Arvinas Inc (ARVN) 2025 Q2 法說會逐字稿

Thank you for standing by at this time. I would like to welcome everyone to Arvinas second quarter 2025 earnings call. (Operator Instructions)

感謝您此刻的支持。歡迎大家參加 Arvinas 2025 年第二季財報電話會議。（操作員指示）

I would now like to turn the conference over to Jeff Boyle, Arvinas, Vice President of Investor Relations. Please go ahead.

現在，我想將會議交給 Arvinas 投資者關係副總裁 Jeff Boyle。請繼續。

Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our second quarter 2025 financial results, which is available in the investor and media section of our website at arvinas.com.

大家早安，感謝大家的收看。今天早些時候，我們發布了一份新聞稿，其中包含我們 2025 年第二季的財務業績，您可以在我們網站 arvinas.com 的投資者和媒體部分查閱。

Joining the call today are John Huston, our business's Chief Executive Officer, President and Chairperson; Noah Berkowitz, our Chief Medical Officer; Angela Cacace, our Chief Scientific Officer; and Andrew Saik, our Chief Financial Officer.

今天參加電話會議的有我們公司的執行長、總裁兼董事長約翰·休斯頓 (John Huston)、我們的首席醫療官諾亞·伯科維茨 (Noah Berkowitz)、我們的首席科學官安吉拉·卡卡斯 (Angela Cacace) 和我們的首席財務官安德魯·賽克 (Andrew Saik)。

Before we begin the call, I'll remind you that today's discussion contains forward-looking statements that involve risks, uncertainties, and assumptions. These risks and uncertainties are outlined in today's press release and in the company's recent filing with the Securities and Exchange Commission, which I urge you to read. Our actual results may differ materially from what is discussed on today's call.

在我們開始通話之前，我要提醒您，今天的討論包含涉及風險、不確定性和假設的前瞻性陳述。這些風險和不確定性在今天的新聞稿和公司最近向美國證券交易委員會提交的文件中都有概述，我建議您閱讀。我們的實際結果可能與今天電話會議上討論的結果有重大差異。

And now I'll turn the call over to John. John?

現在我將把電話轉給約翰。約翰？

Thanks, Jeff. Good morning, everyone, and thank you for joining us today. As outlined in our second quarter earnings release this morning, our business is in a solid position with strong momentum.

謝謝，傑夫。大家早安，感謝大家今天加入我們。正如我們今天上午發布的第二季財報所述，我們的業務狀況穩固，發展勢頭強勁。

It was an eventful and exciting quarter at Arvinas, with significant clinical and regulatory progress across our pipeline of PROTAC degraders. We continued making significant strides across our early-stage programs, where we are enrolling patients in three Phase 1 trials across our neural and oncology portfolio, including the recently-initiated trial with our KRAS G12 degrader, ARV-806.

這是 Arvinas 一個多事且令人興奮的季度，我們的 PROTAC 降解劑產品線在臨床和監管方面取得了重大進展。我們在早期計畫中繼續取得重大進展，我們正在招募患者參加我們神經和腫瘤學產品組合中的三項 1 期試驗，包括最近啟動的 KRAS G12 降解劑 ARV-806 試驗。

During the quarter, we also presented compelling first-in-human data from ARV-102, our LRRK2 degrader, and preclinical data for our BCL6 degrader, ARV-393. I'm also pleased to share an update on our antigen receptor degrader, luxdegalutamide, which we licensed to Novartis in 2024. We are pleased to see that Novartis is rapidly progressing the asset and announced the recent initiation of two combination Phase 2 trials that will further advance luxdegalutamide towards patients.

在本季度，我們還展示了 ARV-102（我們的 LRRK2 降解劑）的引人注目的首次人體數據，以及我們的 BCL6 降解劑 ARV-393 的臨床前數據。我也很高興與大家分享我們抗原受體降解劑 luxdegalutamide 的最新進展，我們於 2024 年將藥物授權給諾華公司。我們很高興看到諾華正在快速推進該資產，並宣布最近啟動兩項聯合 2 期試驗，這將進一步推動 luxdegalutamide 面向患者的推廣。

One trial is Metastatic castration-resistant prostate cancer, and the other is Metastatic hormone-sensitive prostate cancer, and both will identify recommended Phase 3 doses, and we believe further validate our ability to develop potentially best-in-class protein degraders.

一項試驗是轉移性去勢抵抗性前列腺癌，另一項試驗是轉移性荷爾蒙敏感性前列腺癌，兩項試驗都將確定建議的 3 期劑量，我們相信這進一步驗證了我們開發潛在的最佳蛋白質降解劑的能力。

As a reminder, our license agreement with Novartis includes up to $1 billion in development, regulatory, and commercial milestones, as well as tiered royalties. The accomplishments from across our portfolio are the latest in a long stream of success to that of Arvinas. At the same time, we have recognized the ongoing need to enhance our financial position and set Arvinas up for future success.

提醒一下，我們與諾華的授權協議包括高達 10 億美元的開發、監管和商業里程碑，以及分級特許權使用費。我們投資組合中所取得的成就是 Arvinas 長期成功的最新成果。同時，我們認識到需要不斷提高我們的財務狀況並為 Arvinas 未來的成功做好準備。

To that end, last quarter, we announced a company-wide restructuring that extended our cash runway and included two key elements. First, we reprioritized our research pipeline, cutting a number of programs, and continuing investment in our assets with the greatest potential value. And second, we streamlined operations across the organization by reducing our workforce by approximately one-third.

為此，上個季度，我們宣布了全公司範圍的重組，延長了我們的現金流，並包含兩個關鍵要素。首先，我們重新調整了研究管道的優先順序，削減了一些項目，並繼續投資於具有最大潛在價值的資產。其次，我們透過減少約三分之一的員工來精簡整個組織的運作。

While difficult, these decisive actions bolstered our financial profile and drove efficiencies across the company. They also enabled us to turn our full attention to our near-term imperatives, which are, first, working with Pfizer or identifying another partner to advance vepdeg towards commercial launch. Second, achieving critical data milestones from our pipeline in the next 12 months. And third, carefully allocating capital to support those milestones efficiently.

雖然很困難，但這些果斷的行動增強了我們的財務狀況並提高了整個公司的效率。它們也使我們能夠將全部注意力集中在近期的當務之急上，首先是與輝瑞合作或尋找另一個合作夥伴來推動 vepdeg 的商業化上市。第二，在未來 12 個月內實現我們管道中的關鍵數據里程碑。第三，謹慎分配資金以有效地支持這些里程碑。

I'll return to those three imperatives in a few moments, but I'd first like to say a few words about the recent announcement of my planned retirement and the CEO transition for Arvinas. Having recently strengthened our financial profile and with a clear line of sight into those near-term imperatives, the board and I agreed it is the right time to initiate a search for a new CEO.

稍後我將回到這三個命令，但首先我想談談我最近宣布的退休計劃和 Arvinas 執行長的過渡。由於我們最近增強了財務狀況，並且對短期內需要解決的問題有了清晰的認識，董事會和我一致認為現在是開始尋找新執行長的最佳時機。

As with any public company, succession planning is a priority for a board of directors, and I have been talking to the board about the potential timing of this transition for well over a year. While there never seems to be a good time, we agreed that waiting until after our first pivotal data readout was essential. We are now conducting a rigorous and thoughtful CEO search process, spearheaded by independent directors on our nominating and corporate governance committee, with the assistance of a leading executive search firm.

與任何上市公司一樣，繼任計畫是董事會的首要任務，一年多來我一直在與董事會討論這項過渡的潛在時機。雖然似乎從來沒有一個好時機，但我們一致認為，等到我們第一次讀取關鍵數據之後是必要的。目前，我們正在進行一項嚴格而周到的執行長搜尋流程，由我們提名和公司治理委員會的獨立董事牽頭，並由一家領先的高階主管搜尋公司協助。

The board is fully engaged and intense on finding the right CEO to lead Arvinas into our next chapter and help shape our long-term strategy to create value for shareholders and deliver on our mission to serve patients.

董事會全力以赴，熱切地尋找合適的首席執行官，帶領 Arvinas 邁入新的篇章，並幫助制定我們的長期策略，為股東創造價值，並履行為患者服務的使命。

I'm also honored to continue as chair of the Arvinas board once I step down from the CEO role. For now, our long-term strategy is driven by the imperatives I mentioned above, advancing Vepdeg to launch by Pfizer or another partner, achieving critical data milestones, and efficiently allocating capital.

我也很榮幸能夠在卸任執行長一職後繼續擔任 Arvinas 董事會主席。目前，我們的長期策略是由我上面提到的必要條件驅動的，推動 Vepdeg 由輝瑞或其他合作夥伴推出，實現關鍵數據里程碑，並有效分配資本。

I'll spend a few minutes discussing our vepdeg strategy before turning the call over to Noah and Angela, who will provide updates and discuss upcoming milestones for our clinical programs. Andrew will then provide a financial overview and some thoughts on capital planning.

我將花幾分鐘時間討論我們的 vepdeg 策略，然後將電話轉給 Noah 和 Angela，他們將提供最新資訊並討論我們臨床計畫即將實現的里程碑。然後，安德魯將提供財務概述和一些有關資本規劃的想法。

First, regarding Vepdeg, our collaboration with Pfizer was signed in 2021 with the intention for Vepdeg to be developed as a monotherapy and in combinations across the adjuvant first and second line settings. With that plan, the idea of having 50-50 co-development and commercialization was very attractive. We are now on the threshold of Vepdeg potentially becoming a best-in-class treatment in its first indication, second-line monotherapy treatment in ESR1, ER+/HER2- metastatic breast cancer.

首先，關於 Vepdeg，我們與輝瑞於 2021 年簽署了合作協議，旨在將 Vepdeg 開發為單一療法以及在輔助一線和二線治療中的聯合療法。根據該計劃，50-50 共同開發和商業化的想法非常有吸引力。我們現在正處於 Vepdeg 成為其首個適應症、ESR1、ER+/HER2- 轉移性乳癌二線單藥治療領域最佳治療藥物的門檻。

However, the recent decision to remove the combination pivotal trials from our development plans with Pfizer has created a situation where the 50-50 co-commercialization agreement no longer makes sense and we're actively reworking our collaboration.

然而，我們最近決定將聯合療法關鍵試驗從與輝瑞的開發計劃中刪除，這使得 50-50 的共同商業化協議不再有意義，我們正在積極重新制定合作關係。

Should the negotiations lead to Vepdeg being returned to Arvinas, we are prepared to seek a party to commercialize and further develop Vepdeg. Reaching a positive conclusion for Vepdeg is a critical step in maximizing its value while also allowing us to focus on our promising clinical pipeline.

如果談判的結果是 Vepdeg 歸還給 Arvinas，我們準備尋求一方對 Vepdeg 進行商業化和進一步開發。對 Vepdeg 得出積極的結論是最大化其價值的關鍵一步，同時也使我們能夠專注於我們有前景的臨床管線。

Preclinical data has shown that ARV-102, ARV-393 and ARV-806 are all differentiated from inhibitors and other degraders. With compelling clinical data milestones over the next year, we believe our maturing pipeline will be a significant value driver for the company and our shareholders.

臨床前數據顯示ARV-102、ARV-393和ARV-806均與抑制劑和其他降解劑有所區別。隨著明年臨床數據取得令人矚目的里程碑，我們相信，我們日益成熟的產品線將成為公司和股東的重要價值驅動力。

Taken together, we are advancing a very exciting pipeline and applying our PROTAC technology to new areas in both neuroscience and oncology where we can truly differentiate from other mechanisms of action. Operating from a strong financial position, underpinned by an extended cash runway, efficient capital allocation and a development strategy that unlocks the potential of our platform to bring patients important treatments, we are confident in our path forward and in our ability to maximize value for shareholders and benefits for patients.

總的來說，我們正在推進一個非常令人興奮的管道，並將我們的 PROTAC 技術應用於神經科學和腫瘤學的新領域，在這些領域我們可以真正區別於其他作用機制。我們擁有強大的財務狀況，擁有充足的現金流、高效的資本配置以及釋放平台潛力、為患者帶來重要治療的發展策略，我們對未來充滿信心，並有能力為股東創造最大價值、為患者帶來最大利益。

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

說完這些，我會把電話轉給諾亞。

Thanks, John, and good morning, everyone. Our pipeline continues to progress at a remarkable pace, demonstrating the vast potential of our PROTAC platform. I'll begin with our most advanced neuroscience program, ARV-102.

