Arcus Biosciences Inc (RCUS) 2025 Q1 法說會逐字稿

Hello, everyone. And welcome to Arcus Biosciences first quarter 2025 earnings and financial results call. My name is Lydia, and I'll be your operator today. After the prepared remarks, there'll be an opportunity to ask questions (Operator Instructions) I'll now hand you over to Pia Eaves, Vice President of Investor Relations to begin. Please go ahead.

大家好。歡迎參加 Arcus Biosciences 2025 年第一季財報與財務業績電話會議。我叫莉迪亞 (Lydia)，今天我將擔任您的接線生。準備好發言後，將有機會提問（操作員指示），現在我將把您交給投資者關係副總裁 Pia Eaves 開始。請繼續。

Good afternoon. And thank you for joining us on today's conference call to discuss Arcus' first quarter 2025 financial results and pipeline updates. I'd like to remind you that on this call management will make forward looking statements, including statements about our cash runway, our projected 2025 revenue and our expected clinical development milestones and timelines.

午安.感謝您參加今天的電話會議，討論 Arcus 2025 年第一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陳述，包括有關我們的現金流量、我們預計的 2025 年收入以及我們預期的臨床開發里程碑和時間表的陳述。

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.

除歷史事實外，所有陳述均反映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向美國證券交易委員會提交的最新 10-Q 表季度報告中有所描述。

Today, you'll hear from our CEO, Terry Rosen; CMO, Richard Markus; COO, Jennifer Jarrett; and CFO, Bob Goeltz. We'll also be joined by our President, Juan Jaen for questions after the prepared remarks. With that, I'll turn the call over to Terry.

今天，您將聽到我們的執行長 Terry Rosen、首席行銷長 Richard Markus、營運長 Jennifer Jarrett 和財務長 Bob Goeltz 的演講。在準備好的發言之後，我們的總統胡安·哈恩 (Juan Jaen) 也將與我們一起回答問題。說完這些，我會把電話轉給特里。

Thank you very much, Pia. And thanks to all for listening in today. While the world around us has been somewhat or maybe definitely tumultuous, at Arcus, we've really remained focused on execution and that execution goes with speed, efficiency and most importantly, rigor.

非常感謝，Pia。感謝大家今天的收聽。雖然我們周圍的世界有些或肯定是動盪的，但在 Arcus，我們真正仍然專注於執行，並且執行伴隨著速度、效率，最重要的是嚴謹。

And so before we get into the details, I want to emphasize three points that will be apparent in our discussion today. So first off, our late stage portfolio is rich but our number one priority is unequivocally casdatifan. So far, the more data that we generate the better it looks.

因此，在我們討論細節之前，我想先強調今天討論中會出現的三點。首先，我們的後期投資組合非常豐富，但我們的首要任務無疑是 casdatifan。到目前為止，我們產生的數據越多，它看起來就越好。

So our goal is simple, to bring cas to market and to patients as quickly as possible and create maximal value for this program. Second, we are well capitalized and our long term strategy has positioned us well to advance dom, quemli and cas through their respective initial Phase 3 readouts.

因此，我們的目標很簡單，盡快將 CAS 推向市場並惠及患者，並為該專案創造最大價值。其次，我們資本充足，我們的長期策略使我們能夠順利推進 dom、quemli 和 cas 完成各自的初始第 3 階段讀數。

Nonetheless, we are always cognizant of the macro environment and we are committed to ensuring our resource deployment reflects our ongoing assessment of priorities so that our cash runway extends as long as possible. Third, we expect to have a steady flow of data for casdatifan over the next couple of years that will reinforce the advantages relative to both casdatifan and TKI monotherapy.

儘管如此，我們始終關注宏觀環境，並致力於確保我們的資源部署反映我們對優先事項的持續評估，以便我們的現金流量盡可能延長。第三，我們預計未來幾年卡達替凡將獲得穩定的數據流，這將增強其相對於卡達替凡和 TKI 單一療法的優勢。

And in that vein, we are thrilled that our abstract describing initial data from the cas plus cabo cohort of ARC-20 was accepted for an oral presentation at ASCO. This is the same combination we are evaluating in our first [patient] (technical difficulty) quarter and these data should provide further support for the study. This will also be the third oral presentation of casdatifan data at a major medical conference in just seven months and there are a lot more to come.

從這個角度來看，我們很高興我們的描述 ARC-20 cas plus cabo 隊列初始數據的摘要被接受在 ASCO 上進行口頭報告。這是我們在第一季（技術難度）評估的相同組合，這些數據應該為研究提供進一步的支持。這也將是短短七個月內第三次在大型醫學會議上口頭報告 casdatifan 數據，未來還會有更多報告。

Now some important granularity around the casdatifan program. In our Phase 1b ARC-20 study, we now have eight cohorts evaluating different dosing regimens, combinations and settings for cas and clear cell RCC. This is why ARC-20 will generate meaningful data over the next two years that will serve several important purposes.

現在圍繞 casdatifan 程序有一些重要的細節。在我們的 1b 期 ARC-20 研究中，我們現在有 8 個隊列評估針對 cas 和透明細胞 RCC 的不同給藥方案、組合和設定。這就是為什麼 ARC-20 將在未來兩年內產生有意義的數據，用於幾個重要目的。

First, continued elucidation of casdatifan's differentiated efficacy profile relative to that of elastizudafan and derisking of our first Phase 3 study PEAK-1. Second, continuing to drive the already extraordinary investigator enthusiasm for PEAK-1 to support its rapid enrollment.

首先，繼續闡明卡斯達替芬相對於埃拉西達芬的差異化療效特徵，並降低我們第一個 3 期研究 PEAK-1 的風險。其次，繼續推動研究人員對 PEAK-1 的極大熱情，以支持其快速招募。

And third, demonstrating the opportunity for casdatifan in earlier line settings where casdatifan has the potential to ultimately displace TKIs. Before I turn the call over to Richard, I would like to touch on a few additional topics starting with our development plan and our long term vision for casdatifan.

第三，證明了卡他替芬在早期治療中的機會，卡他替芬有可能最終取代 TKI。在我將電話轉給理查德之前，我想談談幾個額外的話題，從我們的發展計劃和我們對 casdatifan 的長期願景開始。

Our Phase 3 trial PEAK-1 will evaluate cas plus cabo versus cabo in clear cell RCC patients who have received prior immunotherapy. For our first registrational trial, we chose to combine cas with cabo, because cabo is the gold standard and most widely used TKI in the setting.

我們的 3 期試驗 PEAK-1 將評估 cas 加 cabo 與 cabo 對已接受免疫治療的透明細胞 RCC 患者的效果。對於我們的第一次註冊試驗，我們選擇將 cas 與 cabo 結合起來，因為 cabo 是黃金標準並且是該環境中使用最廣泛的 TKI。

In fact, in our ARC-20 monotherapy cohorts, 78% of patients received prior cabo, that's greater than 3 times more than any other TKI. Clinicians are extremely comfortable administering and managing the toxicities of cabo and because of this, there's an extraordinary amount of interest in PEAK-1.

事實上，在我們的 ARC-20 單藥治療組中，78% 的患者曾接受過 cabo 治療，這一比例比其他 TKI 都要高出 3 倍以上。臨床醫生非常熟悉 Cabo 的給藥和控制毒性，因此，人們對 PEAK-1 產生了極大的興趣。

Also, because HIF-2 alpha inhibition affords relatively benign safety profile with the primary AEs being on target anemia and hypoxia, we do not believe cas will have meaningful overlapping toxicities with cabo. As such, the key objectives of our upcoming ASCO presentation are to clearly demonstrate that these two molecules can be safely combined and that we can add efficacy to that of cabo monotherapy. We expect the data shared at ASCO will demonstrate exactly this.

此外，由於 HIF-2 阿爾法抑制具有相對良性的安全性，主要不良事件是目標貧血和缺氧，我們認為 cas 不會與 cabo 產生有意義的重疊毒性。因此，我們即將在 ASCO 上進行演示的主要目標是清楚地證明這兩種分子可以安全地結合，並且我們可以為 Cabo 單一療法增加療效。我們期望 ASCO 分享的數據能夠準確證明這一點。

Longer term, given the strength of cas' efficacy and safety profile, our vision is to develop cas in TKI free regimens and even to displace TKIs in earlier lines of RCC treatment. TKIs have been very effective in treating RCC. Almost every RCC patient receives a TKI during the course of their treatment, but TKIs come with debilitating side effects that meaningfully impact quality of life.

從長遠來看，鑑於 cas 的療效和安全性，我們的願景是開發無需 TKI 的 cas 方案，甚至取代早期 RCC 治療中的 TKI。TKI 在治療 RCC 方面非常有效。幾乎每個 RCC 患者在治療過程中都會接受 TKI 治療，但 TKI 會帶來嚴重的副作用，嚴重影響生活品質。

This can not be overstated. So we believe, there is a huge opportunity to develop cas in earlier lines driving a long sought paradigm shift enabling patients to avoid TKI therapy for as long as possible. This in fact reflects a core element of Arcus' high level strategy in oncology, driven by the advances in the understanding of tumor biology in the last decade, being a leader in the development of innovative cancer therapeutics with improved efficacy that preserve quality of life during treatment.

這一點無論如何強調也不為過。因此，我們相信，在早期領域開發 cas 有著巨大的機會，這將推動人們長期尋求的範式轉變，使患者能夠盡可能長時間地避免 TKI 治療。這實際上反映了 Arcus 在腫瘤學領域的高水平戰略的核心要素，該戰略受到過去十年來對腫瘤生物學理解的進步的推動，在開發創新癌症療法方面處於領先地位，提高了療效，並在治療期間保持了生活質量。

Specifically, we're collaborating with AstraZeneca to combine cas with their anti-PD-1 anti-CTLA-4 bispecific antibody for volrustomig to create the first TKI free HIF-2 alpha combination option for first line RCC. I want to repeat that, this will be the first TKI free HIF-2 alpha combination option looked at in first line RCC.

