Roivant Sciences Ltd (ROIV) 2024 Q1 法說會逐字稿

Good morning, ladies and gentlemen. Thank you for standing by. Welcome to the Roivant's First Quarter 2023 Earnings Conference Call.

早上好，女士們，先生們。謝謝你的支持。歡迎參加 Roivant 2023 年第一季度收益電話會議。

(Operator Instructions) After the speaker's presentation, there will be a question-and-answer session. (Operator Instructions)

（操作員說明） 演講者演講結束後，將進行問答環節。 （操作員說明）

I will now hand the conference over to your speaker host today, Stephanie Lee. Please go ahead.

現在我將把會議交給今天的演講主持人斯蒂芬妮·李。請繼續。

Good morning, and thanks for joining today's call to review Roivant's financial results for the company's first quarter ended June 30, 2023. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant; and Mayukh Sukhatme, President and Chief Investment Officer for Roivant.

早上好，感謝您參加今天的電話會議，審查 Roivant 公司截至 2023 年 6 月 30 日的第一季度財務業績。我是 Roivant 的 Stephanie Lee。今天的演講嘉賓是 Roivant 首席執行官 Matt Gline；以及 Roivant 總裁兼首席投資官 Mayukh Sukhatme。

For those dialing in via conference call, you can find the slides being presented today as well as the press release announcing these updates on our IR website at www.investors.roivant.com. We'll also be providing the current slide numbers as we present to help you follow along.

對於那些通過電話會議撥入電話的人，您可以在我們的投資者關係網站 www.investors.roivant.com 上找到今天演示的幻燈片以及宣布這些更新的新聞稿。我們還將提供當前的幻燈片編號，以幫助您跟進。

I'd like to remind you that we'll be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties.

我想提醒您，我們將在今天的演示中做出某些前瞻性陳述。我們強烈建議您查看我們向 SEC 提交的信息，以獲取有關這些前瞻性陳述以及相關風險和不確定性的更多信息。

And with that, I'll turn it over to Matt.

有了這個，我會把它交給馬特。

Thank you, Stephanie, and thank you, everybody, for joining this morning and for listening.

謝謝斯蒂芬妮，謝謝大家今天早上的加入和聆聽。

It's only been a short -- actually 6 weeks since our last call, as our last call was for the K. So comparatively a little bit fewer our updates, but an exciting -- certainly an exciting quarter ended June 30 and a lot to talk about today. I'm going to give just a brief -- a brief sort of update on the state of the business as well as an update on the quarter and VTAMA sales. And then actually, what we're going to spend the bulk of time on today is, we've been getting more questions about brepocitinib, and we've actually gotten some new data there in Crohn's disease. So we're going to share that and talk through again a reminder of sort of how we're thinking about that program as we approach the lupus data in the back half of the year and more beyond.

這只是很短的時間——實際上距離我們上次電話會議已經過去了6 週，因為我們上次電話會議是針對K 的。因此，我們的更新相對較少，但令人興奮——當然是一個令人興奮的季度，截至6 月30 日，有很多話要說。關於今天。我將簡單介紹一下業務狀況以及本季度和 VTAMA 銷售額的最新情況。實際上，我們今天要花大部分時間的是，我們收到了更多關於 brepocitinib 的問題，而且我們實際上已經獲得了一些有關克羅恩病的新數據。因此，我們將分享這一點，並再次討論，以提醒我們在處理今年下半年及以後的狼瘡數據時如何考慮該計劃。

And so with that, I'm going to get started, just starting on Page 5. As an overall reminder, we continue to be pleased with the progress we've made in the business. During the 6/30 quarter, we completed our tenth consecutive positive Phase III trial that was the during -- during 1 study, the second study of VTAMA and atopic dermatitis, which we continue to be proud of that track record and which has now led to 6 FDA-approved products across Roivant and the Sumitomo collaboration.

因此，我要開始，從第 5 頁開始。總而言之，我們仍然對我們在業務中取得的進展感到滿意。在6 月30 季度，我們完成了第十次連續積極的III 期試驗，這是一項研究期間，即VTAMA 和特應性皮炎的第二項研究，我們繼續為這一記錄感到自豪，現在已領先Roivant 和住友合作的 6 種 FDA 批准產品。

As of 6/30, we had just under $1.5 billion in cash on the balance sheet, which, as we've guided before, comfortably funds us into the second half of 2025 with a lot of clinical data, both generated recently and even more coming in the near future. And we're very proud of our pipeline at this point. We have -- we think is among the strongest I&I pipelines with, by our estimate, over $15 billion in peak sales potential supported by VTAMA, but also a number of critical first and best-in-class programs behind it.

截至6 月30 日，我們的資產負債表上有近15 億美元的現金，正如我們之前所指導的那樣，這些現金可以通過大量臨床數據輕鬆地為我們提供進入2025 年下半年的資金，這些數據都是最近生成的，甚至更多即將到來。目前我們對我們的管道感到非常自豪。我們認為，我們是最強大的 I&I 管道之一，據我們估計，VTAMA 支持的峰值銷售潛力超過 150 億美元，而且其背後還有許多關鍵的一流項目。

On Slide 6, and it's funny because this is a relatively, as I said, a quiet moment. But 2022 has been, and I expect will continue to be an extraordinary year for us as a business. As a reminder, up until now, in addition to continued progress on the VTAMA commercial launch, and we'll come to that in a second, we've generated positive data in now both large randomized controlled studies, Phase III studies in atopic dermatitis for VTAMA, which, as we've said before, will support our filing for additional indication there at the beginning of next year, an approval hopefully next year as well.

在幻燈片 6 上，這很有趣，因為正如我所說，這是一個相對安靜的時刻。但 2022 年對於我們企業來說一直是、而且我預計仍將是不平凡的一年。提醒一下，到目前為止，除了 VTAMA 商業發布方面的持續進展（我們稍後會談到）之外，我們還在兩項大型隨機對照研究、特應性皮炎的 III 期研究中產生了積極的數據對於VTAMA，正如我們之前所說，它將支持我們在明年初提交額外指示，並有望在明年獲得批准。

And then we've also now put out 2 important data sets, one in January and one in June, demonstrating the efficacy and our overall enthusiasm for RVT-3101, our anti-TL1A antibody, which obviously has gotten a lot of discussion. That program is obviously one of the most important in our pipeline. Now we are currently underway with our Phase II Crohn's study and in the midst of preparations for our Phase III study in ulcerative colitis, which we will share more detail on in the near future. Still coming for the year are 2 pretty important events. One, which I expect we'll get some questions on, I know Immunovant has spoken a lot about recently, is the upcoming single-ascending dose and multiple-ascending dose data for IMVT-1402, our next-generation anti-FcRn antibody at Immunovant. Obviously, that data, we think, has the potential to show that we have a best-in-class program there, and we're really looking forward to putting it out.

然後我們現在還發布了 2 個重要的數據集，一個在 1 月，一個在 6 月，展示了我們的抗 TL1A 抗體 RVT-3101 的功效和整體熱情，這顯然引起了很多討論。該計劃顯然是我們管道中最重要的計劃之一。現在，我們正在進行克羅恩病的 II 期研究，並正在準備潰瘍性結腸炎的 III 期研究，我們將在不久的將來分享更多細節。今年還有兩件非常重要的事件。其中一個，我希望我們會收到一些問題，我知道Immunovant最近已經談論了很多，是即將推出的IMVT-1402的單次遞增劑量和多次遞增劑量數據，IMVT-1402是我們的下一代抗FcRn抗體，免疫劑。顯然，我們認為這些數據有可能表明我們擁有一流的程序，並且我們真的很期待將其推出。

There's a number of other data sets in our FcRn franchise and sort of more broadly in the FcRn field coming in the near future as well. And then as I mentioned, the topic on which we'll spend the most time this morning is brepocitinib. We had -- that's our dual inhibitor of TYK2 and JAK1 of Priovant. That program has it's -- what would be one of 2 registrational studies in SLE, a Phase IIb study reading out in the fourth quarter of this year. And actually just a lot going on generally there as well, and it's a program that I think is just starting to get some attention, but it's really sort of earlier on people's radar.

我們的 FcRn 專營權中還有許多其他數據集，並且在不久的將來也會在 FcRn 領域中提供更廣泛的數據集。正如我提到的，今天早上我們花最多時間討論的話題是布雷波西替尼。我們有——這是我們的 Priovant 的 TYK2 和 JAK1 雙重抑製劑。該計劃將成為 SLE 的兩項註冊研究之一，一項將於今年第四季度宣讀的 IIb 期研究。實際上那裡也發生了很多事情，我認為這個項目才剛剛開始引起一些關注，但它確實是人們關注的較早的項目。

So all of that situates on Slide 7 in our late-stage pipeline, which again, we are very excited about in terms of its breadth and in terms of the importance of many of the mechanisms we're working on. And again, the remaining programs in that pipeline, like namilumab and RVT-2001 that are earlier stage higher SKU opportunities that we'll share more about as we get data, which will happen sort of starting at the end of this year with 2001 and beyond with namilumab.

因此，所有這些都位於我們後期管道中的幻燈片 7 中，我們再次對其廣度和我們正在研究的許多機制的重要性感到非常興奮。再說一遍，該管道中的其餘項目，如 namilumab 和 RVT-2001，是早期階段較高 SKU 的機會，我們將在獲得數據後分享更多信息，這將在今年年底從 2001 年開始進行，超越納米魯單抗。

So with that, I'm just going to go into a brief update on where we are on VTAMA, starting on Slide 9. So look, we continue to be bluntly very excited about the progress that we are making here. We continue to see monthly scripts increase. We continue to see docs enthusiastic. We continue to hear a lot of enthusiasm for our AD data. We continue to make payer progress, as I'll talk about in a moment and continue to see improvements in revenue, which is ultimately the bottom line at the moment. So we're just very pleased with the growth there. We've got now over 11,500 unique prescribers, who have written over 200,000 scripts, which is pretty extraordinary for just over a year on the market. It's a really strong start from our perspective.

因此，我將從幻燈片 9 開始簡要介紹 VTAMA 的進展情況。因此，我們仍然對我們在這裡取得的進展感到非常興奮。我們繼續看到每月腳本增加。我們繼續看到文檔的熱情。我們繼續聽到人們對我們的 AD 數據充滿熱情。我們將繼續推動付款人進步，正如我稍後將討論的那樣，並繼續看到收入的改善，這最終是目前的底線。所以我們對那裡的增長感到非常滿意。我們現在擁有超過 11,500 名獨特的處方者，他們編寫了超過 200,000 個處方，這對於市場上僅僅一年多的時間來說是相當非凡的。從我們的角度來看，這是一個非常強勁的開始。

On Slide 10, I just want to give a sort of payer update. So we're up to about 130 million lives covered, just a tick under 80% of commercial lives, plus 87 million government lives. This is the kind of coverage we dreamed of having maybe 18 months after our launch. This is really exactly where we need to be from a government perspective. We are on formulary with all 3 of the major PBMs. So we're in good shape from a major PBM perspective. We have 4 additional national health plan formularies. We have a bunch of progress across some of the regional and smaller plans. We are in a great place from a coverage perspective.

