleased to say that in February of this year, we achieved another $5 million milestone payment in our Astellas T cell engager collaboration as a result of Astellas selecting a collaboration clinical candidate to advance into GLP toxicology studies. We look forward to continued progress with Astellas as well as strong execution in our discovery programs with Bristol-Myers Squibb, Amgen, Moderna and Regeneron.

我們的合作關係對於我們在 2024 年和 2025 年仍然非常重要。我很高興地說，今年 2 月，由於安斯泰來選擇了合作臨床候選藥物來推進 GLP 毒理學研究，我們在安斯泰來 T 細胞接合劑合作中又獲得了 500 萬美元的里程碑付款。我們期待與安斯泰來繼續取得進展，並期待與百時美施貴寶、安進、Moderna 和再生元合作的發現項目能夠取得強勁執行。

Right now, the majority of our partner discovery programs are masked T cell engagers, an area in which CytomX and our partners continue to see significant potential. Regarding our first partner T cell engager program entered into the clinic, CX-904, we communicated earlier this year a reduction in capital allocation to this program given our overall pipeline priorities and pending ongoing dialogue with our partner, Amgen, regarding potential next steps.

目前，我們合作夥伴的大多數發現項目都是掩蔽 T 細胞接合劑，CytomX 和我們的合作夥伴繼續看到該領域的巨大潛力。關於我們進入臨床的第一個合作夥伴 T 細胞接合器項目 CX-904，考慮到我們的整體產品線優先級以及與我們的合作夥伴安進就潛在的後續步驟進行的持續對話，我們在今年早些時候表示將減少對該項目的資本配置。

Based on CX-904 clinical observations to date and our respective priorities, CytomX and Amgen have jointly decided not to continue CX-904 development. We continue T cell engager discovery work with Amgen. We remain optimistic about the potential of future mass T cell engagers and really look forward to making additional progress on this modality within our partnerships.

根據迄今為止 CX-904 的臨床觀察和我們各自的優先事項，CytomX 和安進共同決定不再繼續 CX-904 開發。我們繼續與安進公司合作進行 T 細胞接合劑的發現工作。我們對未來大規模T細胞接合劑的潛力仍然持樂觀態度，並真誠期待在我們的合作夥伴關係下在這種方式上取得進一步進展。

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

說完這些，讓我把電話轉給克里斯，詢問我們的財務狀況的最新情況。

Thank you, Sean. Throughout 2024, we remain disciplined in our capital allocation with a focus on progressing our clinical pipeline towards initial Phase 1 data. Entering 2025, we are now positioned to achieve initial data readouts for CX-251 and CX-801. As Sean highlighted earlier, in January of this year, we made a focused set of trade-offs that extend our cash runway and direct capital primarily to our lead programs, CX-251 and CX-801.

謝謝你，肖恩。在整個 2024 年，我們將繼續嚴格執行資本配置，專注於推進臨床管線向初始第 1 階段資料邁進。進入 2025 年，我們現在預計將實現 CX-251 和 CX-801 的初始數據讀數。正如肖恩之前強調的那樣，今年 1 月，我們進行了一系列有針對性的權衡，延長了我們的現金流，並將資金主要投入到我們的主導項目 CX-251 和 CX-801。

Now I'll turn to our 2024 financial results. As of December 31, 2024, we ended the year with $100.6 million in cash, cash equivalents and investments compared to $174.5 million in cash at the end of 2023. With our prioritization efforts, we expect that our cash balance will continue to fund CytomX operations into the second quarter of 2026. Consistent with our prior approach to cash runway guidance, our cash guidance does not assume any additional milestones from existing collaborations or any new business development which we have a strong track record of achieving.

