Ventyx Biosciences Inc (VTYX) 2023 Q2 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Ventyx Biosciences Second Quarter 2023 Earnings Conference Call.

女士們、先生們，下午好，歡迎參加 Ventyx Biosciences 2023 年第二季財報電話會議。

(Operator Instructions) As a reminder, this conference call is being recorded.

（操作員說明）謹此提醒，本次電話會議正在錄音。

I would now like to turn the call over to Dr. Marty Auster, Ventyx Chief Financial Officer. Sir, you may begin.

我現在想將電話轉給 Ventyx 財務長 Marty Auster 博士。先生，您可以開始了。

Thank you, Loui, and good afternoon, everyone. Welcome to Ventyx Biosciences conference call and webcast where we'll be discussing our second quarter 2023 financial results and providing a business update for you. As a reminder, the company's most recent investor presentation can be found on our website at www.ventyxbio.com in the Investors, News & Events section.

謝謝你，路易，大家午安。歡迎參加 Ventyx Biosciences 電話會議和網路廣播，我們將在其中討論 2023 年第二季的財務業績並為您提供業務更新。請注意，該公司最新的投資者介紹可以在我們網站 www.ventyxbio.com 的投資者、新聞和活動部分找到。

Before we begin today, I'd like to remind everyone that this conference call and webcast will contain forward-looking statements about the company, including without limitation, statements about the anticipated timing of commencement, enrollment and completion of clinical trials for our product candidates, anticipated timing of release and clinical trial data, the market opportunity for our product candidates and the expected time frame for funding operations with our current cash, cash equivalents and marketable securities.

在今天開始之前，我想提醒大家，本次電話會議和網路廣播將包含有關公司的前瞻性聲明，包括但不限於有關我們產品候選者臨床試驗的預期開始、註冊和完成時間的聲明、預期發布時間和臨床試驗數據、我們候選產品的市場機會以及利用我們當前現金、現金等價物和有價證券進行融資業務的預期時間框架。

These statements are subject to risks and uncertainties that could cause actual results to differ. Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward-looking statements are discussed in greater detail in our most recent periodic reports filed with the SEC, including our Form 10-Q for the quarter ended June 30, 2023, which we filed just a few minutes ago.

這些陳述存在風險和不確定性，可能導致實際結果有所不同。我們最近向SEC 提交的定期報告（包括截至6 月的季度的10-Q 表格）中更詳細地討論了可能導致實際結果或結果與此類前瞻性陳述中表達或暗示的結果存在重大差異的因素. 2023 年 3 月 30 日，我們幾分鐘前提交的。

Please note that these forward-looking statements reflect our opinions only as of the date of this call, and we undertake no obligation to revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events, except as required by law.

請注意，這些前瞻性陳述僅反映我們截至本次電話會議之日的意見，我們沒有義務根據新資訊或未來事件修改或公開發布這些前瞻性陳述的任何修改結果，法律要求的除外。

With that, I'll hand the call over now to Dr. Raju Mohan, Ventyx's Founder and CEO. Raju, please go ahead.

現在，我將把電話轉交給 Ventyx 創辦人兼執行長 Raju Mohan 博士。拉朱，請繼續。

Thanks, Marty, and good afternoon, everyone. Thank you for joining our Second Quarter 2023 Financial Results Conference Call. It's hard to believe that we're already in August and how the first half has flown by. As you may have recalled from the R&D discussions in January and from our recent press releases, it's been a tremendously productive first half of the year for Ventyx, and I am very proud of our team's execution across the entire pipeline.

謝謝，馬蒂，大家下午好。感謝您參加我們的 2023 年第二季財務業績電話會議。很難相信我們已經進入八月了，上半年就這樣過去了。您可能還記得一月份的研發討論以及我們最近的新聞稿，今年上半年對於 Ventyx 來說是非常富有成效的，我對我們團隊在整個管道中的執行力感到非常自豪。

So let me run through this afternoon's agenda. I will begin by providing a high-level business update. And then I'll hand the call over to Bill Sandborn, our President and Chief Medical Officer, who will provide updates across our drug development programs. And finally, Marty will present an overview of our second quarter 2023 financial results before opening the call for Q&A.

讓我回顧一下今天下午的議程。我將首先提供高水準的業務更新。然後我會將電話轉交給我們的總裁兼首席醫療官 Bill Sandborn，他將提供我們藥物開發項目的最新資訊。最後，Marty 將在開始問答之前概述我們 2023 年第二季的財務表現。

So let me start by saying at Ventyx, we've always believed that novel oral therapies are poised to play a significant long-term role in the treatment of numerous immune diseases, indications that are currently dominated by injectable biologics, including indications such as psoriasis, inflammatory bowel disease, psoriatic arthritis, lupus and others. These large but underpenetrated markets currently exceed over $50 billion in annual sales, and we believe that as clinicians and patients are offered the choice of using a pill, an oral drug instead of an injectable therapy. There is a potential for a meaningful shift in market share as well as the general expansion of the treated populations in each of the diseases I referenced earlier.

因此，首先讓我在 Ventyx 說，我們一直相信新型口服療法將在眾多免疫疾病的治療中發揮重要的長期作用，這些疾病目前以注射生物製劑為主，包括牛皮癬等適應症、發炎性腸道疾病、銀屑病關節炎、紅斑性狼瘡等。這些龐大但滲透率不足的市場目前年銷售額超過 500 億美元，我們相信臨床醫生和患者可以選擇使用藥丸、口服藥物而不是注射療法。我之前提到的每種疾病的市場份額都有可能發生有意義的轉變，並且治療人群也將普遍擴大。

We have seen an overall increase in excitement around the promise of oral therapies, encompassing different targets and indications. And we believe that our portfolio of internally discovered compounds positions us at the forefront of this revolution in oral therapies, and I am proud we are currently conducting 5 Phase II trials across our wholly owned pipeline of novel small molecules.

我們看到，圍繞著不同標靶和適應症的口服療法的前景總體上令人興奮。我們相信，我們內部發現的化合物組合使我們處於這場口服療法革命的前沿，我很自豪我們目前正在我們全資擁有的新型小分子管道中進行 5 項 II 期試驗。

Let me begin with the compounds. As you know, our allosteric TYK2 inhibitor VTX958 is in Phase II development for plaque psoriasis, Crohn's disease and psoriatic arthritis. All diseases, where TYK2 place a direct role in modulating IL-23, a key cytokine indicated in the pathology of disease progression.

讓我從化合物開始。如您所知，我們的變構 TYK2 抑制劑 VTX958 正處於針對斑塊型乾癬、克隆氏症和乾癬性關節炎的 II 期開發中。在所有疾病中，TYK2 在調節 IL-23 中發揮直接作用，IL-23 是疾病進展病理學中顯示的關鍵細胞因子。

As previously discussed, we are aiming to achieve trough coverage of TYK2 IC90 at the highest Phase II dose across all the trials. In June, we announced that we completed patient enrollment in the Phase II SERENITY trial of VTX958 and moderate-to-severe plaque psoriasis. This is an important milestone for Ventyx and I'd like to thank our entire team for all their efforts. With enrollment now complete, we look forward to reporting top line data from the Phase II SERENITY trial in the fourth quarter of this year.

如前所述，我們的目標是在所有試驗中以最高 II 期劑量實現 TYK2 IC90 的谷值覆蓋。 6 月，我們宣布完成了 VTX958 和中重度斑塊狀乾癬 II 期 SERENITY 試驗的患者入組。這是 Ventyx 的一個重要里程碑，我要感謝我們整個團隊的所有努力。隨著註冊現已完成，我們期待在今年第四季度報告 II 期 SERENITY 試驗的主要數據。

On the development of an extended release tablet, ER tablet for VTX958, we continue to make progress towards the target product profile and remain confident that we will have an optimized once-daily tablet to advance into Phase III trials in 2024. As previously discussed, our development strategy incorporates an iterative process that allows us to sequentially evaluate multiple prototype formulations in humans. We look forward to providing a detailed update in the fourth quarter.

在開發緩釋片劑（適用於VTX958 的ER 片劑）方面，我們繼續朝著目標產品概況取得進展，並仍然有信心我們將擁有一款優化的每日一次片劑，並於2024 年進入III期試驗。如前所述，我們的開發策略包含一個迭代過程，使我們能夠順序評估人體的多個原型配方。我們期待在第四季度提供詳細的更新。

In June, we announced that we completed enrollment in the ongoing Phase II trial of VTX002 in patients with moderate to severely active ulcerative colitis. I'd like to again congratulate the Ventyx team on this important milestone. We look forward to reporting top line results from this trial early in the fourth quarter of this year. We believe we are the first company to demonstrate a greater magnitude of reduction in absolute lymphocyte counts or ALC, relative to etrasimod and ozanimod in similar Phase II trials. We believe we are exploiting the full production potential of this mechanism by a greater direction of ALC or validated by a marker and believe that this may translate into differentiated efficacy relative to other drugs developed for ulcerative colitis.

