Arcus Biosciences Inc (RCUS) 2023 Q4 法說會逐字稿

Hello, and welcome to the Arcus Biosciences' full year/Q4 2023 earnings call. My name is Elliott, and I'll be coordinating your call today. (Operator Instructions)

您好，歡迎參加 Arcus Biosciences 的 2023 年全年/第四季財報電話會議。我叫艾利歐特，今天我將協調您的電話。（操作員說明）

I'd now like to hand over to Pia Eaves, Vice President of Investor Relations. The floor is yours.

現在我想將工作交給投資者關係副總裁 Pia Eaves。地板是你的。

Hello, everyone, and thank you for joining us on today's conference call to discuss Arcus's fourth-quarter 2023 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 cash runway and our expected clinical development, milestones, and timelines.

大家好，感謝您參加今天的電話會議，討論 Arcus 2023 年第四季的財務業績和管道更新。我想提醒您，在這次電話會議上，管理層將做出前瞻性聲明，包括有關我們的現金跑道以及我們預期的臨床開發、里程碑和時間表的聲明。

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 annual report on Form 10-K, which has been filed with the SEC. We strongly encourage you to review our filings.

除歷史事實外的所有陳述均反映了管理層當前的信念和期望，並涉及可能導致我們的實際結果與所表達的結果不同的風險和不確定性。這些風險和不確定性在我們已向 SEC 提交的 10-K 表格年度報告中進行了描述。我們強烈建議您查看我們的備案文件。

Today you'll hear from our CEO, Terry Rosen; COO, Jennifer Jarrett; CMO, Dmitry Nelson; and CFO, Bob Goeltz. We will also be joined by our President, Juan Jaen, for questions after the prepared remarks.

今天您將聽到我們執行長 Terry Rosen 的演講；營運長詹妮弗·賈勒特；首席行銷長德米特里·尼爾森；和財務長鮑勃·戈爾茨。我們的主席胡安·哈恩也將在準備好的演講後與我們一起回答問題。

During today's call, we'll refer to slides in our corporate deck, which can be found on the Investors section of our website.

在今天的電話會議中，我們將參考公司幻燈片中的幻燈片，這些幻燈片可以在我們網站的投資者部分找到。

With that, I'll now turn it over to Terry.

有了這個，我現在將把它交給特里。

Thanks very much, Pia. And thank you all for joining us today. We've really come a long way since our founding nine years ago. And I think it's fair to say we have evolved into an integrated biopharmaceutical company. We got seven molecules in clinical development, a broad late-stage portfolio, multiple mid-stage clinical trials, a robust discovery engine, and now something, I think, new, a line of sight to commercialization.

非常感謝，皮婭。感謝大家今天加入我們。自九年前成立以來，我們確實取得了長足的進步。我認為可以公平地說我們已經發展成為一家綜合性生物製藥公司。我們有七個處於臨床開發階段的分子，一個廣泛的後期產品組合，多個中期臨床試驗，一個強大的發現引擎，現在我認為，新的東西，商業化的視線。

With $1.2 billion in cash and equivalents and runway into 2027, we're well positioned to deliver on the promise of the late-stage pipeline that we've built. With our three new registrational trials, we're going to continue to invest in our early-stage programs.

憑藉 12 億美元的現金和等價物以及到 2027 年的跑道，我們完全有能力兌現我們已建立的後期管道的承諾。透過我們的三個新的註冊試驗，我們將繼續投資於我們的早期計畫。

We also have a partnership with Gilead as well as collaborations with Taiho, Exelixis, and AstraZeneca. And I think it's very fair to say without these partnerships and the resources that these companies provide, we would not be able to execute on everything that we're doing.

我們還與吉利德 (Gilead) 建立了合作夥伴關係，並與 Taiho、Exelixis 和阿斯特捷利康 (AstraZeneca) 進行了合作。我認為可以公平地說，如果沒有這些合作夥伴關係和這些公司提供的資源，我們將無法執行我們正在做的一切。

All of our programs target markets that are massive and really are the sweet spots of large pharmaceutical companies. All-comer patient populations in lung cancer, gastric cancer, pancreatic cancer, and renal cell carcinoma, RCC.

我們所有的項目都針對龐大的市場，並且確實是大型製藥公司的最佳選擇。肺癌、胃癌、胰腺癌和腎細胞癌 (RCC) 的所有患者群體。

Our funding and partnerships enable us to not only pursue these settings but to compete and compete effectively and aggressively. We're really doing what we're saying we're doing.

我們的資金和合作夥伴關係不僅使我們能夠追求這些環境，而且使我們能夠有效、積極地競爭。我們確實在做我們所說的話。

We also continue to build for the long term, with a broad pipeline of potential best-in-class and first-in-class product candidates that will continue to replenish organically with our drug discovery engine.

我們也繼續著眼於長期發展，擁有廣泛的潛在一流和一流候選產品管道，這些管道將繼續透過我們的藥物發現引擎進行有機補充。

Today, we have three advanced clinical-stage programs, dom plus zim, our Fc-silent and anti-TIGIT. It's a very differentiated molecule and our anti-PD-1 antibody. Quemli, our small molecule CD73 inhibitor; AB521, our HIF-2 alpha inhibitor, which is as of today known by its generic name casdatifan or Cas.

今天，我們有三個先進的臨床階段項目：dom plus zim、我們的 Fc-silent 和 anti-TIGIT。它是一種非常差異化的分子，也是我們的抗 PD-1 抗體。Quemli，我們的小分子 CD73 抑制劑； AB521 是我們的 HIF-2 α 抑制劑，目前其通用名稱為 casdatifan 或 Cas。

Dom zim is in Phase 3 and we expect to initiate Phase 3 studies for both Cas and Quemli by early next year. So we'll have four molecules all with distinct mechanisms in Phase 3 in 2025. We also have some exciting data sets coming in the first half of this year for another molecule and these really are exciting.

Dom zim 正處於第三階段，我們預計在明年初啟動 Cas 和 Quemli 的第三階段研究。因此，到 2025 年，我們將在第三階段出現四種具有不同機制的分子。今年上半年我們還獲得了另一種分子的一些令人興奮的數據集，這些數據確實令人興奮。

Etruma, that's our A2 receptor antagonist, and it's (inaudible) support further investment in the molecule. We made a lot of progress across all these programs in 2023, presenting two large datasets for dom zim in two different cancers and another large data set just last month for Quemli in pancreatic cancer.

Etruma，這是我們的 A2 受體拮抗劑，它（聽不清楚）支持對該分子的進一步投資。2023 年，我們在所有這些項目上取得了很大進展，推出了 dom zim 在兩種不同癌症中的兩個大型數據集，以及上個月推出的 Quemli 在胰腺癌中的另一個大型數據集。

I want to start today by reviewing these programs and data sets and I will spend a few minutes on the recent Gilead partnership updates and finish with some new data for Cas, our HIF-2 alpha inhibitor.

我想從今天開始回顧這些程序和數據集，然後我將花幾分鐘時間了解最近的吉利德合作夥伴關係更新，並以我們的 HIF-2 α 抑製劑 Cas 的一些新數據結束。

So starting with our anti-TIGIT program, dom zim. Our primary competitors in this space are Merck and Roche. We have the only Fc-silent anti-TIGIT antibody in late-stage clinical development. So with dom's potentially best-in-class profile, that's optimized dosing regimens as well as a broad development program focused on lung and gastric cancers, we're really in a very strong competitive position.

那麼從我們的反 TIGIT 程式 dom zim 開始。我們在這個領域的主要競爭對手是默克和羅氏。我們擁有唯一處於後期臨床開發階段的 Fc 沉默抗 TIGIT 抗體。因此，憑藉 dom 潛在的同類最佳概況、優化的給藥方案以及專注於肺癌和胃癌的廣泛開發計劃，我們確實處於非常強大的競爭地位。

Our conviction in dom zim is supported by good dataset that we presented in the last 12 months and are summarized on slide 9 of our corporate deck. First, in ASCO last year, we presented data from our randomized Phase 2 ARC-7 study showing a PFS hazard ratio of 0.67 for dom zim relative to zim monotherapy in first-line PD-L1 high non-small cell lung cancer.

我們對 dom zim 的信念得到了我們在過去 12 個月中提供的良好數據集的支持，並在我們公司幻燈片 9 中進行了總結。首先，在去年的 ASCO 上，我們展示了隨機 2 期 ARC-7 研究的數據，顯示在一線 PD-L1 高非小細胞肺癌中，dom zim 相對於 zim 單藥治療的 PFS 風險比為 0.67。

We also presented data from our Phase 2 EDGE-Gastric study, where we evaluated dom zim plus chemo in first-line upper GI cancers at the ASCO Plenary session in November. These data demonstrated an impressive six-month landmark PFS rates of 93% in PD-L1 high patients, 77%. overall. This really compares quite favorably to the historical benchmarks for anti-PD-1 plus chemo that are in the 50% to 60% range.

我們也展示了 2 期 EDGE-胃研究的數據，我們在 11 月的 ASCO 全體會議上評估了 dom zim 聯合化療對一線上消化道癌症的療效。這些數據表明，PD-L1 高患者的 6 個月里程碑式 PFS 率為 93%（77%），令人印象深刻。全面的。與抗 PD-1 加化療的歷史基準（50% 至 60%）相比，這確實相當有利。

Our development program for dom zim is focused on settings where we have the best chance to be market leader. Today, we have three Phase 3 trials enrolling, and we expect both STAR-121 and STAR-221, our chemo combo trials and PD-L1 all-comers for first-line non-small cell lung cancer in upper GI cancers respectively to complete enrollment this year.

我們的 dom zim 開發計劃專注於我們最有機會成為市場領導者的環境。今天，我們有三個 3 期試驗正在入組，我們預計 STAR-121 和 STAR-221、我們的化療組合試驗和 PD-L1 all-comers 分別用於治療上消化道癌症的一線非小細胞肺癌今年招生。

In fact, we can share now today that we anticipate STAR-221 will be fully enrolled by the middle of this year. Due to the extremely rapid enrollment of STAR-221 and relatively short OS for the standard of care, we expect STAR-221 to be the first of our Phase 3 trials to read out. And importantly, with no other Phase 3 trials ongoing with the anti-TIGIT antibodies in this setting, we expect to have a significant first-to-market advantage.

事實上，我們今天可以分享的是，我們預計 STAR-221 將在今年年中完全註冊。由於 STAR-221 的入組速度極快，且護理標準的 OS 相對較短，我們預期 STAR-221 將成為我們第一個進行的 3 期試驗。重要的是，由於在這種情況下沒有正在進行抗 TIGIT 抗體的其他 3 期試驗，我們預計將擁有顯著的率先上市優勢。

Meanwhile, we continue to invest in the expansion of our dom zim program. We and Gilead will initiate STAR-131, which will evaluate dom zim plus chemo in peri-operative lung cancer. This is an exciting early-stage and potentially curative setting. We also expect to initiate a fourth Phase 2 study in a setting outside of lung in GI cancers.

同時，我們繼續投資擴大 dom zim 計劃。我們和吉利德將啟動 STAR-131，該計畫將評估 dom zim 聯合化療對圍手術期肺癌的療效。這是一個令人興奮的早期階段且具有潛在療效的環境。我們也預計在肺癌以外的胃腸道癌症中啟動第四項 2 期研究。

Beyond our dom zim program today, we'll be sharing data from the dose escalation phase of our ARC-20 Phase 1b trial of Casdatifan or AB521. The 100 milligram expansion cohort of ARC-20 enrolled quickly and it completed enrollment ahead of schedule November of last year.

除了今天的 dom zim 計劃之外，我們還將分享 Casdatifan 或 AB521 的 ARC-20 1b 期試驗的劑量遞增階段的數據。ARC-20的100毫克擴展隊列入組迅速，並於去年11月提前完成入組。

Later today, we'll touch on what we're seeing so far in these data. The competitor here is Merck with their shift to alpha inhibitor, belzutifan, which was just approved for advanced renal cell RCC. But we believe that Cas has a best-in-class profile, and that's addressing a very well-recognized limitation of belzutifan.

今天晚些時候，我們將討論迄今為止在這些數據中看到的內容。這裡的競爭對手是默克公司，他們轉向α抑制劑belzutifan，該藥物剛被批准用於晚期腎細胞腎細胞癌。但我們相信 Cas 擁有一流的配置，這解決了 belzutifan 眾所周知的限制。

What we've seen thus far in ARC-20 has given us confidence that our molecule has a superior profile to belzutifan. We're advancing Cas rapidly and are on track to initiate a Phase 3 study early next year.

