Xencor Inc (XNCR) 2023 Q4 法說會逐字稿

Good afternoon and thank you for standing by. Welcome to Xencor's fourth-quarter and year-end 2023 conference call. (Operator Instructions) Please be advised that today's conference is being recorded at the company's request.

下午好，感謝您的支持。歡迎參加 Xencor 2023 年第四季和年終電話會議。(操作員指示)請注意，今天的會議是應公司要求錄製的。

Now I would like to turn the call over to your speaker today, Charles Liles, Head of Corporate Communications and Investor Relations. The floor is yours.

現在我想將電話轉給今天的發言人、企業傳播和投資者關係主管查爾斯·萊爾斯 (Charles Liles)。現在請您發言。

Thank you and good afternoon. Earlier today, we issued a press release which outlines the topics we plan to discuss today is available at www.xencor.com. Providing comments on the call are Bassil Dahiyat, President and Chief Executive Officer; Nancy Valente, Chief Development Officer; and Dane Leone, Senior Vice President, Corporate Strategy. After the prepared remarks and presentation, we will then open up the call for your questions. And we will then be joined by John Desjarlais, Chief Scientific Officer; and John Kuch, Chief Financial Officer.

謝謝您，下午好。今天早些時候，我們發布了一份新聞稿，概述了我們今天計劃討論的主題，可在 www.xencor.com 上查閱。總裁兼執行長 Bassil Dahiyat 在電話會議上發表評論；南希‧瓦倫特 (Nancy Valente)，首席開發長；以及企業策略資深副總裁 Dane Leone。在準備好的演講和演示結束後，我們將開始回答您的問題。然後首席科學官 John Desjarlais 將加入我們；以及財務長約翰·庫奇（John Kuch）。

Slides that we are using today should be visible here on the webcast that we've made available for download on the events and presentations page of our website. Before we begin, I would like to remind you that during the course of the conference call, Xencor management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, plans and objectives of management, future operations, the company's partnering efforts, capital requirements, future product offerings and research and development programs.

我們今天使用的幻燈片應該可以在我們網站的活動和演示頁面上下載的網路直播中看到。在我們開始之前，我想提醒您，在電話會議期間，Xencor 管理層可能會做出前瞻性陳述，包括有關公司未來財務和經營業績、未來市場狀況、管理計劃和目標、未來運營、公司的合作努力、資本要求、未來產品供應和研發計劃的陳述。

These forward-looking statements are not historical facts, but rather are based on our current expectations and beliefs and are based on information currently available to us. The outcome of the events described in these forward-looking statements are subject to known and unknown risks, uncertainties and other factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements, including but not limited to those factors contained in the Risk Factors section of our most recently filed annual report on Form 10-K. With that, I'll pass the call over to Bassil.

這些前瞻性陳述不是歷史事實，而是基於我們目前的預期和信念，並基於我們目前所掌握的資訊。這些前瞻性陳述中所描述的事件的結果受已知和未知的風險、不確定性和其他因素的影響，這些因素可能導致實際結果與這些前瞻性陳述預期的結果有重大差異，包括但不限於我們最近提交的 10-K 表年度報告中「風險因素」部分中包含的因素。說完這些，我會把電話轉給巴西爾。

Thanks, Charles, and welcome, everyone. Today we'll cover a few business highlights from 2023. briefly review our clinical pipeline, and provide a data update of vudalimab and prostate cancer. You can refer to our press release for more information about the last quarter and full year. We've focused our pipeline and discovery work on our T-cell engagers because of growing validation for their potential in solid tumors.

謝謝，查爾斯，歡迎大家。今天，我們將介紹 2023 年的一些業務亮點。您可以參閱我們的新聞稿，以了解有關上一季和全年的更多資訊。我們將我們的產品線和發現工作重點放在 T 細胞接合劑上，因為它們在實體腫瘤中的潛力得到越來越多的證實。

Supporting this is the continued advance of vudalimab in prostate cancer, we'll provide an update today and the start of a trial in front-line lung cancer for vudalimab. And we've decided to reduce our investment in our cytokine drug candidate as part of this focusing.

支持這一點的是武達利單抗在前列腺癌治療中的持續進展，我們今天將提供最新消息，並開始對武達利單抗在一線肺癌治療中的試驗。作為這項重點關注的一部分，我們決定減少對細胞激素候選藥物的投資。

Our partnerships and licenses played a significant role for us last year. First, with validating data for our XmAb 2+1 CD3 platform from our partner, Amgen, with their Xaluritamig data in prostate cancer and two Phase 1 programs started in our CD28 bispecific collaboration with J&J. And we significantly strengthened our balance sheet with a partial monetization of our Ultomiris and Minjuvi royalties. As a result of that and robust milestone and royalty revenues, we ended 2023 with $697 million and expect runway into 2027.

去年，我們的合作夥伴關係和許可證對我們發揮了重要作用。首先，利用我們的合作夥伴安進公司 (Amgen) 的 XmAb 2+1 CD3 平台的驗證數據，以及他們在前列腺癌方面的 Xaluritamig 數據，以及我們與強生公司在 CD28 雙特異性合作中啟動的兩個 1 期項目。而我們透過將 Ultomiris 和 Minjuvi 特許權使用費部分貨幣化，顯著增強了我們的資產負債表。由於這一點以及強勁的里程碑和特許權使用費收入，我們在 2023 年底實現了 6.97 億美元的收入，並預計到 2027 年將實現這一目標。

Now, onto our pipeline. The focus of our clinical pipeline is bispecific T-cell engagers for solid tumors, an area with rapidly growing promise. Solid tumors have been challenging for antibody in cell therapies, but recent data, some of which will review momentarily, suggests that CD3 and CD28 bispecifics can play a role as therapies in a range of solid tumors.

現在，進入我們的管道。我們的臨床研究重點是針對實體腫瘤的雙特異性T細胞接合劑，這是一個具有快速成長前景的領域。實體瘤一直是細胞療法中抗體的挑戰，但最近的數據（其中一些將很快進行回顧）表明，CD3 和 CD28 雙特異性抗體可以在一系列實體瘤中發揮作用。

Key programs for us addressing this opportunity are XmAb819 and ENPP3 by CD3 XmAb bispecific for renal cell carcinoma and XmAb808, a B7-H3 by CD28 XmAb bispecific in prostate and other cancers. Both are advancing a dose escalation in Phase 1. And right behind them is XmAb541, a CLDN6 by CD3 bispecific that we expect to start Phase 1 the first half of this year.

我們抓住這一機會的關鍵項目是針對腎細胞癌的雙特異性CD3 XmAb XmAb819 和 ENPP3，以及針對前列腺癌和其他癌症的雙特異性CD28 XmAb B7-H3 XmAb XmAb。兩藥均在第一階段推進劑量遞增。緊隨其後的是 XmAb541，這是一種 CLDN6 x CD3 雙特異性抗體，我們預計今年上半年啟動第 1 階段研究。

For vudalimab, we initiated a new study. Its first frontline study in non-small cell lung cancer based both on our Phase 1 data in lung cancer and external data suggesting potential advantages against stent checkpoint therapy in this setting. And we've made progress with our metastatic castration-resistant prostate cancer studies, both in combination with chemo and monotherapy and work with encouraging monotherapy data we're going to present in a moment. Finally, we're wrapping up our Phase 1 work next quarter for both XmAb564 and 662, taking the PK/PD and safety data in hand to establish initial product profiles and moderating the field for further validation of these cytokines before we do any additional development.