6 月，我們宣布完成了正在進行的 VTX002 II 期試驗的入組，該試驗針對中度至重度活動性潰瘍性結腸炎患者。我想再次祝賀 Ventyx 團隊實現這一重要里程碑。我們期待在今年第四季初報告該試驗的主要結果。我們相信，在類似的 II 期試驗中，相對於依曲莫德和奧扎莫德，我們是第一家證明絕對淋巴球計數或 ALC 大幅降低的公司。我們相信，我們正在透過 ALC 的更大方向或透過標記物驗證來充分利用該機制的生產潛力，並相信這可能會轉化為相對於針對潰瘍性結腸炎開發的其他藥物的差異化功效。

Our aspiration for this asset have always been very clear, which are to demonstrate efficacy in moderate-to-severe UC patients that is differentiated from both etrasimod and Zeposia, ozanimod, and it's a competitor with or superior to levels achieved by biologics. This efficacy profile if achieved, should position VTX002 as a potential class-leading safe oral agent in UC. And Bill will provide more color on this progress -- Bill will provide more color on progress of this trial.

我們對這項資產的願望一直非常明確，即證明其在中重度 UC 患者中的療效，該療效不同於 etrasimod 和 Zeposia、ozanimod，並且它是與生物製劑達到的水平相媲美或優於的水平。如果實現這一功效，VTX002 將成為治療 UC 的潛在領先安全口服藥物。比爾將為這一進展提供更多資訊——比爾將為該試驗的進展提供更多資訊。

Beyond these lead programs, we continue to advance our novel NLRP3 inhibitor portfolio, including our peripheral compound, VTX2735, which is now in Phase II trials in CAPs patients and our CNS-penetrant NLRP3 inhibitor VTX3232, for which we recently announced initiation of dosing in Phase I trial in healthy volunteers.

除了這些主導項目之外，我們還繼續推進我們的新型NLRP3 抑制劑產品組合，包括我們的外周化合物VTX2735（目前正在CAP 患者中進行II 期試驗）和我們的CNS 滲透性NLRP3 抑製劑VTX3232（我們最近宣布開始在CAP 患者中給藥）在健康志願者中進行的第一階段試驗。

So in summary, I'm very proud of our team's execution during the first half of the year, and we look forward to generating important Phase II data for both VTX002 and VTX958 in the fourth quarter.

總而言之，我對我們團隊上半年的執行力感到非常自豪，我們期待在第四季為 VTX002 和 VTX958 產生重要的 II 期資料。

So with that, I'll hand the call over to Bill for a more detailed pipeline discussion. Bill?

因此，我將把電話轉給比爾進行更詳細的管道討論。帳單？

Thank you, Raju, and good afternoon, everyone. I'm excited to provide a brief pipeline update today and to highlight recent progress across our portfolio. I'll begin with our allosteric TYK2 inhibitor VTX958. You will recall that we have 3 ongoing Phase II trials for VTX958, the SERENITY trial in moderate to severe plaque psoriasis, the HARMONY trial in moderately to severely active Crohn's disease and the TRANQUILITY trial in active psoriatic arthritis.

謝謝拉朱，大家下午好。我很高興今天能夠提供簡短的管道更新，並強調我們產品組合的最新進展。我將從我們的變構 TYK2 抑制劑 VTX958 開始。您可能還記得，我們​​正在進行3 項針對VTX958 的II 期試驗：針對中度至重度斑塊型乾癬的SERENITY 試驗、針對中度至重度活動性克羅恩病的HARMONY 試驗以及針對活動性銀屑病關節炎的TRANQUILITY 試驗。

As Raju mentioned, we announced in June that we completed the patient enrollment in the SERENITY trial in plaque psoriasis. The SERENITY trial includes a target enrollment of approximately 200 patients randomized to 1 of 4 VTX958 doses or to placebo and the primary efficacy endpoint is the proportion of subjects achieving PASI-75 at week 16.

正如 Raju 所提到的，我們在 6 月宣布，我們完成了斑塊型乾癬 SERENITY 試驗的患者入組。 SERENITY 試驗的目標納入約 200 名患者，隨機接受 4 劑 VTX958 劑量中的 1 劑或安慰劑，主要療效終點是在第 16 週達到 PASI-75 的受試者比例。

As previously disclosed, we are exploring multiple dose cohorts in this Phase II trial ranging from an anticipated minimally therapeutic dose at the low end to a high dose that is expected to achieve TYK2 IC90 coverage at trough as measured by IL-12 and IL-23.

如同先前所揭露的，我們正在該 II 期試驗中探索多個劑量組，範圍從低端的預期最低治療劑量到預計達到 TYK2 IC90 覆蓋谷值的高劑量（透過 IL-12 和 IL-23 測量） 。

Our team did an excellent job enrolling this trial in around 6 months with enrollment now complete, and we are very excited to report topline data from the Phase II SERENITY trial during the fourth quarter.

我們的團隊在大約 6 個月內完成了這項試驗的出色工作，現已完成註冊，我們非常高興能夠報告第四季度 II 期 SERENITY 試驗的主要數據。

In addition to the SERENITY trial, we continue to make progress enrolling the HARMONY trial in Crohn's disease and the TRANQUILITY trial in psoriatic arthritis, and we expect to have more to say about our progress on these trials before the end of the year.

除了 SERENITY 試驗之外，我們還在克羅恩病的 HARMONY 試驗和銀屑病關節炎的 TRANQUILITY 試驗方面繼續取得進展，我們預計在今年年底之前能夠更多地介紹我們在這些試驗上的進展。

Now moving to VTX002, our potential best-in-class S1P1 receptor modulator in development for ulcerative colitis at the Phase II stage. Recall that we had previously shared data from Phase II open-label extension, demonstrating that our high dose of 60 milligrams is achieving steady-state absolute lymphocyte count reductions in the approximately 70% or more range as compared to approximately 50% for etrasimod and ozanimod.

現在轉向 VTX002，這是我們正在開發的潛在同類最佳 S1P1 受體調節劑，用於治療潰瘍性結腸炎，處於 II 期階段。回想一下，我們之前分享過II 期開放標籤擴展的數據，顯示我們的60 毫克高劑量正在實現約70% 或更多範圍內的穩態絕對淋巴細胞計數減少，而艾曲莫德和奧扎莫德約50% 。

And our thesis remains that this differentiated pharmacodynamic effect may translate into improved efficacy in ulcerative colitis based on our analysis of consistent observed efficacy-driven dose response across both ulcerative colitis and multiple sclerosis trials evaluating S1P1 receptor modulators.

我們的論文仍然認為，基於我們對評估S1P1 受體調節劑的潰瘍性結腸炎和多發性硬化症試驗中一致觀察到的療效驅動劑量反應的分析，這種差異化的藥效作用可能會轉化為潰瘍性結腸炎療效的改善。

As Raju mentioned, we announced in June that we completed enrollment in the ongoing Phase II study of VTX002 in patients with moderately to severely active ulcerative colitis. This trial includes a target enrollment of approximately 180 patients randomized to 1 of VTX002 doses or placebo for a 13-week induction treatment period, followed by a 39-week blinded long-term extension period.

正如 Raju 所提到的，我們在 6 月宣布，我們完成了正在進行的 VTX002 II 期研究的入組，該研究針對的是中度至重度活動性潰瘍性結腸炎患者。該試驗的目標招募約 180 名患者，隨機接受 1 劑 VTX002 或安慰劑，進行 13 週的誘導治療期，然後是 39 週的盲法長期延長。

The primary endpoint is the proportion of subjects achieving clinical remission at week 13 as defined by the modified Mayo score. I want to join Raju and congratulating the team on this accomplishment. It is no small feat to enroll a large Phase II ulcerative colitis trial in a challenging and dynamic environment, and I'm grateful for the dedication and perseverance of our team.

主要終點是根據修改後的 Mayo 評分定義，在第 13 週達到臨床緩解的受試者比例。我想加入 Raju 並祝賀團隊的成就。在充滿挑戰和動態的環境中參加大型 II 期潰瘍性結腸炎試驗並不是一件容易的事，我感謝我們團隊的奉獻和堅持。

We are now looking forward to reporting top line data from this trial early in the fourth quarter. We expect to report Phase II top line data for VTX002 in ulcerative colitis ahead of the Phase II top line data for VTX958 in psoriasis.

