Arcus Biosciences, Inc. (RCUS) 2026 Q1 法說會逐字稿

Hello, everyone. Thank you for joining us, and welcome to the Arcus Biosciences' first quarter 2026 business update and financial results. (Operator Instructions) I will now hand the conference over to Holli Kolkey, VP of Corporate Affairs. Holli, please go ahead.

各位好。感謝各位加入，歡迎參加 Arcus Biosciences 2026 年第一季業務更新與財務結果電話會議。(接線員指示) 現在我將把會議交給企業事務副總裁 Holli Kolkey。Holli，請開始。

Good afternoon, and thank you for joining us on today's conference call to discuss Arcus's first quarter 2026 financial results and pipeline update. I'd like to remind you that on this call, management will make forward-looking statements, including statements about our development strategies and our expectations regarding the advantages and opportunities afforded by our investigational products, our clinical development milestones and time lines, our projected cash runway and our financial outlook.

各位午安，感謝各位參加今天的電話會議，討論 Arcus 2026 年第一季財務結果與研發管線更新。我想提醒各位，在本次電話會議中，管理團隊將作出前瞻性陳述，包括關於我們的開發策略，以及我們對於研究中產品所帶來的優勢與機會、臨床開發里程碑與時程、預估現金可支撐期間（cash runway）與財務展望的預期。

All statements other than historical facts reflect the current beliefs and expectations of management and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that has been filed with the SEC. For today's call, please refer to our latest corporate presentation posted in the Investors section of our website.

除歷史事實之外的所有陳述，均反映管理團隊目前的信念與預期，並涉及可能導致實際結果與所述內容不同的風險與不確定性。這些風險與不確定性已載於我們最近向美國證券交易委員會（SEC）提交的 Form 10-Q 季度報告中。就今天的電話會議而言，請參閱我們在公司網站「投資人」專區所發布的最新公司簡報。

This afternoon, you will hear from our CEO, Terry Rosen; Chief Medical Officer, Richard Markus; President, Juan Jaen; and CFO, Bob Goeltz. With that, I'd like to turn the call over to Terry.

今天下午，您將聽到我們的執行長 Terry Rosen、首席醫療長 Richard Markus、總裁 Juan Jaen，以及財務長 Bob Goeltz 的發言。接下來，我想把電話交給 Terry。

Thanks very much, Holli. And thanks, everyone, for joining us this afternoon. We're starting a new era for Arcus with full ownership of our lead program, casdatifan, our Phase III kidney cancer study, PEAK-1, enrolling rapidly, a clear path to win in the frontline and the next generation of molecules for inflammation and immunology that can be advanced rapidly into and through development, and with that, the strategic optionality imparted by a rich portfolio of wholly owned molecules and programs.

非常感謝你，Holli。也感謝各位今天下午加入我們。Arcus 正邁入新時代：我們已完全擁有主力計畫 casdatifan；我們的第三期腎癌研究 PEAK-1 招募進展迅速；我們在一線治療具備清晰的致勝路徑；同時也擁有可快速推進至並完成開發的下一代發炎與免疫學分子；此外，憑藉豐富的自有分子與計畫組合，我們也具備更大的策略選擇性。

We are at an inflection in value creation for patients and shareholders that will continue to accelerate over the next 12 to 18 months. Arcus has proven to be a highly productive company, creating and advancing a steady stream of potential best-in-class molecules for patients with cancer and inflammatory and autoimmune diseases.

我們正處於為病患與股東創造價值的轉折點，且在未來 12 到 18 個月將持續加速。Arcus 已證明自己是一家高度高產出的公司，持續創造並推進一系列可能同級最佳（best-in-class）的分子，用於癌症以及發炎與自體免疫疾病患者。

We believe that discovery is not a commodity, and we have built exceptional small molecule medicinal chemistry and drug discovery capabilities. Our scientists utilize proven biology to create unmatched medicines designed to raise the standard of care. Since its inception, Arcus has advanced molecules from program initiation to IND filing in a short of 18 months and accelerated platform and signal-seeking studies to move from proof-of-concept Phase I studies to randomized Phase II and registrational Phase III trials in just a few years. Today, the company is laser-focused on casdatifan, which represents a market opportunity of more than $5 billion in kidney cancer alone.

我們相信「發現」並非商品化能力，因此我們建立了卓越的小分子藥物化學與藥物發現能力。我們的科學家運用經驗證的生物學，打造無可匹敵、旨在提升照護標準的藥物。自公司成立以來，Arcus 能在短短 18 個月內將分子從計畫啟動推進至 IND 申請，並加速平台與訊號探索研究，使其在短短數年內從概念驗證的一期研究推進至隨機分派的二期與註冊性三期試驗。目前，公司高度聚焦於 casdatifan，僅在腎癌領域就代表超過 50 億美元的市場機會。

I want to stress that casdatifan's efficacy advantages are underpinned by much better molecular properties and a superior pharmacodynamic profile. This profile reflects the key capabilities in Arcus that I described earlier. The simple fact is that casdatifan hits its target much harder and in a more sustained way than belzutifan.

我想強調，casdatifan 的療效優勢是建立在更佳的分子特性與更優越的藥效動力學（pharmacodynamic）特徵之上。這樣的特徵反映了我先前所描述 Arcus 的關鍵能力。簡而言之，casdatifan 對其標的的抑制更強、且更持久，優於 belzutifan。

As illustrated on Slide 6, this is a point we've emphasized since the data first emerged. These data are clear and they're striking. We believe this fundamental differentiation between casdatifan and belzutifan and the limitations of belzutifan's pharmacodynamic profile and durability of effect are undoubtedly contributors to, if not the principal driver of, the outcome of LITESPARK-012. And the pharmacodynamic advantages of casdatifan will continue to result in improved clinical outcomes across the lines of therapy. I want to emphasize this point.

如投影片 6 所示，這是自數據首次出現以來我們就一直強調的重點。這些數據清楚且令人震撼。我們相信，casdatifan 與 belzutifan 之間這項根本性的差異，以及 belzutifan 在藥效動力學特徵與作用持久性上的限制，無疑是 LITESPARK-012 結果的促成因素之一，甚至可能是主要驅動因素。而 casdatifan 的藥效動力學優勢，將持續在各治療線別帶來更佳的臨床結果。我想再次強調這一點。

This dramatic difference in profile has been evidenced since late last year. It is not esoteric. Its manifestations on clinical outcomes are dramatic and are at the core of our differentiation. No results to date are surprising. Our top priorities for 2026 are clear.

這種特徵上的巨大差異，自去年年底以來就已經有證據支持。這並非艱深難懂的概念。其在臨床結果上的呈現非常顯著，且正是我們差異化的核心。截至目前沒有任何結果令我們感到意外。我們 2026 年的首要任務非常明確。

One, complete enrollment for PEAK-1, our second-line Phase III study; and two, initiate a Phase III study in the frontline patient population. With the recent outcome of LITESPARK-012, casdatifan has a clear path to consolidate a fragmented frontline setting as the first HIF-2 alpha inhibitor in this setting. Let me spend a moment on why casdatifan is at the center of everything we do.

第一，完成 PEAK-1（我們的二線三期研究）的受試者招募；第二，在一線病患族群啟動一項三期研究。隨著 LITESPARK-012 的最新結果，casdatifan 在一線治療上具備清晰路徑，可在此分散的市場中整合版圖，成為該治療情境下第一個 HIF-2 alpha 抑制劑。我想花點時間說明為何 casdatifan 是我們所有工作的核心。

We believe casdatifan can transform the treatment paradigm in clear cell renal cell carcinoma, and our development strategy is designed to generate evidence to secure cas as a backbone therapy so that every patient has the opportunity to benefit from cas across each line of therapy. PEAK-1 represents our fast-to-market strategy.

我們相信 casdatifan 能改變透明細胞腎細胞癌的治療典範，而我們的開發策略旨在產生證據，確立 cas 作為基礎骨幹治療（backbone therapy），讓每位病患都有機會在各治療線別中受益於 cas。PEAK-1 代表我們的快速上市（fast-to-market）策略。

This is designed to build on the clinician enthusiasm that we've seen for cas as an experimental agent and to generate the data to support the approval of a foundational treatment for clear cell RCC as rapidly as possible. Enrollment in PEAK-1 is accelerating, and we're on track to complete enrollment by year-end 2026. We're confident that PEAK-1 will establish cas plus cabo as the new standard of care in the IO experience setting. The peak sales opportunity for cas in this setting alone is more than $2 billion. At the same time, we are aggressively building a holistic strategy to embed cas across the treatment paradigm.

此策略旨在延續我們所見臨床醫師對 cas 作為試驗性藥物的熱忱，並盡可能快速產生支持核准所需的數據，使其成為透明細胞 RCC 的基礎治療。PEAK-1 的招募正在加速，我們預計可在 2026 年底前完成招募。我們有信心 PEAK-1 將確立 cas 加 cabo 成為 IO 經治（IO experience）治療情境下的新照護標準。僅此一情境下，cas 的峰值銷售機會就超過 20 億美元。同時，我們也正積極建立一套全面策略，將 cas 深度嵌入整體治療典範之中。

We have been making tremendous progress in the frontline setting with multiple IO combinations now enrolling in ARC-20 and generating data in support of our first-line strategy. These approaches offer the greatest potential for long-term survival for patients. One of our key objectives today is to make very clear our integrated development strategy for casdatifan. It's actually quite straightforward, and here's how we believe things will play out. In the first line, our bedrock therapy will be cas, ipi, anti-PD-1.

在一線治療方面，我們已取得重大進展：多種 IO 聯合療法目前正在 ARC-20 中招募，並產生支持我們一線策略的數據。這些方法為病患帶來長期存活的潛力最大。我們今天的一項關鍵目標，是非常清楚地說明 casdatifan 的整合式開發策略。其實相當直接，我們認為事情將如下發展。在一線治療中，我們的基石療法將是 cas、ipi、anti-PD-1。

We believe that we can drive the 35% share of ipi/nivo to a regimen with greater than 50% of the important first-line market. While the IO regimen of ipi/nivo is the dominant therapy today, there's a segment of physicians that's always going to want to reach for TKI, particularly for patients with a fast-growing bulky tumor. Therefore, we will also be developing a cas combination inclusive of the TKI, a TKI with a well-established track record of both efficacy and safety that will allow the patient to have cas/cabo as a subsequent regimen.