現在我將談談我們 2024 年的財務表現。截至 2024 年 12 月 31 日，我們年底的現金、現金等價物和投資為 1.006 億美元，而 2023 年底的現金為 1.745 億美元。透過我們的優先努力，我們預計我們的現金餘額將繼續為 CytomX 的營運提供資金，直至 2026 年第二季。與我們先前的現金跑道指導方法一致，我們的現金指導不假設現有合作或任何新業務發展能帶來任何額外的里程碑，而我們在這方面有著良好的記錄。

As Sean mentioned earlier, we recently achieved a $5 million milestone in our Astellas T cell engager collaboration and we are funded to continue to execute programs under our research alliances. Turning to revenue and operating expenses for the year. Total revenue was $138.1 million compared to $101.2 million for the corresponding period in 2023. The increased revenue was attributed to our BMS collaboration as well as our collaboration with Moderna, Astellas, and Regeneron.

正如肖恩之前提到的，我們最近在與安斯泰來 T 細胞接合器合作中取得了 500 萬美元的里程碑，並且我們獲得了資金繼續執行研究聯盟下的專案。談到今年的收入和營運費用。總收入為 1.381 億美元，而 2023 年同期為 1.012 億美元。收入的成長歸功於我們與 BMS 的合作以及與 Moderna、Astellas 和 Regeneron 的合作。

Total operating expenses for the full year were $113.1 million compared to $107.7 million in 2023. 2024 operating expenses increased $5.4 million, primarily due to a $5 million milestone payment to AbbVie for initiation of Phase 1 for CX-2051. Excluding this milestone, operating expenses were essentially flat to 2023.

全年總營運費用為 1.131 億美元，而 2023 年為 1.077 億美元。 2024 年營運費用增加了 540 萬美元，主要原因是向 AbbVie 支付了 500 萬美元的里程碑付款，用於啟動 CX-2051 的第一階段。除此里程碑外，到 2023 年，營運費用基本持平。

The R&D increased by $5.7 million from last year to $83.4 million in 2024, also driven by the milestone payment for CX 2051 Phase 1 start. G&A expenses were essentially flat during 2024, decreasing by $0.3 million to $29.7 million for the year ended December 31, 2024. We remain committed to disciplined capital allocation and resource management, and we believe we are well positioned to progress our promising pipeline, deliver value to shareholders and ultimately bring new treatment options to cancer patients.

研發費用較去年增加了 570 萬美元，到 2024 年將達到 8,340 萬美元，這也是受到 CX 2051 第一階段啟動里程碑付款的推動。2024 年，一般及行政費用基本持平，截至 2024 年 12 月 31 日的年度減少了 30 萬美元，至 2,970 萬美元。我們始終致力於嚴謹的資本配置和資源管理，並相信我們有能力推進我們有前景的管道，為股東創造價值，並最終為癌症患者帶來新的治療選擇。

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

說完這些，我會把電話轉回給肖恩，請他做最後發言。

Thanks, Chris, and thanks, everyone, for joining us today. We look forward to sharing additional updates in the coming months, including the first look at how CX-2051 is performing in colorectal cancer. To close out, I want to recognize and sincerely thank the patients who join our studies, their families, our clinical investigators and our dedicated team here at CytomX. We've never been more committed to our vision, mission and values at CytomX, and we look forward to an exciting year ahead. With that, operator, let's go ahead and open up the call for Q&A.

謝謝克里斯，也謝謝大家今天加入我們。我們期待在未來幾個月分享更多更新，包括首次了解 CX-2051 在大腸癌中的表現。最後，我要表揚並真誠感謝加入我們研究的患者、他們的家人、我們的臨床研究人員以及 CytomX 的專業團隊。我們從未像現在這樣致力於 CytomX 的願景、使命和價值觀，我們期待著激動人心的一年。接線員，好了，讓我們開始問答環節。

(Operator Instructions) Roger Song, Jefferies.

（操作員指示）Roger Song，Jefferies。

Great. Maybe just one related to 2051. So given you're enrolling patients progressing and then how should we think about the first half data update in terms of the patient number and then what kind of data we're going to show, what's the expectation for the data readout for the first half?