我們現在期待在第四季初報告該試驗的頂線數據。我們預計將在 VTX958 治療乾癬的 II 期頂線數據之前報告 VTX002 治療潰瘍性結腸炎的 II 期頂線數據。

Finally, I'll touch briefly on our portfolio of novel NLRP3 inhibitors. We announced in June that we had initiated dosing in a Phase I trial of our CNS-Penetrant NLRP3 inhibitor, VTX3232 in healthy volunteers. This is a 2-part single ascending and then multiple ascending dose trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTX3232, including serial cerebrospinal fluid sampling to assess CNS exposure. We have a Phase II proof-of-concept trial underway with VTX2735, our peripheral NLRP3 inhibitor and familial cold autoinflammatory syndrome, or FCAS, which is the most common subpopulation of cryopyrin-associated periodic syndromes, or CAPS.

最後，我將簡單介紹一下我們的新型 NLRP3 抑制劑產品組合。我們在 6 月宣布，我們已開始在健康志願者中進行中樞神經系統滲透性 NLRP3 抑制劑 VTX3232 的 I 期試驗。這是一項由兩部分組成的單次遞增劑量試驗，然後多次遞增劑量試驗，旨在評估VTX3232 的安全性、耐受性、藥物動力學和藥效學，包括連續腦脊髓液取樣以評估CNS暴露。我們正在進行一項關於VTX2735 的II 期概念驗證試驗，VTX2735 是我們的外周NLRP3 抑製劑和家族性感冒自身炎症綜合徵(FCAS)，它是冷熱蛋白相關週期性綜合徵(CAPS) 最常見的亞群。

I'll reiterate that both with NLRP3 -- with both of our NLRP3 inhibitors, our goal is to establish a potential best-in-class profile in terms of safety, pharmacokinetics and pharmacodynamics and to ensure that these compounds are Phase II ready. We believe that this approach will create strategic optionality and will unlock the value of these programs in a wide range of indications for future development.

我要重申的是，無論是NLRP3 還是我們的兩種NLRP3 抑制劑，我們的目標是在安全性、藥物動力學和藥效學方面建立潛在的同類最佳特性，並確保這些化合物已做好II 期臨床準備。我們相信，這種方法將創造策略選擇性，並將在未來發展的廣泛適應症中釋放這些項目的價值。

With peripheral NLRP3 inhibition, this includes large cardiovascular, dermatologic and rheumatic disease indications. And with NLRP3 inhibition in the CNS, this includes neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, among others.

透過週邊 NLRP3 抑制，這包括大的心血管、皮膚病和風濕性疾病適應症。透過中樞神經系統中的 NLRP3 抑制，這包括帕金森氏症和阿茲海默症等神經退化性疾病。

In conclusion, this is a very exciting period for Ventyx with important topline Phase II data for VTX002 and VTX958 just around the corner in the fourth quarter of this year.

總之，對於 Ventyx 來說，這是一個非常令人興奮的時期，VTX002 和 VTX958 的重要第二期臨床數據即將在今年第四季獲得。

I'd like to thank our team again for their efforts during the quarter. Before moving on to question and answer, I'll hand the call back to Marty for a brief discussion of our financial results. Marty?

我要再次感謝我們的團隊在本季所做的努力。在進行問答之前，我會將電話轉回給馬蒂，以簡要討論我們的財務表現。馬蒂？

Thanks, Bill. So you'll find more detail on our financial results also in press release issued after the bell today as well as in our 10-Q, which filed also after market close today.

謝謝，比爾。因此，您也可以在今天盤後發布的新聞稿以及也在今天收盤後提交的 10-Q 報告中找到有關我們財務表現的更多詳細資訊。

I'll summarize our second quarter results briefly here though. R&D expenses in the quarter were $48.6 million compared to $14.7 million in the second quarter of 2022, and this reflects the advancement of our pipeline in the later stages of clinical testing, including the execution of the ongoing Phase II trial of VTX002 in ulcerative colitis, and the broader Phase II program for VTX958 with Phase II trials being conducted in psoriasis, Crohn's disease and psoriatic arthritis.

不過，我將在這裡簡要總結我們第二季的業績。本季的研發費用為 4,860 萬美元，而 2022 年第二季為 1,470 萬美元，這反映了我們的管道在臨床測試後期階段的進展，包括正在進行的 VTX002 治療潰瘍性結腸炎的 II 期試驗，以及更廣泛的VTX958 II 期計劃，其中正在進行針對銀屑病、克羅恩病和銀屑病關節炎的II 期試驗。

G&A expenses were $8.6 million for the second quarter 2023 compared to $5.7 million in the year ago period, reflecting growth of the company and net loss of $53.3 million for the second quarter of 2023 compared to a net loss in the second quarter of '22 of $20.0 million.

2023 年第二季的一般管理費用為860 萬美元，而去年同期為570 萬美元，反映了公司的成長以及2023 年第二季的淨虧損為5,330 萬美元，而2020 年第二季的淨虧損為5330 萬美元。2 千萬美元。

Cash, cash equivalents and marketable securities were $332.3 million as of June 30, 2023. This compares to $376.9 million in cash, cash equivalent and marketable securities on March 31, 2023. We continue to believe our current cash, equivalents and marketable securities are sufficient to support our planned operations into 2025.

截至2023 年6 月30 日，現金、現金等價物及有價證券為3.323 億美元。相較之下，截至2023 年3 月31 日，現金、現金等價物及有價證券為3.769 億美元。我們仍相信我們目前的現金、現金等價物和有價證券足以支持我們到 2025 年的計畫營運。

This concludes our prepared remarks for the afternoon's call, and I'll now turn the call back over to the operator to begin the Q&A session, and I'll be joined by our CEO, Raju Mohan; President and CMO, Bill Sandborn; and our CBO, Chris Krueger.

我們為下午的電話會議準備的演講到此結束，現在我將把電話轉回接線員以開始問答環節，我們的首席執行官拉朱·莫漢 (Raju Mohan) 將加入我的行列；總裁兼首席行銷長 Bill Sandborn；還有我們的首席預算長克里斯·克魯格 (Chris Krueger)。

Operator?

操作員？

(Operator Instructions) And our first question will come from Michael Yee with Jefferies.

（操作員說明）我們的第一個問題將來自 Jefferies 的 Michael Yee。

Maybe a 2-part question on the upcoming TYK2 results for you. I know a lot of people kind of point to Bristol's data, BID dosing, you kind of get to 67%, 69% PASI-75. You look at some of the Nimbus data. I guess they were in that range and then at 33% PASI-100. How do you think about whether you want to be relative to the profile of some of those, I guess, higher the better, of course. But what would you want to see there and say, "Hey, look, we're better at cross (inaudible) person. And then the second part of that is, what does that lead you to believe for Crohn's, which would then follow that? And maybe it's the PD marker for IL-13. Maybe Bill could walk through what you see in psoriasis? And then how does the IL-13 data playing at that to give you confidence on Crohn's?

也許有一個關於即將到來的 TYK2 結果的兩部分問題。我知道很多人都指向布里斯託的數據，BID 劑量，你可以達到 67%、69% PASI-75。您查看一些 Nimbus 資料。我猜他們在這個範圍內，然後是 33% PASI-100。你如何看待你是否想要與其中一些人的形象相關，我想，當然，越高越好。但你想在那裡看到什麼並說：「嘿，看，我們更擅長脾氣暴躁（聽不清）的人。然後第二部分是，這會讓你相信克羅恩病，然後接下來那？也許這是IL-13 的PD 標記。也許Bill 可以介紹一下您在牛皮癬中看到的情況？那麼IL-13 數據如何發揮作用，讓您對克羅恩病有信心？

Yes. Thanks, Mike. So yes, Bill, why don't you? You can take both of those.

是的。謝謝，麥克。所以是的，比爾，你為什麼不呢？你可以把這兩個都拿走。

Yes. So I think in terms of where we would like to arrive, really, if we get into the zone that the Nimbus Takeda product achieved, especially where you see the PASI-100 up into the 30s, that's really getting up into a solid area of efficacy for an oral agent. And that's generally the zone that was seen recently with the protagonist Janssen oral IL-23 antagonist as well. So -- and then every -- but all of these are somewhat short of what you see with the monoclonal antibodies, the IL-23. And so I think the aspirational floor has been set with some of these other oral sort of second-generation agents. And you want to hit into that zone and above that would be further differentiating. So that's sort of how we see it and where we would hope to land as a low watermark.