對於武達利單抗，我們啟動了一項新的研究。這是針對非小細胞肺癌的首個第一線研究，基於我們在肺癌方面的第 1 期數據和外部數據，顯示在這種情況下支架檢查點治療具有潛在優勢。我們在轉移性去勢抵抗性前列腺癌研究方面取得了進展，包括與化療和單一療法相結合的研究，以及我們稍後將展示的令人鼓舞的單一療法數據。最後，我們將在下個季度完成 XmAb564 和 662 的第一階段工作，利用 PK/PD 和安全性資料建立初步產品概況，並在進行任何額外開發之前對這些細胞因子進行進一步驗證。

Underpinning our T-cell engagers are XmAb-bispecific technology. It lets us address the solid tumor opportunity by engineering our antibodies with the format and affinities designed to give tumor selectivity in the context of each tumor targets, particular expression levels in tissue distributions. Solid tumor targets in particular need a customized approach because they're distributed more broadly than human tumor targets, which have already been successfully addressed by CD3 bispecifics in lymphoma and myeloma.

我們的 T 細胞接合器的基礎是 XmAb 雙特異性技術。它讓我們能夠透過設計抗體來解決實體腫瘤的問題，這種抗體具有針對每個腫瘤標靶的腫瘤選擇性和組織分佈中的特定表現量。實體腫瘤標靶尤其需要客製化方法，因為它們比人類腫瘤標靶分佈更廣泛，而人類腫瘤標靶已透過 CD3 雙特異性抗體成功解決淋巴瘤和骨髓瘤問題。

Our plug-and-play antibody modules let us do this work rapidly. And as a result, we've got a growing pipeline of molecules with our 2+1 design, which is particularly helpful with selectivity for solid tumors. And here is the first clinical proof of concept for our XmAb 2+1 CD3 format, Xaluritamig, which targets STEAP1.

我們的即插即用抗體模組讓我們能夠快速完成這項工作。因此，我們透過 2+1 設計獲得了越來越多的分子管線，這對於實體腫瘤的選擇性特別有幫助。這是我們的 XmAb 2+1 CD3 格式 Xaluritamig 的第一個臨床概念驗證，其目標是 STEAP1。

Our partner, Amgen, presented very promising efficacy and tolerability data at ESMO last October in late-line prostate cancer, usually considered a cold tumor for immunotherapy. This target was challenging due to the limited accessible binding regions outside the cell membrane and non tumor expression. So we're very encouraged to see this early data for the molecule in 2+1 format.

我們的合作夥伴安進公司去年 10 月在 ESMO 上展示了針對晚期前列腺癌的非常有希望的療效和耐受性數據，這種癌症通常被認為是免疫療法的冷腫瘤。由於細胞膜外可及的結合區域有限且無腫瘤表達，因此此目標具有挑戰性。因此，我們很高興看到 2+1 格式的分子早期數據。

Amgen's announced they are nearing completion of the Phase 1 study and are planning additional studies in earlier lines of therapy, so we'll be eagerly awaiting their updates. Now, our own lead XmAb 2+1 CD3 bispecific is XmAb819, targeting ENPP3 in renal cell carcinoma. We chose ENPP3 as a target because it has exactly the kind of expression profile we want for a CD3 solid tumor target, much higher expression on tumor than normal tissues and nearly uniformly high expression on clear cell renal cell carcinoma. Plus, it has potential for use in select patients in a range of other tumors.

安進公司宣布他們即將完成第一階段的研究，並計劃在早期的治療方法上進行額外的研究，所以我們將熱切地等待他們的更新。現在，我們自己的領先XmAb 2+1 CD3 雙特異性抗體是XmAb819，針對腎細胞癌中的ENPP3。我們選擇 ENPP3 作為靶點，因為它具有我們想要的 CD3 實體瘤靶點的表達譜，在腫瘤上的表達比正常組織高得多，在透明細胞腎細胞癌上的表達幾乎均勻地高。此外，它也可能用於治療一系列其他腫瘤的特定患者。

Also, we think renal cell carcinoma has a need for new mechanisms beyond checkpoint inhibitors and TKIs and a directly cytotoxic antibody could be well-positioned. 819 design gives us selectivity we wanted in vitro, and we're continuing to advance in dose escalation with both IV and subcutaneous dosing and expect to make significant progress this year toward target dose levels.

此外，我們認為腎細胞癌需要檢查點抑制劑和 TKI 以外的新機制，而直接細胞毒性抗體可能具有良好的應用前景。 819 設計使我們獲得了體外所需的選擇性，並且我們正在繼續推進靜脈和皮下給藥的劑量遞增，並期望今年在目標劑量水平方面取得重大進展。

I'll shift now to XmAb808, our new T-cell engager mechanism CD28 targeting. The goal here is to activate T cells via the signal two pathway, which powerfully amplifies and sustained T-cell responses. We designed 808 bispecific format and affinities to try to drive this activation in a tumor-specific way by requiring sufficient binding to its tumor antigen, B7-H3 to turn on CD28 signaling. A key part of our approach is a lower potency CD28 binding domain that we think could give us control of CD28 signaling and improved tolerability.

現在我將轉到 XmAb808，我們的新 T 細胞接合機制 CD28 標靶。這裡的目標是透過訊號二路徑活化 T 細胞，從而強力放大和維持 T 細胞反應。我們設計了 808 雙特異性格式和親和力，試圖透過要求與其腫瘤抗原 B7-H3 充分結合來開啟 CD28 訊號，以腫瘤特異性的方式驅動這種活化。我們方法的關鍵部分是較低效力的 CD28 結合域，我們認為它可以讓我們控制 CD28 訊號傳導並提高耐受性。

We picked B7-H3 because it offers high expression across a range of tumor types creating an opportunity to potentially treat multiple cancers in combination with either checkpoint inhibitors or CD3 bispecifics. CD28 targeting has generated a lot of interest among clinicians and across the industry in the current Phase 1 study and combination with pembrolizumab is progressing well in escalation.

我們選擇 B7-H3 是因為它在多種腫瘤類型中都具有高表達，從而有可能與檢查點抑制劑或 CD3 雙特異性藥物聯合治療多種癌症。CD28 標靶治療在目前的 I 期研究中引起了臨床醫生和整個行業的極大興趣，並且與 pembrolizumab 的結合正在逐步取得良好的進展。

Now, our latest CD3 bispecific is set to enter the clinic imminently. XmAb541 targets CLDN6, which is highly expressed on the majority of ovarian cancers and also in several other tumor types. Those have a very promising expression profile. It is a selectivity design challenge because there are multiple closely homologous CLDNs.

現在，我們最新的CD3雙特異性抗體即將進入臨床。XmAb541 靶向 CLDN6，該基因在大多數卵巢癌以及其他幾種腫瘤類型中均有高度表達。這些具有非常有前景的表達譜。這是一個選擇性設計的挑戰，因為存在多個密切同源的 CLDN。

We think we addressed it with careful bindings main engineering and our 2+1 format. XmAb541 INDs opened and we expect to be in patients the first half of this year. We're planning to apply lessons learned for solid tumor CD3 dosing from both internal and external programs to move the study quickly. Now, I'm going to turn it over to Nancy for the vudalimab update.