謝謝，約翰，大家早安。我們的管道繼續以驚人的速度發展，展示了我們的 PROTAC 平台的巨大潛力。我將從我們最先進的神經科學計畫 ARV-102 開始。

We have designed investigational oral PROTAC degraders to cross the blood-brain barrier and selectively degrade, leucine-rich repeat kinase 2, or LRRK2. LRRK2 is a large multi-domain scaffolding kinase that plays a critical role in effective Endolysosomal trafficking.

我們設計了研究性口服 PROTAC 降解劑，以穿過血腦屏障並選擇性降解富亮氨酸重複激酶 2 或 LRRK2。LRRK2 是一種大型多結構域支架激酶，在有效的溶小體運輸中起著關鍵作用。

Unlike traditional small molecule inhibitors that only block LRRK2's kinase activity, LRRK2 degraders eliminate pathologic scaffolding function, GTPase activity and the kinase activity of LRRK2 implicated in this disease.

與僅阻斷 LRRK2 激酶活性的傳統小分子抑制劑不同，LRRK2 降解劑消除了與疾病相關的病理支架功能、GTPase 活性和 LRRK2 激酶活性。

We believe our lead LRRK2 degrader, ARV-102, is particularly well-positioned to be evaluated in two diseases where there are no disease-modifying therapies available. The first is Parkinson's disease, or PD, a disease where increased LRRK2 expression and activity contributes to neurodegeneration and its pathogenesis, making it a rational therapeutic target. And the second is progressive supranuclear palsy, or PSP, a disease where genetic variations in LRRK2 are associated with PSP progression.

我們相信，我們主要的 LRRK2 降解劑 ARV-102 特別適合在兩種尚無疾病改良療法的疾病中進行評估。第一個是帕金森氏症（PD），這種疾病中 LRRK2 表達和活性增加會導致神經退化性變化及其發病機制，使其成為合理的治療目標。第二種是進行性核上性麻痺（PSP），LRRK2 基因變異與 PSP 進展相關的疾病。

Additionally, we have published data associating the tau pathology of PSP with LRRK2-mediated endolysosomal dysfunction, which again makes this a very rational therapeutic target. ARV-102 is the only PROTAC we know of in the clinic to demonstrate deep brain penetration in non-human primates and now blood-brain barrier penetration in humans.

此外，我們也發表了將 PSP 的 tau 病理與 LRRK2 介導的內溶小體功能障礙相關聯的數據，這再次使其成為一個非常合理的治療目標。ARV-102 是我們所知的唯一一種在臨床上能夠證明非人靈長類動物能夠深層滲透腦部並且目前能夠穿透人類血腦屏障的 PROTAC。

As presented at the ADPD Congress, ARV-102 is well-tolerated at single doses up to 200 milligram and at multiple doses up to 80 milligram. No serious adverse events after single and multiple oral doses in healthy volunteers were observed. Single and multiple doses of ARV-102 demonstrated dose-dependent exposure in the central nervous system by Cerebrospinal fluid, or CSF, sampling. This was associated with substantial degradation of LRRK2 protein in the peripheral blood and the CSF and on-target activity with levels of engagement not reported with inhibitors currently in the clinic.

正如在 ADPD 大會上所介紹的那樣，ARV-102 在單劑量高達 200 毫克和多劑量高達 80 毫克時耐受性良好。在健康志願者中單次和多次口服給藥後均未觀察到嚴重不良事件。單劑量和多劑量 ARV-102 透過腦脊髓液 (CSF) 採樣證實在中樞神經系統中呈現劑量依賴性暴露。這與週邊血液和腦脊髓液中 LRRK2 蛋白的大量降解以及靶向活性有關，而這種結合水平目前在臨床上使用的抑制劑尚未報告。

We believe the high levels of target engagement, enhanced potency, and pathway engagement demonstrated with ARV-102 will differentiate it from clinical stage inhibitors, which in preclinical studies have not shown the same ability as ARV-102 to move important biomarkers in the CSF. These PK and PD properties and acceptable safety and tolerability profile support further study of LRRK2 degraders in PD and PSP.

我們相信，ARV-102 所展現出的高水平標靶參與、增強的效力和通路參與將使其有別於臨床階段的抑制劑，後者在臨床前研究中並未表現出與 ARV-102 相同的移動腦脊髓液中重要生物標記的能力。這些 PK 和 PD 特性以及可接受的安全性和耐受性概況支持進一步研究 PD 和 PSP 中的 LRRK2 降解劑。

Dosing of the Phase 1 single ascending dose cohort in patients with Parkinson's disease is complete and we expect to present initial data confirming pathway engagement later this year. We will also initiate multiple dose cohorts in patients with PD in the coming weeks, as well as a trial in PSP in the first half of 2026.

帕金森氏症患者第一階段單次遞增劑量隊列的給藥已經完成，我們預計將在今年稍後提供確認通路參與的初步數據。我們也將在未來幾週內對 PD 患者啟動多劑量組試驗，並在 2026 年上半年對 PSP 患者進行試驗。

In parallel to the advancement of ARV-102, we are making nice progress with ARV-393, our BCL6 degrader, and ARV-806, our KRAS G12D degrader, which entered the clinic in the second quarter. It is too early for me to share clinical results for these exciting new clinical stage assets, but Angela will share some of the compelling preclinical data supporting the advance of both in the clinic.

在 ARV-102 取得進展的同時，我們的 BCL6 降解劑 ARV-393 和 KRAS G12D 降解劑 ARV-806 也取得了良好進展，並於第二季度進入臨床。現在我分享這些令人興奮的新臨床階段資產的臨床結果還為時過早，但安吉拉將分享一些支持這兩項臨床進展的令人信服的臨床前數據。

But first, I would like to provide some regulatory updates regarding Vepdeg. We have submitted the new drug application for vepdeg. This represents another significant first for Arvinas, the first PROTAC degrader to enter clinical trials and have a positive readout in a Phase 3 trial. It's also the first ever new drug application submitted for a PROTAC.

但首先，我想提供一些關於 Vepdeg 的監管更新。我們已經提交了vepdeg的新藥申請。這對 Arvinas 來說又是一個重要的首創，它是第一個進入臨床試驗並在第 3 階段試驗中獲得積極讀數的 PROTAC 降解劑。這也是有史以來第一份提交 PROTAC 的新藥申請。

The NDA was supported by VERITAC-2 data that were presented at the ASCO oral late-breaking session and simultaneously published in the New England Journal of Medicine. The enthusiasm among physicians generated by VERITAC-2 data was very rewarding. Later this year, we plan to present the patient-reported outcomes data from the VERITAC-2 trial. We believe these data disclosures reinforce Vepdeg's profile as a potential best-in-class monotherapy.

該 NDA 得到了 VERITAC-2 數據的支持，這些數據在 ASCO 口頭最新會議上公佈，並同時發表在《新英格蘭醫學雜誌》上。VERITAC-2 數據在醫生中激發的熱情是非常值得的。今年晚些時候，我們計劃展示 VERITAC-2 試驗的患者報告結果數據。我們相信這些數據揭露強化了 Vepdeg 作為潛在的最佳單一療法的形象。

I'll now turn the call over to Angela. Angela?

我現在將電話轉給安琪拉。安吉拉？

Thanks, Noah, and good morning, everyone. ARV-393, our investigational oral PROTAC designed to degrade B-cell lymphoma 6 protein or BCL6 is an exciting asset that demonstrates the power and breadth of our platform.

謝謝，諾亞，大家早安。ARV-393 是我們研究的口服 PROTAC，旨在降解 B 細胞淋巴瘤 6 蛋白或 BCL6，是一項令人興奮的資產，展示了我們平台的強大功能和廣度。

BCL6 is a previously undrug transcription factor, a master regulator of multiple cellular processes during B-cell development, including proliferation, survival, and apoptosis. Altered BCL6 activity has been implicated as an oncogenic driver in several subtypes of non-Hodgkin lymphoma, making it a rational therapeutic target with initial clinical validation emerging.

BCL6 是一種先前未被藥物治療的轉錄因子，是 B 細胞發育過程中多種細胞過程的主要調節器，包括增殖、存活和凋亡。改變的 BCL6 活性被認為是幾種非何杰金氏淋巴瘤亞型的致癌驅動因素，使其成為合理的治療目標，初步臨床驗證正在出現。

PROTAC mediated degradation has the potential to overcome the historically undruggable nature of BCL6. With its iterative activity, ARV-393 potently and rapidly degrades the BCL6 protein, which is critical to overcoming its rapid resynthesis rate and sustaining antitumor activity.

PROTAC 介導的降解有可能克服 BCL6 歷史上無法用藥的性質。ARV-393 憑藉其迭代活性，強效且快速地降解 BCL6 蛋白，這對於克服其快速的再合成率和維持抗腫瘤活性至關重要。

In second quarter of 2025, we presented two sets of preclinical data for ARV-393. First, at the American Association for Cancer Research annual meeting in April, we presented new preclinical data highlighting the therapeutic potential of ARV-393 in combination with standard of care biologics chemotherapy, and small molecule inhibitors targeting cooperative oncogenic drivers. ARV-393 combinations demonstrated increased tumor growth inhibition, including tumor regressions in preclinical models of aggressive B-cell lymphoma.

2025年第二季度，我們公佈了ARV-393的兩組臨床前數據。首先，在四月的美國癌症研究協會年會上，我們展示了新的臨床前數據，強調了 ARV-393 與標準生物製劑化療以及針對合作致癌驅動因素的小分子抑制劑相結合的治療潛力。ARV-393 組合顯示出增強的腫瘤生長抑制，包括侵襲性 B 細胞淋巴瘤臨床前模型中的腫瘤消退。

These data underscore the potential of ARV-393 to become a backbone therapy for development of rational mechanism-informed chemo-free or all oral therapeutic options with the potential to improve patient outcomes and convenience.

這些數據強調了 ARV-393 成為開發合理的機制知情無化療或全口服治療方案的骨幹療法的潛力，並有可能改善患者的治療效果和便利性。

In June, at the European Hematology Association conference, we presented new data demonstrating the potent single agent efficacy of ARV-393 in patient-derived systemic models of angioimmunoblastic T-cell lymphoma and transformed Follicular lymphoma.

6 月份，在歐洲血液學協會會議上，我們展示了新的數據，證明了 ARV-393 在患者來源的血管免疫母細胞 T 細胞淋巴瘤和轉化性濾泡性淋巴瘤系統模型中強大的單一藥物療效。

To our knowledge, these are the first preclinical evidence of an efficacious BCL6 targeted degrader in human models of these diseases. These data highlight the broad utility of ARV-393 across non-Hodgkin lymphoma subtypes with unmet need beyond DLBCL.

據我們所知，這些是針對這些疾病的人類模型中有效的 BCL6 標靶降解劑的第一個臨床前證據。這些數據凸顯了 ARV-393 在非何杰金氏淋巴瘤亞型中的廣泛用途，以及 DLBCL 以外的未滿足需求。

Later this year, we also expect to share preclinical data showing the combinability of ARV-393 with glofitamab, a CD3, CD25-specific antibody and an emerging standard of care for DLBCL that supports our plan to evaluate this combination in an upcoming trial.

今年晚些時候，我們還希望分享臨床前數據，展示 ARV-393 與 glofitamab（一種 CD3、CD25 特異性抗體和 DLBCL 的新興治療標準）的可組合性，這支持我們在即將進行的試驗中評估這種組合的計劃。

We are excited about the potential here given ARV-393's ability to increase CD20 expression. Which provides rationale for the exploration of ARV-393 with CD20 targeted agents and in the context of low or loss of CD20 expression.

鑑於 ARV-393 能夠增加 CD20 表達，我們對這一潛力感到非常興奮。這為探討ARV-393與CD20標靶藥物以及在CD20表達低或缺失的背景下的應用提供了理論基礎。

We also plan to share the initial clinical data with ARV-393 later this year. As you have heard from Noah, I'm pleased to report that we have initiated a phase one clinical trial of ARV-806, our novel PROTAC degrader targeting KRAS G12D. The trial has progressed rapidly through the first patient cohort reflecting strong interest from clinical investigators and underscoring the high unmet need for effective KRAS targeted therapies.

我們也計劃在今年稍後分享 ARV-393 的初步臨床數據。正如您從諾亞那裡聽到的，我很高興地報告，我們已經啟動了 ARV-806 的一期臨床試驗，ARV-806 是我們針對 KRAS G12D 的新型 PROTAC 降解劑。該試驗在首批患者中進展迅速，反映了臨床研究人員的濃厚興趣，並強調了對有效的 KRAS 標靶治療的巨大未滿足需求。

KRAS G12D is a well-characterized oncogenic driver associated with poor prognosis and resistance to standard treatments across major tumor types, including pancreatic, colorectal and non-small cell lung cancer.