偉大的。也許只有一個與 2051 有關。因此，考慮到您正在招募進展中的患者，那麼我們應該如何考慮上半年患者數量的數據更新，然後我們將展示什麼樣的數據，對上半年數據讀數的預期是什麼？

Yes. Roger, thanks for the question. Well, we're expecting it to be a meaningful update. We do anticipate this initial look will include an initial characterization of the safety profile of the drug, up to and including doses, as we said, that we are predicting based on our preclinical work or in the therapeutically active range. We've been pleased with the escalation so far given the prior history with other systemic EpCAM strategies having hit roadblocks very early in dose escalation.

是的。羅傑，謝謝你的提問。好吧，我們期待這是一個有意義的更新。我們確實預計，初步研究將包括對藥物安全性的初步描述，包括劑量，正如我們所說，這是我們根據臨床前工作或在治療活性範圍內進行預測的。鑑於先前其他系統性 EpCAM 策略在劑量增加的早期就遇到了障礙，我們對迄今為止的增加感到滿意。

So from that standpoint, so far, so good. Of course, this initial update or first update -- first presentation of data will include an initial assessment of antitumor activity across these first few cohorts. And that activity data could take the form of pharmacodynamic markers, tumor stabilization, of course, potentially tumor shrinkage. And of course, if we see anything approximating or equivalent to RECIST responses in this very late-line CRC patient population, we would be absolutely thrilled.

從這個角度來看，到目前為止一切都很好。當然，這次初步更新或首次更新——首次呈現的數據將包括對最初幾個群體的抗腫瘤活性的初步評估。此活動數據可以採用藥效動力學標記、腫瘤穩定性，當然還有潛在的腫瘤縮小的形式。當然，如果我們在這個非常晚期的 CRC 患者群體中看到任何接近或相當於 RECIST 反應的結果，我們將會非常興奮。

Yes. Got it. And then in terms of 801, you will give us some update in the second half. And then also you will move -- you say you were moving to the pembro combination. So how should we think about the timing and the criteria moving to the prembro before or after you gave us some data update.

是的。知道了。然後就 801 而言，您將在下半年向我們提供一些更新資訊。然後你也會轉變——你說你正在轉向彭布羅組合。那麼，在您向我們提供一些資料更新之前或之後，我們應該如何考慮轉向 prembro 的時間和標準。

Yes, great question. So as I mentioned, as with 2051, we've been pleased with the operational execution in the 801 study so far, having really just started that, that Phase 1 study and already now being in the fourth dose level. And the starting dose was pretty decent, and that's allowed us to go pretty quickly to now be treating patients with doses that are higher than the approved dose of unmasked interferon alpha.

是的，很好的問題。正如我所提到的，與 2051 一樣，我們對 801 研究迄今為止的運行執行情況感到滿意，該研究實際上剛剛開始，即第 1 階段研究，現在已經處於第四劑量水平。起始劑量相當合適，這使得我們能夠很快地開始使用高於未屏蔽​​幹擾素α核准劑量的劑量來治療患者。

So that's encouraging. And because we've been able to quickly go through those initial cohorts, we do see the potential to -- those first two dose levels, we do see the potential to initiate the KEYTRUDA combo in second half. If I had to guess, I'd say that the sequencing would be the combo initiation would proceed any data presentation, but we do remain on track based on our ongoing translational work, looking at tumor biopsies to be sharing some initial data by the end of the year.

這令人鼓舞。而且由於我們能夠快速完成這些初始隊列，我們確實看到了潛力——前兩個劑量水平，我們確實看到了在下半年啟動 KEYTRUDA 組合的潛力。如果我必須猜測的話，我會說排序將是組合啟動將進行任何數據呈現，但根據我們正在進行的轉化工作，我們確實仍在按計劃進行，期待腫瘤活檢能夠在年底前分享一些初步數據。

Joe Catanzaro, Piper Sandler.