迄今為止我們在 ARC-20 中所看到的情況讓我們相信我們的分子具有優於 belzutifan 的特性。我們正在快速推進 Cas，並預計在明年初啟動 3 期研究。

And last for Quemli, our CD73 inhibitor, we presented overall survival data in pancreatic cancer from our ARC-8 study at ASCO GI last month. With a large pool of dataset, 122 patients, we showed 15.7 months median overall survival for Quemli plus chemo, both with and without zim.

最後，對於我們的 CD73 抑制劑 Quemli，我們上個月在 ASCO GI 上展示了來自 ARC-8 研究的胰臟癌整體存活數據。透過大量資料集（122 名患者），我們顯示 Quemli 合併化療（無論是否使用 zim）的中位總存活期為 15.7 個月。

This compares to the median OS from historical gem nab-paclitaxel studies nine to 11 months in first-line pancreatic cancer. We also conducted a map synthetic control analysis that showed a statistically significant improvement in OS with a hazard ratio of 0.63.

這與歷史上針對一線胰臟癌的寶石白蛋白結合型紫杉醇研究 9 至 11 個月的中位 OS 進行了比較。我們也進行了地圖綜合控制分析，結果顯示 OS 顯著改善，風險比為 0.63。

Based on the strength of this data, we are on track to initiate a Phase 3 pancreatic cancer trial by early next year. With Gilead equity investment in January, we had approximately $1.2 billion of cash on hand and we're really well capitalized to support the breadth of programs that we are pursuing.

根據這些數據的強度，我們預計在明年初啟動胰臟癌 3 期試驗。透過 1 月吉利德的股權投資，我們手頭上有大約 12 億美元的現金，我們的資本非常充足，可以支持我們正在實施的廣泛項目。

At a high level, Gilead's investment accomplishes two things. First, it provides us with runway into 2027, while enabling us to fund Phase 3 programs for four different molecules. Second, it enables us to fund our precommercial activities, and on the other end of the spectrum, to continue supporting our robust discovery engine.

從高水準來看，吉利德的投資完成了兩件事。首先，它為我們提供了通往 2027 年的跑道，同時使我們能夠為四種不同分子的第三階段項目提供資金。其次，它使我們能夠為我們的預商業活動提供資金，並在另一方面，繼續支持我們強大的發現引擎。

I'd like to turn things over to Jen right now to spend a few minutes on the details.

我現在想把事情交給 Jen，讓她花幾分鐘討論細節。

Thanks, Terry. Gilead invested $320 million by purchasing our stock at $21 per share, which represented an effective premium of nearly 40% to our share price just before the announcement, increasing their ownership to 33%. In parallel, Gilead's Chief Commercial Officer, Johanna Mercier, joined our Board. Her addition increases our Board membership to three, provides representation commensurate with our ownership, and bring a very experienced commercial perspective to the Arcus Board.

謝謝，特里。吉利德投資了 3.2 億美元，以每股 21 美元的價格購買了我們的股票，這比我們在宣布這一消息之前的股價有效溢價了近 40%，從而將其所有權增加到了 33%。同時，吉利德首席商務官 Johanna Mercier 也加入了我們的董事會。她的加入使我們的董事會成員增加到三名，提供了與我們的所有權相稱的代表權，並為 Arcus 董事會帶來了非常經驗豐富的商業視角。

The investment calls for two dynamics: one, the expansion of our late-stage clinical development plan; and two, the extension of our cash runway into 2027 and through multiple dataset. Concurrent with the investment, we made a few strategic portfolio changes related to dom zim and Quemli.

這項投資需要兩個動力：一是擴大我們的後期臨床開發計畫；第二，透過多個資料集將我們的現金跑道延伸至 2027 年。在投資的同時，我們對 dom zim 和 Quemli 進行了一些策略性投資組合調整。

First, for dom zim, we closed enrollment of our Phase 3, ARC-10 setting evaluating dom zim in PD-L1 high non-small cell lung to focus our resources and capital on areas with the highest unmet need and greatest market opportunity.

首先，對於dom zim，我們結束了3 期ARC-10 的招募，評估dom zim 在PD-L1 高非小細胞肺中的應用，以便將我們的資源和資本集中在未滿足需求最高和市場機會最大的領域。

The seminal factors that drove our decision with the evolution of the lung cancer treatment paradigm towards increased use of anti-PD-1 plus chemo for patients with PD-L1 high expressing tumors. Therefore, we believe this segment of the patient population is best addressed by our STAR-121 study, our chemo combination study; and PD-L1 all-comer non-small cell lung cancer.

隨著肺癌治療模式的發展，對 PD-L1 高表達腫瘤患者增加使用抗 PD-1 合併化療，推動我們做出決定的重要因素。因此，我們相信我們的 STAR-121 研究（我們的化療聯合研究）能夠最好地解決這部分患者群體的問題；和 PD-L1 全角非小細胞肺癌。

The clinical trial landscape for PD-L1 high lung has also become increasingly crowded with several anti-TIGIT and other investigational therapies. And we were not expected to be first or second in the PD-L1 high chemo-free setting.

PD-L1 高肺的臨床試驗環境也變得越來越擁擠，有多種抗 TIGIT 和其他研究療法。我們預計不會在 PD-L1 高免化療環境中成為第一或第二。

By closing ARC-10, we are now able to focus our energy and resources on rapidly completing enrollment for STAR-121, which is addressing a much larger market opportunity. We'll also initiate a fourth Phase 3 study for dom zim, STAR-131, a potential first-to-market opportunity.

透過關閉 ARC-10，我們現在能夠集中精力和資源來快速完成 STAR-121 的註冊，這將帶來更大的市場機會。我們還將啟動 dom zim 的第四項 3 期研究 STAR-131，這是一個潛在的首次上市機會。

Second, for Quemli, we announced Arcus will be operationalizing and funding a Phase 3 study evaluating Quemli in pancreatic cancer. Gilead retains an option to the pancreatic cancer program with the opportunity to pay a premium to their share of the Phase 3 costs in the future.

其次，對於 Quemli，我們宣布 Arcus 將實施並資助一項評估 Quemli 在胰臟癌中的 3 期研究。吉利德保留了胰腺癌計畫的選擇權，並有機會在未來支付其分攤的 3 期費用的溢價。

While Gilead is not co-funding the study, as you might imagine, they are aware that proceeds from the investment will be used to fund the study. I'll now turn it back to Terry.

正如您可能想像的那樣，雖然吉利德並沒有共同資助這項研究，但他們知道投資收益將用於資助這項研究。現在我將把它轉回給特里。

Thanks, Jen. Now I'd like to switch gears to Cas, HIF-2 alpha inhibitor. This year is essentially going to be coming out for this program as we're planning to release a lot of new data as well as more information on our future development plans.

謝謝，珍。現在我想改用 Cas、HIF-2 α 抑制劑。今年該計劃基本上即將結束，因為我們計劃發布大量新數據以及有關我們未來發展計劃的更多資訊。

We believe that by hitting the HIF-2 alpha target harder than Merck's belzutifan, we can improve outcomes for patients. We'll discuss the pharmacokinetics and pharmacodynamics that support this thesis in more detail shortly. But I'd like to start with the potential areas for differentiation versus belzutifan.

我們相信，透過比默克公司的 belzutifan 更努力地實現 HIF-2 α 目標，我們可以改善患者的治療結果。我們很快就會更詳細地討論支持本論文的藥物動力學和藥效學。但我想從與 Belzutifan 相比的潛在差異化領域開始。

Belzutifan was recently granted approvals monotherapy in third line clear cell RCC after just a three-month FDA review process. This really validated the mechanism and highlighted the high unmet need for new therapies in this market.

經過短短三個月的 FDA 審查過程後，Belzutifan 最近獲得批准用於三線透明細胞腎細胞癌的單一療法。這確實驗證了該機制，並凸顯了該市場對新療法的高度未滿足的需求。

In Merck's Phase 3 LITESPARK-005, belzutifan showed an improvement in PFS over everolimus with a statistically significant hazard ratio of 0.74, which supported its approval. While these results are absolutely encouraging, the study reveals multiple opportunities for new agents to improve upon belzutifan's profile and provide even more benefit to patients.

在默克公司的 3 期 LITESPARK-005 中，belzutifan 的 PFS 較依維莫司有所改善，其統計顯著風險比為 0.74，這支持了其批准。雖然這些結果絕對令人鼓舞，但該研究揭示了新藥有多種機會改善 belzutifan 的概況並為患者提供更多益處。

First, on clinical efficacy in LITESPARK-005, belzutifan had a high rate of primary progression, specifically of 34% PD rate, which was actually higher than that of the everolimus control arm at 22%. This means that over one-third of patients on belzutifan progress at or before their first scan.

首先，就LITESPARK-005的臨床療效而言，belzutifan具有較高的原發進展率，特別是34%的PD率，實際上高於依維莫司對照組的22%。這意味著超過三分之一的服用 Belzutifan 的患者在第一次掃描時或之前出現了進展。

We believe that Casdatifan could stabilize tumor growth faster, resulting in a lower PD rate, and therefore, longer PFS. Second, with an overall response rate of 21.9% in LITESPARK-005, we believe there is room for improvement.

我們相信 Casdatifan 可以更快地穩定腫瘤生長，從而降低 PD 率，從而延長 PFS。其次，LITESPARK-005 的整體回應率為 21.9%，我們認為還有改進的空間。

Third, while LITESPARK-005 showed a statistically significant PFS hazard ratio, the median PFS was only 5.6 months. Cas may result in more durable tumor stabilization shrinkage, therefore, longer median PFS.

第三，雖然 LITESPARK-005 顯示統計上顯著的 PFS 風險比，但中位 PFS 僅為 5.6 個月。Cas 可能會導致更持久的腫瘤穩定收縮，因此中位 PFS 更長。

Fourth, and this is an important part, we believe there's an opportunity for a better tolerated combination regimen. Belzutifan's TKI partner in earlier line ccRCC studies is lenvatinib, which is perceived -- it's really as perceived that way -- to be less well tolerated relative to other TKIs such as (inaudible) and zanza.

第四，這是一個重要的部分，我們相信有機會獲得更好耐受的聯合治療方案。Belzutifan 在早期 ccRCC 研究中的 TKI 合作夥伴是樂伐替尼 (lenvatinib)，人們認為（確實如此）相對於其他 TKI（例如（聽不清楚）和 zanza），其耐受性較差。

Last, we are being very thoughtful in our development strategy for Cas, and we'll focus on settings and combinations where we believe we can be first to market or differentiated relative to belzutifan. And you'll hear more about this over the course of the year.

最後，我們對 Cas 的開發策略非常深思熟慮，我們將專注於我們相信我們可以率先進入市場或相對於 Belzutifan 實現差異化的設定和組合。在這一年裡你會聽到更多關於這方面的資訊。

As you may know, Merck is now projecting that belzutifan has blockbuster potential. Given the opportunity, we're pushing this program as hard as possible. And while our data will be more mature later this year, we want to share as much as possible today to illustrate why we're so excited about this program.

如您所知，默克現在預測 Belzutifan 具有重磅炸彈的潛力。如果有機會，我們將盡最大努力推動該計劃。雖然我們的數據將在今年晚些時候變得更加成熟，但我們今天希望盡可能多地分享，以說明為什麼我們對這個計劃如此興奮。

I'll now turn things over to Dmitry to share new data from our ARC-20 trial evaluating tests Cas in cancer patients.

我現在將把事情交給 Dmitry，分享我們的 ARC-20 試驗的新數據，該試驗評估了癌症患者的 Cas 測試。

Thanks, Terry. I'll start by turning to slide 29 of our corporate deck, which shows design of the trial, including both the dose escalation phase and expansion cohorts. The dose escalation portion enrolled patients with any advanced solid tumor while the dose expansion cohorts are only enrolling patients with second line or later clear cell RCC.

謝謝，特里。我將首先查看我們公司幻燈片的第 29 張幻燈片，其中顯示了試驗的設計，包括劑量遞增階段和擴展隊列。劑量遞增部分招募了任何晚期實體瘤患者，而劑量擴展隊列僅招募了第二線或後期透明細胞腎細胞癌患者。

There are three expansion cohorts; each of which will enroll 30 patients. The first evaluated our go-forward dose of 100 milligrams per day and completed enrollment in November. To satisfy the FDA's requirement for dose optimization, we are also evaluating a 50 milligram dose cohort and another cohort at a higher dose than 100 milligram in the expansion phase. Enrollment of the 50 milligram cohort is nearing completion.