我們相信，我們可以把 ipi/nivo 目前 35% 的市占，推進到一個在重要一線市場中市占超過 50% 的治療方案。雖然 ipi/nivo 的 IO 方案目前是主導療法，但仍有一部分醫師總是會想使用 TKI，特別是針對腫瘤生長快速且腫塊較大的病患。因此，我們也將開發包含 TKI 的 cas 聯合療法；該 TKI 具有已充分建立的療效與安全性紀錄，使病患後續仍可使用 cas/cabo 作為下一個治療方案。

Our second-line treatment now enrolling its registrational trial PEAK-1 will be cas/cabo, building on the standard of care in this line, cabozantinib monotherapy. Finally, we will have a third-line plus regimen cas with another well-established TKI, and we will be investigating this regimen in both belzutifan naive and belzutifan experienced patients.

我們目前正在招募受試者的第二線治療註冊性試驗 PEAK-1 將採用 cas/cabo，建立在此治療線別的標準治療——cabozantinib 單藥治療——之上。最後，我們將在第三線及以上推出 cas 與另一種已被充分驗證的 TKI 的聯合方案，並將在 belzutifan 未治療（naive）與 belzutifan 既往治療（experienced）的患者中研究此方案。

We think this is a very important, kind of cool study. We also plan to explore novel cas combinations in HCC, liver cancer. I would like to emphasize that all of the clinical development plans discussed today are accounted for within our existing budget and have no impact on the guidance and runway that we have provided. We now control in all respects our early-stage pipeline, including our CCR6, CD89 and CD40 ligand programs, all of which are expected to support IND candidates in the next 6 to 18 months. So as we focus our resources, capital, human and otherwise on the late-stage development of casdatifan.

我們認為這是一項非常重要、也很酷的研究。我們也計畫在 HCC（肝細胞癌）/肝癌中探索新穎的 cas 聯合方案。我想強調，今天討論的所有臨床開發計畫都已納入我們現有預算之內，且不會影響我們已提供的指引與資金可支撐期（runway）。我們現在在各方面都完全掌控我們的早期研發管線，包括 CCR6、CD89 與 CD40 ligand 計畫；預期這些計畫將在未來 6 至 18 個月內支持 IND 候選項目。因此，當我們將資源、資本、人力及其他投入聚焦於 casdatifan 的後期開發時。

The follow-on programs in our pipeline are early, but also with clear, early and capital-efficient clinical proof-of-concept opportunity and huge commercial potential. Therefore, we anticipate low spend and short time lines to get the proof-of-concept that will drive disproportionate value creation. Juan will discuss these programs in more detail later on in this call.

我們管線中的後續計畫仍處於早期階段，但也具備明確的、早期且資本效率高的臨床概念驗證（proof-of-concept）機會，以及巨大的商業潛力。因此，我們預期以較低的投入與較短的時間線取得概念驗證，從而帶動不成比例的價值創造。Juan 將在本次電話會議稍後更詳細地討論這些計畫。

If you want to walk away with just one thing from today, it's that Arcus has complete control of its destiny. The core asset of the company is casdatifan, and we have the strategy, data and resources to transform the treatment of clear cell RCC and create a $5 billion-plus drug.

如果你今天只想帶走一個重點，那就是 Arcus 完全掌控自己的命運。公司的核心資產是 casdatifan，而我們具備策略、數據與資源來改變透明細胞型 RCC 的治療，並打造一款年銷售額超過 50 億美元的藥物。

Bob will further elaborate on the enormous commercial opportunity here. We also continue to leverage our demonstrated competitive advantage in small molecule drug discovery, an increasingly scarce capability to generate wholly owned and unique development candidates, the advancement of which further enhances our strategic optionality. With that, I'd like to turn the call over to Richard to discuss our clinical programs.

Bob 將進一步闡述此處龐大的商業機會。我們也持續運用我們在小分子藥物發現方面已證明的競爭優勢——這是一項日益稀缺的能力——以產生完全自有且獨特的開發候選藥物；其推進也將進一步提升我們的策略選擇性。接下來，我想把電話會議交給 Richard，請他討論我們的臨床計畫。

Thanks, Terry. I'd like to start with casdatifan. As Terry described, our development plan is designed to establish casdatifan as a foundational standard of care in clear cell RCC so that all patients have the opportunity to benefit from treatment with a casdatifan-based regimen across multiple lines of therapy. At ASCO GU this year, we presented updated ORR and PFS from our four late-line monotherapy cohorts of ARC-20. As you can see here, the efficacy data continued to improve with longer follow-up at each data presentation.

謝謝你，Terry。我想先從 casdatifan 談起。如 Terry 所述，我們的開發計畫旨在將 casdatifan 確立為透明細胞型 RCC 的基礎性標準治療，讓所有患者都有機會在多個治療線別中受益於以 casdatifan 為基礎的治療方案。在今年的 ASCO GU，我們公布了 ARC-20 四個後線單藥治療隊列更新後的 ORR 與 PFS。如各位在此所見，隨著每次數據發表時的追蹤時間延長，療效數據持續改善。

Moving to Slide 12, where we show the ORRs for the 100-milligram QD cohort, which is the dose and formulation being used in our Phase III studies, the confirmed ORR increased from 35% at the August data cut to 45%. A 45% ORR in this late-line patient population is rather remarkable. It's twice that observed with belzutifan in LITESPARK-005 or any study in this patient population. Similarly, the confirmed ORR for the pooled analysis improved from 31% to 35%, well above the range of ORRs that have been observed with belzutifan. On Slide 13, we show the Kaplan-Meier curve for the 100-milligram cohort.

接著看投影片 12，我們展示 100 毫克 QD（每日一次）隊列的 ORR；這是我們第三期研究所使用的劑量與劑型。確認的 ORR 從 8 月數據截點的 35% 提升至 45%。在這個後線患者族群中，45% 的 ORR 相當令人驚豔。這是 LITESPARK-005 中 belzutifan 或任何同類患者研究所觀察到的兩倍。同樣地，合併分析的確認 ORR 也從 31% 提升至 35%，明顯高於 belzutifan 所觀察到的 ORR 範圍。在投影片 13，我們展示 100 毫克隊列的 Kaplan-Meier 曲線。

As you can see here that the 100-milligram cohort shows an impressive median PFS of 15.1 months after 17.9 months of median follow-up. On the next slide, we show the latest Kaplan-Meier curve for the pooled analysis. The median PFS remained at 12.2 months. So overall, we're seeing PFS that is 2 to 3 times longer with Cas monotherapy than the 5.6 months observed with belzutifan in the same setting. And as is often discussed, while the median is an important benchmark, it's not the only metric that's important.

如各位所見，100 毫克隊列在中位追蹤 17.9 個月後，顯示令人印象深刻的中位 PFS 為 15.1 個月。下一張投影片，我們展示合併分析最新的 Kaplan-Meier 曲線。中位 PFS 仍維持在 12.2 個月。因此整體而言，我們看到 Cas 單藥治療的 PFS 是同一情境下 belzutifan 所觀察到 5.6 個月的 2 到 3 倍。而且如常被討論的，雖然中位數是一個重要的基準，但它並不是唯一重要的指標。

As you can see here and perhaps more impressive is the number of patients still on treatment beyond 18 months and even beyond 24 months. These data clearly support the proposition that casdatifan is the best-in-class HIF-2 alpha inhibitor. And our highest priority now is to maximize the potential of this molecule in ccRCC. Our first registrational trial, which is in the second-line setting, is well underway. Enrollment in the ongoing Phase III study, PEAK-1, is accelerating, and we are on track to complete enrollment by year-end.

如各位所見，或許更令人印象深刻的是，仍在治療中的患者人數在超過 18 個月、甚至超過 24 個月後仍然可觀。這些數據清楚支持 casdatifan 是同類最佳（best-in-class）的 HIF-2 alpha 抑制劑。而我們目前的最高優先事項，是在 ccRCC 中最大化此分子的潛力。我們第一項註冊性試驗（第二線治療情境）進展順利。正在進行的第三期研究 PEAK-1 招募速度正在加快，我們按計畫可在年底前完成招募。

We are confident that PEAK-1 will establish cas plus cabo as a new standard of care in the IO experience setting. With a sole primary endpoint of PFS and a 2:1 randomization favoring the experimental arm and cabo as the control arm, we believe PEAK-1 is optimized for both probability of success and speed to data.

我們有信心 PEAK-1 將把 cas 加 cabo 確立為 IO 既往治療（IO experience）情境下的新標準治療。PEAK-1 以 PFS 作為唯一主要終點，並採用 2:1 隨機分派偏向實驗組、以 cabo 作為對照組；我們認為此設計同時針對成功機率與取得數據速度進行了最佳化。

I'd like to spend some time now on the frontline setting. With the outcome of Merck's LITESPARK-012 last month, Cas has the opportunity to be the first HIF-2 alpha inhibitor option in the frontline setting. Treatment in the frontline is generally bifurcated into IO-IO or a TKI, [anti-PD-x] combination. This currently leads to the conceptual trade-off between longer time to response or higher primary progression, but with the potential for durable responses and long-term survival with the IO-IO option or a faster time to response and lower primary progression but with much more treatment-associated toxicity for the TKI, anti-PD-x options. There's currently no treatment option that has the ability to both rapidly control disease and provide the best chance for long-term survival, while also having a favorable tolerability profile for long-term use.

我現在想花一些時間談談一線治療情境。隨著上個月 Merck 的 LITESPARK-012 結果出爐，Cas 有機會成為一線治療中第一個 HIF-2 alpha 抑制劑選項。一線治療通常分為 IO-IO 或 TKI 與 [anti-PD-x] 的聯合治療。這目前導致一個概念上的取捨：IO-IO 選項可能反應時間較長或原發進展（primary progression）較高，但有機會帶來持久反應與長期存活；而 TKI、anti-PD-x 選項則反應更快、原發進展較低，但治療相關毒性顯著更高。目前尚無一種治療選項能同時快速控制疾病並提供最佳的長期存活機會，同時又具備適合長期使用的良好耐受性。

We believe a Cas plus IO-IO combination in the frontline setting has the potential to deliver on both of these fronts. We are enrolling several cohorts within the ARC-20 study, evaluating Cas combinations in the frontline setting. While the data are maturing, primary progressive disease rates have already been shown to be low, just 7% or 2 out of 30 patients for the Cas plus zimberelimab, our anti-PD-1 cohort. This rate compares favorably to published rates for anti-PD-1 monotherapy or ipi/nivo in the first-line setting. And in fact, it is close to the rate of a TKI-containing regimen but without the need for the TKI.