喬卡坦扎羅、派珀桑德勒。

Great. Maybe a couple on 2051. So I think you've been saying for a little while now that you've entered therapeutically active doses based on preclinical data today, you're saying you're in the seven-dose cohorts. So wondering how many of those seven-dose cohorts sort of fall into that category of predicted to be within therapeutic the active doses. I guess I'm just trying to get a sense of sort of what percent in this initial disclosure will fall within that category.

偉大的。2051 年也許有一對。所以我想您現在已經說過，您已經根據今天的臨床前數據輸入了治療活性劑量，您說您處於七劑量組。因此，想知道這七劑組中有多少劑屬於預計在治療有效劑量範圍內的類別。我想我只是想了解初始披露中有多少百分比屬於該類別。

Yes, so the first couple of cohorts, as we've disclosed previously, were single patient doses -- single patient cohorts at doses that we would predict to be outside of the therapeutic active range. But entering dose level 3, we would predict again, based on the animal modeling that -- and based on what's generally known about Topo-1 ADCs that we will be starting to get into that range.

是的，正如我們之前所揭露的那樣，前幾個隊列是單一患者劑量——單一患者隊列的劑量我們預測超出了治療活性範圍。但是進入劑量等級 3 時，我們會再次預測，基於動物模型 - 並且基於對 Topo-1 ADC 的普遍了解，我們將開始進入該範圍。

And of course, that would increase as we've continued the escalation. So I think a significant number of patients by the time we're ready to share data will have been treated with doses in that range. Of course, I want to emphasize again that this is a late-line patient population. We're enrolling predominantly patients who have had at least three prior lines of systemic therapy. And so we think the bar is fairly low here for actual clinical activity.

當然，隨著事態不斷升級，這種情況還會增加。因此我認為，當我們準備分享數據時，相當多的患者將接受該範圍內的劑量治療。當然，我想再次強調，這是一個晚期患者群體。我們主要招募先前接受過至少三種全身性治療的患者。因此我們認為實際臨床活動的門檻相當低。

Okay, great. And maybe a follow-up. So I think you noted not enrolling based on KRAS status or liver mets. So I'm wondering if any expectations whatsoever potentially seeing differential activity as it relates to some of those features like KRAS status or presence/absence of liver mets or maybe even anything else that you're thinking of.

好的，太好了。或許還有後續行動。所以我認為您提到不根據 KRAS 狀態或肝轉移進行招募。因此，我想知道是否有任何預期可能會看到差異活動，因為它與某些特徵有關，例如 KRAS 狀態或肝轉移的存在/不存在，或者甚至您正在考慮的任何其他特徵。

Yes, there's no obvious biology that would suggest that EpCAM, well, let me start by saying EpCAM expression or just reiterating that EpCAM expression is high in more than 90% of CRC patients. And we've validated that with our own work, and we're measuring EpCAM levels, of course, in every patient that we treat. So we'll have that data for this study. There's no reason to suggest that there's a connection between KRAS mutational status, an EpCAM or livers mets in EpCAM. The point we're making is that we're enrolling the full patient population at this time to characterize the drug across the full CRC population.

是的，沒有明顯的生物學表明 EpCAM，好吧，讓我先說一下 EpCAM 表達，或者只是重申一下，超過 90% 的 CRC 患者的 EpCAM 表達很高。我們已經透過自己的工作驗證了這一點，當然，我們正在測量我們治療的每位患者的 EpCAM 水平。因此我們將獲得用於此項研究的數據。沒有理由表明 KRAS 突變狀態、EpCAM 或肝臟 EpCAM 轉移之間存在關聯。我們要強調的是，我們目前正在招募全部患者群體，以在整個 CRC 群體中確定該藥物的特性。

And we'll see what we get. I mean if it turns out that we get data that suggests that the drug is more suited to a particular subset than we may investigate that. But at this point, we're enrolling a broad patient population.