共有三個擴展隊列；每個將招募30名患者。第一個評估了我們每天 100 毫克的前進劑量，並於 11 月完成了註冊。為了滿足 FDA 對劑量優化的要求，我們也在擴展階段評估一個 50 毫克劑量組和另一個劑量高於 100 毫克的組別。50 毫克隊列的註冊工作即將完成。

Collectively, these expansion cohorts will generate a lot of valuable safety data and efficacy data in clear cell RCC patients. The dose escalation portion employs a three-by-three design where three patients received 20 milligrams followed by three patients who received 50 milligrams, and then three patients who received 100 milligrams oral daily dosing regimens.

總的來說，這些擴展隊列將在透明細胞腎細胞癌患者中產生大量有價值的安全性數據和療效數據。劑量遞增部分採用三乘三的設計，其中三名患者接受 20 毫克，隨後三名患者接受 50 毫克，然後三名患者接受 100 毫克每日口服給藥方案。

The safety results of our healthy volunteer trial enabled us to start in ARC-20, our patient trial, at a relatively high and pharmacologically relevant dose. And we saw no dose-limiting toxicities, allowing us to complete the dose escalation phase with only nine patients.

我們的健康志願者試驗的安全性結果使我們能夠以相對較高且藥理學相關的劑量開始患者試驗 ARC-20。我們沒有發現劑量限制性毒性，使我們能夠僅在九名患者的情況下完成劑量遞增階段。

We subsequently backfilled the 50 milligram dose cohort with three additional patients resulting in 12 patient data set for this portion of the study. Of the 12 patients, four patients have clear cell RCC.

隨後，我們又以 3 名患者回填了 50 毫克劑量的隊列，從而為這部分研究提供了 12 名患者數據集。在 12 名患者中，4 名患者患有透明細胞腎細胞癌。

Slide 30 is important and shows data for Cas and belz on EPO reductions, the peripheral or normal tissue biomarker for HIF-2 alpha inhibition. On the left hand side, the dotted line shows the EPO reductions reported for the 120 milligram or the approved dose of belzutifan in clear cell RCC patients.

幻燈片 30 很重要，顯示了 Cas 和 belz 關於 EPO 減少的數據，EPO 是 HIF-2 α 抑制的外周或正常組織生物標記。左側，虛線顯示了 120 毫克或批准劑量的 Belzutifan 在透明細胞 RCC 患者中報告的 EPO 減少。

In contrast, Cas achieves the same level of EPO suppression at just 20 milligrams, showing here with the purple line. And that is one-fifth of our go-forward dose of 100 milligrams. This means that 20 milligrams is roughly equivalent from a PD perspective to the approved dose of belzutifan and therefore, 100 milligrams of Cas has the potential to achieve a meaningfully greater HIF-2 alpha inhibition.

相比之下，Cas 只需 20 毫克即可實現相同水平的 EPO 抑制，如紫色線所示。這是我們未來 100 毫克劑量的五分之一。這意味著從 PD 角度來看，20 毫克大致相當於 belzutifan 的批准劑量，因此，100 毫克 Cas 有潛力實現有意義的更大 HIF-2 α 抑制。

On the right hand of the slide, you can see that Cas has a linear, almost perfect dose-proportional pharmacokinetic profile. In addition, Cas has a half-life of approximately 21 hours and this enables daily dosing.

在投影片的右側，您可以看到 Cas 具有線性、幾乎完美的劑量比例藥物動力學特徵。此外，Cas 的半衰期約為 21 小時，因此可以每日給藥。

Slide 31 emphasizes the ideal PK of Cas relative to that of belzutifan. And it explains why belzutifan cannot simply be dose higher to achieve greater HIF-2 alpha ambition. On the right, for Cas, we showed that we increased dose from 20 to 100 milligrams at steady-state and we observed roughly five times increase in exposure.

幻燈片 31 強調了 Cas 相對於 belzutifan 的理想 PK。這也解釋了為什麼 Belzutifan 不能簡單地提高劑量來實現更大的 HIF-2 α 目標。在右側，對於 Cas，我們表明我們在穩態時將劑量從 20 毫克增加到 100 毫克，並且我們觀察到暴露量增加了大約五倍。

By comparison, as you can see on the left, when belz' dose increased from 120 to 240 milligrams, the drug exposure only increased by about 30% at steady-state. A 30% increase in exposure is less than the typical patient-to-patient variability at any given dose, and therefore, is not a clinically meaningful increase.

相較之下，如左圖所示，當 Belz 的劑量從 120 毫克增加到 240 毫克時，穩態下藥物暴露僅增加了約 30%。暴露量增加 30% 小於任何給定劑量下典型的患者之間的變異性，因此，這不是具有臨床意義的增加。

This illustrates why dose as high than 120 milligrams of belzutifan are unlikely to result in meaningfully better clinical activity. And in fact, this was demonstrated by Merck in the LITESPARK-013 trial comparing the efficacy of 120 milligrams and 200 milligrams of belzutifan.

這說明了為什麼劑量高於 120 毫克的 bezutifan 不太可能產生有意義的更好的臨床活性。事實上，默克在 LITESPARK-013 試驗中證明了這一點，該試驗比較了 120 毫克和 200 毫克 belzutifan 的功效。

In summary, these data show exactly what we have been predicting that Cas has a best-in-class PK/PD profile, which should result in hitting the target harder and potentially in greater clinical activity relative to belzutifan.

總之，這些數據準確地顯示了我們一直以來的預測，Cas 具有一流的 PK/PD 特徵，這應該會導致比 belzutifan 更難達到目標，並可能具有更大的臨床活性。

Turning now to safety on slide 32, we showed reductions in hemoglobin levels at various doses of Cas relative to the approved dose of belzutifan. Hemoglobin reductions appear to plateau at doses above 50 milligrams for Cas likely due to compensatory mechanisms. And you can see that 100 milligrams daily of Cas resulted in similar reductions of hemoglobin as belzutifan, despite the fact that we are achieving higher doses, much higher doses of potency, corrected drug exposure for Cas. For this reason, we expect Cas's safety profile to be manageable and not meaningfully different than belzutifan.

現在轉向第 32 張投影片的安全性，我們顯示不同劑量的 Cas 相對於 Belzutifan 的核准劑量，血紅素水平有所降低。Cas 劑量超過 50 毫克時，血紅素減少似乎趨於穩定，這可能是由於補償機制所致。您可以看到，每天服用 100 毫克 Cas 會導致與 Belzutifan 類似的血紅蛋白減少，儘管事實上我們正在實現更高的劑量、更高的效力劑量、校正的 Cas 藥物暴露。因此，我們預計 Cas 的安全性是可控的，並且與 belzutifan 沒有顯著差異。

On the next slide, slide 33, we show the AE profile so far in the dose escalation phase of the study. Anemia and hypoxia are expected on-target toxicities related to have HIF-2 alpha inhibition. While we are watching very closely with a median follow-up across all dose levels of the escalation of about 8.8 months so far, these rates do not appear to be higher than the rate seen with belzutifan in historical clinical trials. These data demonstrates that while we believe that we are hitting the target harder, Cas appears to have a similar safety profile to that of belzutifan.

在下一張投影片（投影片 33）中，我們展示了迄今為止在研究劑量遞增階段的 AE 概況。貧血和缺氧是與 HIF-2 α 抑制相關的預期毒性。雖然我們正在非常密切地觀察迄今為止約 8.8 個月的升級中所有劑量水平的中位隨訪，但這些比率似乎並不高於歷史臨床試驗中貝爾祖替芬的比率。這些數據表明，雖然我們相信我們正在更加努力地實現目標，但 Cas 似乎具有與 belzutifan 相似的安全性。

So let me tie this together. We are effectively able to deliver an exposure to Cas that is fivefold greater than -- that which achieves the same level of inhibition of the peripheral biomarker HIF-2 alpha blockade associated with the approved dose of belzutifan with no apparent differences in safety profile.

那麼讓我把它連結起來。我們能夠有效地提供比與已批准劑量的 Belzutifan 相關的外周生物標誌物 HIF-2 α 阻斷劑相同水平的 Cas 暴露量高五倍的暴露量，且安全性方面沒有明顯差異。

While efficacy was not the objective of the dose escalation phase, particularly given the advance stage of patients and the different doses evaluated and the different tumor types included on slide 34, we do summarize what we observed in RCC patients, specifically clear cell RCC patients. As I mentioned earlier, there are four patients spread across the three different dose levels being evaluated 20 milligrams, 50 milligrams, and 100 milligrams.

雖然療效不是劑量遞增階段的目標，特別是考慮到患者的晚期階段、評估的不同劑量以及幻燈片34 中包含的不同腫瘤類型，但我們確實總結了我們在RCC 患者（特別是透明細胞RCC 患者）中觀察到的情況。正如我之前提到的，有 4 名患者分佈在 20 毫克、50 毫克和 100 毫克三種不同劑量水平進行評估。

These are only nine patients with a variety of prior treatment regimens, including at least one anti-VEGF treatment and one anti-PD-1 treatments. Three out of four patients are actually fourth line or later. And for these four RCC patients, two have meaningful tumor reductions, just short of 30%. And the third patient did not experience any tumor growth for over 14 months and still remains on treatment.

這只是 9 名接受過多種既往治療方案的患者，包括至少一種抗 VEGF 治療和一種抗 PD-1 治療。四分之三的患者實際上處於第四線或更高線。對於這 4 名 RCC 患者，其中有 2 名患者的腫瘤縮小了，接近 30%。第三位患者在超過 14 個月的時間裡沒有出現任何腫瘤生長，仍在接受治療。

The time on treatment is impressive for these patients in very late-line setting, ranging from 8.5 to 14.5 months, and two of the four patients still remain on treatment. This indicates the potential of very durable effects of Cas, even with monotherapy in a very advanced patient population.

對於這些晚期患者來說，治療時間令人印象深刻，從 8.5 到 14.5 個月不等，四名患者中的兩名仍在接受治療。這表明即使在非常晚期的患者群體中採用單一療法，Cas 也具有非常持久的作用的潛力。

We are also seeing signs of Cas's ability to bring even aggressive tumor growth under control. For example, one of the four patients I mentioned was very heavily pretreated, had received three prior VEGF TKIs and anti-PD-1 treatment. And this patient had stable disease early on with slight increase in tumor volume, not meeting form of progression per resist.

我們也看到了 Cas 能夠控制侵襲性腫瘤生長的跡象。例如，我提到的四名患者之一接受了非常嚴格的預處理，之前接受過三種 VEGF TKI 和抗 PD-1 治療。該患者早期病情穩定，腫瘤體積略有增加，不符合每次抵抗的進展形式。

And after about 18 months, the tumor volume started to come down. And now after about 10 months and still ongoing on treatment, the patient is nearing a response. I would like to emphasize that while the primary goal of an all-comers dose escalation study is to establish the safety profile and assess the pharmacokinetics and pharmacodynamics, we have already seen clear signs of anti-tumor activity in patients with advanced clear cell RCC. And we believe that tumor shrinkage and the duration beyond one year for patients who have exhausted all available treatment options are very clinically meaningful.

大約18個月後，腫瘤體積開始縮小。現在，經過大約 10 個月的治療，該患者已接近緩解。我想強調的是，雖然所有人劑量遞增研究的主要目標是建立安全性並評估藥物動力學和藥效學，但我們已經在晚期透明細胞腎細胞癌患者中看到了明顯的抗腫瘤活性跡象。我們相信，對於用盡所有可用治療方案的患者來說，腫瘤縮小和持續時間超過一年是非常有臨床意義的。

The ongoing expansion portion of the phase is designed to give us a better read on the efficacy and this is already providing clear support for the initial observations in the dose escalation phase. And I would like to make a few comments on the early data of the expansion portion of the study.

此階段正在進行的擴展部分旨在讓我們更了解療效，這已經為劑量遞增階段的初步觀察結果提供了明確的支持。我想對研究擴展部分的早期數據發表一些評論。

The 100 milligram cohort has completed enrollment in November. So we have a mature and rich data set in hand for 30 clear cell patients treated at 100 milligrams of Cas. While these data are still early, we are already seeing glimpses of Cas's potential for differentiation over belzutifan. We'll share the full dataset at a medical conference later this year, but we did feel it was important to share some highlights of the data today.

100 毫克隊列已於 11 月完成註冊。因此，我們手頭上有 30 名接受 100 毫克 Cas 治療的透明細胞患者的成熟且豐富的數據集。雖然這些數據還處於早期階段，但我們已經看到了 Cas 相對 Belzutifan 的差異化潛力。我們將在今年稍後的醫學會議上分享完整的數據集，但我們確實認為今天分享數據的一些亮點很重要。

First, the majority of patients in the expansion cohort have only had one or two scans and we scan patients approximately every six weeks. So it's about 1.5 to 3 months of follow-up. Nonetheless, even with this very short duration of follow-up, the response rate we are seeing, which includes unconfirmed responses, given how limited the follow-up time is, it's already in line with the response rate seen for belzutifan in LITESPARK-005.