在幻燈片 10 上，我只想提供付款人的最新情況。因此，我們覆蓋了大約 1.3 億人的生活，僅略低於 80% 的商業生活，再加上 8700 萬人的政府生活。這正是我們在發布 18 個月後所夢想得到的報導。從政府的角度來看，這確實正是我們需要做到的。我們已將所有 3 個主要 PBM 納入處方集。因此，從 PBM 的主要角度來看，我們的狀況良好。我們還有另外 4 個國家健康計劃處方集。我們在一些區域計劃和較小的計劃上取得了一系列進展。從覆蓋範圍的角度來看，我們處於一個很好的位置。

And the other thing I'll say is the significant majority of this coverage obviously has no prior off, that's a little bit of a red herring in dermatology where a very few drugs are true prior off, but most importantly, the majority of it is single set through steroid with a very easy to process for that step to be achieved. And so we feel really good about the strength of our coverage, and we think it's underpinning successful commercial model.

我要說的另一件事是，該報導中的絕大多數顯然沒有事先關閉，這在皮膚病學中有點轉移注意力，其中很少有藥物是真正的事先關閉，但最重要的是，其中大部分是單組通過類固醇，非常容易處理以實現該步驟。因此，我們對我們的覆蓋範圍感到非常滿意，我們認為它是成功商業模式的基礎。

You can see a little bit more about that on Slide 11. We did $16.7 million in net revenues for the quarter, which continues to be a solid progression in growth quarter-on-quarter, feel good about that growth and expect to continue to see it to accelerate with both volume and gross net improvements in the future. Gross to net was a hair better, 26% yield over the last quarter. We had pulled, as we said on the prior call, some of the GTN improvements from this quarter to the June 30 quarter back into the 3/31 quarter with some earlier formulary additions.

您可以在幻燈片 11 上看到更多相關信息。本季度我們的淨收入為 1,670 萬美元，季度環比增長仍然穩健，我們對這種增長感到滿意，並預計將繼續看到這一增長未來銷量和總淨值的改善將加速。毛淨收益率比上一季度好一點，為 26%。正如我們在之前的電話會議中所說，我們已將本季度至 6 月 30 日季度的一些 GTN 改進撤回到 3/31 季度，並添加了一些早期的處方。

So I expect to see GTN to progress sort of linearly on the trend line over the course of the year, and I expect to end this fiscal year, call it, in the mid- to high 30s from a yield perspective and still believe very comfortably we'll be on a trajectory to get to that 50% yield that we and others have guided to as we progress. So the contracting and sort of other payer progression is all sort of moving exactly in the direction we needed to, and we think we're in a good shape from a GTN perspective.

因此，我預計GTN 在這一年中會在趨勢線上呈線性增長，並且我預計本財年結束時，從收益率的角度來看，可以稱之為30 多歲左右，並且仍然非常放心地相信隨著我們的進步，我們將按照我們和其他人所指導的目標實現 50% 的收益率。因此，合同和其他付款人進展都在朝著我們需要的方向發展，我們認為從 GTN 的角度來看我們處於良好的狀態。

So that's about it on VTAMA for now. I'm sure we'll get some more questions. Look, I think the continued progress there is exciting to us, and we're excited about all the feedback we're getting. We believe script volumes will continue to increase over the course of this year, especially as our now live DTC campaigns begin to have an impact on volumes. And, yes, we're really also looking forward to getting going in AD next year, which is, as you may remember, about 4x larger market opportunity, where we have some truly exciting and highly differentiated data.

VTAMA 上的內容就到此為止了。我相信我們還會收到更多問題。看，我認為那裡的持續進展讓我們感到興奮，我們對收到的所有反饋感到興奮。我們相信今年腳本數量將繼續增加，特別是當我們現在正在進行的 DTC 活動開始對數量產生影響時。是的，我們也確實期待明年進入廣告領域，正如您可能還記得的那樣，這是大約 4 倍大的市場機會，我們擁有一些真正令人興奮且高度差異化的數據。

So with that, I'm going to turn it over in just a moment to Mayukh, who is going to do a relatively deep dive here on brepocitinib, our dual inhibitor TYK2 and JAK1. And I think it's a program that has been high on our minds, but a little bit below the line for others just because of everything else going on in our pipeline. But it's a really exciting program. It's a very potent agent, which continues to demonstrate strong clinical efficacy. And one of the many reasons we're highlighting it today, which maybe -- we'll talk about as we generated some data. Pfizer had an ongoing study in Crohn's disease that's read out and once again, the agent has shown great promise in another clinical study. We are unlikely, as you know, to progress it in Crohn's disease. But nonetheless, really excited about the data there and what it means for what we're going to do in some of these other places.

因此，我稍後會將其轉交給 Mayukh，他將在這裡對我們的雙抑製劑 TYK2 和 JAK1 brepocitinib 進行相對深入的研究。我認為這是一個我們一直高度重視的計劃，但對其他人來說卻有點低於標準，因為我們的管道中正在進行的其他事情。但這是一個非常令人興奮的計劃。它是一種非常有效的藥物，並持續顯示出強大的臨床功效。我們今天強調它的眾多原因之一，也許我們會在生成一些數據時討論。輝瑞公司正在進行一項針對克羅恩病的研究，該研究已被讀出，該藥物在另一項臨床研究中再次顯示出巨大的前景。如您所知，我們不太可能在克羅恩病方面取得進展。但儘管如此，我對那裡的數據以及它對我們將在其他一些地方所做的事情意味著什麼感到非常興奮。

So with that, let me hand it over to Mayukh to take it away, starting on Slide 13.

那麼，讓我把它交給 Mayukh 來把它拿走，從幻燈片 13 開始。

Yes. Thanks, Matt. Yes -- so yes, please turn to Slide 13. So as Matt said, I want to take the opportunity to talk a little bit about one of -- I think, what I consider one of the sleeping giants within our portfolio. To the extent that brepocitinib has begun to get some notice from investors, I think it's mostly through the lens of being a pivotal study catalyst for Roivant by the end of this year. And while that is true, we do have the lupus data later this year. I think the lupus story is just a small part of what we're trying to build with brepocitinib. And so I want to go through that story afresh, new here today. The punchline, from my perspective, is don't [sleep] on brepocitinib.

是的。謝謝，馬特。是的——所以是的，請轉到幻燈片 13。正如馬特所說，我想藉此機會談談我認為是我們投資組合中沉睡的巨人之一。就 brepocitinib 已開始引起投資者的一些關注而言，我認為這主要是因為到今年年底將成為 Roivant 的關鍵研究催化劑。雖然這是事實，但我們今年晚些時候確實有狼瘡數據。我認為狼瘡故事只是我們試圖用 brepocitinib 構建的一小部分。所以我想今天在這裡重新回顧一下這個故事。從我的角度來看，重點是不要在布雷波西替尼上[睡覺]。

So put simply, brepocitinib is a unique, highly, highly active dual inhibitor of both TYK2 and JAK1 that has already shown spectacular efficacy in a broad range of autoimmune diseases. So as Matt said, we're reporting here for the first time the sixth consecutive positive Phase II study for brepocitinib, this time in Crohn’s disease, which is a study that is being run by Pfizer and (inaudible). And that adds to the string of positive Phase II studies already reported, now covering as you see here on the slide, psoriasis, alopecia, psoriatic arthritis, ulcerative colitis, hidradenitis suppurativa and now Crohn’s disease.

簡而言之，brepocitinib 是一種獨特的、高活性的 TYK2 和 JAK1 雙重抑製劑，已在多種自身免疫性疾病中顯示出驚人的療效。正如馬特所說，我們在這里首次報告 brepocitinib 的第六項連續陽性 II 期研究，這次是針對克羅恩病，這是輝瑞正在進行的一項研究（聽不清）。這增加了已經報告的一系列積極的二期研究，現在涵蓋了牛皮癬、脫髮、銀屑病關節炎、潰瘍性結腸炎、化膿性汗腺炎和現在的克羅恩病。

And we'll go through the rest of the material on this slide in greater detail later, but we think that we really have the potential to become the leading oral therapy in lupus given the dual inhibition of TYK2 and JAK1 should provide greater efficacy than inhibition of either one alone. That is a large global study that is designed to serve as one of 2 registrational studies. And importantly, it is a 52-week study with a 52-week primary endpoint, which is the registrational endpoint that has historically been the most predictive of future studies.

稍後我們將更詳細地介紹這張幻燈片上的其餘材料，但我們認為，鑑於 TYK2 和 JAK1 的雙重抑制應該比抑制提供更好的療效，我們確實有潛力成為狼瘡的領先口服療法單獨其中任何一個。這是一項大型全球研究，旨在作為兩項註冊研究之一。重要的是，這是一項為期 52 週的研究，具有 52 週的主要終點，這是歷史上最能預測未來研究的註冊終點。

Our ongoing single Phase III study in dermatomyositis, which will serve as the basis of an NDA filing shortly after data, is coming up, to the extent that it now seems a little far off. I think as we round out the year and are sitting in the first half of 2024, it will come into focus as a near-term catalyst ever. And that's just the beginning for this program. So we think that, that unique dual mechanism and high demonstrated efficacy of brepocitinib really creates the pipeline and a product approach where we can own a series of specialty rheumatology indications, each of which has high unmet need and blockbuster revenue potential for brepocitinib, and we'll show that in the coming slides. And then finally, we have a long IP runway here with protection to at least 2039.

我們正在進行的皮肌炎單項 III 期研究即將推出，該研究將在數據發布後不久作為新藥申請 (NDA) 備案的基礎，但現在看來還有些遙遠。我認為，當我們進入 2024 年上半年時，它將作為近期催化劑而成為人們關注的焦點。這只是該計劃的開始。因此，我們認為，brepocitinib 獨特的雙重機制和高功效確實創造了管道和產品方法，我們可以擁有一系列特殊風濕病適應症，每個適應症都有很高的未滿足需求和brepocitinib 的巨大收入潛力，我們將在接下來的幻燈片中展示這一點。最後，我們在這裡有一條很長的知識產權跑道，保護至少到 2039 年。

Please turn to Slide 14. So as many of you know, the JAK family consists of 4 isoforms, JAK1, JAK2, JAK3 and TYK2. The JAK family inhibition has proven over the past several years to be an enormously powerful mechanism for treating a wide spectrum of autoimmune disease. While the field has accumulated approval, starting in rheumatology and moving on to a immunodermatology and in IBD, as you see across the top, the underlying biology often remains complex and stubbornly irreducible. Shown here is a simplified schematic detailing a number of key cytokines that have been shown to drive pathobiology of autoimmune disease along with the key JAK isoforms responsible for mediating those signaling pathway.