我們相信，在一線治療情境下，Cas 加 IO-IO 的聯合方案有潛力同時達成這兩個目標。我們正在 ARC-20 研究中招募多個隊列，以評估一線治療情境下的 Cas 聯合方案。雖然數據仍在成熟中，但原發進展疾病（primary progressive disease）比率已顯示偏低：在 Cas 加 zimberelimab（我們的 anti-PD-1）隊列中僅 7%，即 30 名患者中 2 名。此比率與已發表的一線 anti-PD-1 單藥或 ipi/nivo 的比率相比更具優勢。事實上，它接近含 TKI 方案的比率，但不需要使用 TKI。

We're also enrolling a cohort evaluating Cas plus zim plus ipi. Emerging data from these cohorts of ARC-20 will inform the first-line registrational strategy with the goal of finalizing the Phase III study protocol and beginning start-up activities by the end of this year. In parallel, we will shortly begin to evaluate additional Cas plus TKI-containing regimens in the early and late-line settings, including in patients with prior belzutifan experience. This effort contemplates the preference and in fact, the strategic necessity to utilize alternative TKIs as patients advance from one line of therapy to the next. Near term, we expect to have multiple data readouts for casdatifan in 2026.

我們也正在納入一個評估 Cas 加 zim 加 ipi 的隊列。來自 ARC-20 這些隊列的新興數據將為一線註冊性策略提供資訊，目標是在今年年底前定稿第三期研究方案並啟動啟動前準備工作。同時，我們將很快開始在早線與晚線治療情境中評估其他含 Cas 加 TKI 的治療方案，包括既往使用過 belzutifan 的患者。此項工作考量到患者從一線治療進展到下一線治療時，偏好且事實上在策略上必須使用替代性 TKI。短期內，我們預期在 2026 年將有多項 casdatifan 的數據讀出。

First, mature ORR data and initial PFS data for approximately 45 patients treated in the ARC-20 Cas plus cabo cohort in the IO experience setting will be presented at an investor event or at a medical conference, and all patients will have had at least 12 months of follow-up. Second, we will share initial data from the ARC-20 cohorts evaluating Cas in early line settings, including the cohort evaluating Cas plus zim in the first line. We also expect updated data from late-line monotherapy cohorts, including overall survival. Before I hand it over to Juan, I'd like to quickly touch on quemliclustat, our small molecule CD73 inhibitor. CD73 is highly expressed in pancreatic cancer and high CD73 expression is associated with significantly poor prognosis in several tumor types.

第一，在 IO 經驗族群中，ARC-20 的 Cas 加 cabo 隊列約 45 名患者的成熟 ORR 數據與初步 PFS 數據，將於投資人活動或醫學會議上發表，且所有患者都將至少完成 12 個月追蹤。第二，我們將分享 ARC-20 中評估 Cas 於早線治療情境的隊列之初步數據，包括評估 Cas 加 zim 作為一線治療的隊列。我們也預期將更新晚線單藥治療隊列的數據，包括整體存活期。在我把電話交給 Juan 之前，我想快速談一下 quemliclustat，我們的小分子 CD73 抑制劑。CD73 在胰臟癌中高度表達，而 CD73 高表達與多種腫瘤類型顯著較差的預後相關。

In spite of this, as we recently published in Nature Medicine, in our Phase II study, ARC-8, those patients with higher baseline levels of CD73 or adenosine activity were the ones with longer PFS and OS in response to quemli treatment. Pancreatic cancer is one of the most aggressive cancers with an average five-year survival rate of just 13%. In PRISM-1, our Phase III study evaluating quemli plus gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel in the frontline pancreatic study, completed enrollment in September of 2025. Results from this study are expected in the first half of 2027. And if positive, PRISM-1 could represent the first transformative therapy for an all-comer first-line patient population in 30 years.

儘管如此，正如我們近期在《Nature Medicine》發表的結果，在我們的第二期研究 ARC-8 中，基線 CD73 或腺苷活性較高的患者，對 quemli 治療的反應呈現較長的 PFS 與 OS。胰臟癌是最具侵襲性的癌症之一，平均五年存活率僅 13%。在 PRISM-1（我們的第三期研究）中，我們評估 quemli 加 gemcitabine 與 nab-paclitaxel，相較於 gemcitabine 與 nab-paclitaxel 作為一線胰臟癌治療，已於 2025 年 9 月完成收案。此研究結果預期於 2027 年上半年公布。若結果為正向，PRISM-1 可能成為 30 年來首個可改變治療格局、適用於不分族群（all-comer）一線患者的突破性療法。

There's no biomarker requirement and no nonresistant mechanism and data to date have indicated that the regimen was well tolerated. Finally, we recently announced that the Phase III STAR-121 study, evaluating our anti-TIGIT domvanalimab plus zim and chemotherapy, versus pembrolizumab plus chemotherapy as a first-line treatment for metastatic non-small cell lung cancer will be discontinued due to futility. While these are certainly not the results we expected, the study had one important positive outcome. In addition to the assessment of Dom in this trial, STAR-121 also evaluated zim plus chemo as an exploratory endpoint. Zim plus chemo performed consistently with respect to overall survival as compared to pembro plus chemo.

該方案不要求生物標記，且不存在非抗藥性機制；迄今數據顯示此治療方案耐受性良好。最後，我們近期宣布第三期 STAR-121 研究將因無效（futility）而中止；該研究評估我們的抗 TIGIT 藥物 domvanalimab 加 zim 與化療，相較於 pembrolizumab 加化療，作為轉移性非小細胞肺癌的一線治療。雖然這些確實不是我們所預期的結果，但該研究仍有一項重要的正面收穫。除了在此試驗中評估 Dom 之外，STAR-121 也將 zim 加化療作為探索性終點進行評估。就整體存活期而言，zim 加化療的表現與 pembro 加化療一致。

These data are consistent with what was observed in numerous studies with zim. And this randomized data set provides valuable support for the utility of zim as an anti-PD-1 combination partner for Arcus and its collaborators. I'd now like to turn the call over to Juan to discuss our immunology and inflammation programs.

這些數據與多項 zim 研究中的觀察結果一致。而這組隨機化數據集，為 zim 作為 Arcus 及其合作夥伴之抗 PD-1 聯合用藥夥伴的效用提供了寶貴支持。接下來我想把電話交給 Juan，請他討論我們的免疫學與發炎（I&I）研發計畫。

Thanks, Richard. Arcus has an exceptional small molecule discovery team that has demonstrated time and time again the ability to create highly effective drug candidates against difficult targets. We have been utilizing this expertise to create and develop drugs that have the potential to address very large markets in inflammation, allergy and autoimmune diseases. In-house expertise in immunology has been a core aspect of our discovery group since Arcus's founding, having been key to many of our oncology programs. Our team is addressing well-understood and validated mechanisms and has implemented a two-pronged strategy in immunology.

謝謝你，Richard。Arcus 擁有一支卓越的小分子藥物發現團隊，一再證明其針對困難靶點創造高效藥物候選物的能力。我們一直運用這項專長來創製並開發藥物，期望能在發炎、過敏與自體免疫疾病等極大市場中滿足需求。自 Arcus 創立以來，內部免疫學專業一直是我們發現團隊的核心面向，並且對多項腫瘤學計畫至關重要。我們的團隊聚焦於已被充分理解且經驗證的機制，並在免疫學領域採取雙軌策略。

First, we leverage our medicinal chemistry capabilities to design and create small molecule drugs that regulate key cytokines therapeutically validated by existing biologics. Secondly, we target immune cell types that play key roles in human disease and have been historically under studied such as mast cells and neutrophils.

第一，我們運用藥物化學能力，設計並創製可調控關鍵細胞激素的小分子藥物；這些細胞激素已由現有生物製劑在治療上獲得驗證。第二，我們鎖定在人類疾病中扮演關鍵角色、但歷來研究相對不足的免疫細胞類型，例如肥大細胞與嗜中性球。

Our first molecule in the immunology area to enter the clinic will be AB102, a highly selective, orally bioavailable MRGPRX2 antagonist. In the coming weeks, we will be sharing its preclinical profile in an oral presentation at the Society for Investigative Dermatology. The presentation will highlight the ability of AB102 to fully block MRGPRX2-dependent activation and degranulation of mast cells.

我們在免疫學領域首個進入臨床的分子將是 AB102，這是一款高度選擇性、具口服生體可用性的 MRGPRX2 拮抗劑。在未來幾週內，我們將於皮膚科研究學會（Society for Investigative Dermatology）的口頭報告中分享其臨床前特徵。該報告將重點呈現 AB102 能夠完全阻斷依賴 MRGPRX2 的肥大細胞活化與去顆粒作用。

AB102 inhibits all common human MRGPRX2 variants. We have optimized the potency of AB102 under physiological conditions, such as in human blood and serum. Due to its potency under these conditions, we believe that AB102 is a potential best-in-class once-daily oral treatment for chronic spontaneous urticaria and other atopic conditions such as atopic dermatitis and allergic asthma.

AB102 可抑制所有常見的人類 MRGPRX2 變異型。我們已在生理條件下（例如人類全血與血清）優化 AB102 的效力。由於其在這些條件下的高效力，我們相信 AB102 有潛力成為同類最佳（best-in-class）的每日一次口服治療，用於慢性自發性蕁麻疹以及其他異位性疾病，例如異位性皮膚炎與過敏性氣喘。

It is expected to enter the clinic in the third quarter of 2026 with PK data available shortly thereafter and potential for proof-of-concept data in early 2027. In rapid succession, we have selected an oral, small-molecule TNF inhibitor drug candidate, which is a potential treatment for rheumatoid arthritis, psoriasis and inflammatory bowel disease and an orally active small-molecule CCR6 antagonist candidate as a potential treatment for psoriasis.