首先，擴展隊列中的大多數患者只進行了一兩次掃描，我們大約每六週對患者進行一次掃描。所以大約需要1.5到3個月的追蹤時間。儘管如此，即使追蹤時間很短，考慮到追蹤時間有限，我們看到的回應率（包括未經確認的回應）已經與 LITESPARK-005 中 Belzutifan 的回應率一致。

We also have a substantial number of patients early on their treatments who have experienced tumor shrinkage, but have not yet crossed the formal threshold of 30% to meet a response, but this obviously can happen with longer duration of treatment on future scans.

我們還有大量在治療早期的患者經歷了腫瘤縮小，但尚未跨越 30% 的正式閾值來達到緩解，但隨著未來掃描治療持續時間的延長，這種情況顯然可能會發生。

Secondly, we are seeing relatively low primary progression rate and this is the percentage of patients whose best overall response is progressive disease. So these patients have tumor progression on the first scan. This may indicate that Cas's ability -- that Cas can stabilize tumor growth early on during treatment. And this will be an important parameter to monitor in the future as it represents an opportunity to prove upon something that we last reported for belzutifan.

其次，我們看到原發進展率相對較低，這是最佳整體反應為疾病進展的患者的百分比。所以這些患者在第一次掃描時腫瘤就出現進展。這可能表明 Cas 的能力——Cas 可以在治療早期穩定腫瘤生長。這將是未來監控的一個重要參數，因為它代表了一個機會來證明我們上次為 belzutifan 報告的內容。

In summary, we are very encouraged by these early dose escalation and expansion cohort data, which while early have provided an encouraging signal that Cas's PK/PD profile could translate into greater efficacy in the clinic.

總之，我們對這些早期劑量遞增和擴展隊列數據感到非常鼓舞，這些數據雖然早期就提供了令人鼓舞的信號，表明 Cas 的 PK/PD 特徵可以轉化為臨床上更大的療效。

By midyear, we will have a minimum of seven months of follow-up for all 30 patients in the 100 milligram expansion cohort, which should provide a mature look at the overall response rate, and we expect to present these data at a medical conference in the second half of the year.

到年中，我們將對100 毫克擴展隊列中的所有30 名患者進行至少7 個月的隨訪，這將提供對總體緩解率的成熟觀察，我們預計將在2019 年的一次醫學會議上展示這些數據。下半年。

As I mentioned earlier, ARC-20 includes two additional expansion cohorts and we expect this to also be presented over the next 12 to 18 months. We also expect data from STELLAR-09, our study evaluating Cas together with also referred to as zanza sometime in 2025.

正如我之前提到的，ARC-20 包括兩個額外的擴展隊列，我們預計這也將在未來 12 到 18 個月內推出。我們還期望在 2025 年某個時候獲得 STELLAR-09 的數據，該研究評估了 Cas（也稱為 zanza）。

We are full speed ahead to our Phase 3 study and we expect to disclose more on our development plan in the coming months. Terry will outline our other catalysts for 2024. But first, I will turn things over to Bob to discuss our fourth-quarter and full-year financials.

我們正在全速進行第三階段研究，我們預計在未來幾個月內披露更多有關我們開發計劃的資訊。特里將概述我們 2024 年的其他催化劑。但首先，我將把事情交給鮑伯討論我們第四季和全年的財務狀況。

Thanks, Dmitry. As Terry outlined earlier, Arcus continues to be in a very strong financial position. Our cash as of December 31, 2023, was $866 million and increased to $1.2 billion after Gilead's January equity investment. Importantly, our partnership with Gilead is very capital efficient because we share the majority of costs for option programs, 50/50, including multiple Phase 3 studies for dom zim.

謝謝，德米特里。正如 Terry 之前概述的那樣，Arcus 的財務狀況仍然非常強勁。截至 2023 年 12 月 31 日，我們的現金為 8.66 億美元，在吉利德 1 月股權投資後增加至 12 億美元。重要的是，我們與吉利德的合作夥伴關係資本效率很高，因為我們以 50/50 的比例分擔了選項計劃的大部分成本，包括 dom zim 的多項 3 期研究。

Gilead has also committed to pay the $100 million option continuation payment due in July under the collaboration agreement. So we expect our cash balance at the end of 2024 to be between $870 million and $920 million and now expect our cash to fund operations into 2027. This guidance excludes other potential opt-in payments and approval milestones from our partners.

吉利德還承諾根據合作協議支付 7 月到期的 1 億美元選擇權持續付款。因此，我們預計 2024 年底的現金餘額將在 8.7 億至 9.2 億美元之間，現在預計我們的現金將為 2027 年的營運提供資金。本指南不包括我們合作夥伴的其他潛在選擇付款和批准里程碑。

Turning to our P&L, we recognized GAAP revenue for the fourth quarter of $31 million, which compares to $32 million for the third quarter of 2023. Our revenue is primarily driven by our collaboration with Gilead, and we are evaluating the impact of the recent amendment on our revenue for 2024 and beyond.

談到我們的損益表，我們確認第四季的 GAAP 收入為 3,100 萬美元，而 2023 年第三季的收入為 3,200 萬美元。我們的收入主要來自與吉利德的合作，我們正在評估最近的修正案對我們 2024 年及以後收入的影響。

In addition to our partnership with Gilead, we have a partnership with Taiho for dom in Japan. In the fourth quarter, we received a milestone payment of $14 million from Taiho related to their participation in STAR-221 pivotal study and we'll receive another $30 million in the first quarter of 2024 related to their participation in our STAR-221 and STAR-121 pivotal studies. We are also eligible for additional milestone payments of $10 million in the first quarter of 2025 from Taiho related to STAR-121.

除了與吉利德（Gilead）的合作夥伴關係外，我們還與日本 Taiho 的 dom 建立了合作夥伴關係。在第四季度，我們從Taiho 收到了與他們參與STAR-221 關鍵研究相關的1400 萬美元里程碑付款，我們將在2024 年第一季收到與他們參與我們的STAR-221 和STAR 相關的另外3000萬美元-121 關鍵研究。我們也有資格在 2025 年第一季從 Taiho 獲得與 STAR-121 相關的 1000 萬美元額外里程碑付款。

Our R&D expenses for the fourth quarter are stated net of reimbursements from Gilead and were $93 million as compared to $82 million in the third quarter of 2023. In the fourth quarter, non-cash stock compensation represented $9 million of our R&D expenses. The increase in the fourth quarter was related to standard-of-care purchases for our clinical trials.

我們第四季的研發費用扣除吉利德的報銷後為 9,300 萬美元，而 2023 年第三季的研發費用為 8,200 萬美元。第四季度，非現金股票補償占我們研發費用的 900 萬美元。第四季度的成長與我們臨床試驗的標準護理採購有關。

We continue to expect modest increases in R&D expenses as our Phase 3 studies mature. And spend will fluctuate primarily based on the timing of clinical manufacturing activities and the purchase of standard-of-care therapeutics for our clinical trials.

隨著我們的第三階段研究成熟，我們仍然預計研發費用將適度增加。支出的波動主要取決於臨床生產活動的時間安排以及為我們的臨床試驗購買標準治療藥物的時間。

G&A expenses were $29 million for the fourth quarter of 2023 compared to $30 million in the third quarter of 2023. Non-cash stock compensation represented $9 million of our G&A expenses for the fourth quarter. And we expect G&A to remain stable for 2024.

2023 年第四季的一般管理費用為 2,900 萬美元，而 2023 年第三季為 3,000 萬美元。非現金股票補償占我們第四季一般管理費用的 900 萬美元。我們預計 2024 年一般行政費用將維持穩定。

For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-K.

有關我們財務業績的更多詳細信息，請參閱今天早些時候的收益新聞稿和 10-K。

I'll now turn it back to Terry for concluding remarks.

現在我將把它轉回給特里做總結發言。

Thanks very much, Bob. Before we open the floor to questions, I'd like to briefly touch on upcoming catalysts for 2024 beyond the ARC-20 datasets that Dmitry highlighted. There's a lot.

非常感謝，鮑伯。在我們開始提問之前，我想先簡單談談 Dmitry 強調的 ARC-20 資料集之外的 2024 年即將到來的催化劑。有很多。

This will be another data rich year for Arcus. For anti-TIGIT program, we'll be presenting updated data from EDGE-Gastric, our Phase 2 study evaluating dom zim plus chemo in upper GI cancers at ASCO this year. We expect this dataset to include updated ORR and PFS data.

對 Arcus 來說，今年將會是另一個數據豐富的一年。對於抗 TIGIT 項目，我們將展示 EDGE-Gastric 的最新數據，這是我們今年在 ASCO 上評估 dom zim 聯合化療治療上消化道癌症的 2 期研究。我們希望該資料集包含更新的 ORR 和 PFS 資料。

We also look forward to announcing the completion of enrollment for STAR-121 and STAR-221 which will obviously start the clock for potential regulatory filings. We also measure data and insights from ARC-10 at a future medical conference.

我們也期待宣布 STAR-121 和 STAR-221 的註冊完成，這顯然將為潛在的監管備案開始計時。我們也在未來的醫學會議上測量 ARC-10 的數據和見解。

As I mentioned earlier, we presented impressive overall survival data from our Phase 1b ARC-8 trial that was evaluating Quemli in first-line pancreatic cancer. Also related to the adenosine pathway, we have two randomized datasets that we expect to share in the first half of the year for etruma, our A2 receptor antagonist. And we believe these confirm our findings in ARC-8 that adenosine modulation confirmed profound improvement on overall survival.

正如我之前提到的，我們提供了來自 1b 期 ARC-8 試驗的令人印象深刻的總體生存數據，該試驗正在評估 Quemli 在一線胰腺癌中的療效。同樣與腺苷途徑相關的是，我們有兩個隨機數據集，預計今年上半年分享我們的 A2 受體拮抗劑 etruma。我們相信這些證實了我們在 ARC-8 中的發現，即腺苷調節證實了整體存活率的顯著改善。

So first off, Roche will be presenting data from MORPHEUS-PDAC. This is a randomized study operationalized by Roche that evaluated etruma in combination with chemotherapy and atezo, their anti-PD-L1 antibody, versus chemo in pancreatic cancer. So a randomized study that involves the etruma.

首先，羅氏將展示 MORPHEUS-PDAC 的資料。這是羅氏實施的一項隨機研究，評估了 etruma 聯合化療和 atezo（其抗 PD-L1 抗體）與化療在胰腺癌中的療效。這是一項涉及 etruma 的隨機研究。

Second, we submitted data from the third line cohort of ARC-9 presentation at a medical conference. This cohort enrolled 105 patients and evaluated etruma plus zim plus bev plus FOLFOX, versus rego, the current standard of care in third-line colorectal cancer. The presentation will include mature PFS, and importantly, OS data, which we believe are also very supportive of the potential for adenosine modulation when combined with immunogenic chemotherapy to robustly prolonged PFS and OS.

其次，我們提交了在一次醫學會議上展示的 ARC-9 第三線隊列的數據。該隊列招募了 105 名患者，並評估了 etruma 加 zim 加 bev 加 FOLFOX 與目前三線結直腸癌護理標準 rego。簡報將包括成熟的 PFS，重要的是 OS 數據，我們相信這些數據也非常支持腺苷調節與免疫原性化療相結合以大幅延長 PFS 和 OS 的潛力。

So in conclusion, we've covered a lot today, a lot of materials. But if there's one thing to take away from today's call is that Arcus is now fully enabled to execute on its diverse late-stage portfolio with funding into 2027, and that excludes potential future opt-in payments.

總之，我們今天討論了很多內容，很多材料。但如果從今天的電話會議中可以看出一件事，那就是 Arcus 現在完全有能力執行其多樣化的後期投資組合，資金到 2027 年為止，這不包括未來潛在的選擇加入付款。

Our portfolio includes six ongoing and planned Phase 3 trials, multiple Phase 1/2 studies and a discovery engine that's just capable of generating at least one IND per year. Our trials are focused on huge markets by any standard: lung and GI cancer, pancreatic cancer, and RCC, where we're extremely well positioned to compete for potential first-to-market or best-in-class therapies.

我們的產品組合包括六項正在進行和計劃中的 3 期試驗、多項 1/2 期研究以及每年至少能夠產生一項 IND 的發現引擎。我們的試驗集中在以任何標準衡量的巨大市場：肺癌和胃腸道癌症、胰腺癌和腎細胞癌，我們在這些市場上處於非常有利的位置，可以競爭潛在的首個市場或同類最佳療法。

We have a lot going and a lot more to come this year. Thanks for your interest and support for our Arcus as we continue to broaden our portfolio of innovative combination cancer therapies. And we'll be working to bring these treatments to patients as soon as possible.