是的。所以我認為，就我們想要達到的目標而言，如果我們進入 Nimbus Takeda 產品所達到的區域，特別是當你看到 PASI-100 達到 30 年代時，這確實進入了一個堅實的領域口服製劑的功效。這通常也是最近主角楊森口服 IL-23 拮抗劑所看到的區域。所以——然後是每一個——但所有這些都與你在單株抗體 IL-23 中看到的有所不同。因此，我認為一些其他口服第二代藥物已經設定了理想的底線。你想要進入這個區域，超過這個區域將會進一步實現差異化。這就是我們的看法，也是我們希望達到的低水位線。

And then how about what's the readthrough that is to Crohn's? And is it the PD data that you see? Or maybe just clarify that, that gives you the confidence?

那麼克隆氏症的通讀內容又如何呢？你看到的就是PD數據嗎？或者也許只是澄清這一點，這會給你信心？

Yes. I mean we're, of course, speculating on readthrough to Crohn's. So what we know is that with deucravacitinib, doses of 6 twice a day or 12 once a day have not been effective for ulcerative colitis and Crohn's disease. And of course, those total daily doses or regimens are both twice the 6 milligrams once a day dose that's approved for psoriasis with sort of moderate efficacy. And then we know with biologics with inhibition of either interleukin 12, interleukin 23 with Stelara or interleukin inhibition of interleukin 23 alone with Skyrizi or Tremfya and mirikizumab and others that the doses that have been required to optimize efficacy in Crohn's disease are higher than the doses that sort of plateaued efficacy for psoriasis. So it's reasonable to speculate that you would need that more intense target coverage for Crohn's disease as well with blocking Interleukin-23 and Interleukin-12 with TYK2 inhibition. We, of course, need to generate primary data to show that, and our trials are designed to do that.

是的。我的意思是，我們當然是在猜測克隆氏症的通讀。所以我們知道的是，對於 deucravacitinib，每天兩次 6 粒或每天一次 12 粒的劑量對潰瘍性結腸炎和克羅恩病無效。當然，這些每日總劑量或治療方案都是批准用於治療牛皮癬且療效中等的每日一次 6 毫克劑量的兩倍。然後我們知道，使用Stelara 抑制白細胞介素12、白細胞介素23 的生物製劑，或單獨使用Skyrizi 或Tremfya 和mirikizumab 等抑制白細胞介素23 的生物製劑，優化克羅恩病療效所需的劑量高於上述劑量。對牛皮癬的這種穩定療效。因此，我們有理由推測，您需要對克羅恩病進行更強烈的標靶覆蓋，並透過 TYK2 抑制來阻斷 Interleukin-23 和 Interleukin-12。當然，我們需要產生原始數據來證明這一點，我們的試驗就是為了做到這一點而設計的。

So while we have 4 different active dosing groups in the psoriasis trial across a wide range of doses and exposures as I described a few minutes ago, in Crohn's disease, we have just 2 active doses and they're the 2 highest active doses from the psoriasis trial. So we're emphasizing high exposure with the hypothesis that greater exposure will be required in Crohn's disease, and we anticipate being able to read that Crohn's trial out next year.

因此，雖然我們在乾癬試驗中有4 個不同的活性劑量組，其劑量和暴露範圍很廣，正如我幾分鐘前所描述的，但在克羅恩病中，我們只有2 個活性劑量，而且它們是2 個最高的活性劑量。牛皮癬試驗。因此，我們強調高暴露，假設克羅恩病需要更多的暴露，我們預計明年能夠閱讀克羅恩病的試驗。

Our next question will come from Alex Thomson with Stifel.

我們的下一個問題將來自 Alex Thomson 和 Stifel。

Congrats on the progress. I guess 2 for me. Firstly, on the QD formulation, I wonder if you could comment on what has been driving the delay here from the midyear update to Q4 and how much more buffer you have to get QD formulation for Phase III studies next year? And then for the 2 Phase II for ulcerative colitis and psoriasis, I wonder if you could comment on whether discontinuation rates are tracking within your expectations?

祝賀取得的進展。我猜對我來說是2。首先，關於 QD 的製定，我想知道您是否可以評論一下是什麼導致了從年中更新到第四季度的延遲，以及明年 III 期研究的 QD 制定還需要多少緩衝？然後，對於潰瘍性結腸炎和銀屑病的 2 期 II 期治療，我想知道您能否評論一下停藥率是否符合您的預期？

Yes. So I'll say the disclosure of the data, our goal, will always to complete the development by the end of the year. Alex then lead ample buffer. So you got ample buffer to complete the prototype development because the real actual selection of Phase III QD tablet happens after the data comes out from Phase II to understand exactly where we line up with the doses and dose for Phase III, right? So we've always built that and there's plenty of buffer.

是的。所以我想說的是，數據的揭露，我們的目標，始終是在年底前完成開發。亞歷克斯則引領充足的緩衝。所以你有足夠的緩衝來完成原型開發，因為 III 期 QD 片劑的真正實際選擇發生在 II 期數據出來之後，以準確了解我們與 III 期的劑量和劑量的一致性，對嗎？所以我們一直在建造它並且有足夠的緩衝。

Now as we outlined in the R&D Day when we introduced the program to you guys that we had a strategy that sort of the process, you build and test in humans, and establish a relationship between the ER dose, ER prototypes in the IR dose plus multiple formulations that we're doing and testing them in human studies, right? So it's really important for us to get it nailed to have the right final formulation before we begin to make disclosures as we expect, this formulation will be the drug that we take into Phase III, and that's the goal and some reg approval, clinical trial work, this all worked out.

現在，正如我們在研發日向大家介紹該計劃時所概述的那樣，我們有一個策略，即在人體中進行構建和測試，並在 ER 劑量、IR 劑量中的 ER 原型加上之間建立關係我們正在研究多種配方並在人體研究中測試它們，對嗎？因此，在我們開始按照我們的預期進行披露之前，確定正確的最終配方對我們來說非常重要，該配方將是我們進入 III 期的藥物，這就是我們的目標和一些監管批准、臨床試驗工作，這一切都解決了。

So first of all, there's plenty of buffer. We always plan to get this done by the end of the year in time of the Phase II data coming out and then use that prototype to then actually get the actual tablet made manufacture, regulatory stability ready for Phase III start. So there's no impact on Phase III start. And so we're really confident in the process. We believe we made real progress towards achieving the target profile. But honestly, we recognize that our earlier timing of data release was probably a little over-optimistic. So we're looking forward to sharing more details with you in Q4.

所以首先，有足夠的緩衝。我們總是計劃在今年年底第二階段數據出來時完成這項工作，然後使用原型來實際進行平板電腦製造，並為第三階段開始做好監管穩定性準備。所以對三期啟動沒有影響。所以我們對這個過程非常有信心。我們相信，我們在實現目標方面取得了真正的進展。但老實說，我們認識到我們之前發布數據的時機可能有點過於樂觀。因此，我們期待在第四季度與您分享更多詳細資訊。

But the key emphasis is there's no impact to Phase III. We've always built in the buffer, and that includes manufacturing, regulatory stability, packaging and mailing. So just stay tuned for an update somewhere between now and when we have the Phase II data, probably closer to more of the -- when the Phase II comes out.

但重點是對第三階段沒有影響。我們始終建立緩衝區，其中包括製造、監管穩定性、包裝和郵寄。因此，請繼續關注從現在到我們獲得第二階段資料之間的更新，可能更接近第二階段資料發佈時的更新。

And on the discontinuation rate?

那麼停藥率呢？

Yes. So I think we -- it wouldn't be appropriate to give granular really clinical trial data, which was what a specific conversation about that would be. What I would say is these are both sort of shorter term or induction trials, if you will, the ulcerative colitis trial is 13 weeks in duration to the primary endpoint and the psoriasis trial was 16 weeks.

是的。所以我認為我們——提供詳細的臨床試驗數據是不合適的，這就是關於這個問題的具體對話。我想說的是，這些都是短期試驗或誘導試驗，如果您願意的話，潰瘍性結腸炎試驗的主要終點持續時間為 13 週，牛皮癬試驗的持續時間為 16 週。

From an interpretability standpoint, what is typical from a statistical standpoint is if you have patients that discontinue therapy prematurely. And typically, both ulcerative colitis trials and Crohn's trials, psoriasis trials, we'll have some of those for the dichotomous outcome measures, the patients with missing data are treated as failures. So you actually don't lose any statistical power in the analysis with any patients that do require discontinuation. So I think we're well set up in a very conventional fashion to manage any patients that would discontinue, but we won't make any comments beyond that.