具體來說，我們正在與阿斯特捷利康合作，將 cas 與他們的抗 PD-1 抗 CTLA-4 雙特異性抗體結合起來用於 volrustomig，以創建第一個用於一線 RCC 的無 TKI HIF-2 alpha 組合選項。我想重申一下，這將是 RCC 一線治療中第一個不含 TKI 的 HIF-2 阿爾法組合方案。

Anti-PD-1, anti-CTLA-4 is one of the most commonly and widely used first line regimen, particularly in academic centers, because it is TKI free and conveniently prolongs survival. AstraZeneca will operationalize this study as part of their EVOLVE portfolio, so this collaboration enables us to develop cas in the first line setting in an extremely cost and resource efficient manner and with a world class drug developer in oncology.

抗 PD-1、抗 CTLA-4 是最常用和廣泛使用的一線治療方案之一，尤其是在學術中心，因為它不含 TKI，並且可以方便地延長生存期。阿斯特捷利康將把這項研究作為其 EVOLVE 產品組合的一部分來實施，因此，此次合作使我們能夠以極具成本和資源效率的方式與世界一流的腫瘤學藥物開發商一起在第一線開發 cas。

The study is designed to demonstrate the safety of the combination to support late stage development. This provides another opportunity to generate confidence enhancing data for casdatifan based regimens over the next 18 to 24 months.

該研究旨在證明該組合的安全性，以支持後期開發。這為未來 18 至 24 個月內基於卡他替芬的治療方案產生增強信心的數據提供了另一個機會。

Beyond EVOLVE, we've added three cohorts to ARK-20 to evaluate cas and other early line TKI free settings. These are cas plus zim, our anti-PD-1 antibody in first line all comer clear cell RCC, cas monotherapy in first line favorable risk patients and cas monotherapy in patients that have received prior IO but have not yet received the TKI.

除了 EVOLVE 之外，我們還在 ARK-20 中添加了三個隊列來評估 cas 和其他早期 TKI 免費設定。這些是 cas plus zim，我們的抗 PD-1 抗體，用於一線全角透明細胞 RCC，cas 單一療法用於一線低風險患者，cas 單一療法用於已接受過 IO 但尚未接受 TKI 治療的患者。

All three cohorts recently opened for enrollment and have generated significant interest in the investigator community, demonstrating and building on the robust interest in cas and in TKI free regimens. As a result, these cohorts should enroll quickly and generate efficacy data over the next couple of years informing future development opportunities.

所有三個隊列均於近期開放註冊，並引起了研究人員群體的極大興趣，展示並鞏固了人們對 cas 和無 TKI 方案的濃厚興趣。因此，這些群體應該迅速招募並在未來幾年內產生療效數據，為未來的發展機會提供資訊。

While cas has moved front and center in our portfolio, our two other registrational programs, which are targeting massive patient populations with substantial unmet need, continue to advance towards data. For our Fc-silent anti-TIGIT antibody, domvanalimab, the first Phase 3 study to read out will be STAR-221, for which we have guided to 2026.

雖然 CAS 在我們的產品組合中佔據了中心位置，但我們的另外兩個註冊項目針對的是大量未滿足需求的患者群體，它們仍在繼續向數據方向發展。對於我們的 Fc 沉默抗 TIGIT 抗體 domvanalimab，第一個要宣讀的 3 期研究將是 STAR-221，我們已將其指導至 2026 年。

This study is evaluating dom, zim plus chemo versus nivo plus chemo, the standard of care in first line gastric cancer. Later this year, we'll be sharing overall survival data, OS data from the corresponding Phase 2 study EDGE-Gastric. This is evaluating the same regimen in the same setting as STAR-221.

這項研究正在評估 dom、zim 加化療與 nivo 加化療作為第一線胃癌治療的標準方案。今年晚些時候，我們將分享相應的第 2 階段研究 EDGE-Gastric 的整體生存數據和 OS 數據。這是在與 STAR-221 相同的環境下對相同方案的評估。

We expect these data to reinforce confidence in STAR-221, which has an overall survival primary endpoint. The competitive landscape in this field has seen a dramatic shift over the last six months with the Fc-silent anti-TIGIT antibodies, specifically ours and AstraZeneca's anti-TIGIT anti PD-1 bispecific antibody now dominating the Phase 3 landscape.

我們預計這些數據將增強人們對 STAR-221 的信心，該藥物以總體生存期為主要終點。在過去六個月中，該領域的競爭格局發生了巨大變化，Fc 沉默抗 TIGIT 抗體（特別是我們的抗體和阿斯特捷利康的抗 TIGIT 抗 PD-1 雙特異性抗體）目前在 3 期臨床試驗中佔據主導地位。

These two molecules have generated similar positive data in Phase 2 studies in both lung and GI cancers. AstraZeneca is now enrolling 10 different Phase 3 studies for its Fc-silent anti-TIGIT antibody.

這兩種分子在肺癌和胃腸道癌的 2 期研究中都產生了相似的正面數據。阿斯特捷利康目前正在為其 Fc 沉默抗 TIGIT 抗體招募 10 項不同的 3 期研究。

In addition, PRISM-1, our Phase 3 trial of quemli, our small molecule CD-73 inhibitor, in combination with chemotherapy and first line pancreatic cancer is enrolling rapidly. There's been a tremendous enthusiasm for PRISM-1 and as a result, we anticipate the study will now be fully enrolled by the end of 2025, less than 12 months after initiation.

此外，我們的小分子 CD-73 抑制劑 quemli 與化療和第一線胰臟癌聯合治療的 3 期試驗 PRISM-1 正在迅速招募患者。人們對 PRISM-1 表現出極大的熱情，因此，我們預計研究將在 2025 年底（啟動後不到 12 個月）內完成全部招募。

This is our second global Phase 3 study that will complete enrollment well ahead of initial expectations and our goal is to replicate the success with the enrollment of PEAK-1. This brings me to my final key point. Today, we have a strong balance sheet with $1 billion in cash and investments.

這是我們的第二項全球 3 期研究，其招募工作將遠遠提前於最初的預期完成，我們的目標是複製 PEAK-1 招募工作的成功。這就引出了我的最後一個關鍵。今天，我們擁有強勁的資產負債表，現金和投資達 10 億美元。

This is not an accident. While there has been a dramatic shift in the macroeconomic environment, we are always scrutinizing our capital allocation, prioritizing our molecules and programs and leveraging strategic collaborations. For example, those with Gilead, Tycho and AstraZeneca, to maintain a strong balance sheet.

這不是偶然的。儘管宏觀經濟環境發生了巨大變化，但我們始終在仔細審查我們的資本配置，確定我們的分子和專案的優先順序，並利用策略合作。例如，擁有吉利德、Tycho 和阿斯特捷利康的公司，可以維持強勁的資產負債表。

This will be particularly true going forward to ensure that our capital stretches as long as possible and to enable us to continue funding our small molecule research programs. The discovery of casdatifan, an exceptionally high quality molecule against an extremely intractable target is a reflection of the secret sauce of Arcus, which is our research organization and small molecule drug discovery capability.

這對於確保我們的資本盡可能長久地使用以及使我們能夠繼續資助我們的小分子研究計畫尤其重要。卡達提凡 (Casdatifan) 是針對極其棘手的標靶的極高品質分子，它的發現體現了 Arcus 的秘密武器，即我們的研究機構和小分子藥物發現能力。

Our next INDs are likely to come from our inflammation and immunology programs, which have been quietly but rapidly advancing in our focus on the creation of potential first and best-in-class small molecule drug candidates against validated targets. We are going to share more about these programs later in this year.

我們的下一個 IND 可能來自我們的發炎和免疫學項目，這兩個項目一直在悄悄但快速地推進，我們專注於針對已驗證的目標創造潛在的首創和一流的小分子候選藥物。我們將在今年稍後分享更多有關這些計劃的資訊。

With that, I would like to turn the call over to Richard, to speak about casdatifan in greater detail.

說到這裡，我想把電話交給理查德，讓他更詳細地談談 casdatifan。

Thanks, Terry. I'll first recap the highlights of our recent ASCO GU presentation for cas monotherapy in late line clear cell renal cell carcinoma. After that, I'll speak about our upcoming data presentations and near term development plans for cas. I'll start with a reminder of the study design of ARC-20 on slide 9.

謝謝，特里。我將首先回顧我們最近在 ASCO GU 上關於晚期透明細胞腎細胞癌 cas 單一療法的演講亮點。之後，我將談論我們即將進行的數據演示和 cas 的近期發展計劃。我先回顧一下投影片 9 上的 ARC-20 的研究設計。

ARC-20 now includes eight cohorts evaluating cas monotherapy or cas combinations in clear cell RCC. As a reminder, our ASCO GU presentation included data from three of the monotherapy cohorts in late line clear cell RCC. I also want to highlight here the cohort evaluating 100 milligrams of cas plus 60 milligrams of cabozantinib, and this is the same combination and dosing regimen we will evaluate in PEAK-1 and the cohort that is subject of the data presentation at this year's ASCO.

ARC-20 目前包括 8 個隊列，用於評估透明細胞 RCC 中的 cas 單一療法或 cas 組合療法。提醒一下，我們的 ASCO GU 簡報包括晚期透明細胞 RCC 中三種單一療法隊列的數據。我還想在這裡強調一下評估 100 毫克 cas 加 60 毫克卡博替尼的隊列，這是我們將在 PEAK-1 和今年 ASCO 數據展示的主題隊列中評估的相同組合和給藥方案。

Patients in this cohort are all previously treated and have received one or two prior lines of therapy with their most recent prior line being an anti-PD-1, and patients did not need to have received prior TKI therapy, so this is a very similar population to that of PEAK-1. On slide 14, we compare the efficacy assessments for the monotherapy cohorts relative to data from Lightspark V, the Phase 3 study of belzutifan.