今年我們有很多事情要做，還有更多事情要做。感謝您對 Arcus 的興趣和支持，我們將繼續擴大我們的創新組合癌症療法產品組合。我們將努力盡快為患者提供這些治療方法。

We'll now open the floor to questions.

我們現在開始提問。

(Operator Instructions)

（操作員說明）

Terence Flynn, Morgan Stanley.

特倫斯‧弗林，摩根士丹利。

Hi, thanks for taking the question. A two-part one for me. Just wondering on Cas, the HIF-2 alpha program in slide 24, the dose expansion data. Can you just confirm what the ORR was and how many of those we're actually confirmed versus unconfirmed?

您好，感謝您提出問題。對我來說，分為兩個部分。只是想知道幻燈片 24 中的 Cas、HIF-2 alpha 程序、劑量擴展數據。您能否確認 ORR 是多少，以及我們實際確認的 ORR 和未確認的 ORR 有多少？

And then the second part of the question relates to a potential Gilead opt-in on this program. Maybe, Terry, you could just remind us the mechanics of how that type of a decision would work in terms of how little or how much data you would provide to Gilead and then how long they have to make a decision? Thank you.

問題的第二部分涉及吉利德是否可能選擇加入該計劃。特里，也許你可以提醒我們這種類型的決策如何運作，即你將向吉利德提供多少數據，然後他們必須在多長時間內做出決定？謝謝。

Thanks, Terrence. So on the first question, we did share specific ORR intentionally. Actually 70% of the patients have only had one or two scans. So we will wait till the second half of the year to give that number.

謝謝，特倫斯。因此，關於第一個問題，我們確實有意分享了具體的 ORR。實際上70%的患者只做過一兩次掃描。所以我們要等到下半年才能給這個數字。

But we're seeing a number of responses. And in fact, then there's double-digit patients that are stable disease with tumor reduction that may convert to a response.

但我們看到了一些回應。事實上，有兩位數的患者病情穩定，腫瘤縮小，可能會轉化為緩解。

The second part with respect to Gilead opt-in, we have defined very specific criteria together with them. We haven't shared those exactly. But if you look what we've described in general for the relationship, that often occurs when we've generated proof-of-concept data. So you can draw your own conclusions as what's coming later this year. And our belief is that they're very excited about the molecule and the program. But we'll see what they actually decide.

關於吉利德選擇加入的第二部分，我們與他們一起定義了非常具體的標準。我們還沒有確切地分享這些。但是，如果您查看我們對這種關係的一般描述，您會發現這種情況通常發生在我們產生概念驗證資料時。因此，您可以對今年稍後的情況得出自己的結論。我們相信他們對這個分子和這個計畫非常興奮。但我們會看看他們實際上會做出什麼決定。

I'll make one last final point: that is a program that we obviously wouldn't mind taking forward ourself. And we also have had plenty of inbound interest from other companies that might see a strategic fit with the rest of their portfolio.

我要提出最後一點：我們顯然不介意自己推進這個計畫。我們也收到了來自其他公司的大量入境興趣，這些公司可能會發現與其投資組合的其餘部分存在策略契合。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Great. Thanks for the update and all the information. On Cas, is that able to reduce the number of fast progresses you were talking about? And have you seen any complexity in recruiting patients for HIF-2 alpha plus zanza in about two non-approved drugs, if that any way you think affects that patients you get to see?

偉大的。感謝您的更新和所有資訊。在Cas上，是否能夠減少你所說的快速進度？您是否發現在大約兩種未經批准的藥物中招募 HIF-2 α 加 zanza 患者有任何複雜性，如果您認為這會影響您所見的患者？

So we actually have had a number of discussions on this topic. We do not see that we're going to be -- well, flying for the rest of world the future development strategy. We're going into settings that we think makes sense, including with zanza.

所以我們其實已經就這個主題進行了很多討論。我們不認為我們會——嗯，為世界其他地區制定未來的發展策略。我們將進入我們認為有意義的設置，包括贊扎。

And we also -- in parallel, we'll be exploring combination with cabo. So we'll have both of those under our belt. But we feel very good about our ability to enroll. And keep in mind, we're not planning, obviously in the context of this question, to be going after monotherapy at this point.

同時，我們也將探索與 cabo 的結合。所以我們將把這兩個都掌握在我們手中。但我們對自己的入學能力感到非常滿意。請記住，顯然在這個問題的背景下，我們目前不打算進行單一療法。

And so on will be going against the standard of care that doesn't involve belzutifan. And we feel like very well positioned to execute on those trials. And in fact, a huge degree of excitement. We've already had the first ad Board meeting and the enthusiasm for both HIF-2 as a general mechanism from what investigators have seen with belz as well as their anecdotal experience, which is now starting to get to be substantial with Cas makes the field very exciting. So we actually expect very rapid enrollment as we've seen already for this molecule.

等等將違反不涉及belzutifan的護理標準。我們感覺自己處於非常有利的位置來執行這些試驗。事實上，我感到非常興奮。我們已經召開了第一次廣告委員會會議，並且從調查人員在貝爾茲身上看到的情況以及他們的軼事經驗來看，對HIF-2 作為通用機制的熱情，現在隨著Cas 的推出，這一點開始變得實質非常令人興奮。因此，我們實際上預計註冊人數會非常快，正如我們已經看到的這種分子一樣。

Got you. And then just on the rapid progress, are you kind of seen that or reduction (inaudible)?

明白你了。然後就快速進展而言，您是否看到了這一點或減少了（聽不清楚）？

So if you look at LITESPARK-005, which is a Phase 3 study for belzutifan and you can look at what the primary progression rate was in that study and were lower than, we talked to investigators about LITESPARK-005, the primary progression rate, which is relatively high.

因此，如果您查看 LITESPARK-005，這是 belzutifan 的 3 期研究，您可以查看該研究中的主要進展率，並且低於我們與研究人員討論的 LITESPARK-005，主要進展率，這是相對較高的。

What sort of thing that stuck out for them that the results overall were very encouraging. But I think that's one thing that they would love to see improved upon, was the primary progression rate. Just the number of patients, this kind of blew right through belzutifan treatment. So like I said, we're seeing a lower number than that. We think it's another opportunity to improve upon belzutifan and probably more to come on that later in the year.

什麼樣的事情對他們來說是突出的，整體結果非常令人鼓舞。但我認為他們希望看到改進的一件事是初級進展率。光是病人數量，這種就爆過了貝爾祖提凡的治療。正如我所說，我們看到的數字比這個數字低。我們認為這是另一個改進 Belzutifan 的機會，並且可能會在今年稍後出現更多機會。

Thank you so much.

太感謝了。

Kaveri Pohlman, BTIG.

卡維裡·波爾曼，BTIG。

Good evening. Congrats on the progress and thanks for taking my questions. For 521 dose expansion data, the ORR that you provided, can you tell us or provide any color on how pretreated these patients were compared to the LITESPARK-005 trial?

晚安.恭喜您的進展，並感謝您提出我的問題。對於 521 例劑量擴展數據，即您提供的 ORR，您能否告訴我們或提供有關這些患者與 LITESPARK-005 試驗相比的預處理情況的任何資訊？

And the trial, I believe, excludes patients with prior HIF-2 alpha treatment. But do you think higher exposure could make these patients respond to 521?

我相信該試驗排除了先前接受過 HIF-2 α 治療的患者。但您認為更高的暴露量會使這些患者對 521 產生反應嗎？

So, Dmitry, why don't you talk a little bit about the treatment of those patients in the expansion study?

那麼，德米特里，為什麼不談談擴展研究中這些患者的治療情況呢？

Sure. Yes, thanks for the question. So regarding the prior treatments, the inclusion criteria for the expansion cohort allow for patients in a slightly earlier setting than in the dose escalation phase. So in the dose escalation phase, we required people to have exhausted all reasonable treatment options. And therefore, third to fourth line was what we expect.

當然。是的，謝謝你的提問。因此，關於先前的治療，擴展隊列的納入標準允許患者處於比劑量遞增階段稍早的環境中。因此，在劑量遞增階段，我們要求人們用盡所有合理的治療方案。因此，第三到第四行就是我們所期望的。

In the expansion cohort, we are still seeing a fairly similar profile of pretreatment. And that's something we think is, let's say, what we are expecting. It also puts our early efficacy observations in a positive daylight. Many patients in the expansion cohort also had two or three prior VEGF TKIs, and they all are required to have PD-1.

在擴展隊列中，我們仍然看到相當相似的預處理情況。我們認為這就是我們所期待的。這也使我們的早期療效觀察結果變得積極起來。擴展隊列中的許多患者之前也接受過兩到三種 VEGF TKI，並且他們都需要有 PD-1。

So if I summarize it, we do allow slightly earlier stage patients second line and beyond. Where in the escalation phase, it would have been third line and beyond. But overall so far, the prior treatments are very, very similar.

因此，如果我總結一下，我們確實允許稍早階段的患者接受第二線及以上的治療。在升級階段，它可能是第三線及以上。但總的來說，到目前為止，之前的治療方法非常非常相似。

As to the belzutifan question, it is an interesting question. It is something I think worthwhile thinking about. However, including patients now with belzutifan prior treatment, I think will make it really hard to interpret the data. Because one reason could be that patients did not respond because the target wasn't hit hard enough.

至於belzutifan問題，這是一個有趣的問題。這是我認為值得思考的事情。然而，包括現在接受過 Belzutifan 治療的患者，我認為這將使得數據的解釋變得非常困難。因為原因之一可能是患者沒有反應，因為目標沒有受到足夠的打擊。

It could be complete, let's say, resistance for HIF-2 targeting. I think that looking at the belzutifan data, if you look at the primary progression rate, a number of those patients presumably would have been hard to get under control. Those might benefit.

比方說，它可能完全抵抗 HIF-2 靶向。我認為，看看 Belzutifan 的數據，如果你看看主要進展率，其中許多患者可能很難控制。這些可能會受益。

But patients -- there could definitely be patients who have resistance to HIF-2 alpha targeting. And so I know it's not a simple answer. I think for a clean efficacy signal right now, that's why we are excluding prior HIF-2 treatment because it's too complicated. And one patient who progresses on belzutifan would not be the other patient. So that would have to be explored in a more detailed setting where you really capture the detail of prior treatments.

但是患者——肯定有一些患者對 HIF-2 α 標靶有抵抗力。所以我知道這不是一個簡單的答案。我認為現在要獲得明確的療效訊號，這就是我們排除先前的 HIF-2 治療的原因，因為它太複雜了。服用 Belzutifan 後出現進展的一名患者不會是另一名患者。因此，必須在更詳細的環境中進行探索，才能真正捕捉先前治療的細節。

That's helpful.

這很有幫助。

(multiple speakers) prior lines of treatment in that expansion cohort, (technical difficulty) in front of me. So four of the 30 were second line. So it was a minority of the patients in that arm. Nine were third line and then the remainder, so that's 19 were for fourth line or later. (multiple speakers)

（多個發言者）該擴展隊列中先前的治療方案（技術難度）就在我面前。所以 30 人中有 4 人是二線。所以這只是該組患者中的少數。9 個是第三行，然後是其餘的，所以 19 個是第四行或更高版本。（多個發言者）

As a reminder, (inaudible) five again, a Phase 3 setting for belz. The inclusion criteria was one to three prior lines. So patients with more than three prior lines were excluded from that study.

提醒一下，（聽不清楚）又是五個，貝爾茲的第三階段設定。納入標準是一到三個先前的品系。因此，具有超過三種先前治療線的患者被排除在該研究之外。

Go ahead, Kaveri. Did you have a follow-up?

繼續吧，卡維裡。你有後續行動嗎？

I just thought if I can ask another question for MORPHEUS-PDAC, can you tell us what you're expecting in terms of efficacy, especially OS, and whether you expect etruma to perform better or worse than Quemli? And if outcomes from this trial could change anything, what are your plans to initiate a Phase 3 trial for Quemli?

我只是想如果我可以向 MORPHEUS-PDAC 提出另一個問題，您能告訴我們您對功效（尤其是 OS）方面的期望嗎？以及您是否期望 etruma 比 Quemli 表現更好或更差？如果這次試驗的結果可能會改變任何事情，那麼您計劃啟動 Quemli 的第三階段試驗是什麼？

So, Kaveri, it doesn't change anything. And what you'll see is the OS data, just say they're going to be similar to what you saw for ARC-8.

所以，卡維裡，這不會改變任何事情。您將看到的是作業系統數據，只需說它們將與您在 ARC-8 中看到的類似。

Now just two interesting component. There is actually -- they have a gem-abraxane control arm in the study. So it is randomized. Our study, as you know, we conducted this synthetic control analysis, which gave us great data.