我們認為我們透過精心綁定主要工程和我們的 2+1 格式解決了這個問題。XmAb541 IND 已開放，我們預計今年上半年開始治療患者。我們計劃運用內部和外部專案對實體瘤 CD3 給藥的經驗教訓來快速推進研究。現在，我將把話題交給 Nancy，讓她介紹 vudalimab 的最新情況。

Thanks, Bassil. I'm excited about the encouraging new data we have just shared from the prostate cancer monotherapy cohort. We could go to the next slide. This cohort is part of the overall vudalimab program, which consists of four studies. Based on the outcome of the Phase 1 study, we moved into two tumor-specific expansions initially, the study 717-04 in metastatic castrate resistant prostate cancer in combination with standard of care chemo and other agents and study 717-05 that included patients with gynecologic malignancies and a monotherapy metastatic castrate resistant prostate cancer cohort, which I'm going to further describe.

謝謝，巴西爾。我對我們剛剛分享的前列腺癌單一治療隊列的令人鼓舞的新數據感到非常興奮。我們可以轉到下一張投影片。該隊列是整個 vudalimab 計劃的一部分，該計劃由四項研究組成。根據第 1 期研究的結果，我們最初進入了兩項針對腫瘤的擴展研究，研究 717-04 針對轉移性去勢抵抗性前列腺癌，聯合標準化療和其他藥物治療；研究 717-05 包括婦科惡性腫瘤患者和單一療法治療轉移性去勢抵抗性前列腺癌的患者群，我將進一步描述。

The next slide. The prostate monotherapy cohort required patients to have RECIST measurable disease, including visceral sites and lymph node, and the patients had to have progressed after all other appropriate therapy. vudalimab was given every three weeks based as a flat dose, based on our PK analysis of earlier studies. You can see that this study enrolled a heavily pretreated patient population that had exhausted available standard of care therapies with a median of four prior therapies. 100% received prior anti-androgen therapy, although one received prior chemotherapy and 86% were ECOG 1 performance status.

下一張投影片。前列腺單藥治療組要求患者俱有 RECIST 可測量疾病，包括內臟部位和淋巴結，且患者必須在所有其他適當治療後出現進展。根據我們對早期研究的 PK 分析，vudalimab 以固定劑量每三週給藥一次。您可以看到，這項研究招募了一群接受過大量治療的患者，這些患者已經用盡了現有的標準治療方法，平均接受過四種治療方法。 100％ 的患者曾接受過抗雄性激素治療，但其中 1 人曾接受化療，且 86％ 的患者為 ECOG 1 體能狀態。

As noted, the study protocol required patients with measurable disease at baseline, which is why we see a high rate of visceral metastases and high median baseline PSA. Reduction in target lesions and disease control are encouraging for such a heavily pretreated patient population as you can see on the right with a RECIST response rate of 35% and a disease control rate of 50%. And the spider plot shows we have several lasting responses and one patient with stable disease past 48 weeks.

如上所述，研究方案要求患者在基線時具有可測量的疾病，這就是為什麼我們看到內臟轉移率高和中位基線 PSA 高的原因。對於如此大量接受過治療的患者群體來說，標靶病變的減少和疾病的控制是令人鼓舞的，如您在右側看到的，RECIST 反應率為 35%，疾病控制率為 50%。蜘蛛圖顯示，我們有幾次持久的反應，並且有一名患者在 48 週內病情穩定。

The PSA reduction was also seen in three patients, giving a deep PSA 90 rate of 25% and a fourth patient with nearly a 50% PSA who is still on study. To describe one especially poor prognostic patient who responded well to vudalimab, this patient had three liver mets, a total disease burden of 12 centimeters and a PSA at baseline of 180 nanograms per ml and achieved a confirmed PR of PSA90 was in response for over 22 weeks.

三名患者的 PSA 也出現降低，其 PSA 90 深度比率為 25%，第四名患者的 PSA 接近 50%，目前該患者仍在接受研究。描述一名對武達利單抗反應良好但預後特別差的患者，該患者有 3 處肝轉移，總疾病負擔為 12 厘米，基線 PSA 為 180 納克/毫升，並實現了 PSA90 的確認 PR，反應時間超過 22 週。

The treatment emergent adverse events highlights the tolerability has been generally well managed by dose modifications with only two treatment discontinuations. Unfortunately, there has been one case of Grade 3 immune-mediated hepatitis. The patients treatment course, was complex, and this is the only known Grade 5 immune-mediated hepatitis event in over 240 patients that we've treated with vudalimab today.

治療中出現的不良事件凸顯了耐受性，透過調整劑量通常可以得到很好的控制，只中斷過兩次治療。不幸的是，已經出現一例3級免疫介導性肝炎。患者的治療過程非常複雜，這是我們目前使用武達利單抗治療的 240 多名患者中唯一已知的 5 級免疫介導性肝炎事件。

Reviewing specific immune-related adverse events, generally, the events are what we'd expect with checkpoint inhibitor therapy. The rate of grade three events that you can see on the right were generally limited and specific to several patients. Overall, we are encouraged by the tolerability profile of the Q3 week flat dosing schedule with vudalimab.

回顧特定的免疫相關不良事件，一般來說，這些事件是我們在檢查點抑制劑治療中所預期的。您可以在右側看到的三級事件的發生率通常有限，並且僅針對幾名患者。總體而言，我們對武達利單抗 Q3 週固定劑量方案的耐受性感到鼓舞。

In summary, we have observed encouraging single agent activity in heavily pretreated patient population. This is consistent with the data from the Phase 1 study in prostate cancer, where we had patients with 6 and 10 months duration of response. Vudalimab's safety profile is consistent with other checkpoint inhibitors, and we observe limited treatment discontinuations. Now I will turn this over to Dane to share comparative data to place these results in context.

總之，我們觀察到在接受過大量治療的患者族群中，單一藥物的活性令人鼓舞。這與前列腺癌第 1 期研究的數據一致，研究中患者的反應持續時間為 6 個月和 10 個月。Vudalimab 的安全性與其他檢查點抑制劑一致，我們觀察到治療中斷的情況有限。現在，我將把這個交給 Dane，讓他分享比較數據，以便將這些結果放在上下文中。

Thanks, Nancy. As you can see on the next slide, these emerging data support us enrolling more patients into the monotherapy cohort. We put the data into the context of the broader novel therapeutic landscape under development. It really is clear why we and our investigators during our discussion at ASCO GU were so encouraged about continuing this study.

謝謝，南希。正如您在下一張幻燈片中看到的，這些新興數據支持我們招募更多患者加入單一治療隊列。我們將數據放入正在開發的更廣泛的新型治療前景中。很明顯，為什麼我們和我們的研究人員在 ASCO GU 的討論中如此鼓勵繼續這項研究。

When you compare the baseline characteristics of our patients versus our peer studies, vudalimab monotherapy cohort is among the most heavily pretreated and has the most advanced disease upon enrollment as shown by nearly all having ECOG 1 and all having measurable disease. Comparatively, only the Xaluritamig dose escalation study has enrolled similar patients that are very late-line and poor performance status.

當您將我們患者的基線特徵與同行研究進行比較時，您會發現，武達​​利單抗單藥治療組是接受過最嚴格預處理的患者群之一，並且入組時疾病最為嚴重，幾乎所有患者均具有 ECOG 1 且均具有可測量的疾病。相較之下，只有 Xaluritamig 劑量遞增研究招募了類似的非常晚期且體能狀況較差的患者。

Despite the remarkably advanced patient population, patients treated with vudalimab have comparable resist response rate versus the peer studies in this table and experienced deep PSA90 responses. Importantly, we think that resist response and deep PSA response are required for translating into effective durability of response and ultimately survival outcomes for these patients.