我們將會看到我們得到了什麼。我的意思是，如果我們得到的數據表明該藥物更適合特定的子集，那麼我們可能會對此進行調查。但目前，我們正在招募廣泛的患者群體。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

This is Priyanka on for Anupam. Just kind of following up on the previous line of questions, since the enrolled patients in the CX-251 Phase 1 trial is now being preselected for EpCAM expression, is there a published literature, for example, to help guide what level of expression would be beneficial?

這是 Priyanka 為 Anupam 表演的。只是想繼續上一連串的問題，由於 CX-251 第 1 階段試驗中入組的患者現在正在接受 EpCAM 表達的預選，是否有已發表的文獻來幫助指導哪種水平的表達是有益的？

Yes. There's a broad literature EpCAM expression across most tumors, including colorectal. And I think it's well established that EpCAM is highly expressed in this tumor type. In fact, EpCAM was first described as a colorectal cancer marker a very long time ago, actually. So yes, I think it's pretty well established that CRC is a high kind of expresser in most patients.

是的。文獻中廣泛報導 EpCAM 在大多數腫瘤中表達，包括大腸直腸腫瘤。我認為 EpCAM 在這種腫瘤類型中高度表達是眾所周知的。事實上，EpCAM 很久以前就被描述為結直腸癌標記。所以是的，我認為已經充分證實 CRC 在大多數患者中具有高表達。

And I anticipate that our clinical results will validate that.

我預計我們的臨床結果將證實這一點。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

Just on the prioritization of CRC for your EpCAM ADC. Is that driven by the expression levels you kind of talked about and just kind of well known within the space or you've already seen signals there. And you've also seen any signals outside CRC to date.

僅針對您的 EpCAM ADC 的 CRC 進行優先排序。這是由您談到的表達水平所驅動的嗎？是在該領域內眾所周知的嗎？還是您已經在那裡看到了訊號？到目前為止，您還看到了 CRC 以外的任何訊號。

Yes. Peter, that's helpful to help me clarify and reiterate that this Phase 1 study of 2051 is being conducted entirely in the CRC setting. So we're only enrolling metastatic CRC patients. And as I mentioned, patients who have been treated, the patient population that we're seeing that we're treating are for the most part, have, for the most part, been treated with at least three prior lines of systemic therapy. .

是的。彼得，這有助於幫助我澄清和重申，2051 年的第一階段研究完全在 CRC 環境中進行。因此我們只招募轉移性 CRC 患者。正如我所提到的，接受治療的患者，我們看到的正在治療的患者群體，大部分都接受過至少三種全身療法的治療。。

So the question is, okay, why? Why focus in CRC, several answers to that. First of all, when you just look at EpCAM biology and the target itself, CRC is really the indication that jumps out with the highest, broadest, most consistent, most homogeneous expression from patient to patient. And as I said, it's actually where EpCAM was first described as a tumor marker. That said, EpCAM is highly expressed in most other solid tumors.

所以問題是，為什麼？為什麼要關注 CRC，對此有幾個答案。首先，當您只看 EpCAM 生物學和目標本身時，CRC 確實是在不同患者之間具有最高、最廣泛、最一致、最同質表達的指徵。正如我所說，EpCAM 實際上首次被描述為腫瘤標記。也就是說，EpCAM 在大多數其他實體腫瘤中均有高度表現。

So this is a pipeline in a product opportunity in the long run if we see a signal in CRC.

因此，如果我們在 CRC 中看到訊號，從長遠來看，這是一個產品機會中的管道。

There's no question about that. The other reason to select CRC is the unmet need, the unmet need is just huge. And so it's an area where patients need new treatments. They've been waiting for them for decades, and we're trying to make a difference here. And then the third is that this drug candidate with a topo-1 inhibitor was really always designed with colorectal cancer in mind is the first place to go because there's not much -- that's been -- it's kind of a wide open field, ADCs in colorectal cancer, and we know that CRC responds to topo-1 inhibition.