現在只有兩個有趣的組件。事實上，他們在研究中有一個寶石-abraxane 控制臂。所以它是隨機的。如您所知，我們的研究進行了全面控制分析，為我們提供了大量數據。

The thing about ARC-8 is that it's a larger end. But on the other hand, the MORPHEUS study, we have randomized arm and they both point to the same answer.

ARC-8 的特點是它的末端較大。但另一方面，在 MORPHEUS 研究中，我們有隨機分組，它們都指向相同的答案。

So to me, that's the big takeaways. You have two studies that affect adenosine in two different ways, but bottom line are removing the effects of adenosine. They're both producing what we would say are pretty profound effects on overall survival, which is, you know, to us very important.

所以對我來說，這是最大的收穫。您有兩項研究以兩種不同的方式影響腺苷，但底線是消除腺苷的影響。它們都對整體生存產生了我們所說的相當深遠的影響，這對我們來說非常重要。

Insofar as the etruma versus Quemli, we've had that question in mind for some time. At this point, we'll still say other than in some very specific settings where there may be known non-CD73 mechanisms for adenosine formation from adenosine triphosphate, we would say we'll hold judgment as to which might be better.

就埃特魯瑪與奎姆利而言，我們已經考慮這個問題已經有一段時間了。在這一點上，我們仍然會說，除了在一些非常具體的情況下，可能存在已知的從三磷酸腺苷形成腺苷的非 CD73 機制之外，我們會說我們會判斷哪個可能更好。

You can make rationale for both de novo. If you forced me to pick one, I would still go with CD73 inhibition with the idea being that if you could block the formation of something versus have to reverse the actions of something, that tends to be better, but that will play out it over time.

您可以從頭開始為兩者提供理由。如果你強迫我選擇一個，我仍然會選擇 CD73 抑制，其想法是，如果你可以阻止某些東西的形成，而不是必須逆轉某些東西的行為，那往往會更好，但這會結束它時間。

I think by that time -- the big take-home message is by the time you see these three datasets combined, I think it's going to read very positively on adenosine modulation as a mechanism that has a meaningful role, particularly in the context of immunogenic chemotherapy as a standard of care where there's headroom for improvement.

我認為到那時——最重要的訊息是當你看到這三個數據集結合起來時，我認為它將非常積極地解讀腺苷調節作為一種具有有意義作用的機制，特別是在免疫原性的背景下化療作為一種護理標準，還有改進的空間。

That's very helpful. Thank you.

這非常有幫助。謝謝。

Thank you.

謝謝。

Jonathan Miller, Evercore ISI.

喬納森·米勒，Evercore ISI。

Hi, guys. Thanks for taking the question. I would love to ask about HIF-2's time to response and maybe some context about how ORR could evolve from here.

嗨，大家好。感謝您提出問題。我很想詢問 HIF-2 的回應時間，以及 ORR 如何從這裡演變的一些背景資訊。

Obviously, you're talking about already reaching a similar level to a LITESPARK and hinting that you would expect your ORR to be mature by midyear. But what's your expectation? What's the evolution from here to there? How much more ORR would you expect to see in later scans?

顯然，您正在談論已經達到與 LITESPARK 類似的水平，並暗示您希望您的 ORR 在年中成熟。但你的期望是什麼？從這裡到那裡有什麼演變？您預計在以後的掃描中會看到多少 ORR？

And then relatedly, given a linear PK up to 100 milligrams in the escalation cohorts so far, do you expect that 50 milligrams could also show differentiation versus Merck? Could you put a little bit of that dose optimization in context for me as well?

與此相關的是，考慮到迄今為止在升級隊列中線性 PK 高達 100 毫克，您是否認為 50 毫克也能顯示出與默克的差異？您能否為我介紹一下劑量優化的一些情況？

Those are some great questions on. So I'll let me start with the first one that gets a little bit to your kinetics. So that's all anecdotal from to date, but let's first put a line in the sand. LITESPARK-005 is roughly 3.8 months median time to response.

這些是一些很好的問題。所以我將從第一個對你的動力學有一點影響的開始。這就是迄今為止的所有軼事，但讓我們先劃清界線。LITESPARK-005 的中位反應時間約 3.8 個月。

The way things are looking, you played around with numbers, it looks like at least at the outset that we're doing perhaps better than that. And we'll see how that plays out. And obviously, they'll reach the opportunity for deeper response, longer PFS. As you know, those really aren't independent variables.

從目前的情況來看，你玩弄了數字，看起來至少在一開始我們做得可能比這更好。我們將看看結果如何。顯然，他們將有機會獲得更深入的反應、更長的 PFS。如您所知，這些實際上不是自變數。

So hitting that target harder at the outset, maybe driving kinetics that are known to be not particularly (inaudible). Although we have seen a couple of later patients having dramatic tumor reduction after multiple scans.

因此，從一開始就更加努力地實現該目標，也許驅動動力已知並不是特別好（聽不清楚）。儘管我們已經看到一些後來的患者在多次掃描後腫瘤明顯縮小。

On your second question, even though we didn't say anything about it in the script and it's even earlier, what I'll tell you is the 15 milligram cohort, it's almost fully enrolled. So that's going to be another 30 patient. And honestly if you just took a look and not even all the patients have had a single scan yet, but it actually works pretty good.

關於你的第二個問題，儘管我們在劇本中沒有說，而且時間更早，但我告訴你的是15毫克隊列，它幾乎已經全部入組了。這將是另外 30 名患者。老實說，如果你只是看了一下，甚至還沒有所有患者都進行過一次掃描，但它實際上效果很好。

And the kinetics, that's where I would tell you on the first group of patients that have had scans. And so I don't want to get -- as you know, I could get ahead of the skis because I tend to be pretty transparent with what we've seen. But the first group of patients are seeing some pretty significant reductions. And so feeling optimistic both about the kinetics and we're looking hard to fit this clearly more than pharmacologically relevant.

至於動力學，這就是我要告訴你的關於第一組接受掃描的患者的情況。所以我不想——正如你所知，我可以領先於滑雪板，因為我傾向於對我們所看到的事情非常透明。但第一組患者的病情出現了相當顯著的下降。因此，我們對動力學感到樂觀，我們正在努力尋找比藥理學相關的更明確的證據。

And it does look like on the early, early efficacy readout, that's playing out. As we stated, 20 milligrams was essentially giving the same effect as the approved dose of belzutifan on the PD marker in the 50-milligram dose. Certainly, if you had known any different and it was labeled 100 from what we've seen, you would say it fits right in. But that's way too early to say that's how it's going to play out.

從早期的療效讀數來看，這確實正在發揮作用。正如我們所說，20 毫克劑量基本上與 50 毫克劑量的 Belzutifan 對 PD 標誌物的批准劑量具有相同的效果。當然，如果您知道任何不同之處並且它被標記為 100，與我們所看到的不同，您會說它完全適合。但現在說事情會如何發展還為時過早。

Makes sense. And then one more also on the escalation side of things. Obviously, only very few of those patients were RCC patients. Could you tell us about some of the other indications in that escalation set where you might have seen clinical activity?

說得通。然後還有一個問題是事態升級。顯然，這些患者中只有極少數是腎細胞癌患者。您能否告訴我們您可能已經看到臨床活動的升級集中的其他一些跡象？

Yes. So there is a mix of tumor types. And so I would say there really wasn't anything like any other tumor types. And they're all, you know, patients have received multiple prior lines of therapy.

是的。因此，存在多種腫瘤類型。所以我想說，確實沒有其他腫瘤類型。你知道，他們都是之前接受過多種治療的患者。

We did have two patients with RCC non-clear cell that -- non-clear cell RCC. Interestingly, one of the patient has had a nice response, and it's still on treatments. So It's not 30% tumor reduction but they've been on treatment for many, many months and continues to be on treatment. So, you know, it seems to indicate that the drug has activity in non-clear cell RCC as well.

我們確實有兩位非透明細胞腎細胞癌患者，即非透明細胞腎細胞癌。有趣的是，其中一名患者的反應良好，並且仍在接受治療。所以這並不是腫瘤減少了 30%，但他們已經接受了很多很多個月的治療，並且仍在繼續接受治療。所以，你知道，這似乎顯示該藥物對非透明細胞腎細胞癌也有活性。

Okay. Makes sense. Thank you.

好的。說得通。謝謝。

Thanks, Jonathan.

謝謝，喬納森。

Yigal Nochomovitz, Citigroup.

伊格爾·諾霍莫維茨，花旗集團。

Hi, Terry and team. Did you say what the doses were for the two RCC patients that showed the tumor reductions just short of 30%? And then I have another question on Phase 3.

嗨，特里和團隊。您是否說過兩位 RCC 患者的腫瘤縮小率接近 30% 的劑量是多少？然後我還有一個關於第三階段的問題。

I believe (inaudible) was the 100 mg dose. And the other, I think, was the 20 mg roughly.

我相信（聽不清楚）是 100 毫克劑量。另一個，我想，大約是 20 毫克。

Yeah. It's (inaudible) the four patients, they hit all covered by -- I think Jen got that right. Definitely one was 100 and definitely the other one was either 20 or 50. They're probably looking well.

是的。這是（聽不清楚）四個病人，他們都被覆蓋了——我認為 Jen 說得對。其中一個肯定是 100，另一個肯定是 20 或 50。他們看起來可能很好。

Go ahead, Yigal.

繼續吧，伊格爾。

Okay. And at this point, as far as what you would do for the Phase 3 dose, I mean, you finished the dose expansion for 100 milligram first. Doesn't mean that that's going to be the base case for Phase 3, right? I mean, you could go at 50. You also said you're evaluating a higher dose up to 200. Although I don't know what that is. What's the base case for Phase 3? Is that still TBD?

好的。此時，就您將如何進行第 3 階段劑量而言，我的意思是，您首先完成了 100 毫克的劑量擴展。這並不意味著這將是第三階段的基本情況，對嗎？我的意思是，你可以在50歲的時候去。您還說您正在評估高達 200 的更高劑量。雖然我不知道那是什麼。第三階段的基本狀況是什麼？這還待定嗎？

The base case is 100. It really comes down to, Yigal, unless we see something dramatic from any of the -- either of the other arms, which obviously are being done to support the -- that we've got the optimal dose from ultimately a regulatory standpoint.

基本情況是 100。歸根結底，伊格爾，除非我們從其他任何一個部門看到一些戲劇性的事情，這顯然是為了支持我們從最終的監管角度獲得了最佳劑量。

We felt that if you look at the Merck data and you look at what they've achieved and you look at their waterfalls and you look at their kinetics that once we've established that fivefold increase over matching the peripheral PD marker, that we felt like you should be maximizing the response in the tumor.

我們認為，如果你看看默克的數據，看看他們所取得的成就，看看他們的瀑布，看看他們的動力學，一旦我們確定了與外圍 PD 標記匹配的五倍增長，我們覺得就像你應該最大化腫瘤的反應。

So as a practical call. Because you know, oftentimes when you -- and it's unusual -- more unusual in cancer, but when you have a very safe drug at some point, you say, this, from a practical standpoint makes sense.

所以作為一個實際的調用。因為你知道，通常當你——這很不尋常——在癌症中更不尋常，但當你在某個時候有一種非常安全的藥物時，你會說，從實際的角度來看，這是有道理的。

But if we see something in these other expansion cohort that would cause you to feel like there was something different, we would consider doing something alternatively. But right now, we're on a trajectory to that 100 milligram dose.

但如果我們在其他擴展隊列中看到某些東西會讓你覺得有什麼不同，我們會考慮採取替代措施。但現在，我們正朝著 100 毫克劑量的方向前進。

The other thing that's nice about safety profile is appearing very clean.

安全性設定檔的另一個好處是看起來非常乾淨。

Yigal, sorry. Just to clarify, the patient responses, one was a 100 mg and one was 50 mg.

伊格爾，對不起。澄清一下，病人的反應是，一種是 100 毫克，一種是 50 毫克。

Okay, got it. And then you mentioned LITESPARK-005 a bunch of times. So obviously, that was versus everolimus. So for Phase 3, I'm assuming you'd want to go up against those belzutifan. But I don't know. Is that the right assumption?

好，知道了。然後你多次提到 LITESPARK-005。很明顯，這是與依維莫司相比。所以對於第三階段，我假設你想對抗那些貝爾祖蒂凡。但我不知道。這是正確的假設嗎？

Yes. So the thing -- and once we described exactly what we're doing, so we're not going to be going into that same monotherapy setting. So we'll actually be going in a setting where belzutifan would be the standard of care and we will go against the standard of care. And we'll say a little bit more about that as the year goes along. But that was part of the strategy when we consider what would be the best place to go first.