KRAS G12D 是一種特徵明確的致癌驅動基因，與胰腺癌、結直腸癌和非小細胞肺癌等主要腫瘤類型的不良預後和對標準治療的抗藥性有關。

ARV-806 has demonstrated compelling preclinical activity with high potency and clear differentiation from both KRAS inhibitors and other degraders currently in the clinic. Notably, because of the catalytic activity of our PROTAC, ARV-806 has shown it can overcome KRAS resynthesis and increased expression, a major clinically relevant emerging mechanism of resistance that existing inhibitors have failed to address.

ARV-806 已證明具有引人注目的臨床前活性和高效力，並且與目前臨床中的 KRAS 抑制劑和其他降解劑有明顯的區別。值得注意的是，由於我們的 PROTAC 的催化活性，ARV-806 已證明它可以克服 KRAS 的再合成和表達增加，這是現有抑制劑無法解決的主要臨床相關的新興抗藥性機制。

Our PROTAC binds to and degrades both the active and inactive forms of KRAS G12D, achieving potent and durable elimination of the target rather than inhibition in all models tested. In preclinical studies, ARV-806 achieved in vitro potency approximately 25 times greater than KRAS inhibitors and 40 times greater than the leading clinical stage degrader, demonstrating strong potential for differentiation from both KRAS inhibitors and degraders currently in the clinic.

我們的 PROTAC 可與 KRAS G12D 的活性形式和非活性形式結合並降解，從而在所有測試模型中實現對目標的強效和持久消除，而不是抑制。在臨床前研究中，ARV-806 的體外效力比 KRAS 抑制劑高出約 25 倍，比領先的臨床階段降解劑高出 40 倍，顯示出與目前臨床中的 KRAS 抑制劑和降解劑有很強的區分潛力。

Furthermore, ARV-806 exhibits dose-dependent, selective, robust antitumor activity culminating in regressions across preclinical models of KRAS G12D mutant cancers. These results highlight the strong therapeutic potential of ARV-806 and support its continued and rapid advancement in the clinic. We look forward to updating you on our clinical progress and anticipate sharing preclinical data from ARV-806 and the first ever data from our oral pan-KRAS degrader program later this year.

此外，ARV-806 表現出劑量依賴性、選擇性、強大的抗腫瘤活性，最終導致 KRAS G12D 突變癌症的臨床前模型消退。這些結果凸顯了ARV-806強大的治療潛力，並支持其在臨床上的持續快速發展。我們期待向您通報我們的臨床進展，並預計在今年稍後分享 ARV-806 的臨床前數據以及我們的口服泛 KRAS 降解劑計畫的首批數據。

With that, I'll turn the call over to Andrew to review our quarterly financial information.

說完這些，我將把電話轉給安德魯來審查我們的季度財務資訊。

Thanks, Angela, and good morning, everyone. I'm pleased to provide financial highlights for the second quarter ended June 30, 2025 and expand on our approach to capital allocation and development strategy. As a reminder, detailed financial results for the second quarter are included in the press release we issued this morning.

謝謝，安琪拉，大家早安。我很高興提供截至 2025 年 6 月 30 日的第二季財務亮點，並詳細說明我們的資本配置和發展策略方法。提醒一下，第二季的詳細財務結果包含在我們今天早上發布的新聞稿中。

During the quarter, we took significant action to reduce costs and increase efficiency across the organization. These actions included a reprioritization and reduction to our research portfolio, as well as a reduction of approximately one-third of our total workforce. When combined with the announced changes to our Vepdeg development plan, our cash runway was extended into the second half of 2028.

本季度，我們採取了重大措施來降低成本並提高整個組織的效率。這些措施包括重新調整和減少我們的研究組合，以及減少約三分之一的員工總數。結合我們宣布的 Vepdeg 發展計畫變更，我們的現金流將延長至 2028 年下半年。

These changes will make us leaner and more efficient as we work towards a promising stretch of catalysts over the next 12 months. As I mentioned previously, the restructuring was focused on reducing internal costs without having an impact on the clinical stage programs that will drive value over the next several years. We will maintain our disciplined and focused approach to capital allocation and our development strategy will be focused on bringing pipeline programs through major clinical inflection points.

這些變化將使我們在未來 12 個月內努力實現一系列有希望的催化劑，從而使我們更加精簡和高效。正如我之前提到的，重組的重點是降低內部成本，同時不會對未來幾年推動價值的臨床階段項目產生影響。我們將保持嚴謹而專注的資本配置方式，我們的發展策略將專注於推動管道專案實現重大臨床轉折點。

With respect to Vepdeg, we anticipate relatively minimal costs for the market in the coming months. Our current agreement with Pfizer includes establishing a go-to-market strategy that will benefit both sides of the partnership. While we continue to believe that Vepdeg is a potentially best-in-class asset, given the changes to the development plan, we have determined that it is no longer viable for us to build out our commercial infrastructure as we had previously planned.

對於 Vepdeg，我們預計未來幾個月市場成本相對較低。我們目前與輝瑞的協議包括制定對雙方都有利的市場進入策略。雖然我們仍然相信 Vepdeg 具有潛在的最佳資產，但考慮到開發計劃的變化，我們已確定按照先前的計劃建造商業基礎設施已不再可行。

As John said earlier, we are in active discussions with Pfizer to rework our collaboration to determine the most efficient way to make this important drug available to patients if approved. Across our pipeline, we have a rich set of capitalists coming up in the next year for both our oncology and neuroscience portfolios. With our strong balance sheet, we have sufficient resources to move these exciting programs forward to key value inflection points.

正如約翰之前所說，我們正在與輝瑞公司積極討論重新制定合作方案，以確定在獲得批准後讓患者獲得這種重要藥物的最有效方法。在我們的整個研發管線中，明年我們將為我們的腫瘤學和神經科學投資組合引入一批富有的資本家。憑藉我們強大的資產負債表，我們擁有足夠的資源將這些令人興奮的項目推向關鍵的價值轉折點。

We've seen great clinical success here in the past, both in the development of Vepdeg in partnership with Pfizer and in the platform validating out-licensing of luxdegalutamide to Novartis. We are excited to continue development of the next generation of Intravenous PROTAC.

我們過去曾在這裡看到巨大的臨床成功，無論是與輝瑞合作開發 Vepdeg，還是在驗證平台將 luxdegalutamide 授權給諾華。我們很高興繼續開發下一代靜脈注射 PROTAC。

I'll now briefly touch on some key financial highlights for the second quarter of 2025. At the end of the second quarter, we had approximately $861.2 million in cash, cash equivalents, and marketable securities on the balance sheet compared with $1.04 billion as of December 31, 2024.

現在我將簡要介紹 2025 年第二季的一些關鍵財務亮點。截至第二季末，我們的資產負債表上擁有約 8.612 億美元的現金、現金等價物和有價證券，而截至 2024 年 12 月 31 日為 10.4 億美元。

Revenue for the three months and the June 30, 2025 totaled $22.4 million compared to $76.5 million for the three months and the June 30, 2024. The decrease of $54.1 million was primarily driven by $45.6 million of decreased revenue from the Novartis license agreement and the Novartis asset agreement, both of which were entered into during the three months and the June 30, 2024 and were completed by December 31, 2024 as the technology transfer of our ongoing planned clinical trials of luxdegalutamide were transitioned to Novartis.

截至 2025 年 6 月 30 日的三個月總收入為 2,240 萬美元，而截至 2024 年 6 月 30 日的三個月總收入為 7,650 萬美元。減少 5,410 萬美元主要是由於諾華許可協議和諾華資產協議的收入減少了 4,560 萬美元，這兩項協議均於本季度及 2024 年 6 月 30 日簽訂，並於 2024 年 12 月 31 日完成，因為我們正在進行的計劃中的 luxdegalam 臨床轉移

Revenue from the Vepdeg collaboration agreement with Pfizer decreased $6.8 million related to the removal of 2 Phase 3 trials from the development plan during the first quarter of 2025. General and administrative expenses were $25.3 million in the second quarter compared to $31.3 million for the same period of 2024.

Vepdeg 與輝瑞的合作協議收入減少了 680 萬美元，因為 2025 年第一季從開發計畫中刪除了 2 個 3 期試驗。第二季的一般及行政費用為 2,530 萬美元，而 2024 年同期為 3,130 萬美元。

The decrease of $6 million was primarily driven by a decrease in personnel and infrastructure related costs of $4.8 million and professional fees of $2.2 million, partially offset by an increase in costs related to developing our commercial operations of $1.1 million.

減少 600 萬美元主要是由於人員和基礎設施相關成本減少 480 萬美元以及專業費用減少 220 萬美元，但部分被與開發商業運營相關的成本增加 110 萬美元所抵消。

Research and development expenses were $68.6 million in the second quarter compared to $93.7 million for the same period of 2024. The decrease of $25.1 million was primarily driven by a decrease in the Vepdeg program of $10 million, a decrease in the Vepdeg and luxdegalutamide program of $9.5 million and decreases in personnel expenses and non-program specific expenses of $10.3 million, offset by an increase in the LRRK2 program of $2.1 million and the KRAS program of $1.5 million.

第二季研發費用為 6,860 萬美元，而 2024 年同期為 9,370 萬美元。減少 2,510 萬美元主要是由於 Vepdeg 項目減少 1,000 萬美元、Vepdeg 和 luxdegalutamide 項目減少 950 萬美元以及人員費用和非項目特定費用減少 1,030 萬美元，但 LRRK2 項目增加 210 萬美元和 KRAS 項目增加了 150 萬美元。

Restructuring costs in the quarter amounted to $7.4 million of cash expenses, consisting primarily of employee related expenses, which were offset by a reversal of non-cash employee stock compensation and bonus expenses of $6.4 million. The announced restructuring is now complete and the full benefit in terms of cost reduction will be seen starting in the third quarter.

本季重組成本為 740 萬美元的現金支出，主要包括員工相關費用，但被 640 萬美元的非現金員工股票薪酬和獎金支出的沖銷所抵消。宣布的重組現已完成，成本削減的全部效益將從第三季開始顯現。

We are maintaining our prior cash runway guidance into the second half of 2028. We are focused on staying disciplined by investing in areas that will maximize shareholder value as we move towards important catalysts in the coming months.

我們將維持先前的現金流預測至 2028 年下半年。在接下來的幾個月裡，我們將朝著重要的催化劑邁進，專注於保持紀律，投資於能夠最大化股東價值的領域。

In addition, we will continue to look at ways to reduce costs and increase efficiency while continuing to focus on our goals of progressing our very promising early pipeline.

此外，我們將繼續尋找降低成本和提高效率的方法，同時繼續專注於推進我們非常有前景的早期管道的目標。

With that, I'll turn the call over to John for closing remarks. John?

說完這些，我會把電話交給約翰來做最後的發言。約翰？

Thanks, Andrew. As you've heard, we've seen multiple near-term milestones across our clinical development and regulatory efforts. Our programs offer a rich set of catalysts over the next 12 months, including clinical data from ARV-102 and ARV-393 and potentially initial clinical data from ARV-806 and of course, the potential for the first ever approval of a PROTAC.

謝謝，安德魯。正如您所聽到的，我們在臨床開發和監管工作中看到了多個近期里程碑。我們的計畫將在未來 12 個月內提供一系列豐富的催化劑，包括 ARV-102 和 ARV-393 的臨床數據以及 ARV-806 的潛在初步臨床數據，當然還有 PROTAC 首次獲得批准的可能性。

During this time, we will also advance ARV-102 in its ongoing trial in patients with Parkinson's and initiate a trial with ARV-102 in Progressive Supranuclear Palsy.

在此期間，我們也將推進 ARV-102 在帕金森氏症患者中的持續試驗，並啟動 ARV-102 在進行性核上性麻痺的試驗。

Before opening the call for Q&A, I'd like to reiterate our confidence in our near-term plan to create value for patients and shareholders. This includes advancing Vepdeg to launch by Pfizer or another party, achieving the important data milestones I just described and allocating capital to ensure we reach those milestones efficiently. While we made sweeping changes in the first half of 2025, we are always evaluating the best ways to create shareholder value.

在開始問答環節之前，我想重申我們對為患者和股東創造價值的近期計劃的信心。這包括推動輝瑞或其他方推出 Vepdeg，實現我剛才描述的重要資料里程碑，並分配資金以確保我們有效地實現這些里程碑。雖然我們在 2025 年上半年做出了徹底的改變，但我們始終在評估創造股東價值的最佳方式。

With that, I'll turn the call over to Jeff to begin the Q&A portion of the call. Jeff?