該隊列中的患者均接受過治療，並且已經接受過一到兩種療法，最近的療法是抗 PD-1 療法，患者不需要接受過先前的 TKI 療法，因此該群體與 PEAK-1 群體非常相似。在投影片 14 上，我們將單一療法組的療效評估與 belzutifan 的 3 期研究 Lightspark V 的數據進行了比較。

Importantly, we enrolled a more advanced patient population than that of Lightspark V. In fact, approximately one third of our patients would not have been eligible for Lightspark V.

重要的是，我們招募的患者群比 Lightspark V 更為先進。事實上，大約三分之一的患者不適合接受 Lightspark V 治療。

Though we recognize the limitations of cross trial comparisons, cas performed better on every efficacy measure in every cohort despite this more advanced patient population. Rates of primary progressive disease were close to half that of belzutifan. Confirmed ORR was consistently higher than that of belzutifan and two cohorts achieved confirmed ORRs greater than 30%. The ORRs for belzutifan monotherapy studies have ranged from 18% to 21.9%.

雖然我們認識到交叉試驗比較的局限性，但儘管患者群體更為先進，但 cas 在每個隊列的每個療效指標上都表現得更好。原發性進展性疾病的發生率接近貝祖替凡的一半。確認的 ORR 始終高於貝祖替凡，且兩個隊列的確認 ORR 均超過 30%。貝祖替凡單藥治療研究的 ORR 範圍為 18% 至 21.9%。

So the casdatifan ORR is trending about 50% higher. For disease control rate or DCR, over 80% of patients should benefit from casdatifan versus just 61% for belzutifan. Lastly, the median PFS of 9.7 months for the 50 milligram BID cohort was meaningfully longer than the 5.6 months for belzutifan, and the median PFS had not even been reached for the 50 milligram QD and 100 milligram cohorts.

因此，卡他替尼的 ORR 趨勢大約會上升 50%。對於疾病控制率或 DCR，超過 80% 的患者應該會從 casdatifan 中受益，而只有 61% 的患者會從 belzutifan 中受益。最後，50 毫克 BID 組的中位 PFS 為 9.7 個月，明顯長於貝祖替凡的 5.6 個月，而 50 毫克 QD 和 100 毫克組的中位 PFS 甚至尚未達到。

However, when we pooled data from the 50 milligram BID and 50 milligram QD cohorts, the median PFS was 13 months, so significantly longer than that of belzutifan. slide 11 shows the waterfall and spider plots for the 100 milligram QD dose and these data give us confidence in the selection of 100 milligrams QD as a dose for our Phase 3 studies of cas.

然而，當我們匯總 50 毫克 BID 和 50 毫克 QD 隊列的數據時，中位 PFS 為 13 個月，明顯長於 belzutifan。幻燈片 11 顯示了 100 毫克 QD 劑量的瀑布圖和蜘蛛圖，這些數據讓我們有信心選擇 100 毫克 QD 作為 cas 第 3 階段研究的劑量。

On slide 12, we show the spider plots for the 50 milligram BID and 50 milligram QD cohorts, which highlight the durability of casdatifan's efficacy. Across all three cohorts, remarkably, only two of the 26 confirmed responders have progressed and many of the stable disease patients clearly derive benefit and will therefore contribute meaningfully to the median PFS.

在幻燈片 12 上，我們展示了 50 毫克 BID 和 50 毫克 QD 組的蜘蛛圖，突顯了 casdatifan 療效的持久性。值得注意的是，在所有三個隊列中，26 名確診的應答者中只有 2 名出現進展，而許多病情穩定的患者明顯受益，因此將對中位 PFS 做出有意義的貢獻。

We have a number of upcoming data presentations for ARC-20, and these are summarized here on slide 5. First up will be initial data from our cas plus cabo cohort at ASCO. A key objective of this data set will be to demonstrate that these molecules can be safely combined.

我們即將發布一些有關 ARC-20 的數據演示，這些演示在第 5 張幻燈片中進行了總結。首先是來自 ASCO 的 cas plus cabo 隊列的初始數據。該資料集的一個關鍵目標是證明這些分子可以安全地組合。

In addition, given that we had approximately 25 patients enrolled by the end of the year, we plan to present overall response rate data for those patients who are eligible for two or more scans at the data cutoff. So to be clear, the ORR denominator will include all patients who were enrolled at least 12 weeks prior to the data cutoff, regardless of the number of scans actually recorded.

此外，鑑於我們在年底前已招募了大約 25 名患者，我們計劃在數據截止時提供有資格進行兩次或兩次以上掃描的患者的總體回應率數據。因此需要明確的是，ORR 分母將包括在資料截止前至少 12 週入組的所有患者，無論實際記錄的掃描次數是多少。

I also want to point out that the data included in the ASCO abstract are from a prior data cut and the ASCO oral presentation will feature data from a more recent data cut. Later in the year, we expect to present more mature data from all four monotherapy cohorts of ARC-20 in late line clear cell RCC. In 2026, we plan to share more mature data from the cas plus cabo combination cohort as well as an initial data from the newly added cohorts evaluating the TKI-3 regimens in early line settings.

我還想指出，ASCO 摘要中包含的數據來自先前的數據，而 ASCO 口頭報告將採用較新數據的數據。今年晚些時候，我們預計將提供 ARC-20 在晚期透明細胞 RCC 中所有四種單一療法治療組的更成熟的數據。2026 年，我們計劃分享來自 cas 加 cabo 組合隊列的更多成熟數據，以及來自新添加的隊列的初始數據，以評估早期治療中 TKI-3 方案的效果。

Now on to the development plan, slide 16, which shows the design of PEAK-1 where we are evaluating cas plus cabo versus cabo in IO experienced patients who had one prior line of immunotherapy. Target enrollment is 700 patients and we expect the study will enroll quickly for several reasons.

現在討論開發計劃，幻燈片 16，它展示了 PEAK-1 的設計，我們正在評估 cas 加 cabo 與 cabo 在接受過一線免疫治療的 IO 患者中的效果。目標招募人數為 700 名患者，由於多種原因，我們預計研究很快就會招募到患者。

First, as Terry mentioned earlier, we are using cabo, the most widely used and preferred TKI, in both arms of the study. Second, patients will be randomized 2:1 between the experimental arm and the control arm. And third, there's already very substantial awareness of cas in the clinician community, and we expect to include multiple ARC-20 sites in the PEAK-1 study.

首先，正如 Terry 之前所提到的，我們在研究的兩個部分中都使用了最廣泛使用和最受歡迎的 TKI cabo。其次，患者將以 2:1 的比例隨機分配到實驗組和對照組。第三，臨床醫師群體對 CAS 的認識已經非常深入，我們期望在 PEAK-1 研究中納入多個 ARC-20 站點。

Merck is running a somewhat similar study called Lightspark XI, which is evaluating belzutifan plus a TKI and is now expected to read out in 2027. However, there are some important differences I'd like to highlight. First, while PEAK-1 has cabo in both study arms, Lightspark XI has lenvatinib in the experimental arm but cabo in the control arm. And using different TKIs in the same experiment could add risk to the trial outcome for Lightspark XI.

默克公司正在進行一項類似的研究，名為 Lightspark XI，該研究正在評估 Belzutifan 與 TKI 的療效，預計將於 2027 年得出結果。然而，我想強調一些重要的區別。首先，雖然 PEAK-1 在兩個研究組中都有 cabo，但 Lightspark XI 在實驗組中有 lenvatinib，而在對照組中有 cabo。並且在同一實驗中使用不同的 TKI 可能會增加 Lightspark XI 試驗結果的風險。

In addition, we are using a single primary endpoint of PFS in PEAK-1 rather than a dual endpoint of OS and PFS, which is being used in Lightspark XI. And given how quickly we expect PEAK-1 to enroll and the anticipated timing of the PFS primary endpoint, we have significantly narrowed the gap between our readout and that of Lightspark XI.

此外，我們在 PEAK-1 中使用 PFS 的單一主要終點，而不是 Lightspark XI 中使用的 OS 和 PFS 的雙終點。並且考慮到我們預期 PEAK-1 的入組速度以及 PFS 主要終點的預期時間，我們已顯著縮小了我們的讀數與 Lightspark XI 之間的差距。

Meanwhile, in the IO naive setting, our strategy is very different. In this setting, Merck is evaluating belzutifan in combination with pembro and lenvatinib. In contrast, we are collaborating with AstraZeneca to evaluate cas plus volrustomig, AstraZeneca's anti-PD-1 CTLA-4 bispecific.

同時，在 IO 簡單設定中，我們的策略非常不同。在這種情況下，默克正在評估 belzutifan 與 pembro 和 lenvatinib 的聯合治療。相較之下，我們正在與阿斯特捷利康合作評估阿斯特捷利康的抗 PD-1 CTLA-4 雙特異性抗體 cas plus volrustomig。

And as Terry mentioned, this is a highly attractive TKI free combination that may enable patients to remain on therapy for several years while avoiding TKI related toxicities. We have not yet disclosed the design of the study but we expect to share more information very soon, and we think you'll be excited about our strategy in this setting. I'd now like to turn the call over to Jen to speak about the market opportunity for casdatifan.

正如 Terry 所提到的，這是一種非常有吸引力的無 TKI 組合，可以讓患者繼續接受治療數年，同時避免 TKI 相關的毒性。我們尚未披露研究的設計，但我們希望很快分享更多信息，我們認為您會對我們在這種環境下的策略感到興奮。現在我想把電話轉給 Jen，讓她談談 casdatifan 的市場機會。

Thank you, Richard. RCC is a unique oncology market and that metastatic patients can remain on therapy for many years. In fact, five year survival is becoming the norm in this disease and patients will cycle through multiple treatments, often staying on treatment for well over a year even in the second line setting.