從可解釋性的角度來看，從統計學的角度來看，典型的情況是患者過早停止治療。通常，潰瘍性結腸炎試驗和克隆氏症試驗、牛皮癬試驗，我們都會有一些用於二分結果測量的試驗，缺乏數據的患者被視為失敗。因此，在對任何需要停藥的患者進行分析時，實際上不會失去任何統計功效。因此，我認為我們已經以非常傳統的方式做好了準備，以管理任何將停止治療的患者，但除此之外我們不會發表任何評論。

Our next question will come from Vikram Purohit with Morgan Stanley.

我們的下一個問題將來自摩根士丹利的 Vikram Purohit。

2 from our side. First, I would just love to get your thoughts on 2 commercial performance to date and how it's impacted if it has your view of the commercial opportunity for a therapy like (inaudible) psoriasis? And then secondly, maybe a question for Marty. Could you just remind us what level of pipeline development has contemplated into your current cash guidance and runway? And how far the runway gets you for the current set of new programs?

2 從我們這邊。首先，我很想聽聽您對迄今為止的 2 項商業業績的看法，以及您對（聽不清楚）牛皮癬等療法的商業機會的看法，以及它會如何影響？其次，也許有個問題要問馬蒂。您能否提醒我們，您目前的現金指導和跑道已考慮到什麼程度的管道開發？目前的一系列新計劃能讓您走多遠？

So maybe Marty can take both questions and start with the commercial sort of thing and then go back to the second one.

所以也許馬蒂可以回答這兩個問題，從商業類的事情開始，然後再回到第二個問題。

Yes. This is very great to get both of them. So in terms of commercial performance, I think we're quite encouraged by the early days of it. Obviously, there is -- still has been providing quarterly updates about the commercial performance in the space. They're getting substantial significant market share relative to the other approved oral therapy on the market in psoriasis. They're continuing to kind of see share coming from all different avenues, which is highly encouraging. That includes sort of treatment-naive (inaudible) therapy patients in psoriasis, conversions from the other alternative therapy, oral therapy Otezla, conversions from patients currently taking biologics who are seeking to get off of injectables and move to oral.

是的。能得到他們兩個真是太好了。因此，就商業表現而言，我認為我們對它的早期階段感到非常鼓舞。顯然，仍然在提供有關該領域商業表現的季度更新。相對於市面上其他核准的牛皮癬口服療法，它們獲得了相當大的市場份額。他們繼續看到來自不同管道的份額，這是非常令人鼓舞的。其中包括從未接受過治療（聽不清楚）的乾癬患者、從其他替代療法（口服療法 Otezla）轉變而來、目前正在服用生物製劑、尋求擺脫注射劑轉向口服療法的患者。

We think long term about the market opportunity here, this is a $25 billion global cost of therapeutics. We think that oral agents overall are going to play a very significant and substantial meaningful portion of that market. Currently, the oral portion of that market is just about 10% or so. We think that's going to grow meaningfully from here. We think TYK2 is going to be a major player in that class, obviously with the introduction of Sotyktu and then obviously, our own development and other TYK2 products (inaudible) we think look attractive that are coming online in the next several years. So I think that all looks pretty favorable.

我們從長遠角度考慮這裡的市場機會，全球治療成本高達 250 億美元。我們認為，總體而言，口服製劑將在該市場中發揮非常重要且實質的作用。目前，該市場的口服部分僅佔10%左右。我們認為這將從這裡開始有意義地增長。我們認為TYK2 將成為該類別中的主要參與者，顯然是隨著Sotyktu 的推出，然後顯然是我們自己的開發和其他我們認為看起來很有吸引力的TYK2 產品（聽不清楚），這些產品將在未來幾年內上線。所以我認為一切看起來都很有利。

Shifting over to the cash guidance question, Vikram. So our cash guidance is forecast to bring us into 2025. And what that includes then is sort of Phase III prep work and the ability for us to kind of be able to be on track for Phase III launches in 2024 for both the VTX002 ulcerative colitis program as well as the VTX958 in psoriasis. It includes completion of the VTX958 Phase II programs in Crohn's disease as well as in psoriatic arthritis, both of which we're expecting to report data in 2024.

轉向現金指導問題，維克拉姆。因此，我們的現金指導預計將帶我們進入 2025 年。其中包括 III 期準備工作，以及我們能夠在 2024 年為 VTX002 潰瘍性結腸炎進行 III 期啟動的能力。計劃以及 VTX958 治療牛皮癬。其中包括完成克隆氏症和乾癬性關節炎的 VTX958 II 期項目，我們預計在 2024 年報告這兩個項目的數據。

It includes completion of the Phase I ozanimod that Bill described earlier for VTX3232. Our CNS directed an NLRP3 inhibitor as well as our Phase II proof-of-mechanism trial in CAPS patients with VTX2735. It does not obviously then get us through completion of those Phase III trials for psoriasis or you see that allows us to kind of be positioned to commence and allows us to complete all the other ongoing clinical work that's happening now, if we continue to kind of advance obviously, will have additional capital needs eventually.

它包括 Bill 之前為 VTX3232 描述的第一階段 ozanimod 的完成。我們的中樞神經系統針對使用 VTX2735 的 CAPS 患者進行了 NLRP3 抑制劑以及 II 期機制驗證試驗。顯然，這並不能幫助我們完成銀屑病的 III 期試驗，或者你看，如果我們繼續進行的話，這可以讓我們做好開始並完成目前正在進行的所有其他臨床工作的準備。進展明顯，最終將產生額外的資金需求。

Our next question will come from Yasmeen Rahimi with Piper Sandler.

我們的下一個問題將由亞斯明·拉希米 (Yasmeen Rahimi) 和派珀·桑德勒 (Piper Sandler) 提出。

This is Jon Hjelm speaking in for Yas Rahimi at Piper. Our first question is, as we will be eager to do our comparisons of SERENITY to other oral psoriasis agents, which PASI score in your view is the most reflective of drug activity in dose ranging? Second, what type of activities have been completed in regards to Phase III prep across VTX958 and VTX002?

我是 Jon Hjelm，代表 Piper 的 Yas Rahimi 發言。我們的第一個問題是，因為我們渴望將 SERENITY 與其他口服乾癬藥物進行比較，您認為哪個 PASI 評分最能反映劑量範圍內的藥物活性？其次，VTX958和VTX002的III期準備工作已經完成了哪些類型的活動？

Yes, I'll deal with the second question, and then I'll have Bill address the first one. So as we guided in the last earnings call, we've initiated all necessary activities around Phase III prep for both programs. So this includes CMC work, drug substance, drug product, regulatory preparation for end of Phase II meetings, all of the clinical studies that are needed to support that certain domain PK study. So all that has been well planned and it's still on track.

是的，我將處理第二個問題，然後我將讓比爾解決第一個問題。因此，正如我們在上次財報電話會議中所指導的那樣，我們已經圍繞這兩個項目的第三階段準備啟動了所有必要的活動。因此，這包括 CMC 工作、原料藥、藥品、第二階段會議結束的監管準備，以及支持特定領域 PK 研究所需的所有臨床研究。所以一切都已計劃周全，並且仍在按計劃進行。

Again, we're planning for data release in the fourth quarter and then moving on seamlessly to Phase III start. So yes, all necessary activities, there'll be no delay due to anything that was not planned or executed both on the CMC side, the drug side, the clinical side and all the other planning that goes to close to these trials. So Bill, why don't you address the first one, first question?

同樣，我們計劃在第四季度發布數據，然後無縫地進入第三階段的啟動。所以，是的，所有必要的活動，都不會因為 CMC 方面、藥物方面、臨床方面以及所有其他接近這些試驗的計劃未計劃或執行的任何事情而延遲。那麼比爾，你為什麼不解決第一個問題呢？

Sure. So what is the utility of the different PASI outcome measures for Phase II dose finding? We have both Phase II data fully published with Sotyktu and in abstract form with the Takeda Nimbus product. But we also have Phase II trial data with a number of the anti-IL-23 antibodies. And what you see across both the TYK2 inhibitors and the antibodies is that, first of all, we know that psoriasis is exclusively sensitive to IL-23 inhibition. So you see relatively high levels of, respectively, of PASI-75, PASI-90 and PASI-100 as you go up on dosing.