說完這些，我會把電話轉給傑夫，開始電話的問答部分。傑夫？

Thanks, John. Operator, can you please open the queue? Thank you.

謝謝，約翰。接線員，您可以開啟隊列嗎？謝謝。

(Operator Instructions) Ed Tenthoff, Piper Sandler.

（操作員指示）Ed Tenthoff，Piper Sandler。

Thank you very much. Andrew, just one quick housekeeping. The restructuring chart that you mentioned, was that primarily in the GNA line? And then I have a pipeline question for you guys.

非常感謝。安德魯，只需做一點簡單的家事。您提到的重組圖表主要在 GNA 線路嗎？然後我有一個管道問題想問你們。

Yeah, hey, Ted. No, it was actually split up between research and development and GNA. And indeed, most of the stock-based comments would have been recorded in the R&D section.

是的，嘿，泰德。不，它實際上是由研發部門和 GNA 分開的。事實上，大多數以股票為基礎的評論都會被記錄在研發部分。

Great, that makes sense. Awesome. So can you give us a little bit more color on what to expect from 102 data this year? I know that we've still got more to hear about the healthy volunteers for the multiple attending cohorts. But what should we expect from the single attending doses from Parkinson's patients? Thanks.

太好了，這很有道理。驚人的。那麼，您能否向我們詳細介紹今年 102 數據的預期情況？我知道，我們還需要聽到更多關於多個參加活動的團體的健康志工的資訊。但是，我們對帕金森氏症患者的單次治療劑量有何期待？謝謝。

Thanks, Ted. The trials were going well. And I'll hand over to Noah to give you some of the details.

謝謝，泰德。試驗進展順利。我將把時間交給諾亞，讓他向大家介紹一些細節。

Hi, Ted. Thanks for the question. Yeah, good morning. So as you said, I think you summed it up. We expect that a conference, an upcoming conference, to summarize the full healthy volunteer data set that we assembled.

你好，泰德。謝謝你的提問。是的，早安。正如你所說，我認為你總結得很好。我們希望即將召開的會議能總結我們收集的完整健康志工資料集。

And in addition to that, if things work out, we'll be able to present some [SADs] data, which will, I'm not going to go into the details of what we'll present exactly, but should be able to signal that we're on track with when you compare it to the healthy volunteer funds.

除此之外，如果一切順利的話，我們將能夠提供一些 [SAD] 數據，我不會詳細介紹我們將要提供的內容，但當你將其與健康志願者基金進行比較時，應該能夠表明我們正走在正確的軌道上。

Great. All right, looking forward to that and excited about the emerging pipeline.

偉大的。好的，我很期待這一點，並對新興的管道感到興奮。

Jonathan Miller, Evercore ISI

喬納森·米勒，Evercore ISI

Hi, guys. Thanks so much for taking my question and congrats on, as I should say, congrats is the wrong word, but good job on getting your restructuring going. I'd love to follow up on that 102 question.

嗨，大家好。非常感謝您回答我的問題，並祝賀您，正如我應該說的，“祝賀”這個詞並不恰當，但您成功地完成了重組工作。我很樂意跟進這 102 個問題。

Maybe it's a little too early to say exactly what you'll give us in patients this year, but maybe could you talk a little bit about what you hope to see in a more full patient data set? What are your bars for success in patients that can give you confidence going into later on an efficacy readout?

也許現在說您今年將在患者身上提供什麼結果還為時過早，但您能否談談您希望在更完整的患者數據集中看到什麼？您對患者的成功有何標準，可以讓您對日後的療效讀數充滿信心？

Thanks, Jonathan. Noah?

謝謝，喬納森。諾亞？

Sure. Jonathan, so thanks for the interest here. I think we've outlined that we expect to start a Parkinson's disease multiple-dose study over the course of the next month or so. While I can't really comment about when those data will be presented, the idea is that we're enrolling patients with the insights gained from healthy volunteers regarding a dose range, and that will allow us to establish in patients who have higher baseline LRRK2 levels, and also patients that are more elderly, because healthy volunteers tend to be very young, like a little more than college age and Parkinson's disease are going to be more than twice that on average, I suspect.

當然。喬納森，非常感謝你的關注。我想我們已經概述了我們預計將在下個月左右開始帕金森氏症多劑量研究。雖然我無法評論這些數據何時會公佈，但我們的想法是，我們會根據從健康志願者那裡獲得的關於劑量範圍的見解來招募患者，這將使我們能夠在基線 LRRK2 水平較高的患者以及年齡較大的患者中建立模型，因為健康志願者往往非常年輕，比如剛過大學年齡，而我懷疑帕金森病患者的平均年齡將是這個數字的兩倍多。

So we'll be able to demonstrate that we have the same exciting results that we previously reported in healthy volunteers of orally bioavailable brain penetrant PROTAC, and the ability to move biomarkers, which also now we have much more insight into than we did many months ago, right?

因此，我們將能夠證明，我們獲得了與之前在健康志願者中報告的口服生物可利用腦滲透劑 PROTAC 相同的令人興奮的結果，以及移動生物標誌物的能力，現在我們對此的了解比幾個月前要多得多，對嗎？

So we continue to do work to understand what are the best biomarkers that we can track and are going to be most predictive of an impact in the endolysomal trafficking and neuroinflammation that is characteristic of Parkinson's disease and PSP. And so we expect we can start tracking this in real patients rather than the healthy volunteers.

因此，我們將繼續努力，了解我們可以追蹤的最佳生物標記是什麼，這些生物標記將最能預測帕金森氏症和 PSP 特有的內溶體運輸和神經發炎的影響。因此，我們希望能夠在真實患者而不是健康志願者身上開始追蹤這一點。

Awesome. Thank you. And then maybe on the BCL6, you mentioned in the press release in this call, the glofitamab combination results to present this year, but you've presented on a number of different combos preclinically. Can you give us a sense of where you might want to start in patients? What combo therapies you might want to start with?

驚人的。謝謝。然後也許關於 BCL6，您在本次電話會議的新聞稿中提到，glofitamab 組合的結果將於今年公佈，但您已經在臨床前展示了許多不同的組合。您能否告訴我們您可能想從哪裡開始對患者進行治療？您可能想從哪些組合療法開始？

I think we've been, I've been signaling in conversations, you know, we can certainly speak clearly -- very directly about it here, that our interest for BCL6 is to learn what -- find the dose in monotherapy. It's something we're obligated to do, but the real interest is moving forward in combinations, in particular in DLBCL. And I think it should be clear to everyone that bispecifics and second line plus DLBCL, and maybe eventually in not that far in the future, in first line are important drugs in that space.

我想我們已經在談話中暗示過，你知道，我們當然可以非常直接地清楚地談論它，我們對 BCL6 的興趣在於了解——找到單一療法的劑量。這是我們有義務去做的事情，但真正感興趣的是聯合治療，特別是在 DLBCL 領域。我認為每個人都應該清楚，雙特異性抗體和二線加 DLBCL，甚至可能在不久的將來，一線藥物都是該領域的重要藥物。

So if we can combine with bispecifics in human beings and get results that look anything like what we've seen preclinically, we think we're well positioned for a new modality of therapy with a real orthogonal approach that enhances the activity of the bispecifics.

因此，如果我們能夠將其與人類的雙特異性抗體結合起來，並獲得與臨床前看到的結果相似的結果，我們認為我們已做好準備，採用真正的正交方法開發一種新的治療方式，以增強雙特異性抗體的活性。

And remember, one of the great combination properties here is that we recognize that our ARV-393 can increase the expression of CD20, which could potentially make the bispecifics even more active. And on top of that -- we've been reporting out the great potency with our drugs, that if that translates into the clinic, then that gives us a great competitive advantage against the only other degrader that's in the clinic currently.

請記住，這裡的一大組合特性是，我們認識到我們的 ARV-393 可以增加 CD20 的表達，這可能會使雙特異性更加活躍。最重要的是，我們一直在報導我們的藥物具有強大的效力，如果這種效力能夠轉化為臨床應用，那麼這將使我們在與目前臨床中唯一的其他降解劑的競爭中佔據巨大的優勢。

Thanks so much.

非常感謝。

Derek Archila, Wells Fargo.

德里克·阿奇拉，富國銀行。

Good morning. This is Carl calling for Derek. Thank you for the question. So I guess for ARV-102, could you talk a little bit more on the elevated blood to level in PD patients? How much should we expect and how to maybe feel confident that similar more than 50% degradation can be achieved in CSF?

早安.這是卡爾呼叫德里克。謝謝你的提問。因此我想對於 ARV-102，您能否再多談談 PD 患者血液水平升高的情況？我們應該期待多少以及如何才能確信 CSF 可以實現類似的 50% 以上的降解？

And then on the next deck, the label potentially, could you talk about maybe the base case what could be some potential differentiations you could expect for your competitors? Thank you so much.

然後在下一個平台上，標籤可能，您能否談論一下基本情況，您可以預期您的競爭對手會有哪些潛在的差異？太感謝了。

I think I captured the second question with vepdeg, but there was a lot of cracking in the transmission to the first question. Did anyone here catch that?

我認為我已經用 vepdeg 捕獲了第二個問題，但是在傳輸到第一個問題時出現了很多破解。這裡有人注意到了嗎？

Yeah, could you maybe just repeat the first question?

是的，您能重複第一個問題嗎？

Yeah, of course.

是的，當然。

Just the first. Sorry about that.

只是第一個。很抱歉。

Okay. So for the ARV-102, I think the question is the elevated block to level in PD patients. Could you talk about the expectation of the elevation and how to feel confident that more than 50% degradation in CSF can be achieved?

好的。因此對於 ARV-102，我認為問題在於 PD 患者的阻斷程度是否升高。您能否談談對升高的預期以及如何確信可以實現 CSF 超過 50% 的降解？

Yeah, so I think it's a great question. So fundamentally, I think it's been established by external sources that there's increased LRKK2 protein expression in the brain and in the CSF of patients with Parkinson's disease. In our own hands, we've already seen in the SAD that there are higher baseline levels of Parkinson's, LRKK2, than we observed in the healthy volunteers. So that's already kind of consistent, but not a surprise to us at all. That was the expectation.

是的，我認為這是一個很好的問題。因此從根本上來說，我認為外部來源已經證實帕金森氏症患者的大腦和腦脊髓液中 LRKK2 蛋白表達增加。在我們自己的研究中，我們已經看到 SAD 患者的帕金森氏症 LRKK2 基線水平高於健康志願者的水平。所以這已經是一致的了，但對我們來說一點也不意外。這就是我們所期望的。

In terms of one of the great properties of the degrader that I think differentiates it beautifully from an inhibitor is that we've already established in the healthy volunteers that we can get really good target engagement in the brain, right?

就降解劑的一大特性而言，我認為它與抑制劑的完美區別在於，我們已經在健康志願者身上證實，我們可以在大腦中獲得非常好的目標參與度，對嗎？

And we know that the inhibitors just don't do that well, right? They're only achieving 30% or so inhibition in the brain. They're not -- we know preclinically, they're not reaching deep brain regions as effectively as our degrader can. So we're getting higher engagement. And because we have a degrader here, which has that iterative property that at even lower exposures, you get continued degradation of the target. We think that we should be well poised to reduce LRKK2 levels. That's the underlying premise that's been borne out in preclinical models. We've shown it in healthy volunteers. And now we think we can confirm it in the multiple doses in Parkinson's disease patients.

我們知道抑制劑的效果不太好，對吧？它們僅實現了大腦中 30% 左右的抑制。它們不是——我們在臨床前就知道，它們不能像我們的降解劑那樣有效地到達大腦深層區域。因此我們的參與度更高了。因為我們這裡有一個降級器，它具有迭代屬性，即使在較低的曝光下，目標也會持續降級。我們認為我們應該做好降低 LRKK2 水平的準備。這是臨床前模型證實的基本前提。我們已經在健康志工身上證明了這一點。現在我們認為我們可以透過對帕金森氏症患者進行多劑量試驗來證實這一點。

Regarding the second question, I think the question was, what differentiates us essentially with our depth data from competitors in the space? And more or less, it comes down to efficacy, the better PFS that's been seen when compared to Fulvestrant control, monotherapy control, which in our hands, we're talking about three months improvement, which other drugs really haven't achieved.

關於第二個問題，我認為問題是，我們的深度數據與該領域的競爭對手有何本質差異？或多或少，這取決於療效，與氟維司群對照、單一療法對照相比，PFS 更好，在我們手中，我們談論的是三個月的改善，而其他藥物實際上還沒有達到這一點。

On top of that, we have, we're leaning into some PRO data that you'll see soon that show that the patients experienced the drug very well. Certainly the adverse event profile is more attractive, which is to say that there's a lot of GI toxicity seen with other agents in this space. We have reported half or even 33% of that when you compare to different drugs. And I think that that combination of benefit risk really stands out for PROTAC when compared to other agents.