預期將於 2026 年第三季進入臨床，之後不久即可取得 PK 數據，並有望在 2027 年初取得概念驗證（proof-of-concept）數據。緊接著，我們已選定一款口服小分子 TNF 抑制劑藥物候選物，作為類風濕性關節炎、乾癬與發炎性腸道疾病的潛在治療；同時也選定一款具口服活性的 小分子 CCR6 拮抗劑候選物，作為乾癬的潛在治療。

Both of these molecules are expected to enter the clinic in 2027. We are very excited about the potential for our I&I programs to provide improved options for patients, and we are working to advance these into the clinic as rapidly as possible. I'd now like to turn the call over to Bob to discuss the market opportunity for casdatifan and our financial results.

這兩個分子預期都將於 2027 年進入臨床。我們對 I&I 計畫為患者提供更佳治療選擇的潛力感到非常振奮，並正努力以最快速度推進至臨床。接下來我想把電話交給 Bob，請他討論 casdatifan 在市場上的機會以及我們的財務結果。

Thanks, Juan. Before I get into the quarterly financials, I'd like to spend some time on the multibillion-dollar market opportunity in RCC for casdatifan. Sales for RCC drugs in just the major markets are anticipated to grow to $13 billion by 2030. Historically, the market has been dominated by two classes of therapy, IO and TKIs. There have been a number of offerings in both classes, which is why the market is fragmented.

謝謝你，Juan。在我進入本季財務數據之前，我想先花一些時間談談 casdatifan 在腎細胞癌（RCC）中數十億美元規模的市場機會。僅主要市場的 RCC 藥物銷售額預期到 2030 年將成長至 130 億美元。歷史上，市場一直由兩大治療類別主導：IO 與 TKI。這兩個類別都有多種產品供應，因此市場呈現分散。

In contrast, there are only two HIF-2 alpha inhibitors on the horizon, and we believe our data have demonstrated clear advantages over our only competitor. We have a clear path to consolidate the market and entrench casdatifan as the primary backbone therapy. The development plan that Terry and Richard described is designed to accomplish this objective. If we look at the sales for the sole marketed HIF-2 alpha inhibitor, belzutifan, which is currently approved only in late-line clear cell RCC, is already generating annual run rate sales of nearly $1 billion, only scratching the surface. With casdatifan, we are also targeting earlier line settings, the IO experienced population with PEAK-1 and the IO naive first-line population with our next pivotal study.

相較之下，未來可望上市的 HIF-2 alpha 抑制劑僅有兩款，而我們相信數據已顯示我們相對於唯一競爭對手具有明確優勢。我們有清晰路徑可整合市場，並使 casdatifan 成為主要的基礎骨幹治療（backbone therapy）。Terry 與 Richard 所描述的開發計畫正是為了達成此一目標而設計。若我們觀察目前唯一已上市的 HIF-2 alpha 抑制劑 belzutifan 的銷售情況，其目前僅核准用於晚線透明細胞 RCC，但已產生接近 10 億美元的年化銷售運行率，仍僅觸及市場表面。透過 casdatifan，我們也鎖定更早線的治療情境：以 PEAK-1 鎖定 IO 經驗族群，並以我們下一項關鍵性試驗鎖定 IO 未治療的一線族群。

These earlier line settings have larger patient populations and longer durations of therapy, both of which contribute to a much larger market opportunity. Specifically, our PEAK-1 study targets approximately 20,000 patients in the major markets in the IO experience setting. We believe our commercial opportunity here exceeds $2 billion. In the first line, the opportunity is even greater. With the lack of HIF-2 alpha inhibitor competition in the front line, our goal is to grow the IO-IO share from roughly 1/3 of the market to more than 1/2 by adding Cas.

這些較早線別的治療設定擁有更大的病患族群與更長的治療期間，兩者皆促成更大的市場機會。具體而言，我們的 PEAK-1 研究在 IO 經驗族群設定的主要市場中，鎖定約 20,000 名病患。我們相信此處的商業機會超過 20 億美元。在第一線，機會更大。由於前線缺乏 HIF-2 alpha 抑制劑的競爭，我們的目標是透過加入 Cas，將 IO-IO 的市占率從約 1/3 提升至超過 1/2。

In fact, our market research indicates that oncologists overwhelmingly prefer the promise of a Cas plus IO-IO over a TKI-containing regimen. As Richard mentioned, we also plan to investigate a regimen with IO and TKI in the frontline to address the remainder of the market. We believe the opportunity for casdatifan in the frontline exceeds $4 billion. One point I'd really like to emphasize as we think about the commercial opportunity is duration of treatment. We've seen impressive data in late-line monotherapy with many patients on therapy beyond 18 months.

事實上，我們的市場調查顯示，腫瘤科醫師壓倒性地偏好 Cas 加上 IO-IO 的前景，而非含 TKI 的療程。如 Richard 所提，我們也計畫在前線研究 IO 與 TKI 的療程，以涵蓋其餘市場。我們相信 casdatifan 在前線的機會超過 40 億美元。在思考商業機會時，我特別想強調的一點是治療持續時間。我們在後線單藥治療中看到令人印象深刻的數據，許多病患的治療時間超過 18 個月。

We plan to share updated data later this year. As we think about earlier lines of therapy, we believe there is the potential for meaningful upside resulting from the durability of effect. Conceptually, we think strong HIF-2 alpha inhibition holds the promise of a long-term tail effect. All in, we think Cas has a peak sales opportunity of $5 billion to $10 billion. As a reminder, we own all of the commercial rights to Cas other than in Japan and certain other Southeast Asian countries held by our partner, Taiho.

我們計畫在今年稍晚分享更新數據。當我們思考更早線別的治療時，我們相信由於療效的持久性，存在顯著上行空間的可能。在概念上，我們認為強效的 HIF-2 alpha 抑制有望帶來長期的尾端效應。總體而言，我們認為 Cas 的峰值銷售機會為 50 億至 100 億美元。提醒一下，除日本及由合作夥伴大鵬藥品（Taiho）持有的部分其他東南亞國家外，我們擁有 Cas 的所有商業權利。

Now let's turn to the financials. Arcus is well positioned to advance its full pipeline with $876 million in cash at the end of the quarter. We have cash runway until at least the second half of 2028. We expect to end 2026 with approximately $600 million in cash, indicative of the declining spend we expect over the year. As Terry outlined, Arcus is entering a new era with more control over our pipeline investments.

現在讓我們轉到財務面。Arcus 在本季末擁有 8.76 億美元現金，具備推進完整產品線的良好條件。我們的現金可支撐營運至至少 2028 年下半年。我們預期 2026 年底現金約為 6 億美元，反映我們預期今年支出將下降。如 Terry 所概述，Arcus 正進入一個新時代，對我們的產品線投資擁有更高的掌控度。

While we are building a plan to take full advantage of the casdatifan opportunity, we are also sequencing these investments such that any significant growth in overall spend will be largely incurred after the PEAK-1 readout. As a result of the wind down of Dom and reduced spend on quemli, together with broader spend management, we expect to significantly reduce our overall R&D spend in 2026 and 2027 compared to 2025. For example, as our late-stage efforts have become focused on casdatifan, we have decreased our head count by approximately 10%. Let me transition to the financials for the quarter. For our P&L, we recognized GAAP revenue for the first quarter of $17 million.

在我們制定計畫以充分把握 casdatifan 機會的同時，我們也在安排投資順序，使整體支出若出現任何顯著成長，將主要在 PEAK-1 讀出之後才會發生。隨著 Dom 的收尾以及在 quemli 上的支出降低，再加上更廣泛的支出管理，我們預期 2026 與 2027 年的整體研發支出將較 2025 年顯著下降。例如，隨著我們的後期工作聚焦於 casdatifan，我們已將人力編制減少約 10%。接著我來說明本季財務。在損益表方面，我們第一季認列 GAAP 營收 1,700 萬美元。

Our revenue continues to be primarily driven by our collaboration agreements. We continue to expect to recognize GAAP revenue of $50 million to $65 million for the full year 2026. Our R&D expenses for the first quarter are stated net of reimbursements and were $122 million and included non-recurring workforce costs. Our actions to reduce head count have lowered our ongoing cost structure, which we expect will result in reduced R&D expense in future periods. The discontinuation of STAR-121 and the broader reduction in our Dom-related investment will contribute to a meaningful decrease in R&D expenses as the year goes on.

我們的營收仍主要由合作協議所驅動。我們仍預期 2026 全年將認列 GAAP 營收 5,000 萬至 6,500 萬美元。我們第一季研發費用以扣除補償後列示，為 1.22 億美元，並包含一次性的人力相關成本。我們縮減人力的行動已降低持續性的成本結構，我們預期將使未來期間的研發費用下降。STAR-121 的終止以及更廣泛地降低與 Dom 相關的投資，將在今年後續期間推動研發費用出現顯著下降。

By 2027, we expect more than 80% of our portfolio spend will be directed towards cash development. G&A expenses were $29 million for the first quarter. Total noncash stock-based compensation was $19 million for the first quarter. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-Q.

到 2027 年，我們預期超過 80% 的產品組合支出將投入於 Cas 的開發。第一季的 G&A 費用為 2,900 萬美元。第一季非現金的股份基礎給付總額為 1,900 萬美元。如需更多關於我們財務結果的細節，請參閱我們今日稍早發布的財報新聞稿以及我們的 10-Q。

I will now turn it back to Terry.

我現在把時間交回給 Terry。

Thanks, Bob. That was awesome. Let me close by summarizing the key themes for the remainder of 2026. Casdatifan is our number one priority, and this year will be another transformative year for data and importantly, development as we advance towards commercialization. We expect multiple data sets, Cas plus Cabo data, initial first-line data and overall survival data from late-line monotherapy cohorts, all of which will further reinforce casdatifan's best-in-class profile and support our registrational strategy.

謝謝，Bob。太棒了。我最後以總結 2026 年剩餘時間的關鍵主題作結。Casdatifan 是我們的第一優先事項，而今年將是數據、以及更重要的是開發方面的另一個轉型之年，因為我們正朝商業化邁進。我們預期將有多組數據，包括 Cas 加 Cabo 的數據、初步第一線數據，以及後線單藥隊列的整體存活期數據；這些都將進一步強化 casdatifan 的同類最佳（best-in-class）定位，並支持我們的註冊策略。

PEAK-1 enrollment continues to accelerate, and we're targeting full enrollment by year-end. All of the clinical development plans for casdatifan that were discussed today are accounted for within our existing budgets and have no impact on our guidance or runway. Beyond casdatifan, our PRISM-1 Phase III trial for quemli pancreatic cancer is fully enrolled and on track for a readout in the first half of 2027.