請參閱幻燈片 14。正如你們許多人所知，JAK 家族由 4 個異構體組成：JAK1、JAK2、JAK3 和 TYK2。在過去的幾年裡，JAK 家族抑制已被證明是治療多種自身免疫性疾病的一種非常強大的機制。儘管該領域已經獲得了越來越多的認可，從風濕病學開始，一直到免疫皮膚病學和 IBD，正如您在頂部看到的那樣，潛在的生物學通常仍然複雜且頑固地不可簡化。這裡顯示的是一個簡化示意圖，詳細介紹了許多關鍵細胞因子，這些細胞因子已被證明可以驅動自身免疫性疾病的病理學，以及負責介導這些信號通路的關鍵 JAK 亞型。

While early JAK inhibitors were relatively nonselective, more recently the field has trended towards more specific inhibitors, with JAK1 having the broadest applicability and therefore, unsurprisingly, the first to be explored. You can see here in the dark blue band across the middle are JAK1 inhibitors such as RINVOQ and the cytokines that are most directly impacted. Notably, selective JAK1 inhibitors are able to suppress signaling of IL-6 and interferon gamma, 2 important cytokines linked to autoimmunity that are not suppressed to selective TYK2 inhibition.

雖然早期的 JAK 抑製劑相對無選擇性，但最近該領域已趨向於更特異性的抑製劑，其中 JAK1 具有最廣泛的適用性，因此毫不奇怪，它是第一個被探索的抑製劑。您可以在中間的深藍色條帶中看到 RINVOQ 等 JAK1 抑製劑以及最直接受影響的細胞因子。值得注意的是，選擇性 JAK1 抑製劑能夠抑制 IL-6 和乾擾素 γ 的信號傳導，這兩種與自身免疫相關的重要細胞因子不會受到選擇性 TYK2 抑制的抑制。

Now the TYK2 selective inhibitors, such as the TYK2 are now coming out of the scene in a particular set of indications. They cover a different set of cytokines, which you can see in the light blue on the right. Key among these are IL-12 and 23. The latter of which drives the differentiation and activation of Th17 cells and downstream IL-17 production, a key pathogenic driver of many autoimmune diseases.

現在，TYK2 選擇性抑製劑（例如 TYK2）正在針對一組特定的適應症出現。它們涵蓋了一組不同的細胞因子，您可以在右側的淺藍色中看到它們。其中關鍵是 IL-12 和 23。後者驅動 Th17 細胞的分化和激活以及下游 IL-17 的產生，這是許多自身免疫性疾病的關鍵致病驅動因素。

Now both JAK1 and TYK2 approaches are accumulating a track record of meaningful clinical benefit and commercial success across a range of disease. RINVOQ is already approaching $1 billion from net revenue per quarter, and Sotyktu is also projected to be a multibillion-dollar product. But in spite of their many successes, both of these medicines also have their limitations. Sotyktu, for instance, failed outright in both ulcerative colitis and Crohn's, while RINVOQ has produced lackluster Phase II data in both lupus and [HS].

現在，JAK1 和 TYK2 方法在一系列疾病中都積累了有意義的臨床效益和商業成功的記錄。 RINVOQ 每季度淨收入已接近 10 億美元，Sotyktu 預計也將成為一款價值數十億美元的產品。但儘管取得了許多成功，這兩種藥物也有其局限性。例如，Sotyktu 在治療潰瘍性結腸炎和克羅恩病方面徹底失敗，而 RINVOQ 在治療狼瘡和 [HS] 方面的 II 期數據卻乏善可陳。

We see this at least in part connected to the underlying [biology]. While some disease may be well treatable by selective JAK1 or TYK2 inhibition alone, many others involve multiple inflammatory pathways and may require intervention across multiple [orthogonal axes] to see maximum effect or maybe even to see a meaningful effect at all. The latter is especially true for heterogeneous, highly inflammatory diseases, which have high patient burden for clinically meaningful efficacy has debates and limited. So that's what drove our original hypothesis at Roivant, that the field in its current state may not be slowly maximizing the power of JAK inhibition, that efficacy might be getting left on the table in certain indications with highly specific TYK2 or JAK1 inhibitors.

我們認為這至少部分與潛在的[生物學]有關。雖然某些疾病可能可以通過單獨選擇性JAK1 或TYK2 抑制得到很好的治療，但許多其他疾病涉及多種炎症途徑，可能需要跨多個[正交軸]進行干預才能看到最大效果，甚至可能看到有意義的效果。後者對於異質性、高度炎症性疾病尤其如此，這些疾病對臨床有意義的療效具有很高的患者負擔，但存在爭議和有限。這就是我們Roivant 最初的假設的原因，即該領域目前的狀態可能不會慢慢地最大化JAK 抑制的力量，在某些高度特異性的TYK2 或JAK1 抑製劑的適應症中，其療效可能會被擱置。

So in our search for the right molecule to prove out this hypothesis, we unsurprisingly ended up partnering with Pfizer, probably the company with the longest history and deepest experience with JAKs in the industry. In brepocitinib, we found a highly active, safe and well-characterized molecule with a novel mechanism perfectly suited for what we are looking to do. Simultaneous inhibition of both TYK2 and JAK1, which we can uniquely accomplish with brepocitinib, creates 2 distinct opportunities to deliver differentiated efficacy. For diseases driven largely by type 1 interferon signaling, that is to say interferon alpha and beta, a dual hit on both sides of the heterodimer shown in the bottom in pink, second from the right and schematic on the slide, may allow for greater suppression and thus potentially greater efficacy as compared to hitting TYK2 or JAK1 alone.

因此，在我們尋找合適的分子來證明這一假設的過程中，我們毫不奇怪地最終與輝瑞公司合作，這家公司可能是業內在 JAK 方面歷史最悠久、經驗最豐富的公司。在布雷波西替尼中，我們發現了一種高活性、安全且特徵明確的分子，其新穎的機制非常適合我們想要做的事情。我們可以使用 brepocitinib 獨特地同時抑制 TYK2 和 JAK1，從而創造了 2 個不同的機會來提供差異化​​療效。對於主要由1 型乾擾素信號傳導（即乾擾素α 和β）驅動的疾病，異二聚體兩側的雙重打擊（如底部粉紅色所示（幻燈片右側第二個和示意圖所示） ）可能會產生更大的抑製作用因此與單獨攻擊 TYK2 或 JAK1 相比，潛在的功效更大。

And second, diseases with broad cytokine involvement that include, for instance, both IL-6 and B-cell pathways on one hand, and IL-12, 23 and the IL-17 Th access -- Th17 access on the other may actually be treatable with brepocitinib in a way that would not be possible through either JAK1 or TYK2 inhibition alone. So that's the core hypothesis stated in the bottom line. Brepocitinib will deliver best-in-class efficacy in indications mediated by the TYK2/JAK1 dimer and in diseases requiring broad cytokine coverage.

其次，細胞因子廣泛參與的疾病，例如一方麵包括 IL-6 和 B 細胞途徑，另一方麵包括 IL-12、23 和 IL-17 Th 通路——Th17 通路實際上可能是可以用brepocitinib 治療，而單獨通過JAK1 或TYK2 抑制是不可能的。這就是底線中提出的核心假設。 Brepocitinib 將在 TYK2/JAK1 二聚體介導的適應症和需要廣泛細胞因子覆蓋的疾病中提供一流的療效。

Please turn to Slide 15. So what concretely drove our excitement of brepocitinib? So to start, when we looked at a series of standard cytokine inhibition assays, we saw exactly what we hope to see. So shown here are the results of studies run internally at [Pfizer]. The left panel looks at type 1 interferon signal, a key driver across multiple autoimmune diseases and one where both TYK2 and JAK1 inhibition would be expected to have an effect. That's exactly what you see experimentally with nice inhibition by the leading JAK1 inhibitor and nice inhibition by the leading TYK2 inhibitor.

請翻到幻燈片 15。那麼具體是什麼讓我們對 brepocitinib 感到興奮呢？首先，當我們研究一系列標準細胞因子抑制測定時，我們看到了我們希望看到的結果。這裡顯示的是[輝瑞]內部進行的研究結果。左圖著眼於 1 型乾擾素信號，這是多種自身免疫性疾病的關鍵驅動因素，並且 TYK2 和 JAK1 抑制預計都會產生影響。這正是您在實驗中看到的結果，主要的 JAK1 抑製劑具有良好的抑製作用，而主要的 TYK2 抑製劑也具有良好的抑製作用。

And then importantly, Pfizer's experimental data showed that brepocitinib is able to suppress type 1 interferon signaling as well as or potentially even better than either RINVOQ or SOTYKTU. This is exactly what would have been predicted in the prior slide. We are benefiting from the double hit and thus achieving a greater inhibition of type 1 interferon signal.

重要的是，輝瑞的實驗數據表明，brepocitinib 能夠抑制 1 型乾擾素信號傳導，甚至可能比 RINVOQ 或 SOTYKTU 更好。這正是上一張幻燈片中所預測的。我們受益於雙重打擊，從而實現了對 1 型乾擾素信號的更大抑制。

On the right, we show 2 other critical cytokine drivers. So on the top right, we see type 2 interferon, interferon gamma, which is mediated by JAK1, but not by TYK2. So the pattern of inhibition is again, what you'd expect. You see that RINVOQ and brepocitinib, which are both inhibit JAK 1, have a relatively higher degree of inhibition of interferon gamma compared to a selective TYK2 specific inhibitor SOTYKTU.

右側顯示了另外 2 個關鍵的細胞因子驅動因素。因此，在右上角，我們看到 2 型乾擾素，即γ干擾素，它由 JAK1 介導，但不由 TYK2 介導。所以抑制模式又是你所期望的。您可以看到，與選擇性 TYK2 特異性抑製劑 SOTYKTU 相比，RINVOQ 和 brepocitinib 均抑制 JAK 1，對乾擾素 γ 的抑製程度相對較高。

And then on the bottom right, you see the opposite performance from the single isoform drugs on a cytokine inhibition assay for IL-12 and 23, both of which are TYK2 and not JAK1 median. Here you see a nice inhibition by the SOTYKTU, the TYK2 specific inhibitor, while the action of RINVOQ is much more modest. Again, that's exactly what we'd expect based on the schematic we showed in the prior slide. And again, we see that brepocitinib is a very, very unique TYK2-mediated cytokine outperforming to TYK2 in this assay.

然後在右下角，您可以看到單一同工型藥物在 IL-12 和 23 的細胞因子抑制測定中表現相反，這兩種藥物都是 TYK2 而不是 JAK1 中值。在這裡，您可以看到 TYK2 特異性抑製劑 SOTYKTU 的良好抑製作用，而 RINVOQ 的作用則要溫和得多。同樣，這正是我們根據上一張幻燈片中顯示的原理圖所期望的。我們再次看到，brepocitinib 是一種非常非常獨特的 TYK2 介導的細胞因子，在該測定中優於 TYK2。

So the conclusion is here, let's get to the bottom. On the left, you can see the brepocitinib should achieve greater type 1 interference suppression than is possible by targeting either TYK2 or JAK1 alone by virtue of the dual hit. And on the right, brepocitinib can recapitulate in a single molecule for cytokine suppression profile of both the leading TYK2 agent and the leading JAK1 agent.