儘管患者群體處於晚期階段，接受武達利單抗治療的患者的抗藥性反應率與本表中的同行研究相當，且經歷了深度 PSA90 反應。重要的是，我們認為抵抗反應和深度 PSA 反應是轉化為有效持久的反應和最終這些患者的生存結果所必需的。

Regarding tolerability, using the Q3 week flat dose schedule of vudalimab has supported a manageable safety profile compared to our peers. Overall, considering the early nature of the vudalimab monotherapy cohort, we are encouraged by the clinical benefit for these advanced prostate cancer patients that have been treated well beyond current standard of care, and we look forward to evaluating a larger cohort of patients by year end.

至於耐受性，與我們的同行相比，使用 Q3 週固定劑量方案的 vudalimab 具有可控的安全性。總體而言，考慮到武達利單抗單藥治療隊列的早期性質，我們對這些晚期前列腺癌患者的臨床益處感到鼓舞，這些患者的治療效果遠遠超出了目前的治療標準，我們期待著在年底前對更大的患者隊列進行評估。

Now on the next slide, beyond prostate cancer, we are executing on the start of our frontline non-small cell lung cancer study of vudalimab plus chemotherapy. And we are excited that the study is underway with the first patient dosed in the fourth quarter of last year. And with that, I'll turn back to Bassil for a view of our corporate goals for 2024.

現在在下一張投影片中，除了攝護腺癌之外，我們正在啟動武達利單抗合併化療的一線非小細胞肺癌研究。我們很高興這項研究正在進行中，第一位患者已於去年第四季接受治療。說完這些，我將回到 Bassil 來討論我們 2024 年的企業目標。

Thanks, Dane. Here's a look at our priorities for 2024. We're starting with a strong balance sheet. And as you can see, we're looking forward to this year, really bringing the focus to our solid tumor bispecifics pipeline where we have a lot going on for our CD3 CD28 T-cell engagers and for vudalimab. Of course, we're doing discovery work on additional CD3 CD28 bispecifics, and we'll select our next IND candidate later this year. Operator, we'll now open this call to questions.

謝謝，丹恩。以下是我們 2024 年的優先事項。我們從強勁的資產負債表開始。正如您所看到的，我們期待今年真正將重點放在我們的實體腫瘤雙特異性藥物管線上，我們在 CD3 CD28 T 細胞接合體和 vudalimab 方面有很多進展。當然，我們正在對其他 CD3 CD28 雙特異性抗體進行探索工作，並將在今年稍後選擇下一個 IND 候選藥物。接線員，我們現在開始回答問題。

(Operator Instructions) Jonathan Chang, Leerink Partners.

(操作員指示)Jonathan Chang，Leerink Partners。

Hey, guys. This is Dylan Drakes on for Jonathan. Thanks for taking our question. First of all, would you be able to comment on how investors should be thinking about when they might be able to see initial clinical data from the ENPP3 study?

嘿，大家好。這是 Dylan Drakes 為 Jonathan 表演的。感謝您回答我們的問題。首先，您能否評論一下投資人應該如何考慮何時能夠看到 ENPP3 研究的初步臨床數據？

Sure. I'll take that one. So we're not commenting on data just yet. And what we're trying to do is characterize with a sufficient patient number and follow up that outlines of the effective dose level as we pull together a dosing regime. These are CD3 bispecifics. So you want to have that -- you want to have your priming it step up this. We made great progress and we really hope that this year we'll have a lot more knowledge about it. And then when we get close to having the decision to disclose, we will tell you. So we're not guiding anything there yet.

當然。我要那個。因此我們暫時還不對數據發表評論。我們試圖做的是根據足夠數量的患者來確定治療方案，然後跟進確定有效的劑量水平。這些是 CD3 雙特異性抗體。所以您想要擁有它 — — 您想要讓您的啟動機制提升到這個水平。我們取得了巨大的進步，我們真心希望今年我們能對此有更多的了解。當我們即將做出披露決定時，我們會告訴你。所以我們還沒有在那裡指導任何事情。

Great. Thanks. And if I could just sneak in one more. You guys at this stage, very well compared to the table there. But looking ahead to the go-forward vision for both mono and combination with vudalimab approaches. How do you guys set the bar?

偉大的。謝謝。如果我可以再偷偷溜進去一次就好了。你們現階段的表現與那張桌子相比非常好。但展望單一療法和與武達利單抗聯合療法的未來願景。你們是如何設定標準的？

Yes. I guess maybe the mono first. Nancy, and Dane, you guys want to take that? What's the bar for advance comparables?

是的。我猜也許是單聲道。南希、戴恩，你們想接受這個嗎？預付款可比較的門檻是多少？

Yeah. Sure. Great question. When we look at the patients that we've enrolled into the monotherapy cohort and we'll continue to enroll, these are patients that are as late-line as you can get and have exhausted every standard of care therapy available to them. As such, what we've really decided to do in gauging the signal that we'll have, as we hopefully get a cohort of 20 to 30 patients enrolled over the course of this year, is look at some of the contemporary studies where cabazitaxel has been used as a control arm.

是的。當然。好問題。當我們查看已納入單一療法隊列且將繼續納入的患者時，我們發現這些患者已處於最晚期階段，並且已經用盡了所有可用的標準護理療法。因此，我們希望在今年招募一群 20 至 30 名患者，在評估我們將收到的訊號時，我們真正決定要做的是查看一些使用卡巴他賽作為對照組的當代研究。

And in those studies, namely the control arm for therapy or the very recently reported part two CheckMate 650, you've seen a resist response rate for cabazitaxel in that 11% to 24% range and a PSA 50 response rate of 24% to 37%. This is why we're quite encouraged with what we're seeing in the cohort now with clinical activity of adalimumab monotherapy and hopefully with a larger cohort, more follow up, we can then try and extrapolate what would be needed in terms of survival outcomes.

在這些研究中，即治療的對照組或最近報告的第二部分 CheckMate 650，您已經看到卡巴他賽的抗藥性反應率在 11% 到 24% 範圍內，PSA 50 反應率為 24% 到 37%。這就是為什麼我們對目前在該隊列中看到的阿達木單抗單藥治療的臨床活動感到非常鼓舞，希望透過更大的隊列和更多的隨訪，我們可以嘗試推斷出在生存結果方面需要什麼。

And cabazitaxel for reference is generally come out around eight months for radiographic progression-free survival. And right now, based on some of the durability, seems like we're pretty in pretty good shape.

而卡巴他賽的放射學無惡化存活期一般為 8 個月左右。現在，根據一些耐用性，似乎我們的狀況相當不錯。

And then for the combo cohort, I guess we've got different baselines there to look at?

那麼對於組合隊列，我想我們有不同的基線可供參考？

Yeah, in the combination cohort with docetaxel, you really have to think about what docetaxel might be able to do and what would be post androgen receptor inhibitor exposure for these patients. And again, the landscape will continue to change with Pluvicto. But historically, if you're looking at the TAX 327 study, you'd be looking at PSA 50 response range of 40% to 50% and a fairly low resist response rate of somewhere around 10%. That said, the survival curves are a bit better for that line and that setting with docetaxel monotherapy. But that's kind of what you have to think about when you're doing the combination study with docetaxel at this point.