除此之外，我們正在研究一些 PRO 數據，您很快就會看到這些數據表明患者對該藥物的體驗非常好。當然，不良事件概況更具吸引力，也就是說，該領域的其他藥物存在著許多胃腸道毒性。與其他藥物相比，我們報告的比例只有一半甚至 33%。我認為，與其他藥物相比，PROTAC 的效益風險組合確實非常突出。

Thank you.

謝謝。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi, good morning. Thanks for taking my questions. I maybe wanted to focus on some commercial questions. So as you think about Baptec and the upcoming launch, you're obviously bullish about its place potentially in monotherapy, but you also talked about needing to be careful about how you're prepping for the launch. So how does this work in terms of setting up a sales force? When do you start prepping for that? How has that plan changed relative to what you would have planned for before?

嗨，早安。感謝您回答我的問題。我可能想關註一些商業問題。因此，當您考慮 Baptec 和即將推出的產品時，您顯然對其在單一療法中的潛在地位持樂觀態度，但您也談到需要謹慎準備產品發布。那麼，就建立銷售團隊而言，這是如何運作的呢？你什麼時候開始準備？與您之前的計劃相比，該計劃有何變化？

And then secondly, if Pfizer returns rights for the program to the company, would there be a gap in between when Pfizer returned the rights and when you'd be able to secure a new partner? Or are you kind of in process now for seeking a potential replacement should Pfizer return those rights?

其次，如果輝瑞將該專案的權利歸還給公司，那麼輝瑞歸還權利和你們找到新合作夥伴之間是否存在差距？或者，如果輝瑞公司歸還這些權利，您是否正在尋求潛在的替代者？

Thanks.

謝謝。

Yeah, no, thank you for the question. Yeah, so in the second part, we'll talk about first, clearly we're in negotiation with Pfizer right now. The original deal that we signed in '21 was a 50-50 co-development, co-commercialization, very attractive deal at the time.

是的，不，謝謝你的提問。是的，所以在第二部分中，我們將首先討論，顯然我們現在正在與輝瑞進行談判。我們在 1921 年簽署的原始協議是 50-50 的共同開發、共同商業化，當時非常有吸引力。

We had plans for doing second line monotherapy, first line, I needed an (inaudible). And that would have been a very significant market and a very significant opportunity to share 50-50. With the decision not to go forward with first line or the second line combo, it puts us into a position where Ben, at the moment, is only focused on second line monotherapy.

我們計劃進行二線單藥治療，第一線治療，我需要（聽不清楚）。這本來是一個非常重要的市場，也是一個很重要的 50-50 分成機會。由於決定不繼續進行一線或二線組合治療，我們目前處於這樣的境地：本只能專注於二線單一療法。

So a smaller market really doesn't move the dial for Pfizer in terms of 50-50 and not particularly attractive for our events either. So the dialogue we've been having actively with Pfizer is about how we redo the collaboration so that either they get more of the economics or we get more of the economics. In the scenario where potentially we get the asset back, our plan is clear that we would immediately look to find the next partner that would help to develop them and launch them.

因此，就 50-50 而言，較小的市場實際上不會對輝瑞產生影響，而且對我們的活動也沒有特別的吸引力。因此，我們一直在與輝瑞積極對話，討論如何重新開展合作，以便他們獲得更多的經濟利益，或者我們獲得更多的經濟利益。在我們有可能收回資產的情況下，我們的計劃很明確，我們會立即尋找下一個能夠幫助我們開發和啟動它們的合作夥伴。

Which goes back to the first question, which is, as we stated, we are really not building out a sales force at all. Right now, we're focused on, first of all, getting vepdeg approved and also getting launch ready, which is a relatively minimal amount of money that we're spending between now and the end of the year.

這又回到第一個問題，正如我們所說，我們實際上根本沒有建立銷售團隊。現在，我們首先關注的是獲得 vepdeg 批准並做好發射準備，這是我們從現在到年底花費的相對較少的資金。

So the idea would be that with that launch readiness, if we got the asset back, we'd run an active process and be in a position for another company to take on the development and launch of that fairly rapidly. So we're hoping there wouldn't be a particular gap.

因此，我們的想法是，在做好發布準備的情況下，如果我們收回資產，我們將運行一個積極的流程，並讓另一家公司能夠相當迅速地承擔開發和發布工作。所以我們希望不會有特別的差距。

Okay, but as of today, could there be a gap between when it got approved and when it launched if you are not able to secure the right returns?

好的，但是截至今天，如果您無法獲得正確的回報，那麼在獲得批准和推出之間是否存在差距？

No.

不。

Okay.

好的。

Oh, sorry, say the last bit again. Say the last bit of the question, sorry.

哦，不好意思，再說最後一句。把問題說最後一點，抱歉。

I just wanted to clarify whether there would be a gap in the launch if you wouldn't find a suitable partner in time once it's approved.

我只是想澄清一下，如果在專案獲得批准後無法及時找到合適的合作夥伴，那麼專案啟動是否會出現差距。

So yeah, you said the suitable partner. So at the moment, the plan is there'd be no gap between getting approval, ideally having a partner in place or having Pfizer launch. There'd be no gap at all. I think your question there is if you get the asset back and you don't get a partner -- then yeah, we'd be taking stock of that. Our plan is that we'd find a partner.

是的，您說的是合適的伴侶。因此，目前的計劃是，獲得批准、理想情況下找到合作夥伴或輝瑞公司推出產品之間不會存在差距。根本不會有任何縫隙。我認為你的問題是，如果你收回資產而沒有找到合作夥伴——那麼是的，我們會對此進行評估。我們的計劃是尋找合作夥伴。

Andrew Berens, Leerink Partners.

安德魯貝倫斯，Leerink Partners。

Hi, everyone. This is Amanda on for Andy. We wanted to get your thoughts on the recent readout from the Phase 3 trial evaluating and second line HR positive breast cancer and patients that don't have a PIK3CA mutation, which then would include some ESR1 mutant patients.

大家好。這是 Amanda 為 Andy 主持的節目。我們想聽聽您對最近進行的 3 期試驗結果的看法，該試驗評估了二線 HR 陽性乳癌和沒有 PIK3CA 突變的患者，其中包括一些 ESR1 突變患者。

And we're wondering how does this change or if this changes your outlook for second line ESR1 mutation patients. And if you would ever consider a combination with (inaudible) to address a broader population. Thank you.

我們想知道這會帶來什麼變化，或者這是否會改變您對二線 ESR1 突變患者的前景。您是否考慮過與（聽不清楚）相結合來滿足更廣泛的人群的需求。謝謝。

Thanks for the question. Noah?

謝謝你的提問。諾亞？

Sure. Yeah, so we wouldn't, we really are not surprised by the result. We recognize the opportunity for PIK3 mutation directed drugs to in breast cancer. There is overlap as you had suggested between ESR1 mutations and PIK3CA.

當然。是的，所以我們不會，我們對結果確實不感到驚訝。我們認識到 PIK3 突變導向藥物在治療乳癌方面的機會。正如您所說，ESR1 突變和 PIK3CA 之間存在重疊。

So the question comes down to, whether it's in our modeling and overall where -- my impression is that it will have little impact on the modeling. I could turn it over to my colleague, Alex from commercial to offer further comments. But part of your question was whether we would develop it with an agent like that. And the answer to that is someone may, but we won't because we've already established that we're not doing further development on the drug, initiating new studies and combinations. And it would be something that should be very much of interest to another company. We've already scouted that out, but it's not something we'll be in the market.

所以問題歸結為，它是否存在於我們的建模中以及總體上在哪裡——我的印像是它對建模的影響很小。我可以把它交給我的同事、商業部門的亞歷克斯來提供進一步的評論。但你的問題之一是我們是否會與這樣的代理商合作開發它。答案是，有人可能會這麼做，但我們不會，因為我們已經確定我們不會對該藥物進行進一步開發，也不會啟動新的研究和組合。這應該會引起其他公司的極大興趣。我們已經對此進行了調查，但我們不會將其推向市場。

Li Watsek, Cantor Fitzgerald

李沃特塞克，康托費茲傑拉

Hey, good morning, guys. Thank you for taking our questions and nice progress on the pipeline. I guess for Vepdeg and the submission sounds like, the PDUFA date very soon. Should we anticipate priority review here and any guidance on your part for the global filing strategy? Do you need maybe to wait for more Mature OS data?

嘿，大家早安。感謝您回答我們的問題，管道方面取得了良好的進展。我猜對於 Vepdeg 和提交來說，PDUFA 日期聽起來很快。我們是否應該預期這裡的優先審查以及您對全球申請策略的任何指導？您是否需要等待更多成熟的作業系統資料？

Yeah, but the second part of that question, I'll hand over to Noah. The first part, yeah, we're still awaiting details from the FDA. And as soon as we get that information, we'll pass that on. So we don't have the PDUFA date yet. Noah, do you want to tackle that second part of the question?

是的，但是這個問題的第二部分，我將交給諾亞。第一部分，是的，我們仍在等待 FDA 的詳細資訊。一旦我們獲得該訊息，我們就會將其傳遞出去。所以我們還沒有 PDUFA 日期。諾亞，你想解決這個問題的第二部分嗎？

Yeah, what we've shared, what we've offered guidance to is our filing of the NDA in the US. And obviously, we're waiting on feedback regarding PDUFA date. But regarding global strategy, we haven't offered guidance on that yet. So I think it would be premature to.

是的，我們所分享的、我們所提供的指導是我們在美國提交的保密協議 (NDA)。顯然，我們正在等待有關 PDUFA 日期的回饋。但關於全球策略，我們尚未提供指導。所以我認為現在下結論還太早。

Okay. And then, in terms of finding maybe a potential new partner for Vepdeg in the case that you got the molecule back. Can you elaborate some of the considerations that you prioritize? What's important for you guys in terms of maximizing the value?

好的。然後，如果您取回分子，也許可以為 Vepdeg 找到一個潛在的新合作夥伴。能詳細說明一下您優先考慮的一些因素嗎？對你們來說，在價值最大化方面什麼最重要？

Yeah, great question. I mean, clearly, we believe that Vepdeg is an important drug. We believe it has a lot of value. Because of the partnership we're in with Pfizer and decisions have been made, maximizing that value is going to be somewhat difficult. So that's why we're in discussion with Pfizer about changing the nature of the collaboration.

是的，很好的問題。我的意思是，我們顯然認為 Vepdeg 是一種重要的藥物。我們相信它具有很大的價值。由於我們與輝瑞公司的合作關係以及已經做出的決定，要最大化這一價值將會有些困難。這就是我們與輝瑞公司討論改變合作性質的原因。

And ideally, as I said, either Pfizer or should go forward with the asset more kind of solar economics. And in the scenario where maybe we get the compound back, yes, we'll be looking to partner. Ideally, a partner that does have the kind of the zeal and interest to develop the asset further, both from the US and the global setting.

理想情況下，正如我所說，輝瑞公司應該繼續推動資產多元化的太陽能經濟。在我們可能收回化合物的情況下，是的，我們會尋求合作夥伴。理想情況下，合作夥伴確實有熱情和興趣進一步開發資產，無論是從美國還是從全球角度。

Our involvement in that, I think, would be relatively minimal in terms of development. Our view is that we want Vepdeg in the hands of a partner, be it Pfizer or another company, that really takes the compound forward, launches it, and progresses it with further development.

我認為，從發展角度來看，我們對此的參與相對較少。我們的觀點是，我們希望 Vepdeg 能夠落到合作夥伴手中，無論是輝瑞還是其他公司，能夠真正推動該化合物的發展、將其推出市場，並進一步推進其開發。

Akash Tewari, Jeffries.

阿卡什·特瓦里，杰弗里斯。

Hey, this is Manoj on for Akash. Thanks for taking our question. What are your expectations around the Denali LRRK2 data in the first half of next year? And if that trial fails or doesn't meet expectations, what signals from that study would you be looking for to give confidence for your own degrader program? Thanks.

嘿，我是 Akash 的 Manoj。感謝您回答我們的問題。您對明年上半年 Denali LRRK2 資料有何預期？如果該試驗失敗或未達到預期，您會從該研究中尋找哪些訊號來為您自己的降解程序提供信心？謝謝。

Yes, thanks for the question. If the question was, you know, expectations for the Denali program this year, I think it's a fantastic question. We think that LRRK2 is an outstanding target. And I think the entire key opinion leader community would agree with us on that.