那麼結論就到這裡了，我們來一探究竟吧。在左側，您可以看到 brepocitinib 應該比通過雙重打擊單獨靶向 TYK2 或 JAK1 實現更好的 1 型乾擾抑制。在右側，brepocitinib 可以在單個分子中重現主要 TYK2 藥物和​​主要 JAK1 藥物的細胞因子抑制特徵。

Please turn to Slide 16. That cytokine inhibition experimental data has translated well into a string of Phase II data readouts to date. So as you can see, oral brepocitinib has demonstrated an extremely consistent pattern of meaningful clinical efficacy in every single indication tested. Efficacy results for alopecia, psoriatic arthritis, ulcerative colitis, psoriasis and HS were all statistically significant and consistent with as good or better than any other small molecule inhibitor. The HS data, which I'll cover later, was a relatively recent readout that occurred subsequent to our taking over the drug from Pfizer.

請參閱幻燈片 16。迄今為止，細胞因子抑制實驗數據已很好地轉化為一系列 II 期數據讀數。正如您所看到的，口服布雷波西替尼在每個測試的單一適應症中都表現出了極其一致的有意義的臨床療效模式。對於脫髮、銀屑病關節炎、潰瘍性結腸炎、銀屑病和 HS 的療效結果均具有統計學顯著性，並且與任何其他小分子抑製劑一樣好或更好。我稍後將介紹的 HS 數據是我們從輝瑞公司接管該藥物後相對較新的讀數。

We're also excited to be reporting today the induction results of a large global Phase II Crohn's study run by Pfizer. So I'll provide some additional details in the following slide. Finally, we have another major benefit in the clinical package for brepocitinib. We know what we have on safety as well. So we know that stacking both TYK2 inhibition and JAK1 inhibition does not apparently lead to a safety profile that undercuts the efficacy advantages that we hope to show. Our extensive safety database now consists of over 1,400 patients exposed across 20 different Phase I and Phase II clinical studies for up to 64 weeks. And what we've seen is a well-characterized safety profile in line with approved JAK family inhibitors.

我們今天還很高興地報告輝瑞公司開展的一項大型全球 II 期克羅恩病研究的誘導結果。因此，我將在下面的幻燈片中提供一些其他詳細信息。最後，我們在 brepocitinib 的臨床方案中還有另一個主要優勢。我們也知道我們在安全方面有什麼。因此，我們知道，疊加 TYK2 抑制和 JAK1 抑制顯然不會導致安全性降低，從而削弱我們希望展示的功效優勢。我們廣泛的安全數據庫現在包含 1,400 多名患者，這些患者接受了 20 項不同的 I 期和 II 期臨床研究，為期長達 64 週。我們所看到的是與已批准的 JAK 家族抑製劑一致的良好特徵安全性。

Please turn to Slide 17. So we're pleased to report today the top line results from the induction portion of a Phase II study with brepocitinib in Crohn's disease. This is 151-patient global Phase II study. The primary endpoint was the SES-CD 50 and the key secondary endpoint was the clinical remission rate at week 12, defined as a proportion of patients who achieved a CDAI of less than 150. Both endpoints were highly statistically significant. We think that actually the true efficacy might have been understated on the SES-CD 50 in the study as there ended up being a slight imbalance in baseline severity between the arms, which made it harder to achieve that endpoint for the drug arm.

請參閱幻燈片 17。今天，我們很高興地報告 brepocitinib 治療克羅恩病的 II 期研究的誘導部分的主要結果。這是一項包含 151 名患者的全球 II 期研究。主要終點是 SES-CD 50，關鍵次要終點是第 12 週的臨床緩解率，定義為 CDAI 低於 150 的患者比例。這兩個終點均具有高度統計顯著性。我們認為，實際上，研究中 SES-CD 50 的真實療效可能被低估，因為各組之間的基線嚴重程度最終存在輕微不平衡，這使得藥物組更難達到該終點。

That imbalance would not have an impact on the secondary endpoint since the way that, that endpoint is calculated only takes into account patients who start with a baseline CDAI of greater than or equal to 220. The punchline here is that this is a trial that I'm sure it wasn't on any investor's radar and yet has delivered really strong efficacy. In fact, that 33.5% placebo-adjusted delta on clinical remission, which is used as a co-primary endpoint in registrational studies and is particularly important for prescribers is, in fact, the highest seen in the late-stage study from any drug oral or biologic to date.

這種不平衡不會對次要終點產生影響，因為計算該終點的方式僅考慮以基線 CDAI 大於或等於 220 開始的患者。這裡的要點是，這是我進行的一項試驗。我確信它沒有引起任何投資者的注意，但它卻產生了非常強大的功效。事實上，臨床緩解的 33.5% 安慰劑調整增量（被用作註冊研究中的共同主要終點，對處方者尤為重要）實際上是所有藥物口服藥物的後期研究中所見的最高值。或迄今為止的生物學。

Please turn to Slide 18. So we find ourselves in an enviable position. So we have a highly efficacious molecule that has strong biologic and clinical translation in a variety of large market indications. There are lots of things that we could do with brepocitinib, but our vision with brepocitinib from the start was to really focus on those indications where we could deliver a step function improvement in outcomes for patients, generating maximum impact for patients and maximum return for our investors.

請翻到幻燈片 18。所以我們發現自己處於一個令人羨慕的位置。因此，我們擁有一種高效分子，在各種大型市場適應症中具有強大的生物學和臨床轉化能力。我們可以用brepocitinib 做很多事情，但我們從一開始就對brepocitinib 的願景是真正關注那些我們可以為患者的結果提供階躍功能改善的適應症，為患者產生最大的影響，並為我們的患者帶來最大的回報。投資者。

To that end, we ask ourselves what are the disease indications where the unique properties of brepocitinib will really shine. For us, that came down to a few simple considerations laid out on the left side of the slide. So in the light blue and moving clockwise, the first where is inhibition of both TYK2 and JAK1 required for maximal efficacy? Here we look for biologic rationale for dual TYK2/JAK1 inhibition and corresponding clinical validation. Second, in dark blue, which indications have extremely high morbidity and mortality, creating a need for novel therapies that provide a meaningful efficacy benefit. And third, in pink, there's the indication has few available treatments, including no approved oral therapies.

為此，我們要問自己，在哪些疾病適應症中，布雷波西替尼的獨特特性將真正發揮作用。對於我們來說，這可以歸結為幻燈片左側列出的一些簡單的考慮因素。那麼，在淺藍色中並順時針移動，要獲得最大功效，第一個需要抑制 TYK2 和 JAK1 的地方是什麼？在這裡，我們尋找 TYK2/JAK1 雙重抑制的生物學原理和相應的臨床驗證。其次，深藍色表示該適應症的發病率和死亡率極高，因此需要能夠提供有意義的療效益處的新型療法。第三，粉紅色表示幾乎沒有可用的治療方法，包括沒有批准的口服療法。

And finally, of course, we need to be confident that we could run an efficient experiment, minimizing development and regulatory risk. Put those together, we think that there's an opportunity for brepocitinib to become a leading treatment option in a series of large and uncrowded markets. The next 2 slides will go into more detail on [DM and lupus]. But remember, that's just the beginning.

最後，當然，我們需要相信我們可以進行有效的實驗，最大限度地降低開發和監管風險。綜上所述，我們認為 brepocitinib 有機會成為一系列大型且不擁擠的市場中的領先治療選擇。接下來的 2 張幻燈片將詳細介紹 [DM 和狼瘡]。但請記住，這只是開始。

Please turn to Slide 19. Dermatomyositis is a large orphan indication with a very similar profile to indications like PAH and cystic fibrosis, where oral small molecules have become $1 billion plus products. Over the past 30 years, dermatomyositis has become much better understood and characterized in the medical community. An increasing disease awareness and diagnosis has led to higher incidence and [prevalence] estimates over time. We've done our own analysis with claims data from 2016 to 2020 and estimates that the U.S. adult prevalence sits at 37,000 patients, consistent with recently published estimates as well.

請參閱幻燈片 19。皮肌炎是一種大型孤兒適應症，其特徵與 PAH 和囊性纖維化等適應症非常相似，口服小分子藥物已成為價值超過 10 億美元的產品。在過去的 30 年裡，醫學界對皮肌炎的了解和特徵有了更深入的了解。隨著時間的推移，疾病意識和診斷的不斷提高導致發病率和[患病率]估計值上升。我們對 2016 年至 2020 年的索賠數據進行了自己的分析，估計美國成人患病率為 37,000 名患者，這也與最近發布的估計一致。

So we're looking at a patient population that is already clearly in the large orphan category. This is not an [ultrarare] indication. And as awareness and diagnosis of the disease continues to increase, we expect the number of patients to grow over time. For an autoimmune disease of impacting this many patients, dermatomyositis presents a strikingly high disease burden. There is high mortality with some estimates of up to 40% at 5 years. The characteristic skin rashes shown on the right cover large percentages of the body and lead to significant pain in addition to disfigurement. The vast majority of patients also suffer from proximal muscle weakness, which can severely impact daily living activities. Many patients end up meeting walkers or wheelchairs. Finally, a meaningful proportion of patients suffer from interstitial lung disease.

因此，我們正在研究已經明顯屬於大型孤兒類別的患者群體。這不是一個[極其罕見]的跡象。隨著對該疾病的認識和診斷不斷提高，我們預計患者數量會隨著時間的推移而增加。對於影響這麼多患者的自身免疫性疾病來說，皮肌炎帶來了驚人的高疾病負擔。死亡率很高，有人估計 5 年死亡率高達 40%。右側所示的特徵性皮疹覆蓋了身體的大部分區域，除了導致毀容外，還會導致嚴重的疼痛。絕大多數患者還患有近端肌肉無力，這會嚴重影響日常生活活動。許多患者最終會遇到助行器或輪椅。最後，相當一部分患者患有間質性肺病。

In sum, this is a high mortality, highly inflammatory disease, which covers multiple organ systems and will evolve into a large commercial market. On top of that, there have been no NCEs approved in the past 60 years, and there are no oral therapies in industry-sponsored late-stage development. Steroids, [ISTs] and IVIGs have been used for many years, with the latter recently gaining formal approval. But again, there is not a single modern drug approved for the indication and the current treatment options present high safety and convenience burdens in addition to limited benefit. IVIG, for instance, requires multi-hour infusions for 3 or more days every month and is associated with side effects, including quite a high rate of thrombotic event.