是的。所以，一旦我們準確地描述了我們正在做的事情，我們就不會進入同樣的單一療法環境。因此，我們實際上將進入一個以 belzutifan 為護理標準的環境，而我們將反對該護理標準。隨著時間的推移，我們會更多地談論這一點。但當我們考慮首先去哪裡時，這就是策略的一部分。

Okay. All right. Understood. Thank you.

好的。好的。明白了。謝謝。

Thank you, Yigal.

謝謝你，伊格爾。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Hey, thanks. This is Matt on for Salveen. Maybe just following up on that last question. Could you share any additional details at this point on the Phase 3 design per Cas?

嘿，謝謝。這是薩爾文的馬特。也許只是跟進最後一個問題。目前您能否分享有關每個 Cas 第 3 階段設計的任何其他詳細資訊？

And then secondly, you cited the changing treatment paradigm in first-line PD-L1 high lung cancer away from Keytruda mono as a reason for discontinuing ARC-10 shifting to 121? I was just curious if you could share any details on what data this shifting trend is based on and why you believe this is happening now? Thank you.

其次，您引用了一線 PD-L1 高肺癌治療模式的變化，從 Keytruda mono 作為停止 ARC-10 轉向 121 的原因？我只是好奇您能否分享有關這種變化趨勢基於哪些數據的任何詳細資訊以及您為什麼認為現在正在發生這種情況？謝謝。

Thanks for the two question. I'm going to walk and chew gum at the same time. So two different programs. So what I'll comment is you can think about on RCC -- from a standpoint of both development and the need ultimately commercialization, there's multiple lines where you can think of going.

謝謝你提的兩個問題。我要一邊走路一邊嚼口香糖。所以兩個不同的程序。所以我要評論的是，你可以考慮 RCC——從開發和最終商業化需求的角度來看，你可以考慮走多條路線。

And so we would probably move up a bit from where the third-line population was. And you could think about patients that have received anti-PD-1 and/or TKI. So you wouldn't have belz as standard of care. We feel like that's a great place to go.

因此，我們可能會比三線人口的位置上升一些。您可以考慮接受抗 PD-1 和/或 TKI 治療的患者。所以你不會將貝爾茲作為標準護理。我們覺得那是個值得去的好地方。

Insofar as your question about ARC-10 and the strategy there, so clearly -- let me give a couple of points on that. So clearly, like with main therapies and particularly in cancer, it's one of those places where obviously there's a Goldilocks spot but physicians do and patients tend to be more focused on efficacy than safety within a reasonable bouts.

至於你關於 ARC-10 及其策略的問題，非常清楚 - 讓我就此提出幾點觀點。很明顯，就像主要療法一樣，特別是在癌症方面，這顯然是一個“金髮姑娘點”，但醫生確實如此，而且患者在合理的治療週期內往往更關注療效而不是安全性。

And I think as time goes along and physicians become both more comfortable with the liabilities of a therapy, how they're administered as well as you know, a conviction about the real efficacy, that's what's happened in a very continuous way in this high PD-L1 population.

我認為，隨著時間的推移，醫生對治療的責任、治療的實施方式以及對真正療效的信念越來越滿意，這就是在這種高 PD 中以非常連續的方式發生的事情-L1人口。

You know, going from, you know, anti-PD-1 alone and increasingly to anti PD-1 plus chemo, particularly in a more healthy patient population or with a patient with a bulkier, more rapidly progressing tumor. We think that's only going to be more enhanced particularly with a molecule like dom, which we're already seeing from a study, for example, like EDGE-Gastric, that essentially doesn't bring any additional side effect liability on top of anti-PD-1 post-chemo.

你知道，從單獨抗 PD-1 逐漸轉向抗 PD-1 加化療，特別是在更健康的患者群體或患有體積更大、進展更快的腫瘤的患者中。我們認為，這種作用只會得到更大的增強，特別是像dom 這樣的分子，我們已經從一項研究中看到了這種分子，例如EDGE-Gastric，除了抗藥物之外，基本上不會帶來任何額外的副作用。化療後的 PD-1。

So we think that that's going to further cannibalize that particular approach to treating that population. So we do feel that STAR-121 best addresses that population with the best opportunity to become the standard of care for comers.

因此，我們認為這將進一步蠶食治療該族群的特定方法。因此，我們確實認為 STAR-121 最能滿足該族群的需求，並且最有機會成為新來者的照護標準。

What I'll also say from a biological standpoint, I think one of the important things is you move like down the spectrum from your toxic agents, (inaudible) inhibitors to things that are very much understand the biology. What you really want to start thinking about is less the organ that you're treating than the biology that you're treating. And we do feel -- and you know, the biology that supports anti-TIGIT -- a couple of things.

我還要從生物學的角度說，我認為重要的事情之一是你要從有毒物質、（聽不清楚）抑制劑轉向非常了解生物學的東西。您真正想要開始考慮的不是您正在治療的器官，而是您正在治療的生物。我們確實感覺到——你知道，支持抗 TIGIT 的生物學——有幾件事。

At the highest level, CD155 is a bad thing. If you've got CD155 -- and what CD155 is doing is keeping you from getting all of the mileage that you might otherwise out of anti-PD1 because anti-PD1 relies on CD226 to get its full efficacy. And so when you have CD155 engaging the CD226, you're losing part of what you might otherwise gain.

在最高水準上，CD155是一件壞事。如果您有 CD155，那麼 CD155 的作用就是阻止您獲得抗 PD1 藥物可能發揮的作用，因為抗 PD1 藥物依賴 CD226 才能發揮其全部功效。因此，當 CD155 與 CD226 結合時，您可能會失去部分原本可能獲得的東西。

And that's the whole rationale and now what's being borne out clinically behind anti-TIGIT and why we feel like the best place to go for anti-TIGIT is where you already know that anti-PD-1 works. And you know that PD-L1 all-comer population with chemo is absolutely right down the middle of the fairway for where you want to go with a molecule like that.

這就是整個原理，現在抗 TIGIT 背後的臨床證實是什麼，以及為什麼我們認為抗 TIGIT 的最佳選擇是您已經知道抗 PD-1 有效的地方。你知道，接受化療的 PD-L1 所有人群絕對是你想要使用這樣的分子的地方。

Helpful. Thank you.

有幫助。謝謝。

Robyn Karnauskas, Truist.

羅賓‧卡瑙斯卡斯，真理論者。

Hi, team. All right. Several questions. Thinking about the 200 milligrams of Cas, do you think there'll be a diminishing limit of return if you actually -- would you think you could push the [occupancy] up higher? What are your thoughts in 200 milligram?

大家好。好的。幾個問題。考慮一下 200 毫克的 Cas，如果您真的認為可以將[佔用率]推得更高，您是否認為回報極限會遞減？200毫克你有什麼想法？

Second question is about (multiple speakers), how it differs from zanza? And third might be do you think you could leapfrog in how -- ARC-10 you did a different trial leapfrogged into frontline with 521? Is there a strategy there? Like how do you incorporate your own 801 into that process?

第二個問題是關於（多位發言者），它與 zanza 有什麼不同？第三個問題可能是，你認為你可以如何超越——ARC-10，你做了一個不同的試驗，以 521 的方式躍入前線？那裡有策略嗎？例如您如何將自己的 801 融入流程中？

There's a lot going on there. But maybe you can take those at once.

那裡發生了很多事情。但也許你可以立即拿走這些。

So the second question, what would -- the zanza question was with 801 compound?

那麼第二個問題，贊札問題是 801 化合物？

The 801 -- so for 801, how is it differentiated from zanza (inaudible) only? And could you incorporate that in your clinical trials moving forward, right? You're doing all these zanza clinical trials.

801——那麼對於 801，它與 zanza（聽不清楚）有什麼區別？您能否將其納入您今後的臨床試驗中，對嗎？你正在做所有這些贊札臨床試驗。

The second question would be 200 milligram of Cas, like what do you think is going to happen there? Are you pushing a little bit already? Do you think you get greater efficacy? And third would be could you leapfrog ahead, giving our Phase 1/2b trial and go into first line RCC?

第二個問題是 200 毫克 Cas，你認為那裡會發生什麼事？你已經有點努力了嗎？您認為您會獲得更大的功效嗎？第三個問題是，您能否超越，進行我們的 1/2b 期試驗並進入一線 RCC？

Because you've done really good things in the past by cutting things off and like skipping ahead of other people, given the knowledge you have to get a first-line indication versus (inaudible) indication. Thanks.

因為你過去透過切割事情並喜歡跳到其他人前面做了非常好的事情，考慮到你必須獲得一線指示與（聽不清）指示的知識。謝謝。

Great. I'll start with the 200 milligram, and I'll be brief on that. We do think that's probably overdosing but we want to see it. Because it will also give us some additional safety data. If we do go higher, does it do anything else on the other physiological roles of HIF-2 alpha?

偉大的。我將從 200 毫克開始，我會簡單介紹一下。我們確實認為這可能是用藥過量，但我們希望看到這一點。因為它還會給我們一些額外的安全資料。如果我們確實走得更高，它會對 HIF-2 α 的其他生理作用產生其他影響嗎？

But we do think that the 100 milligram dose is really hitting the target hard enough, but we'll see what we learn from 150 or 200 milligrams. Juan, do you want to take the other one question?

但我們確實認為 100 毫克劑量確實足以達到目標，但我們將從 150 或 200 毫克中學到什麼。胡安，你想回答另一個問題嗎？

Yes, sure. Zansa, as well as cabo, is primarily a VEGF TKI. It inhibits AXL with both molecules with decreased potency, but the clinical activity in the -- is released. Generally accepted to be the result of VEGF inhibition. So 801, we believe, is going to be a more surgically effective inhibitor of AXL, but probably not the first thing you would reach for in the context of RCC where (inaudible), we primarily to go after VEGF TKI.

是的，當然。Zansa 和 cabo 主要是一種 VEGF TKI。它用兩種分子抑制 AXL，但效力降低，但臨床活性被釋放。一般認為是 VEGF 抑制的結果。因此，我們相信 801 將成為一種手術上更有效的 AXL 抑制劑，但可能不是您在 RCC 背景下首先尋求的藥物（聽不清楚），我們主要尋找 VEGF TKI。

So firstly, we see AXL going on things like, you know, STK11 mutant non-small cell lung cancer. And by the way, on 801, since you asked about it, I might as well call of a bit. We have completed the healthy volunteer dosing. PK profile and safety profile were really good.

首先，我們看到 AXL 正在發生類似 STK11 突變非小細胞肺癌的情況。順便說一句，801，既然你問了，我不妨打一下。我們已經完成了健康志願者的給藥。PK 概況和安全概況都非常好。

So this is in, our minds, the first molecule that have the selectivity to really test the actual hypothesis. So we're very excited about that molecule.

因此，這是我們心中第一個能夠選擇性地真正檢驗實際假設的分子。所以我們對這個分子非常興奮。

Jen, do you want to comment, or Dimitry, on the 521 leapfrogging into a frontline setting?

Jen，或 Dimitry，你想對 521 跨越到前線的情況發表評論嗎？

Yeah. Sure.

是的。當然。

Yes, definitely. Go ahead, Dimitry.

當然是。繼續吧，迪米特里。

So we are considering all options and we could leapfrog into the first line. We could keep talking to the adjuvant setting, but we really want to make sure we select the setting for the first registrational trial.

所以我們正在考慮所有的選擇，我們可以跳到第一線。我們可以繼續討論輔助設置，但我們確實想確保我們選擇第一次註冊試驗的設置。

That is a mix of different factors. It has to have the data, let's say, safety and early efficacy data to support it. It has to be a sweet spot when it comes to comparative timelines to Merck. And I guess other considerations about timelines to readout.

這是不同因素的混合。它必須有數據，比如說安全性和早期療效數據來支持它。與默克公司的時間表相比，它一定是一個最佳點。我猜還有關於讀出時間軸的其他考慮因素。

A first-line trial is an interesting market opportunity. But for example, the bar in first line is higher than in second line, the time to readout is longer, of course, in first line and second line. So we are considering all these different options. And we'll make a decision and communicate that in the near-term future what our first opportunity would be that we pursue. But it is a factor -- multiple factors.

一線試驗是一個有趣的市場機會。但例如第一行的條形比第二行的條形高，當然第一行和第二行的讀出時間更長。所以我們正在考慮所有這些不同的選擇。我們將做出決定並傳達在不久的將來我們追求的第一個機會是什麼。但這是一個因素——多個因素。

Great.

偉大的。

And Robyn, since you asked about that, I would like to emphasize, the point of your question conceptually, though, is really good. HIF-2 alpha is going to end up being really important. I think that's why Merck has started to call it out as blockbuster.