是的，在與多西他賽的聯合治療中，你真的必須考慮多西他賽可能發揮什麼作用，以及這些患者接受雄激素受體抑制劑治療後的暴露情況如何。隨著 Pluvicto 的出現，景觀將繼續改變。但從歷史上看，如果您查看 TAX 327 研究，您會看到 PSA 50 響應範圍為 40% 到 50%，而抗蝕劑響應率相當低，約為 10%。也就是說，對於該線和採用多西他賽單藥治療的環境來說，生存曲線要好一些。但這正是您在進行與多西他賽的聯合研究時必須考慮的問題。

Perfect. Thanks so much. I appreciate it.

完美的。非常感謝。我很感激。

Etzer Darout, BMO Capital Markets.

Etzer Darout，BMO資本市場。

Great. Thanks for taking a question. I guess on maybe on the safety profile of belimumab, if there's any anything you can or will incorporate into the study to maybe mitigate this autoimmune hepatitis? Is this something that is just you need to this patient or if there are other things going on that you need to understand? And then also XmAb564, just wondered the decision to pause that. Was that data driven or whatever other contributing factors? If you could comment on that supposing that you have any. Thank you.

偉大的。感謝您回答問題。我想也許是關於貝利木單抗的安全性，您是否可以或將把任何東西納入研究中，以減輕這種自體免疫性肝炎？這是您只需對這位病人做的一些事情嗎，還是還有其他事情需要您了解？然後還有 XmAb564，只是想知道暫停的決定。這是數據驅動的還是有其他因素促成的？如果您有任何意見，請提出評論。謝謝。

Sure. So I'll talk -- going through the XmAb564, then maybe Nancy can take the question on vudalimab safety profile. So for 564, is really driven by our as much as anything by our decision to focus on our T-cell engages, our resources, our capital, and our people. And looking at how the class cytokine generally and IL2 T regs driving cytokine in particular has evolved. there's still, I think, a lot of outstanding data coming in the next year from other companies about efficacy, about how much potential does this class have.

當然。因此我將討論 — — 透過 XmAb564，然後也許 Nancy 可以回答關於 vudalimab 安全性的問題。因此，對於 564 而言，其真正驅動力很大程度上在於我們決定專注於我們的 T 細胞參與、我們的資源、我們的資本和我們的人才。並觀察類細胞激素和 IL2 T regs 驅動細胞因子的一般演化情況。我認為，明年其他公司將會提供大量關於療效以及此類藥物潛力的優秀數據。

And with our study having progressed and giving us a reasonable look at our PK/PD and safety, we think that that's the time to conserve resources and wait and see how the field evolves. We're well positioned to to ramp up again, but it's about focus now. And for 2024, pipeline focus is the key for Xencor. So it was really more just strategy driven. With that maybe, Nancy, you want to touch on the question on vudalimab?

隨著我們的研究取得進展，我們對 PK/PD 和安全性有了合理的認識，我們認為現在是時候節省資源並觀察該領域如何發展了。我們已做好準備再次提昇實力，但現在需要集中註意力。對於 2024 年來說，管道重點是 Xencor 的關鍵。因此這實際上只是由戰略驅動。南希，也許你想談談關於武達利單抗的問題？

Yeah. So I'll go back to the patient with the hepatitis death. And that's the only immune-related hepatitis death we've seen across our program with more than 240 patients treated, both in the monotherapy and combination setting. The patient had responded to therapy, but did have other treatment emergent adverse events before that, including diabetes mellitus and diabetic ketoacidosis, thyroiditis, hyperkalemia, lipase increase. So a bit of a complex course here.

是的。所以我要回去談談那位因肝炎而死亡的病人。這是我們在整個計畫中看到的唯一一例免疫相關性肝炎死亡病例，超過 240 名患者接受了單一療法和聯合療法的治療。患者對治療有反應，但在此之前確實出現其他治療出現的不良事件，包括糖尿病和糖尿病酮酸中毒、甲狀腺炎、高血鉀、脂肪酶升高。所以這裡的課程有點複雜。

We have looked across the entire program, and we don't see anything concerning relating hepatitis. As far as the protocol and the investigators, we have emphasize to the investigators to be watchful for this and communicate it with them. Protocol does include the NCCN guidelines for treatment, and it's also consistent with ASCO guidelines and other Society guidelines like the gastric GEA guidelines for monitoring and treatment. And so we do include screening a baseline for any diseases that might contribute to hepatitis, and we have frequent laboratory monitoring.

我們查看了整個計劃，沒有發現任何與肝炎有關的內容。就協議和調查人員而言，我們已經強調調查人員要注意這一點並與他們溝通。該協議確實包括了 NCCN 治療指南，並且也與 ASCO 指南和其他學會指南（如胃 GEA 監測和治療指南）一致。因此，我們確實對可能導致肝炎的任何疾病進行了基線篩檢，我們經常進行實驗室監測。

Great. Thank you for the color.

偉大的。謝謝你的顏色。

Gregory Renza, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Hi and thank you so much for taking our questions. This is support for Greg. Just to confirm if this monotherapy data was from a particular molecular subtype. I think that was how did the trial used to be characterized? And if I may, secondarily, from the data comparison table, I think the PSA90 look competitive, but PSA50 looks a little lower. Just curious if you have any positives on why the data looked that way?

您好，非常感謝您回答我們的問題。這是對 Greg 的支持。只是為了確認單一療法數據是否來自特定的分子亞型。我認為這就是審判過去的特徵嗎？其次，如果可以的話，從數據比較表來看，我認為 PSA90 看起來很有競爭力，但 PSA50 看起來稍微低一些。我只是好奇，您是否對數據看起來如此有什麼正面的看法？

So I'll touch on the specifics of the trial in the population. So I think just to be careful, there's two studies ongoing that will we're starting prostate cancer with vudalimab. The monotherapy study. the one we discussed today is not subdivided by molecular subtype, it's people with clinically defined high-risk disease, which includes extra pelvic and visceral metastases. So that's a population that's independent of molecular subtype in that regard.

因此我將談談該項人群試驗的具體情況。因此，我認為要小心，目前有兩項正在進行的研究，我們將使用武達利單抗開始治療攝護腺癌。單一療法研究。我們今天討論的不是按分子亞型細分，而是臨床定義的高風險疾病患者，其中包括骨盆外和內臟轉移。因此從這個方面來看，這是一個與分子亞型無關的群體。

The other study, our combination with chemo study, that study is subdivided by molecular subtype. That's a different study. We didn't discuss data for that one today. We're enrolling still accrued patients and more follow-up, and we hope to have a lot more clarity later in the year on that program. And also, I guess first half of next year really bring it all together.

另一項研究是我們與化療相結合的研究，該研究根據分子亞型進行細分。這是一項不同的研究。我們今天沒有討論該數據。我們正在招募仍在累積的患者並進行更多的後續研究，我們希望在今年稍後對該計劃有更清晰的認識。而且我預計明年上半年一切都會順利。

So that -- I just want to make sure that this is not from the molecular subtype dividing study. Maybe on the comparison table, Dane, you want to answer that one on the PSAs?

所以——我只是想確保這不是來自分子亞型分割研究。也許在比較表上，Dane，你想回答有關 PSA 的問題嗎？

Yahs, sure. That's a great question. We looked at quite extensively once we had this data cut and we're able to review the data with our investigators during ASCO GU. What seems to be is somewhat of an artifact of taking patients that are required to have measurable disease at baseline versus other studies that also include bone only. And as you can see on that table, most of our peer studies outside, maybe one with a similar mechanism of action, is more of a mixed patient population. And what we see in those studies is you will get more PSA 50s that don't necessarily correlate to a resist response as some of those patients do not have measurable disease at baseline.