PEAK-1 的收案持續加速，我們目標在年底前完成全數收案。今天討論的所有 casdatifan 臨床開發計畫都已納入我們既有預算之內，對我們的財測指引或現金跑道沒有影響。除 casdatifan 之外，我們針對 quemli 胰臟癌的 PRISM-1 第三期試驗已完成收案，並按計畫於 2027 年上半年讀出。

Juan shared the exciting progress on our I&I portfolio with AB102 expected to enter the clinic in the third quarter and our TNF inhibitor CCR6 antagonist following shortly thereafter. With $876 million in cash and investments and runway into the second half of 2028, we're well positioned to execute on all of these priorities and create significant value for patients and shareholders.

Juan 分享了我們 I&I 產品組合令人振奮的進展，AB102 預計於第三季進入臨床，TNF 抑制劑 CCR6 拮抗劑也將在不久後跟進。憑藉 8.76 億美元的現金與投資，以及可支撐至 2028 年下半年，我們具備良好條件執行所有這些優先事項，並為病患與股東創造顯著價值。

We're moving into a new era for Arcus with full ownership of our lead program casdatifan and a clear strategy to win and transform the frontline setting while rapidly advancing the next generation of wholly owned molecules for inflammation and immunology. We have no doubt that we will be generating disproportionate value for patients and shareholders over the coming 12 to 18 months. Thank you all for joining us. We appreciate your interest and continued support of Arcus, and we will now open the call for questions.

隨著我們完全擁有領先專案 casdatifan，並具備清晰策略以在前線治療情境中勝出並帶來轉變，同時快速推進下一代完全自有的發炎與免疫學分子，Arcus 正邁入新時代。我們毫不懷疑，在未來 12 到 18 個月內，我們將為病患與股東創造不成比例的價值。感謝各位參與。我們感謝您對 Arcus 的關注與持續支持，現在我們將開放提問。

(Operator Instructions) Daina Graybosch, Leerink Partners.

（接線員指示）Daina Graybosch，Leerink Partners。

Tell us about the Cas-TKI frontline combo. Specifically, we all know Merck failed with that triplet mechanistically with bel, lenva, pembro, and that's the LITESPARK-012. We have the press release. We don't know the detailed data. What could you see in that detailed data that would give you more confidence in Cas-TKI IO? And what could you see in the Merck data that would give you less confidence in the TKI combo strategy?

請談談 Cas-TKI 的前線聯合療法。具體來說，我們都知道 Merck 在機轉上以 bel、lenva、pembro 的三聯療法失敗了，也就是 LITESPARK-012。我們已看到新聞稿。但我們不知道詳細數據。在那些詳細數據中，你們可能看到什麼，會讓你們對 Cas-TKI IO 更有信心？而在 Merck 的數據中，你們可能看到什麼，會讓你們對 TKI 聯合策略更沒有信心？

I think we'll see what their data say, but I think the data that are out there tell us a lot already. So if you consider what we discussed at the beginning, that pharmacodynamic difference between casdatifan and belzutifan, not only the depth of response, but particularly the durability. And you think of that as a surrogate for its antitumor activity and a direct measure of its ability to inhibit HIF-2.

我想我們會看看他們的數據怎麼說，但我認為現有的數據其實已經告訴我們很多了。所以如果你回想我們一開始討論的，casdatifan 與 belzutifan 之間的藥效動力學差異，不僅是反應深度，尤其是持久性。而你把那視為其抗腫瘤活性的替代指標，以及其抑制 HIF-2 能力的直接衡量。

I think what you can reconcile very easily is even in the absence of the data from the study itself, if you think about LITESPARK-011 versus LITESPARK-012, the duration of the treatment that you're talking about when you think about PFS roughly for the two different studies, is almost 2x. So if you recognize that belzutifan is whatever that surrogate for HIF-2 inhibition, directly relates to inhibition of the tumor, it's clearly losing that effect with time dramatically.

我認為你很容易就能把這些串起來：即使沒有該研究本身的數據，如果你比較 LITESPARK-011 與 LITESPARK-012，當你用兩個不同研究的 PFS 大致去看你所談的治療持續時間，幾乎是 2 倍。所以如果你認知到 belzutifan 作為 HIF-2 抑制的某種替代指標，與腫瘤抑制直接相關，那它顯然會隨時間大幅失去那個效果。

So you see at least on erythropoietin production, on the average, you've lost that effect within 9 to 13 weeks. So when you think about it in the second-line population, the percentage of times what's bringing benefit is x. And then in the front line, it's much less. Then on top of that, if you think about the regimen, it's pretty toxic regimen. So even pembro-lenva had about a 37% rate of discontinuation.

所以你至少看到在紅血球生成素（erythropoietin）產生方面，平均而言，你在 9 到 13 週內就失去了那個效果。所以當你想到二線族群時，帶來獲益的比例是 x。而在一線時，就少得多。再加上，如果你想到該治療方案，它是相當具毒性的方案。所以即便是 pembro-lenva 也有大約 37% 的停藥率。

We know that the triplet was pretty unfavorable from a patient perspective. So if you think about basically, you're having diminishing effect of the HIF-2 inhibitor on top of a much longer duration of an arm that has more AEs than the control arm. So you're basically getting -- paying a price, but getting less benefit. So it's not surprising that you would end up with a hazard ratio that might not be too favorable.

我們知道三聯療法從病人角度來看相當不利。所以如果你想的是：在一個不良事件（AE）比對照組更多、且療程更長的治療組上，再疊加一個 HIF-2 抑制劑且其效果在遞減。那你基本上就是——付出代價，卻得到更少的益處。所以你最後會得到一個可能不太有利的風險比（hazard ratio），並不令人意外。

For us, we're going to select a TKI that we think has a very favorable -- relative to the TKIs out there, profile. But the most important feature will be that we have a HIF-2 inhibitor that has its robust effect and the durability of that effect is essentially the same on day one as it is on day 730.

對我們而言，我們會選擇一個我們認為相當有利的——相對於現有 TKIs 的——特性概況的 TKI。但最重要的特徵將是：我們的 HIF-2 抑制劑具有強勁的效果，而且該效果的持久性基本上在第 1 天與第 730 天是一樣的。

Jonathan Miller, Evercore.

Jonathan Miller，Evercore。

Congrats on all the progress. I guess looking at a very broad Cas development plan here with a lot of combinations in -- across first-, second-, third-line settings. One thing that's notably absent is any approach in the adjuvant setting, which obviously we know Merck is going after. So I'd love to hear your updated thoughts on adjuvant and why that's missing from the current development plan? And then related to that, I guess, or the flip side of that is relatively recently, recently as well as relatively, you were talking about a more conservative approach to late-stage development for Cas, at least with respect to the number of Phase III trials you would want to start, you were considering going after partnerships to ameliorate the cost of late-stage development.

恭喜各項進展。我想從非常宏觀的角度看，Cas 的開發計畫很廣，涵蓋許多聯合療法——跨一線、二線、三線等不同治療線別。有一點明顯缺少的是任何輔助治療（adjuvant）設定的策略，而我們也知道 Merck 顯然正在推進這一塊。所以我很想聽聽你們對輔助治療的最新看法，以及為什麼目前的開發計畫中沒有這一塊？另外與此相關——或從另一面來看——相對近期、也可以說相對而言，你們曾談到對 Cas 的後期開發採取更保守的做法，至少就你們想啟動的第三期試驗數量而言；你們也在考慮透過合作夥伴來分攤後期開發成本。

Obviously, there's been a bit of a shift there. But Terry and Bob, I heard you say we don't expect to see any impact on runway or the ability to prosecute all these different programs. So I'd love to get a little bit more granularity on the sequencing that you're talking about and when you would start these TKI containing and potential novel combo development efforts to enable you to pursue all of these different approaches without running up against the bandwidth limitations?

顯然，這方面有一些轉變。但 Terry 和 Bob，我聽到你們說不預期會對資金跑道（runway）或推進所有這些不同計畫的能力造成任何影響。所以我希望能更細緻地了解你們所談的時程排序（sequencing），以及你們何時會啟動這些包含 TKI 的、以及可能的新型聯合療法開發工作，好讓你們能在不碰到資源/產能限制（bandwidth limitations）的情況下，追求所有這些不同策略？

Thanks, Jon. And I'll let Bob handle that, and then I may have a few comments to add.

謝謝，Jon。我先請 Bob 來回答，之後我可能再補充幾點。

Yes, in terms of adjuvant setting, I think for us, it comes down to two simple things. One is the size of the opportunity and probably more importantly, is the need. So when you think about that particular setting, we think that it's around 12,000 patients or so that get therapy in the adjuvant setting, it's only the high-risk patients with resection and their treatment is capped in one year.

是的，就輔助治療設定而言，我想對我們來說，歸結為兩個簡單的因素。一是機會的規模，而可能更重要的是需求。所以當你想到那個特定設定，我們認為大約有 12,000 名左右的病人會在輔助治療中接受治療；而且只有完成切除的高風險病人，且其治療期被限制在一年。

And so when you actually do the math on that, we actually think that the opportunity, certainly from a revenue perspective, is probably certainly smaller than the second line and probably even smaller than what could be a third-line regimen with an alternate TKI as we described. I think the other important part is we've had a chance to talk to physicians after seeing the LITESPARK-012 data.

因此當你實際算一算，我們認為這個機會——當然從營收角度——可能確實小於二線，甚至可能也小於我們所描述、以替代 TKI 組成的三線方案所能帶來的機會。我想另一個重要部分是，我們在看到 LITESPARK-012 數據後，有機會與醫師交流。

The bar to add another therapy on top of pembro is considered quite high. In fact, most physicians told us that they actually wouldn't add belzutifan to the regimen even in light of the LITESPARK-012 data. So we actually think it will be a minority of patients that ultimately will receive belzutifan in that setting. So it's prioritization. And frankly, the other settings in first, second and third line are higher on the list for us.