是的，謝謝你的提問。如果問題是對今年 Denali 計劃的期望，我認為這是一個非常棒的問題。我們認為 LRRK2 是一個出色的目標。我認為整個關鍵意見領袖群體都會同意我們的觀點。

The question is, what is the best drug to address that target? And so we see some virtue in an inhibitor, but it has challenges. And I outlined that earlier, that the inhibitor doesn't, it doesn't seem to penetrate the brain as deeply as, let's say, our degrader.

問題是，針對該目標的最佳藥物是什麼？因此，我們看到了抑制劑的一些優點，但它也存在挑戰。我之前概述過，抑制劑似乎不能像我們的降解劑那樣深入大腦。

And on top of it, it doesn't necessarily engage its target as effectively. We have a broader engagement. Not only are we binding it and degrading it, we're eliminating, because of that degradation, the LRRK2 kinase activity, the GTPase activity, gap holding function.

最重要的是，它不一定能有效地打擊目標。我們的參與範圍更加廣泛。我們不僅結合它並降解它，而且由於這種降解，我們還消除了 LRRK2 激酶活性、GTPase 活性和間隙保持功能。

So all of those features make a degrader more attractive than inhibitor. So we think that they may succeed. We know they have the right target. And we're looking forward to learning from their results, learning if there's something about patient selection that could be incorporated and overall, whatever signals can come out of their trial.

因此，所有這些特性使得降解劑比抑制劑更具吸引力。所以我們認為他們可能會成功。我們知道他們的目標是正確的。我們期待從他們的研究結果中學習，了解是否可以納入有關患者選擇的內容，以及總體而言，他們的試驗可以產生什麼訊號。

Evan Seigerman, BMO Capital Markets.

艾文‧塞格曼 (Evan Seigerman)，蒙特婁銀行資本市場。

Hi there. This is Connor McKay on Evan, and thanks for taking our question. We just had a quick one on the submission of VERITAC. Given the current environment in FDA, we were just wondering if you'd be willing to characterize your recent interactions with the agency and maybe comment on level of alignment there.

你好呀。我是 Evan 的 Connor McKay，感謝您回答我們的問題。我們剛剛就 VERITAC 的提交進行了快速討論。鑑於 FDA 的當前環境，我們只是想知道您是否願意描述您最近與該機構的互動，並評論那裡的協調程度。

And then just one quick follow-up on ARV-806. Would you be able to share a little bit more on how you're thinking about positioning this asset versus the pan-KRAS agent you mentioned today? Thank you.

然後對 ARV-806 進行一次快速跟進。您能否進一步分享一下，您如何看待這種資產與您今天提到的泛 KRAS 藥物的定位？謝謝。

Yeah, thanks for the question. The second one, I'll hand over to Noah and Angela. The first one, I'd have to say our whole process with the FDA has gone very smoothly. The interactions have been excellent. Their timing in terms of getting back to us has been really good.

是的，謝謝你的提問。第二個，我將交給諾亞和安琪拉。首先，我必須說我們與 FDA 的整個流程非常順利。互動非常順暢。他們回覆我們的時機非常好。

So even though we know there's lots of pressures on the FDA and it could impact timelines, we haven't seen that yet with our interactions on VERITAC, which is a really good positive thing for us. Noah?

因此，儘管我們知道 FDA 面臨很大壓力，並且這可能會影響時間表，但我們在與 VERITAC 的互動中還沒有看到這種情況，這對我們來說確實是一件好事。諾亞？

Regarding 806, I'll make some comments about clinical and I'll turn it when I'm done to Angela who may have some comments about some of that interesting differentiation clinically. So this drug entered the clinic a little faster than we expected because of great efficiencies at the team level.

關於 806，我將對臨床做出一些評論，完成後我將把它交給 Angela，她可能會對臨床上的一些有趣的區分發表一些評論。因此，由於團隊層面的高效，這種藥物進入臨床的速度比我們預期的要快一些。

Then what we noticed is that there is tremendous appetite for drugs like ours in this space because our cohorts are in demand. So we're advancing through early dose escalation now. We don't -- overall, we expect that there are going to be five or fewer dose levels in this escalation.

然後我們注意到，由於我們的客戶群需求旺盛，因此該領域對我們這類藥物的需求巨大。因此，我們現在正在進行早期劑量遞增。總體而言，我們預計此次升級的劑量水準將為五個或更少。

So that's going to give you a sense of where we're headed. The key is to look at where we are in monotherapy compares ourselves to data that's out for inhibitors and the very, very modest, unimpressive data that have been presented by a degrader in the clinic, which is limited at just limiting toxicity relating to panic function.

這會讓你了解我們的前進方向。關鍵是要看我們在單一療法中處於什麼位置，將我們自己與抑制劑的數據以及臨床中降解劑所提供的非常非常溫和、不起眼的數據進行比較，這些數據僅限於限制與恐慌功能相關的毒性。

So we'll compare ourselves to that we have good go, no-go criteria, but then the intention is to move our [IV inhibitor], which has once a week, possibly once every two week dosing, that's something we'll learn from this first escalation in combination with EGFR inhibitors and with chemotherapy.

因此，我們會將自己與良好的「通過」和「不通過」標準進行比較，但我們的目的是改進我們的 [IV 抑制劑]，每週給藥一次，可能每兩週給藥一次，這是我們從與 EGFR 抑制劑和化療聯合使用的首次升級中學到的東西。

And that's built into our plan. And that allows us to start moving into, eventually first line colorectal cancer and pancreatic cancer and also opportunities in non-small cell lung cancer.

這已經納入我們的計劃中。這使我們能夠開始進入最終的一線結腸直腸癌和胰腺癌治療領域，同時也為非小細胞肺癌治療提供了機會。

I'll turn to Angela.

我要向安琪拉提問。

Sure. Thanks, Noah. So just to comment on some of the other differentiation features of our 806 molecule, it's very potent with respect to its activity. We're 25 times greater in terms of potency for antiproliferative activity with respect to the inhibitors and then 40 times more effective than the clinical staged degrader.

當然。謝謝，諾亞。因此，僅評論我們的 806 分子的一些其他差異化特徵，就其活性而言，它的效力非常強。就抗增殖活性而言，我們的抑制劑的效力高出 25 倍，而就臨床分期降解劑的效力而言，我們的抑制劑的效力高出 40 倍。

The other piece that I'll mention is that catalytic activity that we have overcomes this KRAS resynthesis rate that has been observed as a major mechanism of resistance in the clinic with RMC, certainly with RMC-6236. So it's something, we're excited about. We think this is a very strong differentiator. Of course, we'll see what happens clinically.

我要提到的另一點是，我們的催化活性克服了 KRAS 再合成率，這已被觀察到是 RMC 臨床中產生抗藥性的主要機制，當然也是 RMC-6236 的主要機制。所以這是一件讓我們興奮的事。我們認為這是一個非常強大的區別因素。當然，我們會觀察臨床上發生的情況。

So I hope that helps.

我希望這會有所幫助。

Yes. Thank you.

是的。謝謝。

Srikripa Devarakonda, Truist Securities.

Sriripa Devarakonda，Truist 證券公司。

Hi, this is Anna on for Kripa. Thanks for taking our question. So in regards to 102, I know you mentioned the elevated LRRK2 level in Parkinson's. Could you remind us as to what percent of Parkinson's patients could be eligible for an LRRK2 targeting drug?

大家好，我是 Kripa 的 Anna。感謝您回答我們的問題。因此關於 102，我知道您提到了帕金森氏症中 LRRK2 水平升高。您能否提醒我們，有多少比例的帕金森氏症患者有資格使用 LRRK2 標靶藥物？

And then a second question, just in regards to new adjuvant Vepdeg and that potential data readout, how would this potentially inform any room for Vepdeg to be used earlier in the treatment paradigm and besides commercializing in second line as monotherapy in that six combo, any additional plans for development? Thank you.

然後第二個問題，僅關於新的輔助 Vepdeg 和潛在的數據讀數，這將如何潛在地告知 Vepdeg 在治療範例中更早使用的空間，除了在六種組合中作為單一療法在二線進行商業化之外，還有其他開發計劃嗎？謝謝。

Thank you for the question. Noah, next question from the LRRK2 .

謝謝你的提問。諾亞，下一個問題來自 LRRK2。

Yeah. So LRRK2 levels are higher in the Parkinson's disease patients. Now we haven't made a choice that we're only treating patients with elevated LRRK2. And by the way, I should say that that's something that might be on the table. It's something that we're going to explore. We're going to look at our own data sets as they evolve.We'll look at what's coming out of the Denali program, if it's shared.

是的。因此帕金森氏症患者的 LRRK2 水準較高。現在我們還沒有做出僅治療 LRRK2 升高患者的選擇。順便說一句，我應該說，這可能是正在討論的事情。這是我們要探索的事情。我們將關注我們自己的數據集的演變。如果 Denali 計劃可以共享，我們將關注其結果。

So that's a possibility. If your question implies, genetically, since LRRK2 is so implicated genetically in diseases like Parkinson's disease. If we -- when we move forward in Parkinson's disease, what patients -- what percentage of patients have LRRK2 implicated disease?

所以這是有可能的。如果您的問題從遺傳學角度暗示，因為 LRRK2 在遺傳學上與帕金森氏症等疾病有關。如果我們 — — 當我們研究帕金森氏症時，哪些患者 — — 有多大比例的患者患有 LRRK2 相關疾病？

Well, in idiopathic -- well, in familial Parkinson's, about 15% of patients have LRRK2 mutations. And there's a higher percentage that have LRRK2 pathway mutations that contribute to other types of familial Parkinson's disease. When you look at idiopathic, it's down in the few percent range.

嗯，在特發性——家族性帕金森氏症中，大約 15% 的患者有 LRRK2 突變。並且有更高比例的人患有 LRRK2 通路突變，從而導致其他類型的家族性帕金森氏症。當您觀察特發性疾病時，其發生率下降到了百分之幾。

So, but beyond those LRRK2 mutations themselves, there are all kinds of pathway perturbations that suggest that LRRK2 could be at the center of this endolysomal dysfunction that is characteristic of Parkinson's disease and PD.

因此，除了 LRRK2 突變本身之外，還有各種路徑擾動表明 LRRK2 可能是帕金森氏症和 PD 特徵性內溶體功能障礙的核心。

So you start to have 30% of patients that can have SNPs and other biomarkers that are associated with this LRRK2 dysregulation and may lead to LRRK2 elevation. And we have a particular interest in that subset of patients. And that's why we're engaging in a lot of biomarker analysis. We've been a long time collaborator with the Michael J. Fox Parkinson's disease biomarker initiative. And this is bearing fruit for us.

因此，30% 的患者可能具有與 LRRK2 失調相關的 SNP 和其他生物標記，並可能導致 LRRK2 升高。我們對這部分患者特別感興趣。這就是我們進行大量生物標記分析的原因。我們與邁克爾·J·福克斯帕金森病生物標記計劃長期合作。這對我們來說是碩果累累的。

So I think that we'll, we have no kind of guidance yet about whether we're doing patient selection or patient enrichment or going for old comers. But these are the types of questions we are investing in right now to ensure that we have the best development plan.

所以我認為，我們還沒有關於是否進行患者選擇、患者豐富或尋找老年患者的指導。但這些正是我們現在正在投資的問題，以確保我們擁有最佳的發展計畫。

Now, the second question was about neoadjuvant Vepdeg. So

現在，第二個問題是關於新輔助 Vepdeg 的。所以

And positioning the potential for Vepdeg in an ailing setting.

並在不景氣的環境中定位 Vepdeg 的潛力。

Yeah. So really we have to keep in mind, there have been no evidence to date to suggest that Vepdeg shouldn't be working in the adjuvant setting and in first line. We have every reason to believe that we can be very effective in that space. We know the drug is very tolerable.

是的。所以我們真的必須記住，迄今為止沒有證據表明 Vepdeg 不應該在輔助治療和第一線治療中發揮作用。我們完全有理由相信，我們可以在該領域發揮巨大作用。我們知道這種藥物的耐受性非常好。

Cross-study comparisons suggest maybe we're more tolerable than aromatase inhibitors. That could be very important in both of those settings. There's -- so, but ultimately a decision is being made in this partnership that because of where we are with timing and the interest probably more than with our partner, in this case Pfizer, in first line, that we're just not going to be going forward in those early lines.