當然。那麼不同的 PASI 結果測量對於 II 期劑量發現有什麼用處呢？我們已透過 Sotyktu 完整發布了 II 期數據，並透過 Takeda Nimbus 產品以摘要形式發布了這些數據。但我們也有許多抗 IL-23 抗體的 II 期試驗數據。從 TYK2 抑制劑和抗體中可以看出，首先，我們知道牛皮癬對 IL-23 抑製完全敏感。因此，隨著劑量的增加，您會看到 PASI-75、PASI-90 和 PASI-100 的水平分別相對較高。

But the -- I would say the most sensitive outcome measure seems to be PASI-75. And you will sometimes see sort of a blending of several dose groups across the range of 3 or 4 doses for PASI-75. And then, if you go up PSAI-90 and especially PASI-100 that seems to be more specific or differentiating. So the absolute rates of achieving PASI-100 in particular, will be lower often half or less of what it is with PASI-75 and that tends to separate groups better. And that was seen both with Sotyktu at the 12 milligram once a day dose in Phase II and with the Nimbus Takeda product at the 30-milligram dose that each of the -- on the highest doses and highest exposures have the greatest achievement of PASI-100. So that's sort of how we see it.

但我想說，最敏感的結果指標似乎是 PASI-75。有時您會看到 PASI-75 的 3 或 4 個劑量範圍內的多個劑量組的混合。然後，如果你升到 PSAI-90，尤其是 PASI-100，這似乎更具體或更有區別。因此，達到 PASI-100 的絕對率通常會低於 PASI-75 的一半或更少，這往往會更好地區分群體。在 II 期試驗中，每天一次 12 毫克劑量的 Sotyktu 和 30 毫克劑量的 Nimbus Takeda 產品都可以看到這一點，在最高劑量和最高暴露量上，每一個都取得了 PASI 的最大成就。100.這就是我們的看法。

Our next question will come from Derek Archila with Wells Fargo.

我們的下一個問題將來自富國銀行的德里克·阿奇拉。

Congrats on the progress here. Just 2 quick ones from us. I guess first, can you just remind us how we should be thinking about the geographical diversity from the Phase II trial with VTX002 in terms of like number of U.S. sites versus ex U.S. sites? And then maybe I missed this in the prepared remarks, but I guess when are we going to see the data for VTX2735? And how are you thinking about prioritizing either indications or potentially partnering that asset in the future?

恭喜這裡的進展。我們只有 2 個快速的。我想首先，您能否提醒我們應該如何考慮 VTX002 II 期試驗的地理多樣性，即美國站點數量與美國以外站點的數量相同？也許我在準備好的評論中錯過了這一點，但我想我們什麼時候才能看到 VTX2735 的數據？您如何考慮優先考慮適應症或未來可能與該資產合作？

Bill, why don't you take both of them and then maybe I can add to the future of 2735, to point you begin.

Bill，為什麼不把它們都拿走，然後也許我可以添加到 2735 的未來，以指出你的開始。

Yes. So for geographic diversity, inflammatory bowel disease trials, whether it's ulcerative colitis in the case of VTX002 or Crohn's disease in the case of VTX958. You really require a lot of clinical trial sites as you get into Phase II and you're requiring anywhere from 132 patients target enrollment for Crohn's disease or 180 patients target enrollment for the now enrolled ulcerative colitis trial. So this ended up being multiple countries and worldwide development programs.

是的。因此，對於地理多樣性、發炎性腸道疾病試驗，無論是 VTX002 的潰瘍性結腸炎或 VTX958 的克隆氏症。當您進入 II 期時，您確實需要大量的臨床試驗地點，並且您需要 132 名克羅恩病患者的目標入組或 180 名目前已入組的潰瘍性結腸炎試驗的目標入組患者。所以這最終成為多個國家和全球的發展計畫。

It's typical to have greater enrollment in Eastern Europe, but to have enrollment in Western Europe and North America as well. We are in all of those jurisdictions in the ulcerative colitis trial. I think we won't get into details about exactly the distribution of the trial sites, except to say it's pretty conventional for a Phase II trial, and I feel very comfortable with the geographic mix that we achieved, and we'll report that when we report the data in the fourth quarter.

通常，東歐的入學人數較多，但西歐和北美的入學人數也較多。我們在所有這些管轄區都進行了潰瘍性結腸炎試驗。我認為我們不會詳細介紹試驗地點的具體分佈，只是說這對於第二階段試驗來說是相當傳統的，而且我對我們實現的地理組合感到非常滿意，我們會在什麼時候報告這一點我們報告第四季的數據。

And then for VTX2735, our peripheral NLRP3 inhibitor, we reported a year ago in June, the Phase I SAD and MAD data. And then, the -- we have an ongoing sort of Phase IIa trial in CAPS. So as I mentioned, we do have patients that are now enrolled in the trial. And remember, this is an ultra-rare disease. There's a couple of hundred patients in the U.S. So just if you had 2 patients, that's 1% of the prevalent population. So this is not easy to recruit and the fact that we have patients enrolled. We're pleased with.

然後對於我們的外周NLRP3抑制劑VTX2735，我們在一年前的6月報告了I期SAD和MAD數據。然後，我們正在進行 CAPS 的 IIa 期試驗。正如我所提到的，我們確實有患者現在正在參加試驗。請記住，這是一種極為罕見的疾病。美國有幾百名患者，所以如果有 2 名患者，那就是患病人口的 1%。所以招募並不容易，而且我們已經招募了病人。我們很滿意。

I won't get into the granular detail about where we are in that. But I think we're pleased with the level of screening and enrollment that's going on, and I feel confident that we'll be able to have some data by late in the year with that program.

我不會詳細介紹我們在這方面的進展。但我認為我們對正在進行的篩選和註冊水平感到滿意，我相信我們將能夠在今年年底透過該計劃獲得一些數據。

And then -- and this is Raju. So on development strategy for 2735, as we said on R&D Day and we've sort of continued to reiterate that, we want to get both compounds Phase II ready. So 2735 has finished Phase 1. We're in the middle of some starting some chronic tox studies and with 3232. Again, we are finishing up Phase 1. Expect to have that wrapped up early first half of next year. And again, there, again, we are CMC ready. We are planning on the tox work.

然後——這是拉朱。因此，關於 2735 的開發策略，正如我們在研發日所說的那樣，我們一直在重申，我們希望為這兩種化合物的 II 期做好準備。所以 2735 已經完成了第一階段。我們正在開始一些慢性毒性研究，而 3232 也正在開始。同樣，我們正在完成第一階段。預計明年上半年早些時候結束。再次，再次，我們已準備好 CMC。我們正在計劃毒理學工作。

So we have both compounds faced already in the first -- early first half of next year, and we'll have the data readout from the 2 Phase II trials ongoing for 958 and 002. And we'll just look at the strategy across the portfolio as where we pursue these 2 molecules. But no matter where these go in terms, whether we do it alone or whether we have a partner, we are ready for the Phase II start. And we outlined the opportunities for both drugs. So the peripheral molecule as indications, broad indications that Bill outlined both in cardio, cardiometabolic areas as well as some very specific derm indications.

因此，我們已經在明年上半年早些時候面臨過這兩種化合物，我們將從正在進行的 958 和 002 的 2 個 II 期試驗中讀出數據。投資組合是我們追求這兩個分子的地方。但無論這些進展如何，無論我們是單獨做還是有合作夥伴，我們都為第二階段的啟動做好了準備。我們概述了這兩種藥物的機會。因此，週邊分子作為適應症，比爾在有氧運動、心臟代謝領域以及一些非常具體的皮膚適應症中概述了廣泛的適應症。

And then for 3232, there's a huge excitement in neurodegenerative diseases, including Parkinson. So our goal has always been focus on the Phase II trials. It's ready for Phase III with the 2 compounds and get the NLRP3 portfolio Phase II ready late this year or early first half and then sort of we look at the entire portfolio and decide where we take these 2 molecules.

然後是 3232，神經退化性疾病（包括帕金森氏症）引起了巨大的興奮。所以我們的目標始終是專注於二期試驗。這兩種化合物已經準備好進入 III 期，並在今年年底或上半年年初準備好 NLRP3 產品組合的 II 期，然後我們會查看整個產品組合併決定我們將這 2 個分子用於何處。

(Operator Instructions)

（操作員說明）

And our next question will come from Chris Shibutani with Goldman Sachs.

我們的下一個問題將來自高盛的 Chris Shibutani。

Two questions, if I may. On the psoriatic arthritis opportunity, the Takeda Nimbus is expected to have Phase IIb data that reads out this year. Can you share with us what your expectations are for this trial? And any potential for a read-through in terms of what's your ongoing psoriatic arthritis trials? And the question on Crohn's as far as enrollment in the Phase II, have you observed any changes in particular since Bristol's compound failed its Phase II study. I did note that in those prepared remarks about the S1P UC study, the word perseverance was used.