羅賓，既然你問了這個問題，我想強調一下，你的問題在概念上的意義非常好。HIF-2 alpha 最終將變得非常重要。我認為這就是默克公司開始稱其為重磅炸彈的原因。

AB521 borrowing some weird unforeseen thing, it's a drug. And so the real question is: how do you fully exploit that? And if you ask me about our portfolio, it's definitely something that as we aggressively move towards this first study, we want to look very hard at how do you expand the footprint of the HIF-2 alpha program. That's a really huge opportunity.

AB521借用了一些奇怪的不可預見的東西，它是一種毒品。所以真正的問題是：如何充分利用這一點？如果你問我關於我們的投資組合，這絕對是當我們積極推動第一項研究時，我們希望非常努力地研究如何擴大 HIF-2 alpha 計劃的足跡。這確實是一個巨大的機會。

And we actually think because it's so hard to get a good molecule, you're not going to have anyone come in with a better molecule than us. So we feel we're going to end up better than belz. And it's -- there's not going to be commodity here.

我們實際上認為，因為獲得好的分子非常困難，所以不會有人擁有比我們更好的分子。所以我們覺得我們最終會比貝爾茲更好。這裡不會有商品。

And I like to thank Dmitry for making me feel not so bad pronouncing all these names. So zanza works for me; Cas works through. Thank you very much, Dimitry. Appreciate it.

我要感謝德米特里讓我在念出所有這些名字時感覺不那麼糟糕。所以贊札對我來說很有效； Cas 工作順利。非常感謝你，迪米特里。欣賞它。

My pleasure. Absolutely.

我的榮幸。絕對地。

I'm told that Cas is Cas, not Cas. That's what I've been told.

我聽說Cas就是Cas，不是Cas。這就是我被告知的。

I'll work on that, Terry. I'll work on that. (laughter)

我會努力的，特里。我會努力解決這個問題。（笑聲）

Daina Graybosch, Leerink Partners.

戴娜‧格雷博斯 (Daina Graybosch)，Leerink 合夥人。

Hi, guys. Thanks for the questions. I have three on Cas getting into the PK/PD data. First, on page 31 where you show the area under the curve, I recall initially talking about the value proposition for Cas that you expected a much higher absolute area under the curve.

嗨，大家好。感謝您的提問。我有 3 個關於 Cas 的 PK/PD 數據。首先，在第 31 頁顯示曲線下面積時，我記得最初談論 Cas 的價值主張時，您期望曲線下的絕對面積要高得多。

But what I see here at the 100 milligrams is pretty similar in range to the 120 and 240 milligrams for belzutifan. So I wonder if you can talk to that, that you're ending up in the same range.

但我在這裡看到的 100 毫克劑量範圍與 Belzutifan 的 120 毫克和 240 毫克劑量範圍非常相似。所以我想知道你是否可以談談，你最終處於同一範圍內。

And then on pharmacodynamics, you have two different pharmacodynamic readouts here. First is the percent EPO change on page 30, and then the percent hemoglobin or the absolute change in mean hemoglobin on page 32. Which of these PD readouts do you believe is more correlated to what you expect in efficacy?

然後在藥效學方面，這裡有兩種不同的藥效學讀數。首先是第 30 頁的 EPO 變化百分比，然後是第 32 頁的血紅素百分比或平均血紅素的絕對變化。您認為這些 PD 讀數中的哪一個與您預期的療效更相關？

And if I look at the hemoglobin, you're sort of in range of belzutifan and you're modestly higher, or looks to be modestly higher percent EPO. So my final question is: how much better efficacy do you expect to drive with these similar to modest increases in pharmacodynamic markers versus belzutifan? Thanks.

如果我看一下血紅蛋白，你的血紅蛋白有點在 belzutifan 範圍內，並且你的血紅蛋白稍高，或者看起來 EPO 百分比稍高。所以我的最後一個問題是：與 Belzutifan 相比，您期望透過這些類似的藥效學標記適度增加來提高療效多少？謝謝。

Thanks, Daina. So I'm going to tie it together. So I think the key point I'm going to define what's better PK and what's better PD. So PD, as you know, encompasses everything: tissue penetration, potency differences, pharmacokinetic differences.

謝謝，戴娜。所以我要把它綁在一起。所以我認為關鍵點是要定義什麼是更好的PK和什麼是更好的PD。因此，如您所知，PD 涵蓋一切：組織滲透、效力差異、藥物動力學差異。

So the PD readout, what we're saying -- and we think this is the value proposition, no question -- is that at 20 milligrams of AB521, you're getting the same horsepower. Let's use EPO as the marker that you get out of the approved and used dose of belzutifan.

因此，我們所謂的 PD 讀數（毫無疑問，我們認為這就是價值主張）是，在 20 毫克的 AB521 下，您將獲得相同的馬力。讓我們使用 EPO 作為您從批准和使用的 Belzutifan 劑量中獲得的標記。

Now the PK advantage has nothing to do with an AUC relative to belzutifan. The PK advantage is that when we go to fivefold higher doses than the dose that gives you that equivalent activity on the PD marker, we get fivefold higher exposures.

現在PK優勢與相對於belzutifan的AUC無關。PK 優點在於，當我們使用比 PD 標記物具有同等活性的劑量高五倍的劑量時，我們會得到五倍高的暴露量。

So if there's more water to be squeezed out of the activity stone, we're hitting that with fivefold the equivalent PD dose of belzutifan. So that's the value proposition. The PK advantage is that you can go higher from that maximal effect.

因此，如果有更多的水從活性石中擠出，我們將使用相當於 PD 劑量五倍的 belzutifan 來達到這一目的。這就是價值主張。PK的優勢在於，你可以從最大效果中走得更高。

With respect to hemoglobin or EPO, we don't look at either of those per se as something that's predictive of -- more or less predictive of the activity in the tumor setting.

對於血紅素或 EPO，我們不會將它們本身視為可預測的東西——或多或少可以預測腫瘤環境中的活動。

Can I state it back? So you're hitting at fivefold more dose than what gets you to the pharmacodynamic marker. And you believe that will give you a much better efficacy even though neither of these pharmacodynamic markers with fivefold greater dose really had that much more effect than belzutifan?

我可以回述一下嗎？因此，您所使用的劑量是達到藥效標記物的劑量的五倍。您相信這會為您帶來更好的療效，儘管這些劑量大五倍的藥效學標記物確實沒有比貝爾祖替凡更好的效果？

Yes, that is correct. But not only is it correct, that's what's predicted. And that's what -- that's the difference between the physiological n maximal HIF-2 -- as you know, HIF-2 is a transcription factor. So regulates a hundred things.

對，那是正確的。但這不僅是正確的，而且是預測的。這就是——這就是生理學最大 HIF-2 之間的差異——如你所知，HIF-2 是一種轉錄因子。如此規定百事。

Its effect on EPO have nothing to do with what's going on in the tumor. So we know going in that basically you're going to max out HIF-2 -- or EPO inhibition. And so that just becomes a marker for how hard are you hitting this thing and then the fact that we can go 5x what you can get out of the Merck molecule is what makes us feel good about hitting the tumor harder.

它對 EPO 的影響與腫瘤中發生的情況無關。所以我們知道基本上你會最大限度地發揮 HIF-2 或 EPO 抑製作用。因此，這只是一個標記，表明您對這個東西的打擊力度有多大，然後我們可以從默克分子中獲得 5 倍的效果，這一事實讓我們對更加努力地打擊腫瘤感到滿意。

That's very helpful. Thank you.

這非常有幫助。謝謝。

Thanks, Daina.

謝謝，戴娜。

Li Watsek, Cantor Fitzgerald.

李‧沃塞克，坎托‧費茲傑拉。

Hi, there. This is Rose Marie on Li. Thank you so much for taking our questions. And so to start with casdatifan. Do you happen to see any dose response when it comes to toxicity, the safety profile? And do you have concerns for greater side effects when you go above 100 milligrams? And then one question on your TIGIT programs -- sorry. Go ahead.

你好呀。這是李的羅絲瑪麗。非常感謝您接受我們的提問。首先從卡達替凡開始。當涉及毒性和安全性時，您是否碰巧看到任何劑量反應？當您的劑量超過 100 毫克時，您是否擔心會出現更大的副作用？然後還有一個關於你們的 TIGIT 程序的問題——抱歉。前進。

No, go ahead. You finish your question.

沒有，繼續。你問完你的問題。

So the question for TIGIT, so you said you plan to show some data from the ARC-10 trial which was discontinued. Do you have any color on when this could be and what kind of data we would expect? And would it potentially impact any thinking around the trials that you still have going on? Thank you.

那麼關於 TIGIT 的問題，你說你打算展示一些已停止的 ARC-10 試驗的數據。您是否知道什麼時候會出現這種情況以及我們期望得到什麼樣的數據？它是否可能會影響您仍在進行的試驗的任何思考？謝謝。

Yes. Thanks. So on the dose response, to be clear, the 20 milligram dose that we used is our lowest dose, is already pharmacologically relevant. As we noted on, you're seeing essentially a maximal effect on EPO suppression at that point.

是的。謝謝。因此，就劑量反應而言，需要明確的是，我們使用的 20 毫克劑量是我們的最低劑量，已經具有藥理相關性。正如我們所指出的，此時您基本上會看到 EPO 抑制的最大效果。

So I would just say with three patients and each of the doses with six on the 50, we wouldn't say that we see any meaningful differences, nor do we expect that. And similarly, because of what we know -- and this what gets back to how I was answering Daina's question -- there's either feedback mechanisms or other non-HIF-2-mediated ways that EPO is produced.

因此，我只想說，對於 3 名患者，每劑 50 劑量有 6 劑，我們不會說我們看到任何有意義的差異，我們也不期望出現這種情況。同樣，由於我們所知道的——這又回到了我如何回答戴娜的問題——EPO 的產生要么有反饋機制，要么有其他非 HIF-2 介導的方式。

And so you hit this maximal effect on that endpoint, which to date has been the primary side effect and is very manageable. So that is the anemia that's a correlate of that EPO suppression. And basically that's been very manageable.

因此，您對該端點產生了最大的影響，迄今為止，這是主要的副作用，並且非常容易控制。這就是與 EPO 抑制相關的貧血。基本上這是非常容易管理的。

So at this point, we don't have any expectations that going higher will induce any more of a liability. And we certainly haven't seen it at the 100 milligram dose.

因此，在這一點上，我們並不期望價格走高會帶來更多的責任。我們當然還沒有在 100 毫克劑量下看到過它。

The other place where we're keeping a close eye is, in fact, on hypoxia. That has to do with HIF-2 inhibition in the lung. Again, that may also be something that's maxed. It's normal physiology. It's something that we're paying attention to. Some of these things may also be dependent on individual patients, particularly when you think about EPO, if there are patients would have -- that have compromised kidney function.

事實上，我們密切關注的另一個問題是缺氧。這與肺部的 HIF-2 抑制有關。同樣，這也可能是極限的事。這是正常的生理現象。這是我們正在關注的事情。其中一些因素也可能取決於個別患者，特別是當您考慮 EPO 時，如果有患者的腎功能受損的話。

But the date, we haven't seen anything of concern and we'll just see what happens when we go to a higher dose. And certainly under the initial 30 patients, nothing that we've seen to date has caused us concern. And to make the point, we have not yet seen a DLT.

但到目前為止，我們還沒有看到任何令人擔憂的事情，我們只會看看當我們服用更高劑量時會發生什麼。當然，在最初的 30 名患者中，迄今為止我們所看到的一切都沒有引起我們的擔憂。為了說明這一點，我們還沒有看到 DLT。

On the anti-TIGIT ARC-10 data, that's just something we're considering. We haven't made a decision on that. But if we did do that, the idea would be that we would do our cut of the data and a cleaning of the data when we would extrapolate, that we would have mature PFS minimally.

關於反TIGIT ARC-10數據，這正是我們正在考慮的。我們還沒有就此做出決定。但如果我們真的這麼做了，我們的想法是，當我們推斷時，我們將進行資料切割和資料清理，我們將至少擁有成熟的 PFS。

And at this point, with the data that we have in hand from our other study, it wouldn't affect any of the studies that we're -- it would not be a decision-making data.

此時，根據我們從其他研究中獲得的數據，它不會影響我們正在進行的任何研究——它不會是決策數據。

Got it. Thanks, Terry.

知道了。謝謝，特里。

Ladies and gentlemen, this concludes our Q&A and today's conference call. We'd like to thank you for your participation. You may now disconnect your lines.

女士們先生們，我們的問答和今天的電話會議到此結束。我們衷心感謝您的參與。現在您可以斷開線路。