總而言之，這是一種高死亡率、高炎症性疾病，覆蓋多個器官系統，將演變成一個巨大的商業市場。最重要的是，過去 60 年來沒有任何 NCE 獲得批准，也沒有處於行業資助的後期開發中的口服療法。類固醇、[IST] 和 IVIG 已使用多年，後者最近獲得正式批准。但同樣，沒有一種現代藥物被批准用於該適應症，目前的治療方案除了有限的益處外，還存在很高的安全性和便利性負擔。例如，IVIG 需要每月 3 天或更多天進行數小時輸注，並且會產生副作用，包括相當高的血栓事件發生率。

So we really see DM as one of the major unmet needs in all of autoimmune disease and an opportunity for a modern targeted therapy, particularly in (inaudible) to enter the market and rapidly become a blockbuster product. And while a number of companies are exploring small proof-of-concept studies, there are very few drugs in late-stage development and no oral therapies in Phase III, other than brepocitinib. So looking ahead to a product launch of brepo in this market in just 3 years, we think this has the potential to become a material commercial driver for Roivant as we think about the overall sales across our pipeline over the next 5-plus years.

因此，我們確實將 DM 視為所有自身免疫性疾病中未滿足的主要需求之一，也是現代靶向治療的機會，特別是（聽不清）進入市場並迅速成為重磅產品。儘管許多公司正在探索小型概念驗證研究，但除 brepocitinib 外，處於後期開發階段的藥物很少，並且沒有處於 III 期的口服療法。因此，展望 brepo 產品在短短 3 年內在該市場的推出，我們認為這有可能成為 Roivant 的實質性商業驅動力，因為我們考慮了未來 5 年多的整個管道的整體銷售。

Please turn to Slide 20. We also see this as an indication where the probabilty of success for brepo is very high. With no modern medicines approved for DM, the physicians often experiment with various different therapies to add on a corticosteroid. As a result, through investigator-initiated studies in an extensive body of case report, there is meaningful clinical validation for JAK1 inhibition in DM. This aligns with the pathobiology of the disease, which is driven in large part by type 1 and type 2 interferon signal.

請參閱幻燈片 20。我們也認為這表明 brepo 成功的可能性非常高。由於沒有批准治療糖尿病的現代藥物，醫生經常嘗試各種不同的療法來添加皮質類固醇。因此，通過研究者發起的大量病例報告研究，對 DM 中的 JAK1 抑制進行了有意義的臨床驗證。這與該疾病的病理生物學相一致，該疾病在很大程度上是由 1 型和 2 型乾擾素信號驅動的。

Given no other JAK1 inhibitors are approved or an industry-sponsored development for DM, even if brepo just matched this level of efficacy that will set us up well for clear commercial success, but there's also reason to believe that the addition of TYK2 inhibition can further add to the benefit that brepocitinib will provide, both to enhance potency of type 1 interferon suppression as well as through suppression of IL-12 and 23, which are also involved in DM pathobiology.

鑑於沒有其他JAK1 抑製劑獲得批准，也沒有行業贊助的DM 開發，即使brepo 恰好達到了這一水平的功效，這將為我們取得明顯的商業成功奠定良好的基礎，但也有理由相信，添加TYK2 抑制劑可以進一步增加了 brepocitinib 將提供的益處，既可以增強 1 型乾擾素抑制的效力，也可以通過抑制 IL-12 和 23（它們也參與 DM 病理學）。

Please turn to Slide 21. Given the high unmet need and our high confidence in our clinical success, we took the bold step of moving directly into a Phase III program that involves a single registrational study. Our expectation is that this study, if successful, would support an NDA filing for brepocitinib in DM. The single Phase III study is already well underway, tracking to complete enrollment in 2024 with data and a potential NDA filing in 2025. This time line has us clearly positioned to be the first oral to market by potentially several years and likely also ahead of a few biologics and later stage development.

請參閱幻燈片 21。鑑於大量未滿足的需求以及我們對臨床成功的高度信心，我們採取了大膽的步驟，直接進入涉及單一註冊研究的 III 期計劃。我們的期望是，如果這項研究成功，將支持布雷波西替尼治療糖尿病的 NDA 申請。單項III 期研究已經順利進行，預計將於2024 年完成入組，並在2025 年提交新藥申請（NDA）。這個時間線使我們明確定位為第一個上市的口服藥物，可能需要幾年時間，也可能領先於很少有生物製劑和後期開發。

One idiosyncratic consequence of our decision to move directly into Phase III is that it means that our next catalyst in DM won't be coming until 2025. But that catalyst could be a major inflection point for Roivant as a business, with a potential $1 billion-plus product line immediately to follow. And given this launch would be in an orphan indication with a specialized prescriber base, we would expect the revenue ramp to be significantly steeper than for a volume product like VTAMA. So as you think about modeling (inaudible) over the next 5 years and beyond, we think this is a major first additional value that investors right now may be underappreciated.

我們決定直接進入第三階段的一個特殊後果是，這意味著我們在DM 領域的下一個催化劑要到2025 年才會出現。但這種催化劑可能是Roivant 作為一項業務的一個主要轉折點，潛在價值10 億美元-加上緊隨其後的產品線。鑑於此次推出將是一個孤兒適應症，具有專門的處方者基礎，我們預計收入增長將比 VTAMA 這樣的批量產品陡峭得多。因此，當您考慮未來 5 年及以後的建模（聽不清）時，我們認為這是投資者目前可能被低估的主要附加價值。

Please turn to Slide 22. DM is the first of many orphan indications, where we see a similar opportunity for brepocitinib, and I'll talk about a few more of those in a bit. But first, I want to talk to the other indication where we have an ongoing pivotal study and where we do have a major catalyst coming up later this year, and that's lupus. So lupus is a disease that everyone knows well and that is -- and is one that's gotten an increasing amount of attention from industry in recent years. Hundreds of thousands of patients suffer from lupus in the U.S., many with serious and debilitating disease.

請參閱幻燈片 22。DM 是眾多孤兒適應症中的第一個，我們在其中看到了 brepocitinib 的類似機會，稍後我將討論其中的一些。但首先，我想談談另一個跡象，我們正在進行一項關鍵研究，並且我們確實在今年晚些時候出現了一個主要催化劑，那就是狼瘡。因此，狼瘡是一種人盡皆知的疾病，而且近年來越來越受到業界的關注。在美國，有數十萬狼瘡患者，其中許多人患有嚴重且使人衰弱的疾病。

Only 2 therapies have approved -- been approved in the past 20 years, both injectables. There is a sign of how desperate the field is for [efficacy]. BENLYSTA is doing greater than $1.4 billion in U.S. revenue despite very modest efficacy at between 9% to 14% placebo-adjusted SRI-4. And SAPHNELO, which launched recently, is projected to be a $1 billion-plus product despite mixed Phase III data. One study didn't show (inaudible) significance, while the other showed about 18% placebo-adjusted SRI-4.

過去 20 年來，只有 2 種療法獲得批准，均為註射劑。有跡象表明該領域對[功效]的渴望是多麼迫切。儘管安慰劑調整後的 SRI-4 療效非常有限，僅為 9% 至 14%，但 BENLYSTA 在美國的收入超過 14 億美元。最近推出的 SAPHNELO 預計將成為一款價值超過 10 億美元的產品，儘管 III 期數據參差不齊。一項研究沒有顯示出（聽不清）顯著性，而另一項研究則顯示了約 18% 的安慰劑調整 SRI-4。

Please turn to Slide 23. The limited options reflect an unfortunate reality everyone knows well. Lupus is simply a very challenging disease to treat. It's highly heterogeneous with multiple interconnected inflammatory pathways, acting on T cells, B cells and interferon signaling and multiple impacted organ systems. To date, most attempts to treat lupus involve a molecule acting predominantly across one of the 3 axes. BENLYSTA, for example, depletes B cells, while SAPHNELO suppresses interferon signal. Both have generated meaningful, but ultimately somewhat modest efficacy.

請參閱幻燈片 23。有限的選擇反映了一個眾所周知的不幸現實。狼瘡是一種非常難以治療的疾病。它具有高度異質性，具有多個相互關聯的炎症途徑，作用於 T 細胞、B 細胞和乾擾素信號傳導以及多個受影響的器官系統。迄今為止，大多數治療狼瘡的嘗試都涉及一種主要作用於三個軸之一的分子。例如，BENLYSTA 會消耗 B 細胞，而 SAPHNELO 則會抑制干擾素信號。兩者都產生了有意義的效果，但最終效果有些有限。

And of course, there's a long history of failed attempts at individual cytokine inhibition, indicating [border] cytokine suppression is needed as well. Through dual TYK2 and JAK1 inhibition, brepocitinib is distinctively optimized to address all 3 axes simultaneously. TYK2 arm modulates T cell activities through IL-12 and the IL-17, Th17 axis to IL-23. The JAK1 arm modulates B-cell activity through IL-6, IL-7 and IL-21, and both arms work together to maximally suppress pathogenic type 1 interferon signal.

當然，長期以來，個體細胞因子抑制的嘗試都失敗了，這表明[邊界]細胞因子抑制也是必要的。通過 TYK2 和 JAK1 雙重抑制，brepocitinib 經過獨特優化，可同時處理所有 3 個軸。 TYK2 臂通過 IL-12 和 IL-17、Th17 軸至 IL-23 調節 T 細胞活性。 JAK1 臂通過 IL-6、IL-7 和 IL-21 調節 B 細胞活性，並且兩個臂共同作用以最大限度地抑制致病性 1 型乾擾素信號。

Please turn to Slide 24. Over the past 18 months, we've had readouts from 3 JAK inhibitors in lupus, including Phase III data from Olumiant, a JAK1 and 2 inhibitor; Phase II data from RINVOQ, the JAK1 inhibitor; and Phase II data from SOTYKTU, a TYK2 inhibitor. These data provide clinical evidence for the therapeutic relevance of each of JAK1 and TYK2, respectively, in lupus and as such, increased our confidence in brepocitinib's positive effect. At the same time, none of these molecules have demonstrated particularly compelling benefit with the high watermark so far being SOTYKTU if you [blend it] across roughly the mid-teens placebo-adjusted SRI-4.

請參閱幻燈片 24。在過去 18 個月中，我們獲得了 3 種 JAK 抑製劑治療狼瘡的數據，包括 Olumiant（一種 JAK1 和 2 抑製劑）的 III 期數據； JAK1 抑製劑 RINVOQ 的 II 期數據；以及 TYK2 抑製劑 SOTYKTU 的 II 期數據。這些數據分別為 JAK1 和 TYK2 在狼瘡中的治療相關性提供了臨床證據，因此增加了我們對 brepocitinib 積極作用的信心。與此同時，如果你將其[混合]到大約十幾歲的安慰劑調整後的SRI-4 中，那麼到目前為止，這些分子都沒有表現出特別引人注目的益處，因為SOTYKTU 的高水位。

This is what we might expect, given that unlike brepocitinib, none of these molecules directly targets all 3 inflammatory axes in lupus. So we are cautiously optimistic that through dual TYK2 and JAK1 inhibition, brepocitinib can deliver greater efficacy benefit than we've seen from these other oral therapies and become the leading oral therapy for patients and physicians.