如果可以的話，有兩個問題。關於乾癬性關節炎的機會，武田 Nimbus 預計將在今年公佈 IIb 期數據。您能與我們分享一下您對本次試驗的期望嗎？您正在進行的乾癬性關節炎試驗是否有可能進行通讀？關於克隆氏症的問題，就第二階段的入組而言，您是否觀察到任何變化，特別是自從布里斯託的化合物未能通過第二階段研究以來。我確實注意到，在那些準備好的關於 S1P UC 研究的評論中，使用了「毅力」這個詞。

Yes. No, go ahead.

是的。沒有，繼續。

Yes. I think, the -- you saw the totality of effect at the higher doses with the Nimbus Takeda product in psoriasis as being a bit greater than what was seen with deucravacitinib, particularly with where you end up at the final approved dose. And so given really a meaningful signal with both the 3 milligram BID, as I recall, and 12-milligram or 6 milligram QD and 12 milligram QD doses with deucravacitinib. And to my -- I thought there was a bit of dose response, particularly as you got into the ACR50 to ACR70 for the 12-milligram once-a-day dose with deucravacitinib.

是的。我認為，您看到 Nimbus Takeda 產品在牛皮癬中的較高劑量的總體效果比 deucravacitinib 的效果要好一些，特別是您最終獲得最終批准的劑量。因此，我記得，3 毫克 BID、12 毫克或 6 毫克 QD 和 12 毫克 QD 劑量 deucravacitinib 都給出了真正有意義的信號。對於我來說，我認為存在一些劑量反應，特別是當您每天服用 12 毫克 deucravacitinib 劑量達到 ACR50 至 ACR70 時。

So I anticipate that there would be a positive and meaningful effect across ACR20 and ACR50 and ACR70 for the Nimbus Takeda drugs. I don't know that we know exactly what doses they are doing, that it's reasonable to speculate or anticipate that they would include some of the higher doses from the already completed psoriasis trial. So we do think that the concept of TYK2 inhibition being an effective therapy for psoriatic arthritis is likely to be further confirmed with the Nimbus Takeda data. And we wouldn't be surprised to see an effect that's at least as good and possibly a little better than what was seen with deucravacitinib, and we think that opens up the opportunity for other TYK2 inhibitors with excellent target coverage like VTX958.

因此，我預計 Nimbus Takeda 藥物的 ACR20、ACR50 和 ACR70 將會產生正面且有意義的影響。我不知道我們是否確切地知道他們正在使用什麼劑量，是否可以合理地推測或預期他們將包括已經完成的銀屑病試驗中的一些較高劑量。因此，我們確實認為，Nimbus Takeda 數據可能會進一步證實 TYK2 抑制是治療乾癬性關節炎有效療法的概念。如果看到效果至少與 deucravacitinib 一樣好，甚至可能更好一點，我們不會感到驚訝，我們認為這為其他具有出色靶點覆蓋率（如 VTX958）的 TYK2 抑製劑帶來了機會。

And on the Crohn's enrollment piece?

克羅恩病登記表上呢？

Yes. I mean, we've always resisted being too granular about that as we've gone along. We have a lot of learnings around the -- in my view, we were quite successful in the ulcerative colitis program with getting the right CRO, the right country mix, the right number of sites effectively interacting with the investigators and getting the trial enrolled on a timely basis. And we've taken all those learnings as a young company and applied to the Crohn's program. There are many common sites between the ulcerative colitis and the Crohn's programs, which allowed us to leverage contract negotiations.

是的。我的意思是，在我們的發展過程中，我們一直拒絕對此過於細化。我們有很多經驗教訓——在我看來，我們在潰瘍性結腸炎計畫上取得了相當成功，獲得了正確的CRO、正確的國家組合、正確數量的站點，與研究人員有效互動，並讓試驗註冊在及時依據。作為一家年輕的公司，我們將所有這些經驗教訓應用於克羅恩病計劃。潰瘍性結腸炎和克隆氏症計畫之間有許多共同點，這使我們能夠利用合約談判的優勢。

We had relationships with the sites, with the investigators, with the study coordinators and all those things. And -- so we have all those synergies going for us in the Crohn's trial. And I'll just say from my standpoint, the site activation rates that we had planned were on track. The patient enrollment rates are on track, and I feel confident that we can deliver the results next year. I'm going to wait another quarter or 2 before we start to narrow the band around, when exactly next year. But for our internal metrics, we're absolutely on track for where we intended to be right now and the trajectory is strong to stay on track.

我們與研究中心、研究人員、研究協調員以及所有這些方面都有關係。而且——所以我們在克羅恩病試驗中擁有所有這些協同作用。我只想說，從我的角度來看，我們計劃的網站啟動率已步入正軌。患者入組率步入正軌，我相信我們明年就能取得成果。我將再等一、兩個季度，然後我們就會開始縮小範圍，也就是明年。但就我們的內部指標而言，我們絕對正朝著我們現在的目標前進，而且發展軌跡強勁，能夠保持在正軌上。

Our next question will come from Emily Bodnar with Wainwright.

我們的下一個問題將由艾米麗·博德納爾和溫賴特提出。

Maybe just a follow-up on the previous question on psoriatic arthritis. If you can kind of talk about how you think about the bar for you internally versus subject to Phase II data so far? And then also Bristol has talked about evaluating Sotyktu for other indications like SLE and alopecia. Are those indications that you think might make sense for TYK2 inhibitor? And are those ones that you'd maybe consider for VTX958?

也許只是之前有關銀屑病關節炎問題的後續。您能否談談您對內部標準與迄今為止第二階段數據的看法？然後布里斯託也談到了評估 Sotyktu 的其他適應症，如係統性紅斑狼瘡和脫髮。您認為這些跡象對 TYK2 抑制劑可能有意義嗎？您可能會考慮將這些用於 VTX958？

No. Well, until we have more data with the Nimbus Takeda products, we have sort of another data set with the implied target coverage and things across a range of doses. I think right now, the more benchmark should probably really be what we've seen with deucravacitinib and maybe say that it's -- what we've seen with the 12-milligram dose as opposed to the 6-milligram dose. If you do cross mechanism of action comparisons, those data with the 12-milligram dose actually looked pretty favorable to other agents, even JAK inhibitors.

不。好吧，在我們獲得 Nimbus Takeda 產品的更多數據之前，我們還有另一個數據集，其中包含隱含的目標覆蓋範圍和一系列劑量的內容。我認為現在，更多的基準可能應該是我們在 deucravacitinib 上看到的，也許可以說，它是我們在 12 毫克劑量而不是 6 毫克劑量上看到的。如果您進行跨作用機制比較，12 毫克劑量的數據實際上看起來對其他藥物（甚至 JAK 抑制劑）相當有利。

So let's see as we get some more data in that field, how high the floor can raise, but that's probably how we would think about it. For other indications, I'm not aware that there are any data yet for alopecia. It's interesting. There is some logic to it. And we're, of course, thinking about different indications including whether there are any beyond psoriasis and dermatology, we haven't pulled the trigger to go into that space yet, but we're watching that with interest.

因此，讓我們看看當我們獲得該領域的更多數據時，下限可以提高多高，但這可能是我們的想法。對於其他適應症，我不知道是否有任何關於脫髮的數據。這真有趣。這是有一定邏輯的。當然，我們正在考慮不同的跡象，包括是否有任何超越牛皮癬和皮膚病學的跡象，我們還沒有扣動扳機進入這個領域，但我們正在饒有興趣地觀察這一點。

For lupus, you'll recall that really Interleukin-12, Interleukin-23 inhibition with Stelara was ultimately not effective. And the -- so I'm a little bit skeptical about for IL-23 inhibition with that. But of course, you have the interferon alpha side, and that looks good. So I think for TYK2 inhibition, that's certainly an opportunity for us and one that is differentiated from the IL-12/23 and IL-23 antibodies where lupus cannot be a target.

對於狼瘡，您會記得，Stelara 抑制白細胞介素 12、白細胞介素 23 最終無效。所以我對 IL-23 的抑製作用有點懷疑。當然，你有乾擾素α一面，看起來不錯。因此，我認為對於 TYK2 抑制來說，這對我們來說無疑是一個機會，與 IL-12/23 和 IL-23 抗體不同，狼瘡不能成為標靶。

These are large trials. The endpoints are sort of squishy, if you'll remember, the Phase II study with deucravacitinib in lupus, as I recall, it was 360 patients, about 90 patients per arm for 3 doses plus placebo. It took about 3.5 years to recruit that trial and readout 6-month results. So it's really a long slog. The effect sizes are often in the 10% to 15% range relative to placebo. So you need a lot of patients per group, and we haven't pulled the trigger on that yet, because we think it's a big undertaking. But of course, pending successful and robust data in some of our other ongoing Phase II trials that could be revisited at any time.