在 pembro 之上再加一個治療的門檻被認為相當高。事實上，多數醫師告訴我們，即便考量 LITESPARK-012 的數據，他們其實也不會把 belzutifan 加到該方案中。所以我們實際上認為，最終在那個設定中會使用 belzutifan 的病人只會是少數。所以這是優先順序的問題。坦白說，對我們而言，一線、二線與三線的其他設定優先度更高。

And so that's sort of why we've made the decision that we have from an adjuvant perspective. In terms of the sequencing of the spend, as we highlighted, we have PEAK-1 up and enrolling right now. Our goal is to have the study enrolled by the end of the year. The work towards launching these additional Phase III studies would have us in a position to sort of move those studies forward as early as late this year into next year with obviously probably our highest priority being that frontline combination with ipi and anti-PD-1. But the other studies will be shortly on the heels.

所以這就是我們在輔助治療面向做出目前決策的原因。至於支出時程的排序，如同我們強調的，PEAK-1 目前已啟動並正在收案。我們的目標是在今年年底前完成收案。為了啟動這些額外的第三期研究所做的工作，將使我們最早可在今年稍晚到明年推進這些研究；而顯然我們最高優先順序可能是一線與 ipi 及 anti-PD-1 的聯合療法。但其他研究也會緊接其後。

But if you think about just sort of the general investment profile for the studies, we'll be through the bolus of study start-up for PEAK-1 and the cost profile for PEAK-1 will be starting to decrease as we get into the second half of next year. So we kind of feel like that it's going to be a nice portfolio effect that when we think about these other studies, kicking in really from a spend perspective in late '27 and into '28, we sort of see a generally steady spend profile through the PEAK-1 readout like we described.

但如果你只從研究的一般投資曲線來看，我們將會度過 PEAK-1 的啟動期一次性投入（bolus of study start-up），而且當我們進入明年下半年時，PEAK-1 的成本曲線將開始下降。所以我們覺得會有一個不錯的組合效應：當我們想到其他研究在支出面真正開始啟動，大概會在 2027 年下半年到 2028 年，我們預期在 PEAK-1 讀出（readout）之前，整體支出曲線會如我們所描述地大致維持平穩。

Jon, and I'll -- Bob kind of gave you the line of the spend along with the studies, and I'll give you a little bit more granularity on how we literally see the trials themselves playing out. So the first study, obviously, PEAK-1 that's enrolling, as Bob said, it will be fully enrolled by the end of this year, and then we'll be waiting for readout.

Jon，我會——Bob 已經把支出曲線與研究安排大致說明了，我再更細緻地補充一下我們實際上如何看待各試驗本身的推進方式。所以第一個研究，顯然是正在收案的 PEAK-1；如 Bob 所說，它會在今年年底前完成收案，接著我們就會等待讀出。

We're going full speed ahead and expect that ipi, anti-PD-1 Cas, as we've been talking about for some time, to be getting up and going by the end of this year. We'll see where the TKI inclusive regimen comes in. There's -- without getting into all the detail now, we'll be sorting through whether there's -- that's actually two studies -- two registrational studies or a three-arm study is also a possibility.

我們正全速推進，並預期如同我們談論了一段時間的那樣，ipi、抗 PD-1 與 Cas 的方案將在今年年底前啟動並運作。我們會再看 TKI 納入的治療方案會如何納入。目前先不深入所有細節，我們會釐清是否——其實是兩個研究——兩個註冊性研究，或是三臂研究也有可能。

And then finally, in the later line study that we talk about, we'll start off in ARC-20. And as you know, those are relatively small cohorts that enroll very efficiently. But the other point that I think will be very important within those studies, and we'll get the answers quickly is that we'll be looking at that combination in the third-line plus in belzutifan-naive patients as well. And I think that will establish. It's a cool study, and I think, it's going to establish something (inaudible)

最後，在我們所談到的後線研究中，我們會先從 ARC-20 開始。如各位所知，那些是相對較小的隊列，招募效率很高。但我認為在這些研究中另一個非常重要、而且我們能很快得到答案的點是：我們也會在第三線以上、且為 belzutifan 未治療（naive）的患者中評估該組合。我認為那將會建立——這是一個很酷的研究，我認為它將建立某些東西(聽不清)

(inaudible)

(聽不清)

Yes, I'm sorry, bel's experience in addition to bel's naive. Thank you, Juan. And I think that will nail something that we think we know the answer to, but we'll have those data even this year.

是的，抱歉，是 bel 有治療經驗（experience）以及 bel 未治療（naive）。謝謝你，Juan。我認為這將釘牢一件我們自認知道答案的事，而且我們甚至在今年就會拿到那些數據。

Li Watsek, Cantor.

Li Watsek，Cantor。

Hey guys, congrats on the progress. I guess just one question on the ARC-20 update, especially from the triplet cohort. It sounds like you guys are enrolling the combination with zim plus ipi. Can you clarify if we're going to see the initial data from this cohort this year? And what data points would you want to see to enable a Phase III frontline trial?

各位好，恭喜進展順利。我想就 ARC-20 的更新問一個問題，特別是三聯（triplet）隊列。聽起來你們正在招募 zim 加上 ipi 的組合。能否說明我們是否會在今年看到這個隊列的初步數據？以及你們希望看到哪些數據點，才能推進第一線（frontline）的第三期試驗？

Thanks, Li. So we do think what you'll get to see, and it will be probably in the fall, are the initial data from ipi anti-PD-1 Cas regimen. And essentially, we'll get a sense of the safety data and the rate of primary progression. While there may be some early ORR data, we don't consider that critical. We're most focused on the safety.

謝謝，Li。我們確實認為你們將能看到的——大概會在秋季——是 ipi 抗 PD-1 與 Cas 方案的初步數據。基本上，我們會先了解安全性數據以及原發性進展（primary progression）的比例。雖然可能會有一些早期 ORR（客觀緩解率）數據，但我們不認為那是關鍵。我們最關注的是安全性。

We'll have an agreement with the FDA as to what safety data package they would want to see to enable us to get that Phase III up and going by the end of this year. And then obviously, because that's the first point, but it's also an important point for that regimen is we'll see the rate of primary progression. I think one thing to recognize about that regimen when we think about triplets, doublets, et cetera, is also just I'd like to make the point is, as you know, we've already talked about the rate of primary progression with casdatifan plus anti-PD-1 alone and those initial data are quite favorable where we only saw a 7% rate of primary progression.

我們會與 FDA 就他們希望看到哪些安全性數據套件達成一致，以便讓我們能在今年年底前啟動第三期試驗。然後很明顯，因為那是第一個重點，但對該方案也同樣重要的是：我們會看到原發性進展的比例。我想在我們思考三聯、雙聯等方案時，關於該方案有一點需要認知：如各位所知，我們先前已談過 casdatifan 加上單用抗 PD-1 的原發性進展率，而那些初步數據相當有利，我們只看到 7% 的原發性進展率。

Now if you think about what that Cas, anti-PD-1 ipi regimen is going to look like, you basically get four cycles of ipi at the outset, of course, with Cas and anti-PD-1. But then the duration and the bulk of your therapy is going to be anti-PD-1 plus Cas.

現在如果你去想像 Cas、抗 PD-1 加 ipi 這個方案會長什麼樣子，基本上你在一開始會給四個療程（cycles）的 ipi，當然同時搭配 Cas 與抗 PD-1。但之後治療的持續時間與主要治療量，將會是抗 PD-1 加 Cas。

So both the efficacy that you're seeing with that as well as the safety of that will certainly impact the bulk of the therapy. So we're excited about that regimen. We think we're well on track to be able to start the Phase III by the end of this year and have a good safety data package. And we do plan to share that with the external world as well this year.

因此，你在那段期間看到的療效以及安全性，將會明顯影響治療的主要部分。所以我們對這個方案感到興奮。我們認為進度非常順利，有望在今年年底前啟動第三期，並具備一套良好的安全性數據套件。而且我們也計畫在今年把這些內容對外分享。

Richard Law, Goldman Sachs.

Richard Law，高盛。

Yes, very helpful to see Cas's development laid out in its life for all the different lines of therapy. A couple of questions from me. So looking at the LITESPARK-012 failures in both triplets and dual Cas discontinuation by [AZ] and then all the frontline therapies of doublets or monotherapy so far, what is your confidence that a Cas triplet of any kind either with IO-IO or IO-TKI could be safe enough to succeed in 1L? And I mean, what do you think is the safety bar for 1L? Do you think that those triplets have to show like comparable safety profile to like that IO-IO, IL-TKI doublet for them to work?

是的，把 Cas 在不同治療線別的開發路徑完整鋪陳出來非常有幫助。我有幾個問題。就 LITESPARK-012 在三聯與雙聯中都失敗、以及 [AZ] 隨後停止 Cas，再加上目前為止所有第一線治療（雙聯或單藥）來看，你們對於任何形式的 Cas 三聯——不論是 IO-IO 或 IO-TKI——能否在第一線（1L）達到足夠安全性以成功，有多大信心？另外，你認為第一線的安全性門檻是什麼？你是否認為這些三聯必須展現出與 IO-IO、或 IO-TKI 雙聯相當的安全性概況，才有機會奏效？

So I think we feel very confident based upon what we already know about our molecules with triplets, whether it's a triplet inclusive of a TKI or a triplet with the ipi anti-PD-1. So keep in mind, while we haven't analyzed in detail, and we will later this year, the zim, so that anti-PD-1 Cas, we know that doublet, and we certainly haven't seen anything untoward with that. We know we can combine with cabo well. So what we believe is that the ipi/nivo regimen has been extraordinarily well worked out in terms of dosing of that particular regimen. And as I was mentioning in my response to Li, you're basically going to treat with four cycles of ipi, that's quite worked out.

我想基於我們對自家分子在三聯中的既有認識——不論是納入 TKI 的三聯，或是 ipi 抗 PD-1 的三聯——我們都非常有信心。請記住，雖然我們尚未做詳細分析、而且會在今年稍晚進行，但就 zim（也就是抗 PD-1）加 Cas 這個雙聯而言，我們了解該雙聯，而且我們確實沒有看到任何不良訊號。我們知道它也能與 cabo 很好地合併使用。因此我們相信，ipi/nivo 方案在劑量設計方面已被非常充分地驗證。正如我在回覆 Li 時提到的，你基本上會以四個療程的 ipi 來治療，這部分已相當成熟。

So we believe that we have orthogonal AEs. We haven't seen anything in terms of a clear combination issues. When you think about casdatifan, you're basically bringing those on-target anemia and of course, rarely or certainly more rarely hypoxia. Again, we're going to pick a good TKI. We know that Cas anti-PD-1 is looking good.