毫無疑問。選擇 CRC 的另一個原因是未滿足的需求，未滿足的需求非常龐大。因此，患者需要新的治療方法。他們已經等待了幾十年，我們正努力做出改變。第三，這種含有拓樸異構酶 1 抑制劑的候選藥物在設計時確實始終以治療結直腸癌為首要目標，因為目前為止，結直腸癌領域的 ADC 還很廣闊，而且我們知道 CRC 對拓樸異構酶 1 抑制有反應。

As I mentioned in my prepared remarks, irinotecan is a component of standard of care therapy in the first and/or second line on a global basis is quite effective in the earlier stage of treatment of CRC. So we know that CRC can respond to topo-1 inhibition. So we think for this particular program, we think the combination of the tumor type of interest, the target selection and the effective mechanism, the payload has really been optimized and delivers, I think, compared to some of our prior work with ADCs a higher overall probability of technical success.

正如我在準備好的發言中提到的，伊立替康是全球範圍內一線和/或二線標準治療的組成部分，在 CRC 的早期治療中非常有效。因此我們知道 CRC 可以對 topo-1 抑製作出反應。因此，我們認為對於這個特定的項目，我們認為感興趣的腫瘤類型、目標選擇和有效機制的組合，有效載荷確實得到了優化，並且我認為與我們之前使用 ADC 的一些工作相比，它具有更高的整體技術成功機率。

Just again, to be really clear that if we are fortunate enough to see a signal in CRC, then that would ungate many other tumor types that are known to be responsive to topo-1 inhibition but also express EpCAM at high levels.

再次強調，要明確的是，如果我們夠幸運能夠在 CRC 中看到訊號，那麼這將解除許多其他已知對 topo-1 抑制有反應但也高水平表達 EpCAM 的腫瘤類型的限制。

Got you. Okay. And then just as we think about as you move forward, kind of what's the real bar for success? And are you thinking -- is it third line, fourth line, CRC?

明白了。好的。然後，正如我們所想，隨著您不斷前進，成功的真正標準是什麼？您是否在想—它是第三行、第四行還是 CRC？

Well, in the fourth line, unfortunately, for patients, the bar is low. I mean you've got response rates in the single digits to drugs like Lonsurf, Lonsurf even in combination with bevacizumab, fruquintinib, regorafenib with just a few months of PFS. And so this is a very underserved highly underserved patient population in the fourth line.

不幸的是，對於患者來說，第四線的標準很低。我的意思是，對於 Lonsurf 等藥物的反應率只有個位數，即使 Lonsurf 與貝伐單抗、呋喹替尼、瑞戈非尼聯合使用，PFS 也只有幾個月。因此，這是第四線中醫療服務嚴重不足的患者群體。

It's also what we hear from our advisers and investigators and KOLs is that even in the third-line setting, the current standard of care, which is for the most part, bev-Lonsurf, is also highly inadequate and it's so inadequate that many, many patients in the third-line setting go on to trials or being held on therapy there as a precursor to going on to trials. And so I think that really underscores, number one, how high the unmet need is and really how low the bar is.

我們也從我們的顧問、研究人員和關鍵意見領袖那裡聽說，即使在三線治療中，目前的治療標準（主要是 bev-Lonsurf）也嚴重不足，以至於許多三線治療中的患者在參加試驗之前會繼續參加試驗或在那裡接受治療。所以我認為這確實強調了，第一，未滿足的需求有多高，而標準有多低。

Obviously, we have high ambitions for this drug, but we think for this initial look in this late-stage patient population, we think, quite frankly, any evidence of RECIST responses would be a real win.

顯然，我們對這種藥物抱有很高的期望，但我們認為，對於這個晚期患者群體的初步觀察，坦白說，我們認為任何 RECIST 反應的證據都將是真正的勝利。

Got you. And so that initial look at that Phase 1/2 data, do you want to see tumor shrinkage? What's the bar there, you think, for success in your mind?