交叉研究比較顯示我們可能比芳香酶抑制劑更具耐受性。在這兩種情況下，這可能都非常重要。有 — — 所以，但最終，我們在這次合作中做出了一個決定，由於我們的時機和興趣，可能比我們的合作夥伴（在本例中是輝瑞）在第一線更感興趣，所以我們不會在這些早期的生產線上繼續前進。

And that's why we've been giving so much guidance for our intent to out-license this, or proceed with renegotiation with Pfizer. But I don't think that we should draw any conclusions that there are any problems in the adjuvant setting or in first line.

這就是為什麼我們一直在為我們的授權意圖提供如此多的指導，或者與輝瑞重新進行談判。但我不認為我們應該得出任何關於輔助治療或第一線治療存在問題的結論。

Great. Thank you so much.

偉大的。太感謝了。

Jeet Mukherjee, BTIG.

Jeet Mukherjee，BTIG。

Great. Thanks for taking my question. So perhaps just coming back to the discussions with Pfizer over Vepdeg . You've talked about scenarios where perhaps Pfizer gets more economics or you get more economics or perhaps you find a new partner altogether.

偉大的。感謝您回答我的問題。所以也許只是回到與輝瑞就 Vepdeg 的討論。您曾經談到過這樣的情況：輝瑞可能獲得更多的經濟利益，或者您獲得更多的經濟利益，或者您完全找到了一個新的合作夥伴。

So based upon where your discussions are right now, would you say that you and Pfizer have very different views on how to maximize value for Vepdeg? And are you in active dialogue with other partners? If yes, how are those discussions going? Thanks.

那麼根據您目前的討論情況，您是否認為您和輝瑞對於如何實現 Vepdeg 價值最大化有著截然不同的看法？您是否與其他合作夥伴進行了正向對話？如果是，討論進度如何？謝謝。

Yeah, great question. I would say that Pfizer and Arvinas and the discussions we are having are aligned in terms of what the best way to get value for Vepdeg is. Even though we may have different views about the development future of Vepdeg, I think there's a Pfizer and Arvinas truly believe those values they had there. And that's why we're in these discussions.

是的，很好的問題。我想說，輝瑞和 Arvinas 以及我們正在進行的討論在如何以最佳方式為 Vepdeg 創造價值方面是一致的。儘管我們對 Vepdeg 的發展前景可能有不同的看法，但我認為輝瑞和 Arvinas 確實相信他們所擁有的價值觀。這就是我們進行這些討論的原因。

Clearly, if the asset does come back, and again, that's just one of the scenarios. The other scenario is that Pfizer takes the compound forward. But in the scenario where it comes to us, yes, we'd run an active process, but obviously we cannot run an active process right now because we're in a collaboration with Pfizer and we don't have the ability to do that.

顯然，如果資產確實回來了，那也只是其中一種情況。另一種情況是輝瑞公司將化合物向前推進。但就我們的情況而言，是的，我們會運行一個主動的流程，但顯然我們現在無法運行主動的流程，因為我們正在與輝瑞合作，我們沒有能力做到這一點。

Our belief is if we get the asset back, we run a process, there would be companies extremely interested in taking the asset back and taking a near-approved drug and with the potential to develop it not only in the first-line setting, but even earlier.

我們相信，如果我們收回資產，運行一個流程，就會有公司非常有興趣收回資產並獲取接近批准的藥物，並且有可能不僅在一線環境中開發它，甚至更早。

So we're very pleased with the progress in terms of discussion with Pfizer. Like I say, if they want to take it forward aggressively and launch it themselves, that would be extremely positive. But if they don't, and the outcome is we get the compound, then yes, we'd run an active process.

因此，我們對與輝瑞的討論取得的進展感到非常高興。就像我說的，如果他們想積極推進並自行推出它，那將是非常積極的。但如果他們不這樣做，而結果是我們得到了化合物，那麼是的，我們會運行一個積極的過程。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Hi, this is Tejasan for Ellie. Thanks for sending our question. I think you talked a little bit about some of the preclinical data for the KRAS inhibitors. Can you talk a little bit more about what we should expect with more data later this year and how might that inform what we think about in the phase one?

大家好，我是艾莉的 Tejasan。感謝您發送我們的問題。我想您談到了一些 KRAS 抑制劑的臨床前數據。您能否進一步談談我們對今年稍後將會出現哪些更多數據的期待，以及這些數據將如何影響我們對第一階段的思考？

Great, thanks for the question. I'll hand that over to Angela.

太好了，謝謝你的提問。我會把它交給安琪拉。

So for the KRAS inhibitors for 806, certainly you can expect to see some preclinical data just showing the differentiation profile that we see relative to inhibitors that are in the clinic. We'll also show some additional data just showing the combinability of the molecule. Noah had mentioned with eGFR mechanisms that's difficult with the PAN inhibitors, certainly in the clinic, showing some side effects that would basically preclude that combination.

因此，對於 806 的 KRAS 抑制劑，您當然可以期望看到一些臨床前數據，這些數據僅顯示我們所看到的相對於臨床中的抑制劑的分化概況。我們還將展示一些額外的數據來顯示分子的組合性。諾亞曾提到，eGFR 機制與 PAN 抑制劑的結合有困難，尤其是在臨床上，會表現出一些副作用，基本上會阻止這種組合。

We'll also show data that we think is really compelling from our oral and KRAS program, showing that we're making really great strides there as well. Other additional comparative data that we'll have will include some other models where we're looking at combinability with immuno-oncology approaches and some of the unique features of PROTACs, we think in this space, also with respect to the resistance mechanisms and overcoming that up-regulation that is seen clinically with the inhibitors as well.

我們還將展示我們認為來自口服和 KRAS 計劃的真正令人信服的數據，表明我們在那裡也取得了長足的進步。我們將擁有的其他額外比較數據將包括一些其他模型，我們正在研究與免疫腫瘤學方法的結合性以及 PROTAC 的一些獨特功能，我們認為在這個領域，也涉及抗藥性機制和克服臨床上看到的抑制劑的上調。

So we think we have a very differential profile and it's an exciting opportunity, certainly. And we're seeing that with the over-enrollment and the interest from the investigators that treat patients. So I think it's an exciting time and I'm sure Noah and the team will be sharing clinical data as soon as we have it. Hope that helps.

因此，我們認為我們擁有非常獨特的形象，這無疑是一個令人興奮的機會。我們看到，入組人數過多，治療患者的研究人員也對此很感興趣。所以我認為這是一個令人興奮的時刻，我相信一旦我們獲得臨床數據，諾亞和他的團隊就會立即分享。希望有幫助。

Peter Laqson, Barclays.

巴克萊銀行的彼得‧拉克森 (Peter Laqson)。

Great, thank you so much. Maybe just leading on from the prior question, for the G12D and the updates, when should we expect the initial first in human data update and kind of if you could talk through how enrollment is going and the number of sites that are open and any other details around that trial? And then I have a follow-up.

太好了，非常感謝。也許只是從先前的問題開始，對於 G12D 和更新，我們應該何時期待首次人體數據更新，您是否可以談談招募情況、開放的站點數量以及有關該試驗的任何其他細節？然後我有一個後續問題。

Thanks, Peter. Noah, do you want to take it?

謝謝，彼得。諾亞，你想拿走它嗎？

Sure. So Peter, we just announced that we opened the study for enrollment a little ahead of schedule and the immediate reaction seems to be very favorable. We haven't offered guidance yet on when we will be sharing data, but you're going to get it soon. You'll get the guidance soon, meaning it'll be sometime next year, obviously.

當然。彼得，我們剛剛宣布，我們提前一點開放了這項研究的招生，而且立即得到的反響似乎非常好。我們尚未提供有關何時共享數據的指導，但您很快就會得到它。您很快就會得到指導，顯然這意味著它將在明年的某個時候。

In terms of -- I would suggest just track things on clinicaltrials.gov because it's not, we wouldn't typically be giving you site numbers and things like that for a baseline study.

就此而言——我建議只在 clinicaltrials.gov 上追蹤事情，因為我們通常不會為您提供基線研究的網站編號和類似資訊。

Got it, thank you. And I apologize, I arrived late on the call. For the BCL6, so that's what, 393, the data in the second half, what should we focus on as regards to the data and kind of other metrics that we may be delivering in that data set?

知道了，謝謝。我很抱歉，我遲到了。對於 BCL6，這就是 393，下半年的數據，對於我們可能在該資料集中提供的數據和其他指標，我們應該關注什麼？

Sure, so we've shared that we'll provide some update of our data set, in the second half of this year. I really don't want to get ahead of ourselves and share what that disclosure will be, but the idea is that we're advancing through our dose escalation program, and obviously in dose escalation programs, the data that you're going to see are going to be more like, but before you're done with it, safety and PK and early signs of efficacy.

當然，我們已經分享過，我們將在今年下半年提供一些資料集的更新。我真的不想超越自己並分享披露的內容，但我們的想法是，我們正在推進劑量遞增計劃，顯然在劑量遞增計劃中，您將看到的數據將更像，但在您完成它之前，安全性和 PK 以及療效的早期跡象。

So I think you can look for those. Obviously, as we approach the completion of that, or as we achieve the completion of that dose escalation or ready for expansion, we'd be armed with more efficacy data, but still a focus on target engagement through PK, PD.

所以我認為你可以尋找這些。顯然，當我們接近完成該研究時，或者當我們完成劑量遞增或準備擴大研究時，我們將獲得更多的療效數據，但仍然將重點放在透過 PK、PD 進行目標參與上。

Got it. Would that be kind of like the range of like 10 to 20 patients or, and I presume kind of heavily pre-treated? Any details there?

知道了。這是否類似於 10 到 20 名患者的範圍，或者我推測是經過大量預先治療的？有詳細資料嗎？

Yeah, I would say that's a reasonable guess.

是的，我認為這是一個合理的猜測。

Okay, thank you so much.

好的，非常感謝。

Sudan Loganathan, Stephens.

蘇丹·洛加納坦，史蒂芬斯。

Hey, this is Keith on behalf of Sudan. Thank you for taking our question. So regarding the recent clinical data published by Cellucity on their advanced breast cancer asset, could you kind of just comment on your insights and what your perspective on that data is, and where do you like see that that's competitive positioning within the treatment landscape?

嘿，我是代表蘇丹的 Keith。感謝您回答我們的問題。那麼，關於 Cellucity 最近發布的關於其晚期乳癌資產的臨床數據，您能否評論一下您的見解以及您對這些數據的看法，以及您認為它在治療領域的競爭地位如何？

Thank you.

謝謝。

No, thank you for the question. Noah, I know you've tackled this earlier.

不，謝謝你的提問。諾亞，我知道你之前已經解決過這個問題了。

Yeah, I'm not sure if I have more to add than what was said earlier. We have always recognized that a drug like Cellucity could demonstrate attractive benefit risk in the second line setting and the first line setting. There is overlap between ESR1 mutant and PI3 kinase targeting agents.

是的，我不確定我是否還有比之前所說的更多內容要補充。我們始終認為像 Cellucity 這樣的藥物可以在二線治療和第一線治療中展現出誘人的益處風險。ESR1 突變體和 PI3 激酶標靶劑之間存在重疊。

In the end, what physicians are looking for are oral PROTAC, oral degraders. So in our case, a PROTAC that has an attractive benefit risk profile. So we think we're delivering that. And physicians kind of want to avoid toxicity as much as possible and get all the benefits they can after first line therapy before adding drugs without some toxicity.

最終，醫生們尋找的是口服PROTAC，也就是口服降解劑。因此，在我們的案例中，PROTAC 具有具有吸引力的效益風險狀況。所以我們認為我們正在實現這一目標。醫生希望盡可能避免毒性，並在添加無毒性藥物之前，盡可能獲得第一線治療後的所有益處。

So the impact on market opportunity in that second line setting is probably modest. But we haven't been offering specific guidance on market opportunity. So it's difficult to measure that modesty for you.

因此，對二線市場機會的影響可能不大。但我們尚未提供有關市場機會的具體指導。所以你很難衡量這種謙虛。

Thank you.

謝謝。

Michael Schmidt, Guggenheim Partners.

古根漢合夥公司的麥可‧施密特。

Hi, this is Sarah onto Michael. Thanks so much for taking my question. I wanted to quickly circle back to the oral PROTAC that you mentioned. I would love to hear more details on that and specifically how you would expect to differentiate from later seed pancreas.

大家好，我是 Sarah，我是 Michael。非常感謝您回答我的問題。我想快速回顧一下您提到的口服 PROTAC。我很想聽到更多關於此方面的細節，特別是您如何將其與後期種子胰腺區分開來。

Sorry, we couldn't understand the question. Could you repeat it one more time?

抱歉，我們無法理解這個問題。你能再說一次嗎？

There's a lot of echo.