謝謝你，理查。RCC 是一個獨特的腫瘤市場，轉移性患者可以接受多年的治療。事實上，五年存活期正成為這種疾病的常態，患者將接受多種治療，即使在第二線治療中也常常需要接受一年以上的治療。

As a result, we believe the revenue opportunity for a good RCC drug is very substantial. On slide 17, we highlight the total market opportunity for the first two settings we are pursuing for cas. First, we show the IO naive patient population, which we are addressing with cas plus volru. The addressable population here is about 13,000 patients in the US and 20,000 in other major markets.

因此，我們相信，優質 RCC 藥物的獲利機會非常巨大。在第 17 張投影片上，我們重點介紹了我們正在追求的前兩種設定的整體市場機會。首先，我們展示了未接受 IO 治療的患者群體，我們用 cas plus volru 來解決這個問題。這裡的目標族群是美國約 13,000 名患者，其他主要市場約 2 萬名患者。

Given that, most of these patients progress and go onto subsequent therapies, the addressable patient population for the IO experience setting is very similar. With a two plus year duration of therapy in IO naive patients and a 12 month plus duration of therapy in IO experienced patients, we believe the total market opportunity from these two settings combined is $5 billion. With a better molecule than belzutifan and differentiated combinations and development plan, we should capture a significant share of this market.

鑑於大多數患者病情有所改善並接受後續治療，IO 體驗環境中可針對的患者群體非常相似。對於未接受過 IO 治療的患者，治療持續時間為兩年以上；對於接受過 IO 治療的患者，治療持續時間為 12 個月以上。我們認為，這兩種治療方式的市場總機會可達 50 億美元。憑藉比貝祖替凡更好的分子以及差異化的組合和開發計劃，我們應該能夠佔領這個市場的很大份額。

On slide 18, we show US market share by regimen. TKI based regimens dominate the clear cell RCC market with approximately 65% share in first line and 75% in the second line settings. This explains why our first Phase 3 study will focus on a cas TKI combination and you can see here why we chose cabo as our combination partner. We believe there is a strong clinician preference for cabo.

在投影片 18 中，我們按方案展示了美國的市場份額。基於 TKI 的方案在透明細胞 RCC 市場佔據主導地位，在一線治療中佔有約 65% 的份額，在二線治療中佔有約 75% 的份額。這解釋了為什麼我們的第一階段 3 期研究將集中於 cas TKI 組合，並且您可以在這裡看到我們為什麼選擇 cabo 作為我們的組合合作夥伴。我們相信臨床醫師對 cabo 有著強烈的偏好。

However, as Terry described earlier, our vision is that over time casdatifan will move up in lines of therapy and take share from TKI based regimens, either as monotherapy or in combination with IO treatment, particularly given cas' low rate of primary progressive disease relative to the one competitor, belzutifan.

然而，正如 Terry 先前所描述的，我們的願景是，隨著時間的推移，casdatifan 將在治療領域中不斷提升，並從基於 TKI 的方案中奪取份額，無論是作為單一療法還是與 IO 治療相結合，特別是考慮到 cas 相對於其競爭對手 belzutifan 的原發性進展性疾病發生率較低。

We believe belzutifan's high rate of primary progressive disease is a key reason why it's used today primarily in the third line setting. I will now turn the call over to Bob to review our financials.

我們認為，貝祖替凡的高原發性進展性疾病發生率是其目前主要用於第三線治療的關鍵原因。我現在將把電話轉給鮑伯來審查我們的財務狀況。

Thanks, Jen. Our cash as of the end of the first quarter was $1 billion as compared to $992 million as of the end of 2024. Our cash position was bolstered by a $150 million equity financing, which we completed in February 2025. We expect our cash and existing facilities will enable us to fund operations through our initial pivotal readouts for dom, quemli and cas, which include the PEAK-1 readout.

謝謝，Jen。截至第一季末，我們的現金為 10 億美元，而截至 2024 年底，我們的現金為 9.92 億美元。我們於 2025 年 2 月完成了 1.5 億美元的股權融資，增強了我們的現金狀況。我們預計，我們的現金和現有設施將使我們能夠透過 dom、quemli 和 cas 的初始關鍵讀數（包括 PEAK-1 讀數）來為營運提供資金。

Given the faster than anticipated enrollment of our PRISM-1 trial in pancreatic cancer and the completion of enrollment of STAR-221 last year, we expect 2025 to be a peak year for development expenses. We expect both our dom related and aggregate development expenses to decline meaningfully in 2026 and 2027 inclusive of our investment in casdatifan.

鑑於我們的胰臟癌 PRISM-1 試驗的招募速度快於預期，以及去年完成 STAR-221 的招募，我們預計 2025 年將成為開發費用的高峰年。我們預計，2026 年和 2027 年，包括對 casdatifan 的投資在內，我們的 dom 相關費用和整體開發費用都將大幅下降。

As Terry mentioned, we have also carefully scrutinized our capital allocation and have made pipeline prioritization decisions to ensure we maintain our strong financial position. Turning to our P&L. We recognized GAAP revenue for first quarter of $28 million, which compares to $36 million for the fourth quarter of last year. Our revenue is primarily driven by our collaboration with Gilead.

正如特里所提到的，我們也仔細審查了我們的資本配置，並做出了管道優先決策，以確保我們保持強勁的財務狀況。轉向我們的損益表。我們確認第一季的 GAAP 收入為 2800 萬美元，而去年第四季為 3,600 萬美元。我們的收入主要來自於與吉利德的合作。

We expect to recognize GAAP revenue of $75 million to $90 million for the full year 2025. Our R&D expenses for the first quarter are stated net of reimbursements from Gilead and were $122 million as compared to $111 million in the fourth quarter of last year. G&A expenses were flat at $28 million for the first quarter compared to the fourth quarter of last year.

我們預計 2025 年全年的 GAAP 收入將達到 7,500 萬至 9,000 萬美元。我們第一季的研發費用扣除吉利德的報銷費用後為 1.22 億美元，去年第四季為 1.11 億美元。第一季的一般及行政費用與去年第四季持平，為 2,800 萬美元。

Total non-cash stock based compensation was $16 million for the first quarter compared to $17 million for the fourth quarter of last year. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-Q. I will now turn it back to Terry.

第一季非現金股票薪酬總額為 1,600 萬美元，去年同期為 1,700 萬美元。有關我們財務業績的更多詳細信息，請參閱我們今天早些時候發布的收益新聞稿和我們的 10-Q。現在我將把話題轉回給特里。

Thanks everyone for joining us. We appreciate your interest and your continued support of Arcus. And we'll now open the call for questions.

感謝大家的參與。我們感謝您的關注以及對 Arcus 的持續支持。我們現在開始提問。

(Operator Instructions) Peter Lawson, Barclays.

（操作員指示）巴克萊銀行的彼得·勞森。

I guess, first question was just off the back of your comments about pipeline reprioritization. I wonder if you could talk through that a little bit more and then whether you're exploring the adenosine inhibitor further or if that's the program ended?

我想，第一個問題就是關於您關於管道重新排序的評論。我想知道您是否可以再詳細談談這個問題，然後您是否正在進一步探索腺苷抑制劑，或者該計劃是否已經結束？

Thanks Peter. I'll answer that all together. So as I mentioned, we're always doing this. And in the context of your question about the adenosine modulator, and I think you're probably speaking to the A2 receptor antagonist etruma, that's a perfect example. So we did have a meeting and quite good meeting actually with the FDA on that there's path forward, but our plans right now are not to move forward at this time at least.

謝謝彼得。我會一併回答這個問題。正如我所提到的，我們一直都在做這件事。在您關於腺苷調節劑的問題中，我認為您可能指的是 A2 受體拮抗劑 etruma，這是一個很好的例子。因此，我們確實與 FDA 舉行了一次會議，而且是一次相當不錯的會議，討論如何推進此事，但我們目前的計劃是至少在此時不會繼續推進。

The way I think you should look at our portfolio and how we prioritize things is we have those three late stage programs. Our number one priority of course is casdatifan and dom, zim, as Bob articulated, is on its natural trajectory. We are excited about data coming but spend is winding down.

我認為您應該這樣看待我們的投資組合以及我們如何確定優先事項，那就是我們有這三個後期項目。我們的首要任務當然是 casdatifan 和 dom，正如鮑伯所說，zim 正處於其自然軌跡上。我們對即將出現的數據感到興奮，但支出正在減少。

PRISM-1, our other adenosine related molecule, so the CD73 inhibitor will be fully enrolled this year. So that will be heading towards data shortly. Keep in mind, the standard-of-care there has an OS on the order of 10 months. So we are going to get to a readout pretty quick on that. And then on the other side of things, our early stage portfolio, we have been evolving that too.

PRISM-1 是我們的另一種腺苷相關分子，因此 CD73 抑制劑將於今年全面上市。因此這很快就會成為數據。請記住，那裡的標準護理的 OS 大約為 10 個月。因此我們將很快得到有關該問題的讀數。另一方面，我們的早期投資組合也在不斷發展。

We still have a number of oncology targets but we have been quietly, as I described, pushing along some really great inflammation and immunology targets. And so later this year, I think we will disclose those and you will find those exciting as well. So the way you can kind of look at it is, strong investment, biggest investment in later stage programs, nothing overly heavy on the middle and then keeping the sustainable pipeline with what's a relatively minimal investment, but with really that secret source of Arcus to generate the next IND candidates beyond those we talk about now.

我們仍然有許多腫瘤學目標，但正如我所描述的，我們一直在悄悄地推動一些真正偉大的發炎和免疫學目標。所以我想今年稍後我們會披露這些內容，你也會發現這些內容令人興奮。因此，你可以這樣看待它：大力投資，最大額度投資於後期項目，不對中間階段項目投入過多，然後用相對較少的投資保持可持續的渠道，但真正利用 Arcus 這個秘密來源來生成下一個 IND 候選藥物，超越我們現在談論的那些。

And then on the oral presentation, ASCO. What should we expect to see in the abstract versus the oral presentation, and will you kind of press release beyond the abstract?