明白了。那麼，初步查看第 1/2 階段的數據，您想看到腫瘤縮小嗎？您認為，在您看來，成功的標準是什麼？

Yes. As I already mentioned, I think we're looking at a number of things. We're looking at evidence of pharmacodynamic activity in tumor biopsies, evidence of tumor stabilization because CRC approvals, those drugs I mentioned earlier on that have been approved in the third-line setting, third and/or fourth line for the most part have been approved based on PFS-type measures because it's very difficult to achieve objective responses in this patient population.

是的。正如我已經提到的，我認為我們正在考慮很多事情。我們正在研究腫瘤活檢中的藥效動力學活性證據、腫瘤穩定的證據，因為 CRC 批准，我之前提到的那些已在三線環境中獲得批准的藥物，大多數三線和/或四線藥物都是基於 PFS 類型的測量獲得批准的，因為在這個患者群體中很難獲得客觀反應。

So if you can keep patients from progressing that in and of itself is a success. So evidence of tumor stabilization, evidence of tumor shrinkage and then, of course, the Holy Grail for us in the study is if we can see in this early first look in this late-line patient population is to see if we can deliver objective RECIST responses.

因此，如果你能阻止患者的病情惡化，這本身就是一種成功。因此，腫瘤穩定的證據、腫瘤縮小的證據，當然，研究中我們最希望看到的是，我們能否在早期首次觀察這一晚期患者群體，看看我們是否可以提供客觀的 RECIST 反應。

(Operator Instructions) Mitchell Kapoor, HC Wainwright.

（操作員指示）Mitchell Kapoor、HC Wainwright。

This is Dan on for Mitchell. We wanted to ask where you might present the Phase 1a CRC data. Would this likely be a press release event, any lean towards first quarter or second quarter? And then jumping on the therapeutic active range kind of discussion, how many more dose levels do you plan to test and where does the seventh dose level compared to the nonhuman primate preclinical tox.

這是丹 (Dan) 代替米切爾 (Mitchell)。我們想問您會在哪裡展示第 1a 階段 CRC 資料。這可能是新聞發布會嗎？傾向第一季還是第二季？然後進入治療活性範圍的討論，您計劃測試多少個劑量水平，以及與非人靈長類動物臨床前毒性相比，第七個劑量水平在哪裡。

Yes. Thanks for the questions. In terms of where to present, we're keeping our options open there. So we'll provide further guidance into in due course. In terms of the escalation, the second and third questions are, of course, connected.

是的。感謝您的提問。至於在哪裡展示，我們保留開放的選擇。因此我們將在適當的時候提供進一步的指導。就升級而言，第二個問題和第三個問題當然是相關的。

The escalation into the seventh dose level, Obviously, if we clear that dose level, we'll continue to escalate. We'll have to see how that goes.

升級到第七劑量水平，顯然，如果我們清除該劑量水平，我們將繼續升級。我們得看看事情進展如何。

So at this point that's where we are, and we'll have to see. I would say that the -- when we talk about predictive active range of the drug, that is based on modeling that is including our experience from mouse and cynomolgus monkey experiments together with understanding in general of other topo-1 ADCs and what experience others have had in the clinic with this type of strategy.

所以目前我們處於這個位置，我們只能拭目以待。我想說的是——當我們談論藥物的預測活性範圍時，這是基於建模的，其中包括我們從小鼠和食蟹猴實驗中獲得的經驗，以及對其他拓撲-1 ADC 的一般了解以及其他人在臨床上使用這種策略的經驗。

Thank you. I'm not showing any 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。我不會在隊列中顯示任何其他問題。現在，我想將發言權交還給董事長兼執行長肖恩·麥卡錫博士，請他作最後發言。

Well, thanks, everyone, for joining us today. We look forward to providing additional updates throughout the year, and I hope you all have a good rest of the day.

好吧，感謝大家今天加入我們。我們期待全年提供更多更新，並希望大家今天過得愉快。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。