是的，當然。這是一個很好的問題。我們在獲得這些數據後進行了非常廣泛的研究，並且能夠在 ASCO GU 期間與我們的研究人員一起審查這些數據。與其他僅包括骨骼的研究相比，這似乎是一種選擇在基線時必須具有可測量疾病的患者的方法。正如您在該表中所看到的，我們外部的大多數同行研究（可能具有類似的作用機制）都涉及混合患者群體。我們在這些研究中看到，您會獲得更多的 PSA 50，但這不一定與抵抗反應相關，因為其中一些患者在基線時沒有可測量的疾病。

In our cohort, to really get clinical benefit, those patients will need either a resist response or PSA 90. So I think there's two things there. One is PSA 50 for patients that are this advanced in their disease course, are relevant for survival outcomes, very debatable on. But what is definitely needed is those resist responses and PSA 90s.

在我們的隊列中，為了真正獲得臨床益處，這些患者需要抵抗反應或 PSA 90。所以我認為這裡有兩件事。一個是對於病程處於晚期的患者，PSA 50 與存活結果相關，這點非常有爭議。但絕對需要的是那些抵抗反應和 PSA 90。

Kaveri Pohlman, BTIG.

Kaveri Pohlman，BTIG。

Yeah, good evening. Thanks for taking my questions. My questions are mostly on vudalimab So first, on the safety profile, can you tell us how the safety profile looks in comparison with IPI-NIVO combination and how you are thinking about the dose that will be used going forward?

是的，晚上好。感謝您回答我的問題。我的問題主要關於 vudalimab，因此首先，關於安全性，您能告訴我們與 IPI-NIVO 組合相比，它的安全性如何，以及您如何考慮今後將使用的劑量？

And my second question is also for the go-no-go decision. How many patients you plan to enroll in monotherapy in combination cohort for that? And is efficacy the only factor you're considering to make these decisions? And the last one is also from the same trial, any color you can provide on how many patients had bone disease and were there any responses observed in those patients? Thank you.

我的第二個問題也是關於是否繼續進行的決定。您計劃招募多少名患者參加聯合治療的單一療法？功效是您做出這些決定考慮的唯一因素嗎？最後一個也是來自同一次試驗，您能否說明有多少患者患有骨病以及這些患者是否觀察到了任何反應？謝謝。

Hey, thanks. Great. So that's a set of questions. I think maybe the one that's more just generically descriptive is your first one. Vudalimab safety versus IPI-NIVO, which is a broad kind of amorphous question, but we'll take a crack at it. And what our dose going forward is, Nancy, do you want to jump in on that one?

嘿，謝謝。偉大的。這就是一系列問題。我認為也許更具一般性描述的是你的第一個。Vudalimab 與 IPI-NIVO 的安全性比較，這是一個很廣泛的、不太明確的問題，但我們會努力解決它。那我們接下來的劑量是多少，南希，你想加入這個嗎？

So overall, what we've seen so far is a safety profile that looks similar to other checkpoint inhibitors. So we haven't seen anything that says that this is markedly different in some way that wouldn't be unfavorable to the product. But I guess I could say that overall, I mean, there's a lot of data out there on IPI single monotherapy checkpoint inhibitors as well as combinations. So broadly, we're similar to that. Do you want to --?

總的來說，到目前為止我們看到的安全性特徵與其他檢查點抑制劑相似。因此，我們還沒有看到任何證據表明這在某種程度上有明顯的不同，並且不會對產品造成不利影響。但我想我可以說，總的來說，我的意思是，關於 IPI 單一單一療法檢查點抑制劑以及組合治療有很多數據。所以從廣義來說，我們與此類似。你想要_____嗎--？

Yeah. On the dose going forward, noted in our lung cancer study, the newest study we started as well as in the monotherapy prostate study, which was which was the second newest, we have switched to a Q3 week schedule using flat doses. And I think that's given us a good feeling that the Q3 week might have some benefits over the Q2 week weight-based dosing.

是的。關於未來的劑量，根據我們在肺癌研究中（我們開始的最新研究）以及前列腺單藥治療研究（第二最新的研究）中指出，我們已改為使用固定劑量的 Q3 週計劃。我認為這讓我們感覺很好，第三季度的基於體重的劑量可能比第二季度的基於體重的劑量有一些好處。

With regard to IPI NIVO, even though we've got over 240 patients now, it's still hard to parse out those subtle differences. We don't see the kind of colitis that often bedeviled IPI therapy at high doses. And note, we're giving much higher doses of our drug than the current sort of IPI regime of 1 milligram per kilogram. So I think that's maybe the best we can say comparatively across such a range of studies and whatnot, but generally very checkpoint like.

關於 IPI NIVO，儘管我們現在已經有超過 240 名患者，但仍然很難分辨出這些細微的差異。我們沒有看到大劑量IPI治療時常出現的那種結腸炎。請注意，我們給予的藥物劑量比現行的 1 毫克/公斤的 IPI 方案高得多。所以我認為這也許是我們在如此廣泛的研究和其他研究中所能得出的最好的比較結果，但總體來說非常像檢查點。

And then on your second question, go-no-go number of patients that we hope to have for both the combo and mono, so by first half next year, we're looking at on the order of roughly 30 patients in each of those settings, the chemo study and in particular in the the main cohort, which is our no targetable mutations cohort, which is our now docetaxel combo. And then on our monotherapy study as well. So in that, we're aiming for 20 patients. Hopefully, we'll get pretty close to that and be able to make decisions.

然後關於您的第二個問題，我們希望聯合治療和單藥治療的患者數量都達到或超過一定數量，所以到明年上半年，我們將在每種情況下觀察大約 30 名患者，化療研究，特別是主要隊列，這是我們的無可靶向突變隊列，也是我們現在的多西他賽組合。然後我們再進行單一療法研究。因此，我們的目標是 20 名患者。希望我們能夠接近這個目標並做出決定。

I think it would be helpful. Maybe, Nancy, you could just explain the difference between measurable disease, not measurable disease at baseline because I think that might be helpful for everyone.

我認為這會有幫助。南希，也許你可以解釋一下可測量疾病和基線可測量疾病之間的區別，因為我認為這可能對每個人都有幫助。

Sure. Measurable disease, it has very basically two dimensions. And it's got to be a metastatic site in an organ or a measurable lymph node bigger than a normal lymph node. Non measurable would typically be bone-only disease or if a patient had bone-only disease. Our patients had measurable disease, and they could have also had bone disease on top of that. I can tell you two of the four responders had bone disease in addition to their other measurable disease. So we have seen responses in patients who had bony disease.

當然。可測量的疾病，基本上有兩個維度。而且它必須是器官中的轉移部位，或是比正常淋巴結更大的可測量淋巴結。不可測量通常是僅有骨骼的疾病，或是患者是否患有僅有骨骼的疾病。我們的病人患有可測量的疾病，他們也可能患有骨病。我可以告訴你，四名響應者中，有兩名除了患有其他可測量的疾病外，還患有骨病。我們已經看到了患有骨病的患者的反應。

Got it. That's what I wanted to know. Thank you. Thanks for the color.

知道了。這就是我想知道的。謝謝。謝謝你的顏色。

Brian Cheng, JP Morgan.