所以我們相信不良事件（AE）是正交的（orthogonal）。我們沒有看到任何明確的合併用藥問題。談到 casdatifan，你基本上帶來的是標靶相關的貧血，當然還有較少見、或更少見的缺氧。同樣地，我們會選擇一個合適的 TKI。我們知道 Cas 加抗 PD-1 的表現看起來不錯。

So we think a reasonable TKI will not bring anything untoward there. Keep in mind, we haven't actually seen the Merck data. And I think the thing that you should take away until otherwise is their hazard ratio must have been not good. So that doesn't get to an intrinsic inability to have a triplet. It just says when you're bringing that TKI, when you're bringing belzutifan on top of a pretty rough doublet, and you're treating for a long period of time and you are undoubtedly introducing some new AEs, but you're not having a robust long-term efficacy effect, you're probably not creating a hazard ratio, but we really don't know exactly how that played out.

因此我們認為，一個合理的 TKI 不會在這裡帶來任何不利的情況。請記住，我們其實還沒看到 Merck 的數據。我認為在沒有其他資訊前，你應該得到的結論是：他們的風險比（hazard ratio）一定不理想。所以那並不代表三聯在本質上不可行。它只是表示：當你把那個 TKI 加上去、把 belzutifan 疊加在一個相當「硬」的雙聯之上，並且治療時間很長，你無疑會引入一些新的不良事件，但如果你沒有帶來強而有力的長期療效增益，你大概就無法做出好的風險比；但我們也不確定實際上是如何發展的。

But all the data with our own molecule suggests that casdatifan is a very well-tolerated and robust HIF-2 inhibitor and with an orthogonal AE profile from anything that we plan to combine with. And we'll have all those data within the next six months or so.

但我們自家分子的所有數據都顯示，casdatifan 是一個耐受性非常好、且效果穩健的 HIF-2 抑制劑，並且其不良事件概況與我們計畫合併的任何療法都是正交的。而我們將在接下來大約六個月內取得所有那些數據。

Got it. And then a follow-up on that. Have you seen the efficacy and the safety results from that dual Cas before Astra discontinued it? And will that data be shared to you guys even if Astra does not plan to share that?

了解。接著就此追問一下。在 Astra 停止該雙重 Cas 之前，您是否看過其療效與安全性結果？即使 Astra 不打算對外分享，那些數據也會提供給你們嗎？

So we haven't seen anything other than what we said at the outset. Since they did disclose, you can now know that there were nine patients. We -- What we described was that initial safety signal that was very CTLA-4 and more specifically volru-like when they dosed down volru. But casdatifan at the same 100 milligram dose we didn't see any more of it. And those patients still continue on.

所以，除了我們一開始所說的內容之外，我們沒有看到其他任何資料。既然他們已經揭露，你們現在也知道共有九位病人。我們——我們所描述的是最初的安全性訊號，非常像 CTLA-4 的效應，更具體來說，在他們把 volru 劑量往下調時，呈現出更像 volru 的樣子。但在相同的 100 毫克劑量下，casdatifan 我們就沒有再看到那樣的情況。而且那些病人仍然持續治療中。

And in fact, the interesting thing out of that is, as we've commented before, we didn't see any progression. So that, if anything, we don't even know, quite honestly, that given that it was nine patients, it's not obvious whether that was even purely volru or not. But what is obvious to us, at least as we were thinking about going forward, is that given that ipi/nivo well worked out regimen, well worked out dose, it's time tested. And of course, probably most importantly that you're only going to be carrying your anti-CTLA-4 dosing for four cycles made it a clear regimen for us to want to proceed with all the four things considered, not wanting to have both of those activities for the duration of the therapy.

而且事實上，其中有趣的一點是，如同我們先前評論過的，我們沒有看到任何疾病進展。所以，老實說，考量只有九位病人，並不明顯那是否完全是 volru 造成的，甚至我們也不確定。但對我們而言很明顯的是，至少在我們思考後續推進時，鑑於 ipi/nivo 是一個運作良好、劑量設定成熟、經過時間驗證的方案。當然，或許最重要的是，你的 anti-CTLA-4 給藥只需要四個療程週期，這讓我們在綜合四個因素後，清楚地想要推進這個方案，而不是在整個治療期間同時承擔這兩種活性。

Salim Syed, Mizuho.

Salim Syed，Mizuho。

This is Mike Linden on for Salim. Just one from us on casdatifan in frontline again. Maybe just how you guys are thinking about patient selection for an ipi/nivo plus Cas combination for a Phase III? Like would these be all-comers versus poor intermediate favorable risk patients, things like that? And I guess, how is the thinking around patient selection changed post LITESPARK-012 failure?

我是代 Salim 發問的 Mike Linden。我們這邊只有一個問題，還是關於 casdatifan 在一線治療。想請教你們在規劃第三期（Phase III）時，對於 ipi/nivo 加上 Cas 的組合，病人選擇會怎麼思考？例如會是全體納入（all-comers），還是針對不良／中等／良好風險族群之類？另外，LITESPARK-012 失敗之後，對病人選擇的想法有沒有改變？

Yes. So our patient selection strategy hasn't changed. And in fact, we're thinking of all comers. And we would also be thinking of all comers in so far as a TKI inclusive regimen. So what we're really trying to address there is there's clearly -- we've had at Board meetings, there's clearly a strong preference for a TKI sparing regimen.

是的。所以我們的病人選擇策略沒有改變。事實上，我們考慮的是全體納入（all comers）。而且就包含 TKI 的方案而言，我們也會考慮全體納入。因此我們真正想要解決的是：很明顯——我們在董事會會議上也討論過——對於「不使用 TKI（TKI sparing）」的方案有非常強烈的偏好。

So that's unequivocal, and that's the way we described it as the bedrock of the front line. With that said, it's a little bit one of those things where there's almost a tribalism is the way the investigators in the field would describe it, where there are certain investigators that are very prone, particularly if there is a bulky fast-growing tumor, but even otherwise do want to reach for TKI. So we feel from that overlap of particular patient with particular investigator, there should be a HIF-2 inhibitor containing regimen. And we think we can offer a very good one. So we look at both of those to be in all-comer patient populations.

所以這點毫無疑問，我們也把它描述為一線治療的基石。但話說回來，這有點像某種現象——領域內的研究者會形容為近乎「部落主義」——有些研究者非常傾向使用 TKI，特別是在腫瘤體積大、成長快速時，但即使不是這種情況也會想用 TKI。因此我們認為，從「特定病人」與「特定研究者」的重疊來看，應該要有一個包含 HIF-2 抑制劑的治療方案。而且我們認為我們可以提供一個非常好的方案。所以我們把這兩種情境都視為全體納入的病人族群。

I think, again, the LITESPARK-012 data for us until we see something otherwise, we simply think it has to do -- and certainly, this has to be a contributing factor to that durability of effect, and let's just call it on HIF-2 inhibition with time that we know that's a dramatic difference between our two molecules. And of course, when we look at the choices of what to combine with, keep in mind, we have no commercial predisposition there. I -- Essentially, the world is our oyster. If you look at the front line, there's a number of TKIs used. There's not one that's particularly dominant.

我想，再次強調，對我們而言，在看到其他不同結果之前，LITESPARK-012 的數據我們認為主要是——而且這肯定是影響療效持久性的因素之一——我們就稱之為 HIF-2 抑制隨時間的效果，而我們知道這正是我們兩個分子之間非常顯著的差異。當然，當我們看要與哪些藥物併用時，請記得我們沒有任何商業上的既定偏好。我——基本上，我們的選擇非常多。如果你看一線治療，有多種 TKI 在使用。並沒有哪一個特別占主導地位。

Overall, you have probably 60% of the patients are getting a TKI, but they're spread somewhat evenly. So we've gone and looked and been very strategic about it and looked at what's the smartest TKI from a safety standpoint, it's well used, it's well tested, approved, understood that we should combine within the front line. We know that we're going to have cabo in the second line.

整體而言，大概有 60% 的病人會使用 TKI，但分布相對平均。所以我們已經去評估並採取非常策略性的做法，從安全性角度去看哪一個 TKI 最明智：使用廣泛、經過充分驗證、已核准、大家理解清楚，適合在一線與我們的藥物併用。我們知道在二線我們會有 cabo。

And then we've done the same in thinking about that late-line patient population with what then becomes another TKI that you would use in the late line. And like I said, the other important thing there is that we are going to look at that combination of Cas with that TKI in belzutifan experienced patients and establish that unequivocally. You get the activity that you want to see in that HIF-2 experienced patient.

接著我們也用同樣的方式思考後線（late-line）病人族群：在後線你會使用的另一個 TKI 會是什麼。而且如我所說，另一個重要點是，我們會在使用過 belzutifan 的病人中，評估 Cas 與該 TKI 的組合，並把這件事明確地建立起來。也就是在已接受過 HIF-2 治療的病人身上，你能看到你想要的活性。

Jason Zemansky, Bank of America.

Jason Zemansky，美國銀行（Bank of America）。

This is Jackie on for Jason Zemansky. Congrats on the progress. Just a quick one for you. So what do you think is necessary to drive broad uptake of a TKI-free regimen in the first-line RCC, given how popular TKIs are overall, especially given their ability to rapidly debulk tumors? Or is the goal to compete directly with dual IO therapies?

我是代 Jason Zemansky 發問的 Jackie。恭喜進展順利。我這邊一個簡短問題。鑑於 TKI 整體上非常受歡迎，尤其是它們能快速縮小腫瘤體積，在一線 RCC 中，你認為要推動「不含 TKI」方案的廣泛採用，需要具備哪些條件？或者目標是要直接與雙 IO 治療競爭？

So I think -- so what's interesting is we think there is a strong receptivity towards this. Now one of the most important things that we've seen to date is that casdatifan as a monotherapy, even in the late line, performs -- is good or better than TKI in any line of setting. So if you go -- we have in our deck somewhere, you can actually look that even in the late line casdatifan monotherapy, whether you're looking at ORR or PFS, looks quite good. And the thing that's standing out, and I think this is the issue that was identified with belzutifan at the outset was that rate of primary progression. So I think that's raised the question for HIF-2 inhibition, can you compete with TKI at bringing that tumor under control quick enough that you don't have that high rate of primary progression.