然後是口頭報告，ASCO。我們應該在摘要和口頭陳述中看到什麼，除了摘要之外，您還會發布其他新聞稿嗎？

I am wondering if someone planted that question. It's one we think is important. So the -- I think you should recognize, everyone should recognize the abstract is more of a placeholder abstract. And so the data cut that we'll be sharing at ASCO will be much more recent. And what it will include is, you can think about it as two populations.

我想知道是否有人提出過這個問題。我們認為這很重要。所以——我認為你應該認識到，每個人都應該認識到摘要更像是一個佔位符摘要。因此，我們將在 ASCO 上分享最新的數據。你可以將其視為兩個群體。

First, the safety population will be about 40 patients and then, we'll also want to give you a read on efficacy. So even though probably the median time of follow-up is barely over four months, what we've done is we've assembled all the patients who've had at least two scans. So that gives them the opportunity to potentially have had a confirmed response and we'll be sharing efficacy data for that 25 or so patients.

首先，安全人群約為 40 名患者，然後，我們也會讓您了解療效。因此，儘管追蹤時間中位數可能僅超過四個月，但我們所做的就是將所有接受至少兩次掃描的患者聚集在一起。這樣他們就有機會獲得確認的反應，我們將分享這 25 位左右患者的療效數據。

You will see waterfall plot -- obviously, the data are far too mature to talk about maturity. And I think the data, I think you will find them compelling but you should recognize, given that they are early, they will likely continue to improve beyond what we share at this conference.

您將看到瀑布圖——顯然，數據過於成熟，無法談論成熟度。我認為這些數據令人信服，但您應該認識到，鑑於它們還處於早期階段，它們可能會繼續改進，超越我們在本次會議上分享的內容。

Great, thank you so much.

太好了，非常感謝。

Thank you Peter.

謝謝你，彼得。

Daina Graybosch, Leerink Partners.

Daina Graybosch，Leerink Partners。

Hey, Thank you. I have two really different questions. First on TIGIT. As you pointed out, the TIGIT Phase 3s are dominated by the Fc-silent, yours and Astra bispecific. And let's say we assume, I think you believe that Fc-silent is really the key to maximizing TIGIT benefit. Are you under-investing and ceding leadership to Astra? Can you just remind us what you're learning in Phase 2? And is there a gate of success that you might actually ramp investment back up? And then I have one on cas after that.

嘿，謝謝你。我有兩個截然不同的問題。首先是 TIGIT。正如您所指出的，TIGIT 第 3 階段主要由 Fc 沉默、您的和 Astra 雙特異性組成。假設我們假設，我認為您相信 Fc-silent 確實是最大化 TIGIT 效益的關鍵。您是否投資不足並將領導權移交給阿斯特拉？您能否提醒我們在第二階段學到了什麼？是否存在一個成功之門，讓您實際上可以重新增加投資？然後我又在 CAS 上有一個。

I think -- so first of all, I think we feel very good about the best that we've made, because they're targeting some of the largest IO markets out there. So our study in lung STAR-121 is targeting all comer non-small cell lung cancer patients, obviously, the biggest market there is for anti PD-1. And then our other Phase 3 study, STAR-221, is targeting all-comer gastric cancer patients, which is another really, really good market.

我認為——首先，我認為我們對自己所做的最好的事情感到非常滿意，因為他們瞄準的是一些最大的 IO 市場。因此，我們對肺癌 STAR-121 的研究針對的是所有非小細胞肺癌患者，顯然，這是抗 PD-1 的最大市場。我們的另一項 3 期研究 STAR-221 針對的是所有胃癌患者，這是另一個非常非常好的市場。

So we feel like those are two great bets to make. We do have active discussions going on all the time about other things that we would want to do if those studies read out positively. So I'd say there's other things that are keyed up and ready to go if our first Phase 3 readouts are positive. But we agree with what you're saying.

因此，我們覺得這是兩個值得做出的偉大賭注。我們確實一直在積極討論如果這些研究結果呈現正態勢，我們想要做的其他事情。因此我想說，如果我們的第三階段第一批資料是正面的，那麼還有其他事情已經準備好並且可以開始了。但我們同意你的說法。

And then the other study to point out, Terry's just reminding me is the Phase 3 lung cancer study that we're doing with AstraZeneca, which AstraZeneca is operationalizing PAC-8 and so, they've obviously seen a lot of our data, because we have that partnership on PAC-8. And so we do think that that's something else that's given them even more conviction in their own PD-1 TIGIT program.

然後要指出的另一項研究，特里只是提醒我，是我們與阿斯特捷利康合作進行的 3 期肺癌研究，阿斯特捷利康正在實施 PAC-8，因此，他們顯然已經看到了我們的許多數據，因為我們在 PAC-8 上建立了合作關係。因此，我們確實認為，這也是讓他們對自己的 PD-1 TIGIT 計劃更有信心的原因之一。

And then on cas and the potential for cas to mono to replace TKI in second line, you have that ARC-20 cohort. Is there any particular bar for efficacy you're looking for that would give you conviction to go head-to-head versus a TKI?

然後關於 cas 以及 cas 到 mono 在第二線取代 TKI 的可能性，您有 ARC-20 隊列。您是否在尋找某種特定的療效標準，讓您確信該藥物可以與 TKI 進行正面交鋒？

So I think at this point, we would look at those as a little bit more exploratory. They are different. In the monotherapy, keep in mind in those favorable risk patients, basically the standard these days would be more just watch and wait. So if you see reduction, meaningful reductions in tumor, given the safety profile, we think that could encourage people to want to invest in this.

所以我認為在這一點上，我們會以更具探索性的方式看待它們。它們是不同的。在單一療法中，請記住對於那些風險較低的患者，現在的標準基本上只是觀察和等待。因此，如果看到腫瘤減少，並且有顯著減少，考慮到安全性，我們認為這可能會鼓勵人們願意投資於此。

And keep in mind, those patients could be a couple of years. So the idea there is to get a sense what -- how it looks in those favorable risk patients. I know that's not a patient population that's getting TKI but that's sort of where we are -- one of those areas where we don't necessarily have something numerically in mind, but we are looking to see if there is a signal and we think there is a really good opportunity there.

請記住，這些病人可能要活幾年。因此，我們的想法是了解在那些低風險患者中情況如何。我知道這不是接受 TKI 治療的患者群體，但這就是我們所處的領域之一——我們不一定在腦海中有數字，但我們正在尋找是否存在信號，並且我們認為那裡確實存在一個好機會。

I think I would like to (technical difficulty) our studies that are out there for TKI and mono range anywhere from sort of high teens, 20%. It's a very high end of the range 40%. So if we could be in line with that with a better safety profile, we think that would be really exciting for clinicians.

我想（技術難度）我們針對 TKI 和單核球增多症的研究範圍從十幾歲到 20% 不等。這是 40% 這一範圍的非常高的值。因此，如果我們能夠以更好的安全性來實現這一點，我們認為這對臨床醫生來說將是非常令人興奮的。

We were actually just talking to a clinician yesterday that's one of the high enrollers in our cas, cabo cohort. She just put her first patient on the cohort that you're asking about, the cas mono second line patients and she was very excited about how that patient was doing. And so we look forward to hearing more anecdotes like that.

實際上，我們昨天剛剛與一位臨床醫生進行了交談，他是我們 cas、cabo cohort 中的高招募者之一。她剛剛將她的第一位患者納入您所詢問的隊列，即 cas mono 二線患者，她對該患者的狀況感到非常興奮。因此，我們期待聽到更多類似的軼事。

I think the thing is, is even if you look at our late line study, it's already pointing to something that would tell you you've got a good chance to be better than TKI. And the enthusiasm there really does ramp-up, because of two things. The fact that it is TKI free in the safety profile but also because of the low rate of primary progression.

我認為問題是，即使你看一下我們後期的研究，它已經指向了一些東西，告訴你你很有可能比 TKI 更好。那裡的熱情確實高漲，原因有二。事實上，它在安全性方面不含 TKI，而且原發性進展率低。

That's probably why you haven't seen bells be able to go there and that's really important as you go to the earlier lines. But we feel like we are already seeing numbers even in the later line that would encourage us for the opportunity going earlier as a mono.

這可能是為什麼你沒有看到鐘聲能夠到達那裡的原因，當你走到前面的路線時，這一點非常重要。但我們感覺，即使在後期，我們也已經看到了一些數字，這將鼓勵我們抓住機會，並儘早以單一方式進行開發。

Okay thank you.

好的，謝謝。

Thanks Daina.

謝謝戴娜。

Yigal Nochomovitz, Citigroup.

花旗集團的 Yigal Nochomovitz。

Thanks, can you just talk about the timing for PEAK-1 PFS primary? And then you said Lightspark is going to be dual. So which -- do we know which of these is coming first? And if Lightspark hits on OS and PFS then what's the plan to answer the OS question for PEAK-1? And then under what timeframe would that happen relative to the mark?

謝謝，您能談談 PEAK-1 PFS 初次治療的時間嗎？然後您說 Lightspark 將會是雙重的。那麼——我們知道哪一個會先發生嗎？如果 Lightspark 在 OS 和 PFS 上取得成功，那麼 PEAK-1 的 OS 問題將如何解答？那麼相對於標記而言這會在什麼時間範圍內發生呢？

So there's a lot of questions in there. So first of all, it's too early for us to give (multiple speakers) . So PEAK-1 I think it's too early given we're just about to start the study to give guidance on what we might see PFS data. We talked to some of your -- back of the envelope math to say sign and how likely we think it would take to complete enrollment based on other RCC studies and then what the PFS is expected to be in the control arm and how to get or when you might expect to see a readout.