摩根大通 (JP Morgan) 的 Brian Cheng。

Hey, guys. Thanks for taking my questions today. Maybe a first one is just on the three confirmed responders. I think just kind of piggybacking on what was the question prior to this. What was the background of the three confirmed responders? Can you just kind of give us how many lines they have and give us a sense of what their historical responses or to prior ARR or even see that they had -- some patients had, yes, radiation. So just curious like what are the responses like and I have a follow-up. Thank you.

嘿，大家好。感謝您今天回答我的問題。也許第一個只是關於三個確認的響應者。我認為這只是對先前問題的補充。三位確認響應者的背景是？您能否告訴我們他們有多少條線路，並讓我們了解他們的歷史反應或之前的 ARR，甚至看看他們有沒有——是的，一些病人接受了放射治療。所以我只是好奇回應是什麼樣的，我有一個後續問題。謝謝。

Yeah. Nancy, you could take that, all the details. I'd say they were really, really heavily pretreated in rough shape when we got them.

是的。南希，你可以了解所有細節。我想說，當我們收到它們時，它們經過了非常非常嚴重的預處理，狀況非常粗糙。

They had to be progressing through prior therapies. They had to have at least two prior therapies. I'm looking at the background. And they have anywhere from 3 to like 7 prior therapies, including the XRT. Sorry, I'm just looking at --

他們必須透過先前的治療取得進步。他們必須至少接受過兩次治療。我正在看背景。他們之前接受過 3 至 7 種療法，包括 XRT。抱歉，我只是看看--

Yes, that's a lot of detail, Brian. So we're (technical difficulty) up our notes.

是的，布萊恩，細節很豐富。因此我們（由於技術困難）記錄了下來。

Yeah. So one patient had three prior therapies, not including any radiation. Second patient had three prior therapies. The third patient had six prior therapies. So none of these are with radiation or counting that. And the last patient had two prior therapies. They all included docetaxel or one included carboplatin. Two had prior radiotherapy. Let me just see. I can't really comment on their prior responses. Can they be at an upcoming presentation, we could drill down into each individual patient.

是的。因此，一名患者曾接受過三種治療，不包括任何放射治療。第二位患者之前曾接受過三種治療。第三位患者之前曾接受過六次治療。因此，這些都與輻射無關，也不計算在內。最後一位患者之前接受過兩種治療。它們均含有多西他賽，或其中一個含有卡鉑。其中兩人曾接受放射治療。讓我看看。我實際上無法評論他們先前的回應。他們是否可以出席即將舉行的演講，我們可以深入了解每位患者。

Yes, but suffice to say that they've seen a lot of prior therapy, Brian.

是的，但是可以說他們已經見過很多先前的治療方法了，布萊恩。

Okay. And then on a follow-up here. As you're looking at this data and I think the last time we saw the combo data, maybe back in to see, I think back in 2022, how should we think about the low hanging fruit piece? What is the lowest hanging subset of the mCRPC patients that investors should think of when it comes to vudalimab. And is that high-risk, is that genetically defined? How do you think about the low hanging fruit either with combo or monotherapy? Thanks.

好的。然後在這裡進行後續跟進。當您查看這些數據時，我想我們上次看到組合數據時，也許可以回頭看看，我想回到 2022 年，我們應該如何看待唾手可得的成果？當談到 Vudalimab 時，投資者應該考慮的 mCRPC 患者中懸而未決的最低亞群是什麼。這是高風險嗎？您如何看待聯合療法或單一療法的低成本效果？謝謝。

Yes, I think it's a great question that we're obviously going to have a fuller answer to as we get these cohorts enrolled over the course of this year and can really look for a reliable signal, hopefully and 30 patients per cohort for a monotherapy and for the combination. But the way we're thinking about it now is we just had an update on part 2of CheckMate 650 at ASCO, do you where IPI-NIVO was tried in every foreseeable combination relative to cabazitaxel?

是的，我認為這是一個很好的問題，隨著我們今年招募這些隊列並真正尋找可靠的信號，我們顯然會得到更完整的答案，希望每個隊列有 30 名患者接受單一療法和聯合療法。但我們現在考慮的是，我們剛剛在 ASCO 上對 CheckMate 650 第 2 部分進行了更新，您是否在所有可預見的組合中嘗試了 IPI-NIVO 與卡巴他賽？

The emergent signal that we have in the small end right now is better than anything that was achieved in that study in a comparable patient population post taxane patients. So that's step one. We think we have something differentiated that hasn't been done with an IO therapy before in this heavily pretreated patients, even going back to the table that we have looking across all of our peer studies.

我們目前在小端獲得的緊急訊號比該研究中在可比患者群體中使用紫杉醇類藥物後獲得的任何訊號都要好。這是第一步。我們認為，我們在這些接受過大量治療的患者身上取得了一些差異化成果，這種成果以前從未在IO療法中得到應用，甚至回顧我們所有同行研究的結果。

And then step two is more of a question. I think you're asking of how we see the treatment landscape evolving. As everyone knows, Pluvicto is probably going to be used more and more. They had a good 2023 of commercial uptake in the United States. And so that has to be on our minds as we look through future development. But the interesting point here is the toxicity profile of vudalimab is nonoverlapping with Pluvicto. So that's one.

第二步則更像是個問題。我想您問的是我們如何看待治療前景的演變。眾所周知，Pluvicto 的使用可能會越來越多。到 2023 年，他們在美國的商業應用取得了良好的進展。因此，當我們展望未來發展時，我們必須考慮到這一點。但這裡有趣的一點是，武達利單抗的毒性特徵與 Pluvicto 不重疊。這就是其中之一。

And secondly, there's emerging evidence presented and published late last year that treatment with Pluvicto might actually sensitize the tumor microenvironment to checkpoint targeted therapy. And this all has to be proven out in the clinic with in larger studies. And step one for us is still declining what we think the clinical profile is of vudalimab monotherapy for these have we treated them as patients with measurable disease.

其次，去年年底提出並發表的新證據表明，Pluvicto 治療實際上可能會使腫瘤微環境對檢查點標靶治療敏感。所有這些都需要透過更大規模的臨床研究來證實。我們第一步要做的仍然是拒絕我們認為的武達利單抗單一療法的臨床特徵，我們是否將他們作為可測量疾病的患者進行治療。

But once we understand that, I think there's a number of options how to move forward in an intelligent manner for development of this drug. So we're excited for what we're seeing. Again, early days here, so we don't want to get over our skis. But we'll look for a confirmation of the signal as we move throughout the year.

但一旦我們了解這一點，我認為就有很多選擇可以以明智的方式推進這種藥物的開發。我們對所看到的一切感到非常興奮。再說一遍，這裡還處於早期階段，所以我們不想放棄我們的滑雪。但我們會隨著全年的發展尋找訊號的確認。

Alec Stranahan, Bank of America.

美國銀行的亞歷克·斯特拉納漢（Alec Stranahan）。

Hey, guys. Thanks for taking the question. This is John. I'm on for Alex. Just a first quick question. I think this was briefly mentioned before, but just wanted to check, I didn't catch everything. But won't it be like a good benchmark or like a comparator for us to look at in comparison to the vudalimab monotherapy data presented today? That's my first question.

嘿，大家好。感謝您回答這個問題。這是約翰。我支持亞歷克斯。這只是第一個快速問題。我認為之前曾簡要提到過這一點，但只是想檢查一下，我沒有記住所有內容。但與今天呈現的 vudalimab 單藥治療數據相比，這不是一個很好的基準或比較器嗎？這是我的第一個問題。

Second question on the quality of life data, when can we expect to see some color regarding that if you're keeping track of it? And could you maybe provide some - shed some light on what you're currently observing in the clinic in terms of quality of life and some patient reported outcomes. Thanks.