所以我認為——有趣的是，我們認為市場對此有很強的接受度。目前我們看到最重要的一點是：casdatifan 作為單藥治療，即使在後線，表現——也不輸於、甚至優於任何治療線別中的 TKI。所以如果你去看——我們在簡報某處有放，你其實可以看到，即便在後線使用 casdatifan 單藥，不論看 ORR 或 PFS，看起來都相當不錯。而真正突出的點——我認為這也是一開始 belzutifan 被指出的問題——是原發性進展（primary progression）的比例。因此這就引發了對 HIF-2 抑制的疑問：你能否像 TKI 一樣，夠快把腫瘤控制住，避免出現高比例的原發性進展。

So we believe that belzutifan was forced in the front line to combine with the TKI to address a potential high rate of primary progression, but we actually think that despite the fact that HIF-2 inhibition is well tolerated, it can get the tumor under control quite fast. And the place where we've already seen our evidence of that is in combining with anti-PD-1, where in 30 patients, we only saw two progressors, two primary progressors. So 7%, very much in line with the TKI.

所以我們認為，belzutifan 在一線被迫要與 TKI 併用，是為了處理可能偏高的原發性進展比例；但我們其實認為，儘管 HIF-2 抑制的耐受性良好，它仍然可以相當快速地把腫瘤控制住。而我們已經看到的證據是在與 anti-PD-1 併用時：在 30 位病人中，我們只看到兩位進展者、兩位原發性進展者。也就是 7%，非常符合 TKI 的水準。

So we think there's a receptivity to the TKI-sparing regimen, and we think that the key thing to driving that uptake will be to show that our rate of primary progression and then everything that flows from, that looks like a TKI. The last point I would make is it's almost like there -- the mentality would be like because TKIs are a rougher treatment, it's sort of like when you think about chemotherapy that there's a linkage that sort of in people's minds, they associate rougher, but bringing the tumor more under control.

因此我們認為市場對於不含 TKI 的治療方案具有接受度，而推動採用的關鍵在於證明我們的主要進展（primary progression）發生率，以及由此延伸出的整體表現，看起來能夠達到類似 TKI 的效果。我最後想補充的一點是，這幾乎像是——因為 TKI 是較為辛苦的治療，某種程度上就像你想到化療時一樣，人們心中會有一種連結：他們把「更辛苦」與「能把腫瘤控制得更好」聯想在一起。

Keep in mind that 85% to 90-plus percent of clear cell RCC has HIF-2 as a key driver. So you're hitting the tumor with something that really matters. And we think that's why with a robust HIF-2 inhibitor like casdatifan, you actually can compete with the efficacy effects of a TKI.

請記住，85% 到 90% 以上的透明細胞型腎細胞癌（clear cell RCC）是以 HIF-2 作為關鍵驅動因子。因此你是在用一個真正重要的靶點去打擊腫瘤。我們認為這也是為什麼像 casdatifan 這樣強效的 HIF-2 抑制劑，確實可以在療效上與 TKI 競爭。

Add one other point is like, I think Dr. McKay in our event in the fall indicated this that the reasons you really prefer using ipi/nivo for the most part is it gives the patients the best chance for long-term survival. And the problem is the Achilles heel as Terry described, of the primary progression. So if you could blunt that and still give patients the best chance of long-term survival and we just saw 10-year follow-up data with 40% of patients alive 10 years later, that's a very compelling regimen we think.

再補充一點，我記得 McKay 醫師在我們秋季的活動中提到：之所以多數情況下你會偏好使用 ipi/nivo，是因為它能讓病人獲得最佳的長期存活機會。問題在於，如 Terry 所描述的，其阿基里斯腱是主要進展（primary progression）。因此如果你能抑制這一點，同時仍然讓病人保有最佳的長期存活機會——我們剛看到 10 年追蹤資料顯示有 40% 的病人在 10 年後仍然存活——我們認為那會是一個非常具吸引力的治療方案。

Emily Bodnar, H.C. Wright.

Emily Bodnar，H.C. Wright。

Based on the LITESPARK-011 data, how are you kind of looking at your upcoming Cas plus cabo updated data? And what are you kind of hoping to see to feel confident that you might have a superior profile versus what we saw in the LITESPARK-011 trial?

根據 LITESPARK-011 的數據，你們如何看待即將更新的 Cas 加 cabo 的數據？你們希望看到什麼，才能有信心認為相較於我們在 LITESPARK-011 試驗中看到的結果，你們可能具有更優的整體特徵（profile）？

Yes. So we already feel that confidence, and we're obviously running the Phase III trial. I think you kind of have to think of things holistically. In the end, what you're going to have is a hazard ratio. And what's nice is that since we are both running versus cabo, those will be directly comparable.

是的。我們其實已經有這樣的信心，而我們也正在進行第三期試驗。我認為你必須以整體角度來看。最後你會得到的是一個風險比（hazard ratio）。而好的地方在於，因為我們雙方都是以 cabo 作為對照，因此結果將可直接比較。

While our data when we share later this year, we will still be early, we're going to give Kaplan-Meier curve. We'll have landmark PFS, we'll have ORR. And people will be able to extrapolate to whatever extent how they want to look at those data, but we'll give a very holistic view. I think the other thing that we don't want lost on people because we think it's an interesting other aspect of the data that really will only be emerging. And we'll see how things play out by the time we have some mature data later this year.

我們在今年稍晚分享數據時仍會偏早期，但我們會提供 Kaplan-Meier 曲線。我們會有里程碑式（landmark）的 PFS、也會有 ORR。大家可以在一定程度上依自己的方式去外推、解讀這些數據，但我們會提供非常全面的觀點。我認為另外一點是，我們不希望大家忽略一個我們覺得很有趣、但真正要到後續才會逐步浮現的數據面向。我們也會看看在今年稍晚取得較成熟數據時，整體走勢會如何發展。

So while from a regulatory standpoint, the PFS is what matters, we're going to have data now our -- from our monotherapy cohorts that are getting mature enough that we'll start to get a sense of whether we do bring an OS advantage there, albeit in the late line. And the reason we feel that's important is it just -- depending on how that looks for casdatifan, it will potentially give a good sense that this mechanism can not only drive enhancements in PFS, but bring enhancements to OS. And while that may not be a requirement from a regulatory standpoint, we certainly could see it as an important differentiation that would drive more uptake by clinician, in fact, we start to show that there can be OS enhancement from HIF-2 inhibition, which we believe there's no reason there shouldn't be.

因此，雖然從法規角度來看，PFS 才是關鍵，但我們現在——來自單藥（monotherapy）隊列的數據——已逐漸成熟到足以讓我們開始判斷：即便是在後線治療，我們是否能帶來整體存活（OS）的優勢。我們之所以認為這很重要，是因為——取決於 casdatifan 的表現——它可能提供一個很好的訊號，顯示這個機制不僅能提升 PFS，也能提升 OS。而即使從法規角度這不是必要條件，我們仍然認為這可能是一個重要的差異化因素，能促使臨床醫師更願意採用；事實上，如果我們開始證明 HIF-2 抑制能帶來 OS 的提升，將會推動更多使用，而我們相信沒有理由不會如此。

Yigal Nochomovitz, Citigroup.

Yigal Nochomovitz，花旗集團（Citigroup）。

This is Joohwan Kim on for Yigal. Congrats on the progress. Maybe just to mix in a noncash question. Regarding AB102, while it's still early, is there any color you can provide on the intended proof-of-concept study design, whether you're planning on going into CSD versus AD first? Any color on primary endpoints or level of clinical signal you need to see to give confidence to advance into a future registrational program?

我是代替 Yigal 的 Joohwan Kim。恭喜你們的進展。也許穿插一個與現金無關的問題。關於 AB102，雖然仍在早期階段，你們是否能提供一些資訊，說明預期的概念驗證（proof-of-concept）研究設計？例如你們計畫先進入 CSD 還是先進入 AD？另外，主要終點（primary endpoints）或你們需要看到何種程度的臨床訊號，才能有信心推進到未來的註冊性（registrational）計畫？

So Juan, why don't you describe how we see ourselves going from A to B to C in the near term?

那 Juan，你要不要說明一下我們近期如何看待從 A 到 B 到 C 的推進路徑？

Yes. So at a very high level, we have recognized that while we think we may have a better molecular profile, we have a little bit of ground that we need to make up relative to the couple of existing clinical players. So what we've devised is a fairly accelerated plan for establishing PK tolerability in healthy volunteers, followed by a fairly quick, rapid mechanistic confirmation of biological activity and very quickly progressing into a Phase II study in CSU.

好的。從非常高層次來看，我們已經認知到：即便我們認為分子層面的特徵可能更好，但相較於現有的幾個臨床競爭者，我們仍有一些進度需要追趕。因此我們制定了一個相當加速的計畫：先在健康受試者中建立 PK 與耐受性，接著以相當快速的方式，透過機制性驗證來確認生物活性，並且很快推進到 CSU 的第二期研究。

So we think we will in reasonable speed, catch up and hopefully begin to illustrate the better profile of our drug. In parallel with that, we're thinking about where it might make sense concurrently with that CSU type of Phase II study to demonstrate the value of an MRGPRX2 inhibitor.

因此我們認為，我們將以合理的速度追上進度，並希望開始展現我們藥物更佳的特徵。同時，我們也在思考：在進行這類 CSU 第二期研究的同時，在哪些情境下並行展示 MRGPRX2 抑制劑的價值會是合理的。

Right now, our lead candidate for that additional indication seems to be allergic asthma, but that's still at a very early stage of conceptual framing.

目前，我們針對這個額外適應症的首選候選似乎是過敏性氣喘，但這仍處於非常早期的概念建構階段。

There are no further questions at this time. This concludes today's call. Thank you for attending. You may now disconnect.

目前沒有其他問題。今天的電話會議到此結束。感謝各位參與。您現在可以掛線。