這是我們所期望的，因為與 brepocitinib 不同，這些分子沒有一個直接針對狼瘡的所有 3 個炎症軸。因此，我們謹慎樂觀地認為，通過 TYK2 和 JAK1 雙重抑制，brepocitinib 可以提供比我們從其他口服療法中看到的更大的療效益處，並成為患者和醫生的領先口服療法。

Please turn to Slide 25. We continue to expect top line results from our ongoing study of brepocitinib in lupus in the fourth quarter of this year. As we've stated in previous earnings calls, this is a large global study using the registrational 52-week primary endpoint and as such, it is designed to serve as one of the 2 registrational studies. In the event of a positive outcome, we would expect to rapidly initiate a second confirmatory registrational study.

請參閱幻燈片 25。我們繼續期待今年第四季度我們正在進行的 brepocitinib 治療狼瘡的研究得出最重要的結果。正如我們在之前的財報電話會議中所述，這是一項使用註冊 52 週主要終點的大型全球研究，因此，它旨在作為兩項註冊研究之一。如果取得積極結果，我們預計將迅速啟動第二項驗證性註冊研究。

I do want to emphasize that while we're cautiously optimistic that brepocitinib can deliver data that will position us as the leading oral therapy in lupus, our confidence in the probabilty of success here is not as high as in dermatomyositis. We feel rock solid that we are hitting the pathways that matter. But we, as an industry, have had mixed success in proving out efficacy and regulatory end points, such as SRI-4. Lupus is just a challenging indication in that respect. And it was not the core bet that we underwrote when we in-licensed brepocitinib. That bet rather is the opportunity in dermatomyositis and the string of other large orphan indications that potentially follow. And given the 6 successful Phase III placebo-controlled studies we had to date, our enthusiasm about brepocitinib in these other indications will remain irrespective of our results in lupus.

我確實想強調，雖然我們對布雷波西替尼可以提供使我們成為狼瘡領先口服療法的數據持謹慎樂觀態度，但我們對此成功概率的信心並不像皮肌炎那樣高。我們感覺堅如磐石，因為我們正在走上重要的道路。但作為一個行業，我們在證明功效和監管終點（例如 SRI-4）方面取得了不同程度的成功。在這方面，狼瘡只是一個具有挑戰性的跡象。當我們獲得布雷波西替尼許可時，這並不是我們承保的核心賭注。相反，這個賭注是皮肌炎和隨後可能出現的一系列其他大型孤兒適應症的機會。鑑於我們迄今為止已完成 6 項成功的 III 期安慰劑對照研究，無論我們在狼瘡方面的結果如何，我們對 brepocitinib 在這些其他適應症中的熱情將保持不變。

Please turn to Slide 26. Turning now to these other indications, I just want to highlight 2 in addition to dermatomyositis, where we have a rapid potential path to market with launches that could follow closely behind DM. A couple to highlight here are non-infectious Uveitis, or NIU, and HS.

請轉到幻燈片 26。現在轉向這些其他適應症，我只想強調除皮肌炎之外的 2 個適應症，我們有一條快速的潛在市場途徑，可以緊隨 DM 推出。這裡要強調的兩個是非感染性葡萄膜炎（NIU）和 HS。

Please turn to Slide 27. NIU, like dermatomyositis, is a large orphan indication with a very high disease burden, with approximately 30,000 cases of legal blindness attributable to NIU each year. Unlike DM, there is one approved targeted therapy, HUMIRA, which has generated over $0.5 billion per year in sales despite limited efficacy and almost no indication to specific promotions. The development stage competitive landscape in NIU is even more wide open than in DM with no ongoing Phase III studies at this time for any oral or biologic, an efficacious oral therapy could easily match HUMIRA's peak sales in this indication and with sufficiently compelling data, we could potentially do significantly more.

請參閱幻燈片 27。NIU 與皮肌炎一樣，是一種大型孤兒適應症，疾病負擔非常高，每年約有 30,000 例法定失明病例歸因於 NIU。與 DM 不同的是，有一種獲批的靶向治療藥物 HUMIRA，儘管療效有限且幾乎沒有具體促銷的跡象，但每年的銷售額已超過 5 億美元。 NIU 的開發階段競爭格局比DM 更加開放，目前沒有正在進行的任何口服或生物製劑的III 期研究，有效的口服療法可以輕鬆匹配HUMIRA 在該適應症中的峰值銷售，並且有足夠令人信服的數據，我們可能會做得更多。

Please turn to Slide 28. As with DM, we also have clinical validation of JAK1 inhibition in NIU. Before filgotinib development was discontinued in the U.S., it has generated Phase II data in NIU suggesting JAK1 inhibition may be more efficacious than TNF alpha suppression by HUMIRA. However, the extent and robustness of clinical validation of JAK1 inhibition in NIU is not quite as great as in DM. And so in this indication, rather than moving straight to Phase III, we are conducting a quick proof of concept here. This study also includes dose ranging that would make a potential pivotal study even more efficient. We're excited to report that this study is now fully enrolled with top line data expected in the first quarter of 2024.

請參閱幻燈片 28。與 DM 一樣，我們也在 NIU 中進行了 JAK1 抑制的臨床驗證。在 filgotinib 在美國停止開發之前，它已在 NIU 中產生了 II 期數據，表明 JAK1 抑制可能比 HUMIRA 抑制 TNF α 更有效。然而，NIU 中 JAK1 抑制的臨床驗證的程度和穩健性不如 DM 中那麼大。因此，在這個跡像中，我們不是直接進入第三階段，而是在這裡進行快速概念驗證。這項研究還包括劑量範圍，這將使潛在的關鍵研究更加有效。我們很高興地報告，這項研究現已全部入組，預計將於 2024 年第一季度獲得頂線數據。

Please turn to Slide 29. HS follows a similar pattern to DM and NIU, a highly debilitating disease with a large orphan prevalence increasing over time through increased diagnosis and awareness. Here, too, HUMIRA is the only approved targeted therapy with indication-specific sales of approximately $3 billion per year, again, despite limited efficacy and limited indications specific promotion.

請參閱幻燈片 29。 HS 遵循與 DM 和 NIU 類似的模式，這是一種高度衰弱的疾病，隨著診斷和認識的提高，孤兒患病率隨著時間的推移而增加。在這裡，HUMIRA 也是唯一獲得批准的靶向治療藥物，儘管療效有限且針對特定適應症的推廣也有限，但每年針對特定適應症的銷售額約為 30 億美元。

Please turn to Slide 30. Unlike DM and NIU, HS does have other oral therapies in later-stage development, specifically 2 JAK1 inhibitors. As you can see on this slide, the safety recently generated by brepocitinib is greater both in terms of absolute and placebo-adjusted benefit than that seen from either of these molecules. Brepocitinib's benefit observed in Phase II also surpasses the 42% growth and 16% placebo-adjusted benefit in (inaudible) Phase III program. Notably, brepocitinib's benefit was robust across both TNF naive and TNF refractory patients and was generated despite the study being heavily impacted by COVID-related discontinuation. In fact, the placebo-adjusted benefit among completers was actually 27%, suggesting an opportunity to potentially demonstrate even greater benefit in Phase III than Phase II. This is further supported by HS pathobiology, which involves not only JAK1 mediated inflammatory pathways, but also the clinically validated IL-23, Th17 axis, which is suppressed by TYK2 inhibition, but not JAK1 inhibition.

請參閱幻燈片 30。與 DM 和 NIU 不同，HS 確實有其他處於後期開發的口服療法，特別是 2 個 JAK1 抑製劑。正如您在這張幻燈片中所看到的，最近由 brepocitinib 產生的安全性在絕對效益和安慰劑調整效益方面都比這兩種分子中的任何一種都更高。 Brepocitinib 在 II 期試驗中觀察到的獲益也超過了（聽不清）III 期項目中 42% 的增長和 16% 的安慰劑調整獲益。值得注意的是，儘管該研究受到與新冠病毒相關的停藥的嚴重影響，但布雷波西替尼對 TNF 初治患者和 TNF 難治性患者均產生了顯著的獲益。事實上，完成者的安慰劑調整獲益實際上為 27%，這表明第三階段有可能比第二階段表現出更大的獲益。這得到了 HS 病理學的進一步支持，HS 病理學不僅涉及 JAK1 介導的炎症通路，還涉及臨床驗證的 IL-23、Th17 軸，該軸受到 TYK2 抑制的抑制，但不受 JAK1 抑制的抑制。

Please turn to Slide 31. So I hope I've been able to convey in some small part, how excited we are about the potential for brepocitinib. It's a highly active molecule with a unique mechanism of action and long patent life that sets us up to potentially create the leading oral specialty autoimmune franchise in the pharmaceutical industry. Here on this slide, you see how this pipeline and a product will be built in the coming years. The successful lupus readout later this year clearly tees up a multibillion-dollar commercial opportunity in business alone.

請參閱幻燈片 31。因此，我希望我能夠在一小部分內容中表達出我們對 brepocitinib 的潛力感到多麼興奮。它是一種高度活躍的分子，具有獨特的作用機制和較長的專利壽命，使我們有可能創造製藥行業領先的口服專業自身免疫特許經營權。在這張幻燈片上，您可以看到未來幾年將如何構建該管道和產品。今年晚些時候成功的狼瘡讀數顯然在商業領域帶來了數十億美元的商業機會。

But even without lupus, we have a rapid derisk path to $1 billion-plus commercial launch in DM, with full enrollment of our pivotal study coming next year, data in 2025 and a potential product launch in 2026. And then there's a rapid pipeline of other large orphan indications to follow, each with blockbuster potential, a pivotal program in HS, NIU or both could be initiated in 2024. And we have other large orphan indications to follow with potential proof-of-concept studies planned for 2024.

但即使沒有狼瘡，我們也有一條快速消除風險的道路，可以在DM 領域投入超過10 億美元的商業啟動，我們的關鍵研究將於明年全面註冊，2025 年數據，並有可能在2026 年推出產品。然後有一個快速的管道其他大型孤兒適應症，每個都具有重磅潛力，HS、NIU 或兩者的關鍵計劃可能會在2024 年啟動。我們還有其他大型孤兒適應症，計劃在2024 年進行潛在的概念驗證研究。

With that, I'd like to thank Ben Zimmer and the rest of the Priovant team for all their work on brepocitinib so far and of course, to our colleagues at Pfizer for both partnering with us on this program, and of course, for all their work in discovering the compound and generating this really rich data set. And I'd also like to thank all the investigators, site personnel and importantly to the patients who participate in these trials as well.

在此，我要感謝 Ben Zimmer 和 Priovant 團隊的其他成員迄今為止在 brepocitinib 方面所做的所有工作，當然還要感謝輝瑞的同事在這個項目上與我們合作，當然還要感謝所有他們的工作是發現這種化合物並生成這個非常豐富的數據集。我還要感謝所有研究人員、現場工作人員，重要的是還要感謝參與這些試驗的患者。

And with that, I'll turn it back over to Matt.