這些都是大型試驗。如果你還記得的話，終點有點模糊，我記得，用 deucravacitinib 治療狼瘡的 II 期研究有 360 名患者，每組約 90 名患者接受 3 劑加安慰劑。招募該試驗並讀出 6 個月的結果花了大約 3.5 年的時間。所以這確實是一個漫長的過程。相對於安慰劑，效果大小通常在 10% 至 15% 範圍內。因此，每組需要很多患者，但我們還沒有啟動，因為我們認為這是一項艱鉅的任務。但當然，我們其他一些正在進行的二期試驗正在等待成功和可靠的數據，這些數據可以隨時重新審視。

Our next question will come from Sam Slutsky with LifeSci Capital.

我們的下一個問題將來自 LifeSci Capital 的 Sam Slutsky。

A quick question for Bill. Just on the S1P KRAS. Obviously, suppose your sales in UC, I think, have so far underwhelmed versus earlier expectations. That said, Pfizer obviously believes that a tranche in March is going to be a blockbuster in IBD and they obviously pay a good amount of money to get the drug. I guess as the IBD position, it would be good to get your view on what factors could have contributed to the slow launch of symposia? And then what potential profile for next-gen S1P1 could lead to better uptake or does ultimately result in blockbuster potential like you expect for clinical trials.

問比爾一個簡單的問題。就在 S1P KRAS 上。顯然，假設到目前為止，我認為你們在 UC 的銷售額與之前的預期相比並沒有給人留下深刻印象。也就是說，輝瑞顯然相信 3 月的一批藥物將成為 IBD 藥物的重磅炸彈，而且他們顯然已經支付了大量資金來獲得該藥物。我想作為 IBD 的立場，最好了解您對哪些因素可能導致研討會啟動緩慢的看法？然後，下一代 S1P1 的潛在特徵可能會導致更好的吸收，或者最終產生像您預期的臨床試驗那樣的重磅炸彈潛力。

I'll opine a little bit and then maybe Marty, given all of this life experience could talk a little bit about the launch as well for Symposia. But I think whenever there's a new mechanism of action, robust physician and provider engagement and education is required, therapies usually don't sell themselves. They require an educational and ultimately marketing campaign. And I think the sense from -- that I get from all of my colleagues in the field is that, that just hasn't happened in the robust way with symposia. So I think that plays a lot into it.

我會發表一點意見，然後也許馬蒂（Marty）考慮到所有這些生活經歷，也可以談談 Symposia 的發布。但我認為，只要有新的作用機制，就需要醫生和提供者的積極參與和教育，療法通常不會自行推銷。他們需要教育和最終的營銷活動。我認為，我從該領域的所有同事那裡得到的感覺是，這在研討會上並沒有以強有力的方式發生。所以我認為這很重要。

The drug has also been priced for the multiple sclerosis market. So it's in the $80,000, $90,000, $100,000 range. So as a starting price for an IBD drug, that's kind of high and that really then sets barriers to access. So I think it's heavily those things. I do have the sense that there is a rising experience with using the drug. And it would be interesting to see where Pfizer sets their pricing. I would anticipate that they're going to put a lot more marketing and education muscle behind it and that the launch of etrasimod will really start to grow the class.

該藥物也已針對多發性硬化症市場定價。所以它的價格範圍是80,000美元、90,000美元、100,000美元。因此，IBD 藥物的起始價格有點高，這確實設定了獲取障礙。所以我認為這些事情很重要。我確實感覺到使用這種藥物的經驗正在增加。看看輝瑞如何定價將會很有趣。我預計他們將投入更多的行銷和教育力量，而 etrasimod 的推出將真正開始擴大這個類別。

What are physicians and ultimately, patients looking for, I think it's really heavily about efficacy. And most of our legacy drugs were about 10% better than placebo, so 10% placebo-adjusted remission rates for induction. Some of the newer entrants, RINVOQ is 20% to 25% placebo-adjusted delta, some of the Phase II data with TL1A antibodies, both the Prometheus and Vivian Pfizer molecules had 25% and 20%, respectively. Remission deltas etrasimod depending and you look at it, Phase II was 25%, Phase III was 20% in 1 trial and about 10% in the other trial. Blended average is probably high teens, pushing 20%.

我認為醫生和患者最終在尋找什麼，這在很大程度上與療效有關。我們的大多數傳統藥物比安慰劑好約 10%，因此安慰劑調整後的誘導緩解率為 10%。一些新進入者，RINVOQ 是 20% 至 25% 安慰劑調整的 delta，一些 TL1A 抗體的 II 期數據， Prometheus 和 Vivian Pfizer 分子分別有 25% 和 20%。緩解增量 etrasimod 取決於你看一下，第 II 期為 25%，第 III 期在 1 個試驗中為 20%，在另一個試驗中約為 10%。混合平均值可能很高，達到 20%。

So I think the next-generation drugs that would be really differentiated and exciting, you probably want to see at least the 15%, and ideally 20% or more placebo-adjusted remission rate. And if that's what we're aspiring to. And if we land in that zone, not only the primary endpoint but with consistency in the secondary endpoints and some of the differentiating things like getting complete endoscopic remission and stuff like that, that's going to be very interesting to people.

因此，我認為下一代藥物將真正與眾不同且令人興奮，您可能希望看到至少 15%、理想情況下 20% 或更高的安慰劑調整緩解率。如果這就是我們的願望。如果我們落在這個區域，不僅是主要終點，而且次要終點和一些差異化的東西（例如獲得完全內視鏡緩解之類的東西）都具有一致性，這對人們來說將非常有趣。

Our drug is not aimed at multiple sclerosis. So it could be appropriately priced for an ulcerative colitis market. And we think all of that will be a real opportunity.

我們的藥物不是針對多發性硬化症。因此，它的定價對於潰瘍性結腸炎市場來說可能是合適的。我們認為所有這些都將是一個真正的機會。

Marty, did you want to add anything about the sort of launch trajectory of symposia as you see it?

馬蒂，您是否想為您所看到的研討會的啟動軌跡添加任何內容？

Yes, Bill, I think you hit on a lot of the things that we see and we talk about internally when we hear things from KOLs and folks we engage in the field. I think it's a combination of the factors you cited along with also as you sort of talked around the efficacy there, same on symposia was in the sort of very low double digits. So it wasn't particularly sort of -- it wasn't groundbreaking or exciting efficacy. It's perceived as a slower onset of action drug as well, which has got a better, have fast onset of action, of course, with the active metabolite data that the drug works through.

是的，比爾，我認為當我們從 KOL 和我們在該領域參與的人員那裡聽到事情時，你談到了我們所看到和內部討論的很多事情。我認為這是您引用的因素以及您談到的功效的組合，研討會上的效果也是非常低的兩位數。所以這並不是特別的——它不是突破性的或令人興奮的功效。它也被認為是起效較慢的藥物，當然，根據藥物發揮作用的活性代謝物數據，它具有更好的起效速度。

So I think we've got some benefits with VTX002 that I think are hopefully more attractive attributes to the market. And obviously, we'll be watching closely, as you and our investors will, on how Pfizer's regulatory outcome and commercial launch that goes (inaudible)

因此，我認為 VTX002 為我們帶來了一些好處，我認為這些好處有望對市場更具吸引力。顯然，我們將像您和我們的投資者一樣密切關注輝瑞的監管結果和商業推出的進展（聽不清楚）

Thank you. And at this time, there are no further questions in the queue. So I'd like to turn the floor back over to Dr. Mohan for additional or closing remarks.

謝謝。而此時，隊列中已經沒有其他問題了。因此，我想請莫漢博士發表補充或結束語。

Yes. Great. And then thank you all again, all the analysts, all the investors for your continued interest in Ventyx. Hopefully, we'll connect with you -- with many of you at one of the upcoming conferences we plan to attend in the third quarter. And we're really excited for the fourth quarter approaches. Looking forward to sharing our Phase II topline results with you for both starting with VTX002 in UC and then followed by VTX958 in psoriasis. So thanks. Thank you all once again.

是的。偉大的。然後再次感謝大家、所有分析師、所有投資人對 Ventyx 的持續關注。希望我們能在我們計劃在第三季度參加的即將舉行的會議之一上與你們聯繫。我們對第四季的到來感到非常興奮。期待與您分享我們的 II 期主要結果，首先是 VTX002 治療 UC，然後是 VTX958 治療乾癬。那謝謝啦。再次感謝大家。

Thank you. This concludes today's Ventyx Biosciences Second Quarter 2023 Earnings Conference Call. Please disconnect your lines at this time, and have a wonderful day.

謝謝。今天的 Ventyx Biosciences 2023 年第二季財報電話會議到此結束。請此時斷開線路，祝您有美好的一天。