這裡面有很多問題。所以首先，我們現在給出（多位發言者）因此，我認為 PEAK-1 還為時過早，因為我們才剛開始研究，無法對我們可能看到的 PFS 數據提供指導。我們討論了一些 — — 信封背面的數學計算表明，根據其他 RCC 研究，我們認為完成招募需要多大的可能性，然後預計對照組的 PFS 是多少，以及如何獲得或何時可以看到讀數。

So it's not in the too far distance because we do think this is a study that's going to roll quickly and because it is a PFS readout. On your question on OS or what we're doing, OS is a key secondary endpoint. So to your point, yes, we do think it's important to collect that information and it is a key secondary endpoint in our study. So that data will be collected.

所以這並不是太遙遠的事情，因為我們確實認為這是一項將快速展開的研究，而且因為它是一個 PFS 讀數。關於您關於 OS 或我們正在做的事情的問題，OS 是一個關鍵的次要終點。所以對於您的觀點，是的，我們確實認為收集這些資訊很重要，而且這是我們研究中的一個關鍵的次要終點。這樣數據就會被收集起來。

As far as Lightspark XI, they had it as a dual primary endpoint of OS and PFS. So if they hit on one of those then the study would be successful. You do have to split alpha in that case, because there's two different endpoints versus what we're doing, which is the sole primary.

就 Lightspark XI 而言，他們將其作為 OS 和 PFS 的雙重主要終點。因此，如果他們找到其中之一，那麼研究就成功了。在這種情況下，您確實必須拆分 alpha，因為與我們正在做的相比，有兩個不同的端點，這是唯一的主要端點。

So that can work against you. But they are waiting for that OS endpoint. That is what's giving us the opportunity to really catch-up to them and narrow that gap between when our readout might occur versus theirs.

所以這可能會對你不利。但他們正在等待該作業系統端點。這給了我們真正趕上他們的機會，並縮小我們與他們之間的讀數差距。

Just to put something out there that is out there. Merck recently pushed out that study on clinicaltrials.gov for a second time out to 2027. So whenever you do your back of the envelope calculations while we haven't given guidance that even that potential delta is dramatically close from when we first started contemplating this. And we actually do feel we're going to have -- Jen didn't comment on this, but we've got real tailwinds as we launch this study.

只是把一些已經存在的東西放在那裡。默克公司最近第二次將 clinicaltrials.gov 上的這項研究推遲到 2027 年。因此，無論何時您進行粗略計算，雖然我們還沒有給出指導，但即使那個潛在的增量也與我們第一次開始考慮這個問題時相比非常接近。我們確實感覺到我們將會——Jen 沒有對此發表評論，但我們在啟動這項研究時確實遇到了順風。

The investigator enthusiasm not only is very strong, but from a practical standpoint, because we've invested pretty heavily in these monotherapy cohorts, not only have we engendered a lot of enthusiasm, all kind of anecdotal studies, every one of these investigators has their own interesting story of what they've seen, so they want to jump on this.

研究人員的熱情不僅非常高漲，而且從實際角度來看，由於我們在這些單一療法隊列中投入了大量資金，我們不僅激發了大量熱情，而且各種各樣的軼事研究，每個研究人員都有自己所看到的有趣故事，所以他們想抓住這個機會。

But the other practical matter is that we have got 30 or 40 sites that are going to transition potentially into PEAK-1. So I think we are really going to be hitting the ground running in an unusual way versus going from a standing start.

但另一個實際問題是，我們有 30 或 40 個站點可能將過渡到 PEAK-1。因此我認為我們將以一種不同尋常的方式開始行動，而不是從零開始。

So having the ASCO presentation of the cabo cohort is obviously perfect timing. I think investigators are particularly interested in seeing -- efficacy is obviously important. I think everyone believes we're going to add efficacy but they really want to see o safety and just make sure there's no additional toxicities or overlapping toxicities or drug discontinuations, et cetera, to worry about. And so that will be a very important part of the data presentation.

因此，在 ASCO 上展示 Cabo 隊列顯然是最佳時機。我認為研究人員特別感興趣的是觀察療效——顯然療效很重要。我認為每個人都相信我們會增加療效，但他們真正想看到的是安全性，並確保沒有額外的毒性或重疊毒性或停藥等需要擔心的問題。所以這將是數據呈現的一個非常重要的部分。

Okay, and then post the Gilead decision on cas, is the plan now to just fund this to completion yourselves or would you entertain help from another partner potentially?

好的，然後在 CAS 上發布吉利德的決定，現在的計劃是自己出資完成這個項目，還是會考慮尋求其他合作夥伴的幫助？

So the first thing I want to mention, because I think it's an important point because of a lot of the questions that were out there right at that time. These new data are new. So this will give you yet another look. The cas, cabo data are, we think quite exciting and obviously they were not mature data when Gilead made their decision.

所以我首先想提的是，因為我認為這是一個重要的觀點，因為當時存在著許多問題。這些新數據是新的。因此這將給你另一種視角。我們認為 cas 和 cabo 數據非常令人興奮，而且顯然當吉利德做出決定時，這些數據還不夠成熟。

Getting to the specific question, we feel really confident in our abilities for some of the reasons we were just talking about, we have been working with the molecule, we have been working with the sites. We have got a steering committee that couldn't be better, they are excited.

談到具體問題，我們對我們的能力非常有信心，原因我們剛才提到了，我們一直在研究分子，我們一直在研究站點。我們有一個非常出色的指導委員會，他們非常興奮。

We feel we are in a great position to execute this, not only from a capital position as we talked about, we have the resources, but from the people standpoint, our team has been working with this all along. So our plans are to execute PEAK-1 on our own. With that said, could there be some other collaborations?

我們覺得我們處於一個很好的位置來執行這一目標，不僅從我們談到的資本狀況來看，我們擁有資源，而且從人員的角度來看，我們的團隊一直在為此努力。所以我們的計劃是自己執行 PEAK-1。話雖如此，還會有其他合作嗎？

As we mentioned, we would like to use collaborations in an efficient manner. As an example, the AstraZeneca collaboration, we might do other things like that. And of course, on an opportunistic basis, there could be other things we would do. But the base case you should be thinking about is that we feel very good about our ability to execute this trial in a very efficient and strong manner.

正如我們所提到的，我們希望以有效的方式合作。舉個例子，與阿斯特捷利康的合作，我們可能會做其他類似的事情。當然，從機會主義的角度來考慮，我們還可以做其他事情。但您應該考慮的基本情況是，我們對以非常有效率和強大的方式執行這次試驗的能力感到非常滿意。

Thank you Terry.

謝謝你，特里。

Umer Raffat, Evercore.

烏默·拉法特（Umer Raffat），Evercore。

I have a few here if I may. Perhaps first, the choice of dose being 100 milligrams for your first Phase 3, which admittedly is a cabo combo. Is there anything to read into the choice of that one 100 milligram dose relative to any early data you're seeing on the 150 and 200 milligrams? And I have a couple of follow ups.

如果可以的話我這裡有幾個。也許首先，您的第一階段第 3 階段的劑量選擇為 100 毫克，這無疑是一種 cabo 組合。相對於您所看到的 150 毫克和 200 毫克的早期數據，選擇 100 毫克劑量有意義嗎？我還有一些後續問題。

I mean you can have as many questions as you like, Umer. So nothing based upon any new data that we have seen. We had a really good discussion with the FDA in the context of Project Optimus. The 100 milligram dose, we talked about that, we talked about potentially 150, we talked about potentially 50.

我的意思是，你可以問任意多的問題，烏默爾。因此，根據我們所看到的任何新數據，沒有任何結果。我們在 Optimus 計畫背景下與 FDA 進行了非常好的討論。我們討論過 100 毫克的劑量，我們討論過可能的 150 毫克劑量，我們討論過可能的 50 毫克劑量。

Safety profile of the 100 look great. We feel based upon all the data we've seen that the 100 is essentially on the asymptote for efficacy. What we're seeing with one 150, I think we'll share that at the end of the year. But I would just foreshadow that you're going to see something that looks pretty similar and we'll see just how things play out.

100 的安全概況看起來很棒。根據我們所看到的所有數據，我們認為 100 基本上是功效的漸近線。我認為我們將在今年年底分享我們對 150 的看法。但我預示著你會看到一些非常相似的事情，我們將看看事情如何發展。

One thing that's important to note, for our 50 and 100 milligram doses, we still do not have median PFS. Maybe as we get towards the end of the year and we're sharing data, we'll be there. But obviously, we will have some sort of landmark PFS. And it may be that there is a bit of more AE creeping in on the 150. I couldn't even say that with certainty now.

需要注意的一點是，對於 50 毫克和 100 毫克劑量，我們仍然沒有中位 PFS。也許當我們接近年底並共享數據時，我們就會到達那裡。但顯然，我們將會擁有某種具有里程碑意義的 PFS。並且可能在 150 上會出現更多的 AE。我現在甚至不能肯定地說這一點。

So I think the way to look at the 100 milligram dose is everything we've seen suggests that you're essentially maxing out efficacy there and it's a very safe profile. So there's not a whole lot of rationale to even be thinking about the 150.

因此，我認為，從觀察 100 毫克劑量的角度來看，我們所看到的一切都表明，它基本上可以最大限度地發揮功效，而且非常安全。因此，沒有太多理由去考慮 150 這個數字。

And what about 200?

那麼 200 呢？

Yes, same. I mean, we only look at 200 of dose escalation, didn't see any DLTs, which was good, but we haven't looked at it beyond the dose escalation. And I think as Terry was saying, based on everything we've seen so far, so we now have 30 patients worth of 50 mg, 100 mg, 150 mg data. And I think that all gives us a lot of confidence that 100 mg is the right dose.

是的，一樣。我的意思是，我們只研究了 200 的劑量遞增，沒有看到任何 DLT，這很好，但我們還沒有研究劑量遞增以外的情況。我認為正如特里所說的那樣，根據我們目前所看到的一切，我們現在有 30 名患者的 50 毫克、100 毫克、150 毫克數據。我認為這一切都讓我們非常有信心，100毫克是正確的劑量。

I think the other thing that we're actually thrilled about, it's not a surprise but -- and will draw your attention when you look at the cas, cabo data is an important aspect of that is being able to keep patients on therapy. And the data look we think pretty compelling even though they are early and obviously with time you might see otherwise. But I think you'll come away feeling like efficacy on those patients that have had two scans, looking good, waterfall looks good and the AEs look like cabo by itself plus cas by itself and very well tolerated combination.