有了這個，我會把它轉回給馬特。

Thanks, Mayukh. Appreciate it. And obviously, thank you for that -- a deep dive into the program. Stuck with some questions about it, but I also just want to set people up for the months and frankly, years ahead with it. So looking forward to more there. I'm going to go very quickly through the rest here and then open up for Q&A in just a minute or 2. Starting with on Slides 34 and 35. While we're not going to spend any time today on the TL1A data, it occurred to me as we were finalizing this presentation, the June 30 quarter was the quarter in which we had generated the 56-week maintenance data and that it felt -- it felt weird not to at least (inaudible) to that extraordinary data set. So we've had a couple of calls on that topic so far. The TL1A program is an incredibly exciting opportunity. And we continue to look at the state and find new things to like about it, including the continued improvement into 56 weeks and some of the things that set us up really well for the Phase III program. So more on that to come.

謝謝，馬尤赫。欣賞它。顯然，感謝您深入了解該計劃。我對此有一些疑問，但我也只是想讓人們為未來幾個月甚至幾年做好準備。所以期待那裡有更多。我將快速瀏覽完此處的其餘部分，然後在一兩分鐘內進行問答。從幻燈片 34 和 35 開始。雖然我們今天不會花任何時間討論 TL1A 數據，但它當我們最終完成這份演示文稿時，我突然想到，6 月30 日的季度是我們生成56 周維護數據的季度，而且感覺- 至少不（聽不清）那個非凡的數據集感覺很奇怪。到目前為止，我們已經就該主題進行了幾次通話。 TL1A 計劃是一個令人難以置信的令人興奮的機會。我們繼續關注該州並發現新的值得喜歡的地方，包括 56 週的持續改進以及一些為我們的 III 期計劃做好準備的事情。未來還會有更多相關內容。

As a reminder, on Slide 36, we are now underway, including first patient dose with our Phase II study in Crohn's. The goal here is to get, as I've said it before, dose ranging "out of the way" prior to beginning Phase III in a way where when we look at all of these time lines and stacking together, we think we still have an opportunity to be effectively first-in-class in Crohn's disease by going quickly from this study -- into a Phase III study in Crohn's. So we're very excited about the opportunity for TL1A in Crohn's in addition to UC and look forward to sharing more data next year when the study concludes.

提醒一下，在幻燈片 36 上，我們現在正在進行中，包括克羅恩病 II 期研究的首個患者劑量。正如我之前所說，這裡的目標是在開始第三階段之前“排除”劑量範圍，當我們查看所有這些時間線並將其疊加在一起時，我們認為我們仍然有通過快速從這項研究進入克羅恩病的III 期研究，有機會成為克羅恩病領域的一流藥物。因此，除了 UC 之外，我們對 TL1A 在克羅恩病中的機會感到非常興奮，並期待明年研究結束時分享更多數據。

And then lastly, on the late-stage portfolio on Slide 37. I talked about this a little bit at the beginning. Obviously, we collectively -- likely by Immunovant are going to have an opportunity to get back together in the next couple of months to talk about updates on our FcRn franchise. Most notably, we are expecting imminently within the next 8 months -- I think [Immunovant] September for the single-ascending dose data in October, November for the multiple sending dose data. Data that we think will validate the best-in-class potential for IMVT-1402 our next-generation anti-FcRn.

最後，關於幻燈片 37 上的後期投資組合。我在一開始就談到了這一點。顯然，我們集體——可能是通過Immunovant——將有機會在接下來的幾個月內聚在一起討論我們的FcRn 特許經營權的更新。最值得注意的是，我們預計在接下來的8 個月內即將到來- 我認為[Immunovant] 9 月將提供單次遞增劑量數據，10 月將提供單次劑量遞增數據，11 月將提供多次發送劑量數據。我們認為這些數據將驗證我們的下一代抗 FcRn 藥物 IMVT-1402 的同類最佳潛力。

As a reminder, the hope there is to show that we can continue to suppress IgG to a best-in-class level while also avoiding the impacts on albumin and LDL that have been seen with batoclimab. It's been a busy year for the FcRn field. And the other thing I'll point out is that we just recently saw data from a competitor efgartigimod in CIDP, which was really great data that both continue to underpin and validate the FcRn mechanism. It's now worked -- basically everywhere, it's been studied and showed a potential in a new market, including the one where we have an ongoing Phase IIb study of a relatively similar design to the extent that just right out, we'll have some top line data from that study perhaps next year.

提醒一下，我們希望表明我們可以繼續將 IgG 抑製到同類最佳水平，同時避免使用 batoclimab 時出現的對白蛋白和 LDL 的影響。對於 FcRn 領域來說，這是忙碌的一年。我要指出的另一件事是，我們最近剛剛在 CIDP 中看到了競爭對手 efgartigimod 的數據，這確實是很棒的數據，可以繼續支持和驗證 FcRn 機制。現在它已經發揮作用了——基本上在任何地方，它都經過了研究，並顯示出在新市場中的潛力，包括我們正在進行的IIb 期研究，研究相對相似的設計，在某種程度上，我們將有一些頂級的產品。也許明年就會得到該研究的線數據。

And then the last thing I wanted to briefly shine a spotlight on to on Slide 38 is just we continue to make progress on our various discovery efforts. I've got a slide here on VantAI which is a rapidly progressing effort that we have to use certain advanced machine learning techniques, specifically on induced proximity and protein degradation. One note here, we had previously had a number of efforts in this area, including one at Proteovant, we've now effectively collapsed the Proteovant induced proximity effort into VantAI and have sold the balance of our Proteovant shares to our partner SK.

然後，我想在幻燈片 38 上短暫強調的最後一件事就是我們在各種發現工作上繼續取得進展。我這裡有一張關於 VantAI 的幻燈片，這是一項快速進展的工作，我們必須使用某些先進的機器學習技術，特別是在誘導接近和蛋白質降解方面。這裡需要注意的是，我們之前在這一領域進行了許多努力，包括在Proteovant 的一項努力，我們現在已經有效地將Proteovant 引發的鄰近工作整合到VantAI 中，並將我們的Proteovant 股份的餘額出售給我們的合作夥伴SK。

And so VantAI is now the sort of instantiation of our principal day at Roivant an induced proximity protein degradation, and we are really excited with the early progress there, including some great hiring. Notably, we've now got Michael Bronstein, as VantAI scientist. He's one of the -- really the lions in the field of molecular modeling using machine learning. And so we're really excited to have him on board and some other great hires there as well, but we'll talk more about soon. Real progress coming, and we'll get back on the phone as we've got data to share, but keep an eye on this space as it work.

因此，VantAI 現在是我們在 Roivant 的主要日子的實例，誘導鄰近蛋白降解，我們對那裡的早期進展感到非常興奮，包括一些出色的招聘。值得注意的是，我們現在聘請了 Michael Bronstein，擔任 VantAI 科學家。他是利用機器學習進行分子建模領域真正的佼佼者之一。因此，我們非常高興他和其他一些優秀員工的加入，但我們很快就會討論更多內容。真正的進展即將到來，我們會重新打電話，因為我們有數據要分享，但請密切關注這個領域的運作。

So I'll wrap up very quickly on Slide 40 with brief financial update. Financial picture continues to evolve as we expected. Revenues and so on, we've talked about cash, most notably good into the second half of 2025, as we had discussed before and continuing to keep an eye on that and on managing it across our portfolio with various opportunities coming soon.

我將很快用簡短的財務更新來結束幻燈片 40。財務狀況繼續按照我們的預期發展。收入等等，我們已經討論了現金，尤其是2025 年下半年的現金，正如我們之前討論過的那樣，我們將繼續關注這一點，並在我們的投資組合中管理現金，即將到來的各種機會。

So with that, I will -- I'll stop. Slide 42 is the catalyst map. We've talked about some, but not all of these things coming and just an exciting balance to 2022 ahead -- sorry 2023 ahead. So I'll say thank you to, Mayukh, to the team and to everybody, including patients and investigators who help make this quarter what it was. And I will turn it over to the operator to open the line for Q&A. Thank you, everybody.

因此，我會——我會停下來。幻燈片 42 是催化劑圖。我們已經討論了一些，但不是所有這些即將發生的事情，只是到 2022 年實現令人興奮的平衡 - 抱歉，即將到來的 2023 年。因此，我要向 Mayukh、團隊和所有人表示感謝，包括幫助本季度取得成功的患者和研究人員。我會將其轉交給接線員以開通問答線路。謝謝大家。

(Operator Instructions). Our first question coming from the line of Brian Chen with JPMorgan.

（操作員說明）。我們的第一個問題來自摩根大通的 Brian Chen。

Walk through on brepo. Maybe first on brepo. Given what we saw from other JAKs in SLE specifically, how confident are you that brepo can perform better than Deucrav specifically in SLE. Is there anything that you would want to flag from the baseline characteristics in the ongoing Phase II design to ensure that you can show the differentiation and also make sure the placebo rate is low. Then I have a follow-up.

沿著 brepo 走過去。也許首先是 brepo。考慮到我們從其他 JAK 在 SLE 中具體看到的情況，您對 brepo 在 SLE 中比 Deucrav 的表現有多大信心？在正在進行的第二階段設計中，您是否希望從基線特徵中標記出任何東西，以確保您可以顯示差異化並確保安慰劑率較低。然後我有一個後續行動。

Yes. Thanks, Brian. And maybe I'll take one second to that question and then also hand it over to Mayukh, to see if he's got further comments. Look, I think in terms of the confidence in SLE, and I think you heard Mayukh said, on the one hand, I think there's a strong biological rationale that hitting both TYK2 and JAK1 should provide a meaningful benefit. And so I think that's -- that's an important point. And then I think the second important point is understanding the bar correctly.

是的。謝謝，布萊恩。也許我會花一點時間來回答這個問題，然後將其交給 Mayukh，看看他是否有進一步的評論。聽著，我認為就對 SLE 的信心而言，我想你聽到 Mayukh 說過，一方面，我認為有一個強有力的生物學原理認為同時打擊 TYK2 和 JAK1 應該會帶來有意義的益處。所以我認為這是很重要的一點。然後我認為第二個要點是正確理解酒吧。

And I think if you look closely at the Deucrav data, look, I'm not going to say Deucrav is not an impressive agent. But really, I think the way to read that data is probably sort of mid-teens blended efficacy. And I think if you look at the 3-milligram dose where they showed something more impressive in that I think there was a pretty significant sort of patient population imbalance that suggests to us that the mid-teens is really the bar to beat.