第二個問題是關於生活品質數據，如果您一直在追蹤的話，什麼時候我們可以看到一些相關資訊？您能否提供一些信息，說明您目前在臨床上觀察到的生活品質和一些患者報告的結果。謝謝。

That question is really a question of when we have a totality of a cohort in discussion with our clinical investigators. It is that clinical experience overall for these patients, something that we should move forward. So does that affect the totality of data? We don't know at this point, right? We want to see hopefully 30 patients in each of these cohorts. The monotherapy cohort in the dose type of combination cohort and to have that conversation with our clinical investigators.

這個問題實際上是我們何時與臨床研究人員討論整個隊列的問題。對於這些患者來說，整體而言，這是我們應該推進的臨床體驗。那麼這會影響資料總量嗎？我們現在還不知道，對吧？我們希望在每個隊列中看到 30 名患者。聯合劑量類型的單一療法隊列，並與我們的臨床研究人員進行對話。

So it's a great question, and that's really what we're hoping to answer. In terms of the first part of the question, that's why we provided the data table in the slides because each of these studies that we're looking at, our peer studies are exciting, right? We're excited about Xaluritamig and the clinical response there, but they're also limited in terms of their size and their scope and the comparability of the patients that were enrolled. S

這是一個很好的問題，這正是我們真正希望回答的。就問題的第一部分而言，這就是我們在幻燈片中提供數據表的原因，因為我們正在研究的每一項研究，我們的同行研究都是令人興奮的，對吧？我們對 Xaluritamig 及其臨床反應感到非常興奮，但其規模和範圍以及入組患者的可比性也受到限制。年代

o we don't want to make apples and oranges comparisons of novel agents for the treatment of these prostate cancer patients right now. But I think what we could say is a number of these programs, Xaluritamig is undeniable. And hopefully, our vudalimab monotherapy program as well seem to be surpassing what you could probably expect for late-line chemotherapy from contemporary studies as we mentioned, the cabazitaxel response rates and the CheckMate 650 study and the therapies study.

o 我們現在不想對治療這些前列腺癌患者的新藥物進行蘋果和橘子之間的比較。但我認為我們可以說，在這些計劃中，Xaluritamig 是不可否認的。並且希望我們的武達利單抗單藥治療計劃也能超越您對當代研究對於晚期化療的預期，正如我們所提到的，卡巴他賽的反應率和 CheckMate 650 研究以及治療研究。

And then once you get to earlier lines, of therapy. I think it is a toxicity profile. And again, if it does seem that Pluvicto is sensitizing the tumor microenvironment for IO therapy, we have a therapy that does not have overlapping heme tox and could be an interesting idea to explore down the road.

然後一旦你進入早期治療階段。我認為這是一個毒性概況。再一次，如果 Pluvicto 確實似乎提高了腫瘤微環境對 IO 治療的敏感性，那麼我們就有了一種不具有重疊血紅素毒性的治療方法，這可能是一個值得未來探索的有趣想法。

Thanks for the color.

謝謝你的顏色。

Tara Bancroft, TD Cowen.

塔拉·班克羅夫特（TD Cowen）。

Hi, good afternoon. So my question is more of a general question. So are there any other combos besides chemo that you're considering or really excited about that could increase the robustness of this data? And then specifically referring to the chemo combo, how do you think safety will look in that combination. Is there any update that you can provide on how that's going now in the 1704 study? Thanks.

嗨，下午好。所以我的問題比較像是一般性問題。那麼，除了化療之外，還有其他您正在考慮或非常感興趣的組合可以提高這些數據的穩健性嗎？然後具體提到化療組合，您認為這種組合的安全性如何。您能提供一下 1704 年研究的當前進展嗎？謝謝。

So I guess on the first, other combos other than chemo, we think chemo is a very important one in this setting because it is the predominantly used therapy post androgen still. I think it's really interesting to imagine post Pluvicto treatment, maybe not in concert, given the intriguing immune priming activity that Pluvicto perhaps has from some small studies recently published, I think, at UCSF.

因此，我想首先，除了化療之外的其他組合，我們認為化療在這種情況下非常重要，因為它仍然是雄激素後最常用的治療方法。我認為想像 Pluvicto 治療後的狀況，也許不是協同治療，這真的很有趣，因為從加州大學舊金山分校最近發表的一些小型研究來看，Pluvicto 可能具有有趣的免疫啟動活性。

So I think those are the two top things on our mind now. But I think in the future, as we see our CD28 technology evolve, our XmAb808 program is, of course, aimed partially at least at prostate, maybe even predominantly at the moment. And as that would evolves in combo with pembro, we're certainly keeping our eye on how to maybe use that with vudalimab if the stars align, right? So that's maybe the other other big one that we're thinking of.

所以我認為這是我們現在最關心的兩件事。但我認為在未來，隨著我們看到 CD28 技術的發展，我們的 XmAb808 計劃當然至少部分針對前列腺，甚至可能目前主要針對前列腺。隨著它與 pembro 的聯合使用，我們肯定會密切關注如何將其與 vudalimab 一起使用，如果一切順利，對嗎？這也許是我們正在考慮的另一個大問題。

The future might hold combinations with CD3 bispecifics with molecules like for vudalimab. I think that's something people are looking at. They're just starting to happen in the clinic now. I'm aware of some CD3 solid tumor molecules that are being tested with checkpoints. That's maybe a little bit further off in the future, though.

未來可能會將 CD3 雙特異性抗體與類似 vudalimab 的分子結合。我認為這是人們正在關注的事情。這些現象現在才剛開始在診所出現。我知道一些 CD3 實體瘤分子正在通過檢查點進行測試。不過，這可能還要等一段時間。

And then I guess your second question was on, what can we say about safety from the ongoing 04 study, given that we're not sharing specific data? So maybe Nancy, do you want to comment?

然後我想你的第二個問題是，鑑於我們沒有分享具體的數據，我們可以從正在進行的 04 研究中得出關於安全性的什麼結論？那麼也許南希，你想發表評論嗎？

Yeah, absolutely. So maybe I can share also that since we last presented data, we amended the combination protocol in prostate cancer to remove the carboplatin, all, but the aggressive variant. And we're really focused on the taxane, specifically docetaxel is first-line chemotherapy. And so far, based on feedback from investigators, we seem to be seeing better tolerability with these new regimens and the prior one.

是的，絕對是如此。因此，也許我也可以分享一下，自從我們上次提供數據以來，我們修改了前列腺癌的聯合治療方案，去除了卡鉑等所有藥物，但保留了侵襲性變異。我們真正關注的是紫杉烷，特別是多西他賽作為一線化療。到目前為止，根據研究人員的回饋，我們似乎看到這些新方案和先前的方案具有更好的耐受性。

Operator, we have any other questions?

接線員，還有其他問題嗎？

No, that looks like that's all.

不，看起來就這些了。

Right. Well, thanks, everybody, for joining us today and have a wonderful evening. We look forward to our next update.

正確的。好吧，感謝大家今天的參與，祝大家有個美好的夜晚。我們期待下次更新。

Thank you for participating in today's conference. This does conclude the program. You may now disconnect.

感謝大家參加今天的會議。該計劃確實結束了。您現在可以斷開連線。