有很多迴聲。

Oh, one second. Yes, exactly. The question was about the pancreas and any thoughts on differentiating from later seed pancreas and panrath programs.

哦，等一下。是的，確實如此。問題是關於胰腺的，以及關於如何將其與後期種子胰腺和 Panrath 程序區分開來的任何想法。

Sure, sure. So, you know we differentiate at least with ARV-806 from what we said publicly. But our pancreas program, we aim to have the same level of potency differentiation as well. We do bind to and degrade. So we degrade. We don't, we don't inhibit. So we avoid that upregulation that's observed clinically.

當然，當然。因此，您知道我們至少將 ARV-806 與我們公開說的話進行了區分。但我們的胰臟計劃也旨在達到相同水平的效力分化。我們確實會結合併降解。因此我們墮落了。我們不會，我們不會抑制。因此我們避免了臨床觀察到的上調。

So as you're aware, the clinical inhibitors, the pan-RAS inhibitor has shown a major mechanism of upregulation of KRAS as a resistance mechanism in the clinic.

如您所知，臨床抑制劑，泛 RAS 抑制劑已在臨床中顯示出上調 KRAS 作為抗藥性機制的主要機制。

So they're claiming around, 20% to 30% of patients they're seeing this. It's pretty profound. So we think we have an opportunity there. Our oral pan-KRAS also will have great combinability. We'll speak a bit about some of the differential profiles of our molecule relative to the pan-RAS molecules that are in the clinic.

他們聲稱大約有 20% 到 30% 的患者會出現這種情況。這很深刻。所以我們認為我們有機會。我們的口服泛KRAS也將具有很好的可結合性。我們將稍微談談我們的分子相對於臨床上的泛 RAS 分子的一些差異特徵。

We expect that we'll have greater combinability with the immune stimulatory mechanisms like the KEYTRUDA and other IO agents because we will not inhibit T cell receptor activity. So we think that combinability will also provide a major advantage to other mechanisms clinically. So there's a number of other differential activities that we're observing that we'll be discussing as we move forward and advance the program. But it's an exciting time for us. So stay tuned for more data this year at the triple meeting.

我們預期我們將與 KEYTRUDA 等免疫刺激機制和其他 IO 藥物具有更好的結合性，因為我們不會抑制 T 細胞受體活性。因此我們認為組合性也將為臨床上的其他機制帶來巨大優勢。因此，我們也觀察到了許多其他差異活動，我們將在推進該計劃的過程中進行討論。但對我們來說這是一個令人興奮的時刻。因此，請繼續關註今年三方會議的更多數據。

Great, thank you.

太好了，謝謝。

Terence Flynn, Morgan Stanley.

摩根士丹利的特倫斯弗林。

Hi, good morning. This is Chris on for Terence. Just one question from us. For 393, beyond safety, what do you need to see in order to advance the asset into a combo trial with GlowFit? Thank you.

嗨，早安。這是克里斯 (Chris) 代替特倫斯 (Terence)。我們只想問一個問題。對於 393，除了安全性之外，您還需要看到什麼才能將資產推進到與 GlowFit 的組合試驗中？謝謝。

Thanks, Chris. Noah?

謝謝，克里斯。諾亞？

Sure. So we don't, probably not a lot. Like we weren't expecting any hematopoietic toxicity, which would be the principal toxicity of (inaudible) beyond the CRS seen in the first cycle, but well managed with low fees dosing, dosing over the first month or the first three weeks. So it's just a matter of, reinforcing that we're not seeing any, any unexpected toxicities. And I don't have much more to add to that.

當然。所以我們不會，可能不多。就像我們沒有預料到任何造血毒性，這將是超出第一個週期中看到的 CRS 的主要毒性（聽不清楚），但透過低費用劑量、第一個月或前三週的劑量可以很好地控制。所以這只是一個問題，強調我們沒有看到任何意外的毒性。對此我沒有什麼可補充的。

Pretty clean drug treatment.

相當乾淨的藥物治療。

Yes.

是的。

Yigal Nokomovic, Citi.

花旗銀行的 Yigal Nokomovic。

Hi, this is Juan on for Yigal. Thanks for taking our question. Maybe just one quick one from us. Can you comment on whether AI was utilized to facilitate the compilation and submission of modules for Peptide to the FDA and more broadly, any potential utilization in the early drug development pipeline? Thanks.

大家好，我是 Juan，代表 Yigal。感謝您回答我們的問題。也許我們只需要快速說一句話。您能否評論是否利用人工智慧來促進勝肽模組的編制和向 FDA 提交，以及更廣泛地說，在早期藥物開發流程中是否有任何潛在用途？謝謝。

That's a great question. Supposedly it's a definition of AI. Yeah, we've certainly used a lot of kind of artificial intelligence in all of our research programs. And Angela could talk to the different features of that. Whether or not it was used in the actual NDA application.

這是一個很好的問題。據稱這是人工智慧的定義。是的，我們在所有研究項目中確實使用了許多類型的人工智慧。安琪拉可以談談它的不同特徵。它是否在實際的 NDA 申請中使用。

No, I'm not sure. Well, you know, part of the NDA is a submission process. We do work with, with some vendors. So there is AI that's going on there to our vendors. But in terms of our business overall, or the development part of our business, think of it, AI is being able to help us with a lot of medical writing, right? So we're going to be able to take documents that we have previously generated, across different assets and learn from them.

不，我不確定。嗯，您知道，保密協議的一部分是提交過程。我們確實與一些供應商合作。因此，我們的供應商正在使用人工智慧。但就我們的整體業務或業務發展部分而言，想想看，人工智慧能夠幫助我們完成大量的醫學寫作，對嗎？因此，我們將能夠獲取我們先前跨不同資產產生的文件並從中學習。

These are things we're doing currently and learn from them to impact our medical writing costs and efficiency in the future. Think of it also as something that helps in clinical operations to more efficiently review our vendor management, our contracts, that there's more clear accountability and roles and responsibilities across different contracts for a company that does rely on a lot of externalized, externalized work and cleanups.

這些是我們目前正在做的事情，並從中學到的教訓將影響我們未來的醫學寫作成本和效率。也可以將其視為有助於臨床營運更有效地審查我們的供應商管理和合同，對於依賴大量外部化、外部化工作和清理的公司來說，不同合約之間的責任、角色和職責更加明確。

And then obviously we're using it in all the time with our stats programming, like that's something that's been ongoing. There are many other areas in the company that are beginning to use it. But at least that gives you a sense of how it could have been used for an NDA in our development programs.

顯然，我們一直在統計程式設計中使用它，就像這是一直在進行的事情一樣。公司中的許多其他領域也開始使用它。但至少這讓你了解它如何在我們的開發項目中用作保密協議。

And I can comment on how we're using it in research. So we have computational chemistry and computational biology teams that use AI all the time in machine learning algorithms. We've been applying AI to our PROTAC design features. As we've been in this for 13 years, we've actually accumulated a lot of real world data on PROTAC activity and optimization. We are applying that and learning from it. So we iterate our PROTAC design much faster now.

我可以評論一下我們如何在研究中使用它。因此，我們擁有計算化學和計算生物學團隊，他們在機器學習演算法中一直使用人工智慧。我們一直在將 AI 應用於我們的 PROTAC 設計功能。由於我們已經從事該領域 13 年，我們實際上已經累積了大量有關 PROTAC 活動和最佳化的真實數據。我們正在運用它並從中學習。因此，我們現在可以更快地迭代我們的 PROTAC 設計。

And so we're seeing a big benefit in how we move with speed in research. And so this includes pharmacokinetic properties of these molecules and absorption features as well, which as you probably know, it's really key for PROTAC design.

因此，我們看到了研究速度的快速提升所帶來的巨大好處。因此，這也包括這些分子的藥物動力學特性和吸收特徵，正如您可能知道的，這對於 PROTAC 設計至關重要。

On the computational biology side, we're using it all the time for how do we go about analyzing our ligand identification data. So this enables us to go after previously undrugged targets and optimize those warheads to utilize in PROTACs for targeted protein degradation.

在計算生物學方面，我們一直在利用它來分析我們的配體識別數據。因此，這使我們能夠追蹤先前未使用藥物治療的目標，並優化這些彈頭以利用 PROTAC 進行有針對性的蛋白質降解。

In addition, I would say we use AI to mine real world data from biomarker features that exist in publicly available data sets. And this sets us up well for deep understanding of pathway biology. And this is how we've been approaching our Parkinson's disease and also our PSP, as well as other neurodegenerative diseases and really mining CSF protein changes in those diseases and how to set the clinical group up really well to understand how we might use those biologic features to stratify. So thank you for the question.

此外，我想說我們使用人工智慧從公開資料集中存在的生物標記特徵中挖掘真實世界的資料。這為我們深入了解通路生物學奠定了基礎。這就是我們治療帕金森氏症和 PSP 以及其他神經退化性疾病的方法，我們真正挖掘了這些疾病中的 CSF 蛋白質變化，以及如何很好地設定臨床組以了解如何使用這些生物學特徵進行分層。謝謝你的提問。

Got it. Thanks so much.

知道了。非常感謝。

Tyler Van Buren, TD Cowen.

泰勒範布倫 (Tyler Van Buren)，TD Cowen。

Hi, this is [Ekenna] on for Tyler. Thank you for taking our question. Just to go back to the vepdeg and Pfizer collaboration. Has Pfizer indicated its willingness to revise the collaboration or give back rights to vepdeg? And why would they be motivated to give vepdeg back given the amount they've invested to date?

大家好，我是 [Ekenna]，為 Tyler 服務。感謝您回答我們的問題。回顧一下 vepdeg 和輝瑞的合作。輝瑞表示願意修改合作關係或歸還 vepdeg 的權利？考慮到他們迄今為止投資的金額，他們為什麼會有動力歸還 vepdeg 呢？

Also, wouldn't that require significant cash outlay by Arvinas? And are you willing to use the existing cash on hand with milestones or royalties to do that?

此外，這是否需要 Arvinas 投入大量現金？您是否願意使用現有的現金，透過里程碑或特許權使用費來實現這一目標？

Yeah, just to reiterate, we're in a current 50-50. The attraction for that 50-50 was the planning on second line, first line and new adjuvant trials. Now we're currently left in a situation where it's only second line monotherapy. So less attractive in terms of market size for Pfizer.

是的，重申一下，我們目前的比例是 50-50。這種 50-50 的吸引力在於二線、第一線和新的輔助試驗的規劃。現在我們面臨的情況是，它只是二線單一療法。因此，就市場規模而言，輝瑞的吸引力較小。

They have shown no interest to develop vepdeg further. So that's the first important thing that vepdeg would not be developed further by Pfizer. We're in negotiation right now about what's the best way forward in terms of moving away from the 50-50 collaboration we had where either Pfizer takes the asset and launches it and gets more economics or they hand the compound back to us.

他們對進一步開發 vepdeg 毫無興趣。因此，第一件重要的事情是輝瑞公司不會進一步開發 vepdeg。我們目前正在就擺脫 50-50 合作模式進行談判，在這種模式下，輝瑞要么獲取資產並推出產品，獲得更多經濟效益，要么將化合物返還給我們。

I've said really clearly, I'll say it again, if the compound comes back to us, we are not spending any money on the further development of vepdeg, none at all. We'd be running a process to find a partner who would then ideally launch the drug and ideally further develop the drug.

我已經說得很清楚了，我再說一遍，如果這種化合物回到我們手中，我們不會花任何錢來進一步開發 vepdeg，一點也不會。我們將進行一項流程來尋找合作夥伴，理想情況下，該合作夥伴將推出該藥物，並進一步開發該藥物。

And we'd gain the benefit, the forward benefit of seeing the drug on the market. But we have no plans to further develop vepdeg. If we got the compound back.

我們將獲得利益，看到藥物上市的遠期利益。但我們沒有進一步開發vepdeg的計劃。如果我們拿回了化合物。

Thank you.

謝謝。

That concludes our Q&A session. I'd like to turn the call back over to John Houston for closing remarks.

我們的問答環節到此結束。我想將電話轉回給約翰休斯頓，請他做最後發言。

Thank you, operator. And thanks to everyone for joining us this morning and all the fabulous questions. Obviously, we look forward to providing additional updates in the coming months. But thank you so much for your time today.

謝謝您，接線生。感謝大家今天早上的參與和提出的所有精彩問題。顯然，我們期待在未來幾個月提供更多更新。非常感謝您今天抽出時間。

Ladies and gentlemen, that concludes the day's call. Thank you all for joining. And you may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝大家的加入。現在您可以斷開連線了。