我認為另一件讓我們感到興奮的事情，這並不奇怪，但是 - 當你查看 CAS 時會引起你的注意，cabo 數據的一個重要方面是能夠讓患者繼續接受治療。儘管這些數據還處於早期階段，但我們認為這些數據看起來非常引人注目，而且顯然隨著時間的推移，您可能會發現情況並非如此。但我認為，對於那些已經做過兩次掃描的患者，您會感覺到療效，看起來不錯，瀑布看起來不錯，並且 AE 看起來像 cabo 本身加上 cas 本身，並且耐受性非常好的組合。

And I think one of the really exciting opportunities about the combination too is that if you're just getting TKI mono and you get hand, foot, mouth syndrome or greater hypertension whatever it is, it would typically have to come off your TKI for a bit. In this case, even though you're coming off the TKI, you're still getting a HIF-2 inhibitor. So you're still getting an active drug and that's one of the things that I think positions the combination to perform very well relative to cabo monotherapy, because throughout, in most cases, patients are going to be getting at least one of those two drugs. So if you do get TKI related toxicity, they will stay on cas.

我認為這種組合療法真正令人興奮的機會之一是，如果您剛接受 TKI 單藥治療，並且出現手足口症候群或高血壓等疾病，通常需要暫時停用 TKI。在這種情況下，即使您停止服用 TKI，您仍然會服用 HIF-2 抑制劑。因此，您仍然可以獲得一種活性藥物，我認為這是該組合療法相對於 Cabo 單一療法表現非常出色的原因之一，因為在大多數情況下，患者將至少獲得這兩種藥物中的一種。因此，如果您確實出現 TKI 相關毒性，它們將繼續存在。

So I guess that brings me to my sort of main question here, which is what exactly is the makeup of this post IO cohort in ARC-20, that we're going to see at ASCO or the cohort in general? And I asked because you could have double IO experienced or you could have IO plus VEGF TKI experienced. And my understanding is ORR is a little lower when it's IO plus VEGF TKI versus dual IO. So what exactly is that? And is there any data to read into from your cas mono arm, which is also second line plus and may presumably have some of these post IO patients as well?

所以我想這讓我想到了我主要的問題，那就是我們將在 ASCO 或整個群體中看到的 ARC-20 後 IO 群體的構成到底是什麼樣的？我之所以這樣問，是因為您可能有雙重 IO 經歷，或者您可能有過 IO 加 VEGF TKI 經歷。我的理解是，IO 加 VEGF TKI 與雙 IO 相比，ORR 會稍低。那到底是什麼？是否有任何數據可以讀取您的 cas mono 組，這也是二線加，並且可能也有一些這些 IO 後患者？

So you're right. It's going to be a mix and we'll disclose that mix. And it's in line actually with the Lightspark III study, like a cas plus cabo. One thing that I would mention when you look at patients that got IO, IO versus patients that got IO plus VEGF, so far the ORRs actually look very similar. So there's not seem to be a difference if patients have gotten prior TKI versus just prior IO. Does that make sense?

所以你是對的。這將是一種混合，我們將披露這種混合。它實際上與 Lightspark III 的研究一致，就像 cas plus cabo 一樣。我想提到的一點是，當您觀察接受 IO、IO 與接受 IO 加 VEGF 的患者時，到目前為止，ORR 實際上看起來非常相似。因此，患者之前是否接受過 TKI 治療與是否僅接受過 IO 治療似乎沒有差異。這樣有道理嗎？

And, Jen, do you acknowledge about third (multiple speakers) and would you acknowledge, from cabo point trial about low 30s and ORR is the comp for cabo monotherapy following IO therapy?

而且，Jen，您是否承認關於第三名（多位發言者）的情況，並且您是否承認，從 cabo point 試驗來看，大約 30 秒出頭，並且 ORR 是 IO 治療後 cabo 單藥治療的比較？

I think the cabo alone has a range of four hours depending on what study you look at and what data source you have. So kind of in the 20 to 40. So if you pick 30, that's one of the choices I'd say but it's quite a range across the different data sets there for cabo alone.

我認為，僅卡波就有四個小時的範圍，具體取決於您所研究的內容和所擁有的資料來源。大概在 20 到 40 之間。因此，如果您選擇 30，我認為這是選擇之一，但僅對於 cabo 而言，不同資料集的範圍就相當大。

And the one other relevant data set -- Umer, the one other relevant data set is there was a bell's cabo arm, and that again on the ORR front came in just over 30% and it's PFS in that study. Obviously, we won't have PFS to compare to yet but the PFS there was on the order of 13 months.

另一個相關的數據集——Umer，另一個相關的數據集是貝爾的 Cabo 臂，而 ORR 方面的數據再次超過了 30%，並且在該研究中是 PFS。顯然，我們還沒有 PFS 可以比較，但那裡的 PFS 大約是 13 個月。

And again, just so I'm clear, we talked about 20 to 40 being the range, maybe 30-ish being the midpoint, which is also consistent with the cabo point trial. But the critical thing is, you guys are emphasizing safety not an efficacy advantage. Is that reasonable or do you want to have higher ORR as well?

再次說明一下，我們討論的範圍是 20 到 40，中間值可能是 30 左右，這也與卡波角試驗的結果一致。但關鍵是，你們強調的是安全性而不是功效優勢。這樣合理嗎，還是您也希望獲得更高的 ORR？

Absolutely have both (multiple speakers) . We're just saying both is important and we're just trying to make the point that safety is going to feed into efficacy, because you want to keep patients on drug, you want to avoid dose reductions. So the more we think we can safely combine these two drugs that should further enhance efficacy. The goal is absolutely to show an improvement on both those metrics (technical difficulty) on efficacy and safety that you are getting additive toxicity or even worse toxicity than what you'd expect with either agent alone.

絕對兩者兼具（多位發言者）我們只是說兩者都很重要，我們只是想說明安全性會影響療效，因為你想讓患者繼續服用藥物，你想避免減少劑量。因此，我們認為我們可以安全地結合這兩種藥物，從而進一步提高療效。目標絕對是顯示在功效和安全性這兩個指標（技術難度）上的改進，即您所獲得的毒性是附加的，甚至是比單獨使用任何一種藥物所預期的毒性更嚴重的。

Asthika Goonewardene, Truist.

Asthika Goonewardene，Truist。

This is [Karina] for Asthika. I had a question on casdatifan. So beyond the AstraZeneca study with the -- are there any plans to initiate registrational studies potentially in combination with PD-1s or -- in frontline?

我是 [Karina]，代表 Asthika。我對 casdatifan 有一個疑問。那麼，除了阿斯特捷利康的研究之外——是否有任何計劃啟動與 PD-1 或——一線結合的註冊研究？

So nothing registrational that we've disclosed so far. So as Terry talked about on the call, we did just open a cohort in ARC-20 where we're combining cas with our anti-PD-1 zimberelimab in first line patients. So that's something we could ultimately initiate a registrational study for some sort of more NCCN guideline enabling study, but that's the combination we're super excited about and investigators are super excited about.

因此，到目前為止我們尚未披露任何註冊資訊。正如 Terry 在電話中談到的那樣，我們確實剛剛在 ARC-20 中開設了一個隊列，我們將 cas 與我們的抗 PD-1 zimberelimab 結合用於一線患者。因此，我們最終可以啟動一項註冊研究，以進行某種更符合 NCCN 指南的研究，但這是我們和研究人員都非常興奮的組合。

We think that cohort is going to enroll incredibly quickly, because, again, yes, I think there's a lot of interest in just avoiding TKIs in the frontline setting where patients are still feeling really good and are relatively healthy. So we'll see how that goes with some of these other cohorts that we started and this could be future registrational studies for sure.

我們認為該群體的招募速度會非常快，因為，是的，我認為很多人對在前線環境中避免使用 TKI 很感興趣，因為在前線環境中，患者仍然感覺良好並且相對健康。因此，我們將觀察我們開始的其他一些隊列的進展情況，這肯定可能是未來的註冊研究。

I think the way you should think about our approach is that, basically, we are not just going to be throwing a bunch of spaghetti up on the wall where we jump. We think we have a great molecule but we are not just going to start peppering the world with Phase 3 studies. So we are going to do early work to ensure that any Phase 3 study we do really makes sense.

我認為你應該這樣看待我們的方法：基本上，我們不只是把一堆義大利麵丟到我們跳躍的牆上。我們認為我們擁有一種很棒的分子，但我們不會立即開始向世界推廣第三階段研究。因此，我們將做好早期工作，以確保我們進行的任何第三階段研究都真正有意義。

Okay, that's helpfull, Thank you.

好的，這很有幫助，謝謝。

Li Watsek, Cantor Fitzgerald.

李沃特塞克，康托費茲傑拉。

This is Dan on for Lee. I was wondering if you could kind of set expectations for your combination with the volru and what you're looking for in the IO naive setting and for a potential pivotal frontline trial, what would you be comparing your doublets to?

這是丹代替李上場。我想知道您是否可以對與 volru 的組合設定期望，以及您在 IO 初始設置中尋找的內容以及對於潛在的關鍵前線試驗，您會將您的雙聯與什麼進行比較？

So a lot of good questions and it's a lot of information that we just haven't disclosed yet for competitive reasons. And as Richard alluded to on the call, probably around midyear, which I think we're getting close to, we should be able to talk a lot more about that study. And so right now, really all we can disclose is that the plan is to go by cas with volru in the first line setting.

所以有很多好問題，而且有很多資訊我們由於競爭原因尚未披露。正如理查德在電話中提到的那樣，大概在年中左右，我認為我們已經接近這個時間了，我們應該能夠更多地談論這項研究。因此現在，我們真正可以透露的是，該計劃將在第一線設置中使用 cas 和 volru。

The big issue with EpiNivo and [PEAK] CTLA-4s is that you do have a very high rate of primary progressive disease. So about 25% to 30% of patients don't respond to EpiNivo and just flow right through therapy. And so that's why today actually EpiNivo is typically used in patients that don't have really aggressive disease, so more slower growth tumors.

EpiNivo 和 [PEAK] CTLA-4s 的最大問題是原發性進行性疾病的發生率非常高。因此，大約 25% 到 30% 的患者對 EpiNivo 沒有反應，而是直接接受治療。這就是為什麼如今 EpiNivo 通常用於治療病情較不嚴重、腫瘤生長較慢的患者。

And so one of the reasons why I think Astra was very excited about combining volru and cas is that opportunity to bring down the rate of primary progressive disease given we're seeing a very low rate of primary progressive disease so far with cas. And so what we will be looking for initially is obviously that you can safely combine these two mechanisms, which today we have no reason to believe you couldn't.

因此，我認為 Astra 對結合 volru 和 cas 感到非常興奮的原因之一是，鑑於我們迄今為止看到的 cas 原發性進展性疾病的發生率非常低，有機會降低原發性進展性疾病的發生率。因此，我們最初要尋找的顯然是您可以安全地結合這兩種機制，而今天我們沒有理由相信您無法做到這一點。

And then, we will be looking at some of these early signs of efficacy, particularly the rate of PD and then eventually, we'll be looking at ORRs, et cetera. But we do think that PD rate could be particularly interesting to look at, because you do have that high rate of primary progressive disease with EpiNivo.

然後，我們將觀察一些早期療效跡象，特別是 PD 率，最終我們將觀察 ORR 等等。但我們確實認為 PD 率可能特別值得關注，因為 EpiNivo 的原發性進展性疾病發生率確實很高。

(multiple speakers) there's a huge amount of interest in that combination, I just want to point out. We talked about it on the call, we actually did some market research. And I think we were actually even surprised about how much interest there is in the investigator community to combine these two mechanisms and to try to avoid TKIs on the front lines.

（多位發言者）我只是想指出，人們對這種組合非常感興趣。我們在電話中討論了這個問題，實際上我們做了一些市場調查。我認為我們實際上甚至對研究人員群體對結合這兩種機制並試圖避免在前線使用 TKI 的興趣如此之大感到驚訝。

Okay great, thank you.

好的，太好了，謝謝。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Great, thanks. This is Matt on for Salveen. Maybe first just on cas to follow-up on a prior question. Is it fair to say you guys would consider a commercialization partnership post PEAK-1 or when you're close to reading out PEAK-1 or is that no longer of interest to you? And then on the broader portfolio, any thoughts on the newly announced -- Director from just kind of a portfolio risk perspective?

太好了，謝謝。我是 Salveen 的 Matt。也許首先只是在 CAS 上跟進先前的問題。是否可以說，你們會考慮在 PEAK-1 之後或即將讀完 PEAK-1 時建立商業化合作夥伴關係，或者這不再是你們感興趣的？然後，關於更廣泛的投資組合，您對新宣布的董事從投資組合風險角度有何看法？

So on the first question, our intent is to commercialize. We want to fully leverage the opportunity. We think this is really huge for Arcus. I think we probably consider a partner in Europe but we feel really good about taking this forward and commercializing it. The whole piece for us seems very manageable.

關於第一個問題，我們的目的是商業化。我們希望充分利用這個機會。我們認為這對 Arcus 來說意義重大。我想我們可能會考慮在歐洲尋找合作夥伴，但我們對推動這項進程並將其商業化感到非常高興。對我們來說，整個作品似乎非常容易管理。

I don't have any comments on the latter. I don't think anyone here does. So I would just -- in macro, I would even elevate that our whole sense about everything happening at the FDA when it comes to what we are doing, what we are executing, things have just been business as usual as far as we can tell.

我對後者不發表任何評論。我認為這裡沒有人會這麼做。因此，從宏觀角度來看，我甚至會提升我們對 FDA 發生的一切事情的整體感覺，就我們正在做的事情、我們正在執行的事情而言，據我們所知，一切都一切正常。

So what's happening in the news I have no comment. But from a practical standpoint, we are pretty comfortable with everything we are doing right now that it's proceeding just as it would have six months or one year ago.

因此對於新聞中發生的事情我沒有任何評論。但從實際角度來看，我們對現在所做的一切感到很滿意，一切進展都與六個月或一年前一樣。

Thank you

謝謝

Sure, thanks.

當然，謝謝。

Eva Fortea, Wells Fargo.

伊娃·福爾蒂亞（Eva Fortea），富國銀行。

A couple from us. First, on the full 2025 update forecast. Can you just provide a bit more color on like expectations here in terms of like the different cohorts, number of patients and duration of the follow-up? And the second question, as you mentioned an emerging INI franchise. When should we expect to learn more about this, would this be more towards the end of the year in an R&D day type of event?

我們中的一對夫婦。首先，關於 2025 年的完整更新預測。您能否就不同群體、患者數量和追蹤時長等方面的預期提供更多細節？第二個問題，正如您所提到的新興 INI 特許經營權。我們什麼時候可以了解更多有關這方面的信息，是在年底的研發日類型的活動中嗎？

I could address the first part of the question at least with regards to the follow-up in the fall and it's really looking again at the monotherapy data we had at ASCO GU. We'll have more mature data coming, so we'll have another data cut there. We haven't stated or selected if this will be at a medical conference or other ways of sharing that data. But we will be able to provide updates to that data since we'll have matured a fair bit since the cut at the beginning of this year.

我可以至少回答問題的第一部分，關於秋季的後續行動，這實際上是再次查看我們在 ASCO GU 獲得的單一療法數據。我們將會得到更多成熟的數據，因此我們將在那裡進行另一次數據剪切。我們尚未說明或選擇是否在醫學會議上或以其他方式共享資料。但我們將能夠提供該數據的更新，因為自今年年初削減以來我們已經成熟了相當多。

And on the immunology inflammation front, I think the way to think about that is, conceptually, whether it's an R&D day or part of one of our other releases, we will find a form to describe the breadth of what we are doing and where we sit. And I think it's an exciting portfolio. It takes advantage of what we do well and I think that will be highlighted, the small molecules for challenging targets, where the targets are highly validated, but there is not a great molecule. So we have been building on that.

在免疫學發炎方面，我認為思考這個問題的方式是，從概念上講，無論是研發日還是我們其他版本的一部分，我們都會找到一種形式來描述我們正在做的事情的廣度以及我們所處的位置。我認為這是一個令人興奮的投資組合。它利用了我們擅長的領域，我認為這將得到強調，即針對具有挑戰性的目標的小分子，這些目標已經得到高度驗證，但沒有一個偉大的分子。因此我們一直以此為基礎。

I will remind you, because we are like a real company in terms of with people and we have biology group, we have a good med chem group and all of the associated functions that there is, but our biology is actually more immunology because the roots are in immuno oncology.

我要提醒你，因為就人員而言我們就像一家真正的公司，我們有生物學小組，我們有優秀的醫學化學小組以及所有相關的功能，但我們的生物學實際上更多的是免疫學，因為其根源在於免疫腫瘤學。

And so even though where oncology has been our clinical endpoint, we have a strong immunology group and in fact have invested in that and now we are getting to the point where we can start to talk about those programs with -- we like to talk about things when we have got tangible matter not glint in the eye, and I think that will be very tangible. And all done without machine learning but we have machines.

因此，儘管腫瘤學一直是我們的臨床終點，但我們擁有強大的免疫學團隊，並且實際上已經對此進行了投資，現在我們正處於可以開始討論這些項目的階段——我們喜歡在有實質內容而不是眼中閃光時談論事物，我認為這將是非常有實質內容的。所有這些都不需要機器學習，但我們有機器。

Emily Bodnar, HC Wainwright.

艾米莉·博德納、HC·溫賴特。

Hey, thanks for the question. My first one for cas, the monotherapy doses. Can you comment on how the 100 mg QD cohort is progressing relative to the 50 mg BID cohort and if you're starting to see similar results in terms of median PFS? And if you could just comment on timing for the STAR-121 trial for dom in lung cancer and if there's any timing updates for the top line results?

嘿，謝謝你的提問。我第一次接受 CAS 治療，採用單一療法劑量。您能否評論一下 100 毫克 QD 隊列相對於 50 毫克 BID 隊列的進展情況，以及您是否開始在中位數 PFS 方面看到類似的結果？您能否評論一下 STAR-121 治療肺癌的試驗時間，以及是否有任何關於頂線結果的時間更新？

So there's really no timing update yet on 121 study. Two things, it's still enrolling and then it has OS plus standard care is over 20 months. So it's premature. It's obviously enrolled well and we'll continue to enroll but we haven't said anything on timing there. Nothing to say yet really on the maturing data other than to point out that we haven't reached a median PFS.

因此，121 項研究目前還沒有確切的時間更新。有兩件事，它仍在招生，然後它的操作系統加上標準護理超過 20 個月。所以現在還為時過早。顯然，招生情況很好，我們會繼續招生，但我們還沒有透露時間表。除了指出我們尚未達到中位 PFS 之外，對於成熟的數據實際上沒有什麼可說的。

And so I think as we get towards the end of the year, we don't even know for sure that we will be there. But if we are not we still will be sharing data and it would then undoubtedly include some sort of landmark PFS.

所以我認為，當我們接近年底時，我們甚至不確定我們是否會到達那裡。但即使如此，我們仍然會共享數據，無疑會包含某種具有里程碑意義的 PFS。

Thank you

謝謝

Thank you

謝謝

Thank you. This concludes our Q&A session today as well as the call. Thank you everyone for joining. You can now disconnect your line.

謝謝。今天的問答環節和電話會議到此結束。感謝大家的參與。現在您可以斷開線路。

Thank you.

謝謝。