我認為，如果你仔細觀察 Deucrav 的數據，我不會說 Deucrav 不是一個令人印象深刻的特工。但實際上，我認為讀取這些數據的方式可能是一種十幾歲左右的混合功效。我認為，如果你看一下3 毫克劑量，他們會表現出更令人印象深刻的東西，因為我認為存在相當顯著的患者群體不平衡，這向我們表明，十幾歲左右的人確實是需要克服的障礙。

As far as the baseline characteristics, I think, first of all, as a reminder, this is a study that Pfizer design can run. We think it's a pretty well-designed study, and we've been watching it closely. There were certain things that we didn't control. And as Mayukh mentioned, with lupus is a scary indication for trial execution. But we feel, overall, pretty good. And I think that our study design, for example, was designed to try and flag some more severe baseline criteria, which has historically correlated with success, but we'll obviously see how that plays out later this fall. Mayukh anything to add to that?

就基線特徵而言，我認為，首先提醒一下，這是輝瑞設計可以運行的一項研究。我們認為這是一項設計良好的研究，並且我們一直在密切關注。有些事情是我們無法控制的。正如馬尤克提到的，狼瘡是審判執行的一個可怕跡象。但我們總體感覺還是不錯的。例如，我認為我們的研究設計旨在嘗試並標記一些更嚴格的基線標準，這些標准在歷史上與成功相關，但我們顯然會在今年秋天晚些時候看到它的結果。 Mayukh 有什麼要補充的嗎？

No, no. Not really actually Matt, I think you nailed all the points of domain.

不，不。實際上並不是，馬特，我認為你已經掌握了領域的所有要點。

And maybe just one more follow-up on Immunovant 1402 data coming up next month. Just to prep us for the top line coming up. Can you walk us through how we should gauge the profile at top line in terms of one IgG supression compared to Batoclimab and efgar and more importantly, the impact on albumin and LDL, given the potential variability in the LDL assay.

下個月可能還會發布有關Immunovant 1402 數據的又一個後續數據。只是為了讓我們為即將到來的頂線做好準備。您能否向我們介紹一下，考慮到 LDL 測定的潛在變異性，我們應該如何衡量與 Batoclimab 和 efgar 相比的一種 IgG 抑制的頂線概況，更重要的是，對白蛋白和 LDL 的影響。

Yes thanks, Brian. Great question. Obviously, when we're getting a lot right now, and I'm sure Immunovant is getting a lot too. I think Immunovant spoken a fair amount on this point publicly. I think the -- on IgG suppression, look, we believe we have an equivalently potent molecule here, and we'd like to see equivalently deep IgG suppression as a short answer. Remember, comparing apples-to-apples versus as close as we've got to equivalent time points and things like that. But in general, I think we'd like to see really the same level of deep IgG suppression and certainly, we'd like to feel like we're going to be able to supress IgG comfortably deeper than efgartigimod can. So that's on the IgG suppression points.

是的，謝謝，布萊恩。很好的問題。顯然，當我們現在得到很多的時候，我相信Immunovant也會得到很多。我認為Immunovant 在這一點上公開發表了相當多的言論。我認為，關於 IgG 抑制，看，我們相信我們這裡有一個同等有效的分子，我們希望看到同等深度的 IgG 抑製作為一個簡短的答案。請記住，要進行同類比較和盡可能接近的同等時間點之類的比較。但總的來說，我認為我們希望看到真正相同水平的深度 IgG 抑制，當然，我們希望感覺我們能夠比 efgartigimod 更輕鬆地抑制 IgG。這就是 IgG 抑制點。

On albumin and LDL, obviously, there's a lot of speculation and discussion on this point. The facts are that the variability of the albumin assay is about 5% and the variability of the LDL assay is 10-plus percent. And so I think to within first fractionation with relatively small studies, you want to be comfortably within both of those, smaller is generally better. And my sense is that if the albumin impact in the SAD is relatively modest, that the LDL will follow and because of the variability in the LDL, it will be easier to see -- you've got a few weeks of compounding data after multiple objections. So I'm mostly looking to the albumin in the SAD data. I haven't seen really any of this yet, so I can't say what it's going to look like, but that's what I'm keeping my eye out for.

關於白蛋白和低密度脂蛋白，顯然，對此有很多猜測和討論。事實是，白蛋白測定的變異性約為 5%，而 LDL 測定的變異性則高達 10% 以上。因此，我認為，在相對較小的研究的第一次分割中，你希望在這兩個研究中都感到舒適，通常越小越好。我的感覺是，如果白蛋白對SAD 的影響相對較小，那麼LDL 也會隨之變化，並且由於LDL 的變異性，會更容易看到——在多次分析之後，您會得到幾週的複合數據。反對意見。所以我主要關注 SAD 數據中的白蛋白。我還沒有真正看到過這些，所以我不能說它會是什麼樣子，但這就是我正在密切關注的。

And our next question coming from the line of David Risinger with Leerink.

我們的下一個問題來自 David Risinger 和 Leerink。

So I have questions for both Matt and Mayukh. Matt, could you provide an update on the evaluation of potential monetization of assets and also provide an update on the pursuit of new product acquisition opportunities. And then I'll pause and follow up with a question or 2 for Mayukh.

我有一些問題想問馬特和馬尤克。馬特，您能否提供有關資產潛在貨幣化評估的最新信息，以及有關尋求新產品收購機會的最新信息。然後我會暫停並向 Mayukh 提出一兩個問題。

I appreciate it. And I figured we would get some version of that first question. Look, I think we are in a privileged moment in terms of the amount of clinical data we have generated and will generate soon. That data is both deeply informative to our own strategic future and also exciting to potential partners, acquirers and so on. And it's flattering to be the focus of attention. It's made me wonder a little bit how exactly public speculation happens. But anyway, flattering.

我很感激。我想我們會得到第一個問題的某個版本。看，我認為就我們已經生成和即將生成的臨床數據量而言，我們正處於一個特權時刻。這些數據不僅對我們自己的戰略未來提供了深刻的信息，而且也讓潛在的合作夥伴、收購方等興奮不已。成為關注的焦點真是令人受寵若驚。這讓我有點想知道公眾的猜測究竟是如何發生的。但無論如何，還是很討人喜歡。

Look, I think the short answer is on the monetization side, we're value-oriented, and we're going to have to make these decisions carefully, knowing that a number of our late-stage programs are really rare opportunities with huge potential. And so we don't take any decision on them in either direction lately with the dollar sums at hand being very large and the opportunity for patients being very large.

看，我認為簡短的答案是在貨幣化方面，我們以價值為導向，我們必須仔細做出這些決定，因為我們知道我們的許多後期項目確實是難得的機會，具有巨大的潛力。因此，我們最近不會在任何一個方向上對它們做出任何決定，因為手頭的資金數額非常大，而且患者的機會也非常大。

Certainly, I wouldn't expect us to make any decisions of substance on this point until we started to get some of the Immunovant data in just because that's a pretty important strategic catalyst for us as we think through what the future of Roivant could look like across the rest of our portfolio.

當然，在我們開始獲得一些Immunovant數據之前，我不希望我們在這一點上做出任何實質性決定，因為這對我們來說是一個非常重要的戰略催化劑，因為我們思考Roivant的未來會是什麼樣子我們投資組合的其餘部分。

On the new opportunity side, I will hand that over to Mayukh actually. But I guess the one thing I'll say is this has been a phenomenal asset sourcing opportunity environment for us. Obviously, a year ago today, we would not have been talking about T018. We also wouldn't have been talking about 1402. We hope we've proven that we see some pretty interesting and unique things and that we can bring them in. And I'll say we've got things on our rocket right now that are just as exciting to me bluntly is anything in our late-stage portfolio. And I hope we can convert some of those. And the next year, we'll be talking about them as well. But Mayukh, anything you'd add to that?

在新的機會方面，我實際上會將其交給 Mayukh。但我想我要說的一件事是，這對我們來說是一個非凡的資產採購機會環境。顯然，在一年前的今天，我們不會談論 T018。我們也不會談論 1402。我們希望我們已經證明我們看到了一些非常有趣和獨特的東西，並且我們可以將它們帶入。我會說我們現在已經在火箭上有了這些東西坦率地說，我們後期投資組合中的任何東西都同樣令我興奮。我希望我們能夠轉換其中一些。明年，我們也將討論它們。但是 Mayukh，您還有什麼要補充的嗎？

Not really, Dave. I mean, look, I think that this is -- as Matt said, this has got our sort of normal course of business to be out there looking for new and high-value things. I think that work is ongoing. I feel really good about, as Matt said, things on our rocket. Stay tuned.

不是真的，戴夫。我的意思是，看，我認為這——正如馬特所說，這已經成為我們正常的業務流程，就是去那裡尋找新的、高價值的東西。我認為這項工作正在進行中。正如馬特所說，我對我們火箭上的東西感覺非常好。敬請關注。

And then just a follow-up. So Mayukh, thanks for providing the comprehensive vision for brepocitinib. Could you discuss the decision not to pursue a number of indications despite compelling results, including Crohn's and then if you could also discuss Sotyktu's inverse dose response in SLE and whether there are any potential implications for brepo in SLE or no?

然後只是後續行動。感謝 Mayukh 提供了 brepocitinib 的全面願景。您能否討論一下儘管結果令人信服，但不追求包括克羅恩病在內的許多適應症的決定，然後您是否也可以討論Sotyktu 在SLE 中的逆劑量反應以及brepo 在SLE 中是否有任何潛在影響？

Sorry, I missed just the last part of that question, Dave.

抱歉，我錯過了這個問題的最後一部分，戴夫。

So yes. So on the last part, the slide shows an inverse dose response for Sotyktu in SLE. So as the dosing went up for Sotyktu, the efficacy went down. Just wanted to see if you had any comments on that and whether there may or may not be implications for brepo as a dual agent in SLE as it's dosed up. And as I understand it, you're testing 15, 30 and 45-milligram doses.

所以是的。因此，在最後一部分，幻燈片顯示了 Sotyktu 在 SLE 中的逆劑量反應。因此，隨著 Sotyktu 劑量的增加，療效下降。只是想看看您是否對此有任何評論，以及 brepo 作為 SLE 的雙重藥物在服用後是否會產生影響。據我了解，您正在測試 15、30 和 45 毫克的劑量。

That's right. Matt, do you want to take the indication question?

這是正確的。馬特，你想回答指示問題嗎？

Yes, sure. I mean, look, I think, Dave, it comes down to -- and this was sort of the inherent thesis in brepo as well. I think at the moment that we acquired brepo from Pfizer, it was sort of just in the thick of the sort of turning point on JAK inhibitors because of labeling. And I think our view has been in the face of very compelling data, as you point out, in Crohn's and a number of these other indications, that the competitive landscape there is such that the JAK labeling may be a disadvantage difficult to develop through. I think if you take Crohn's, for example, I think that's an interesting question in the sense that clearly, as we continue to study RINVOQ in IBD pretty aggressively and also the ulcerative TYK2 have struggled a little bit there.

是的，當然。我的意思是，戴夫，我想，這可以歸結為——這也是 brepo 的固有論點。我認為，當我們從輝瑞公司收購 brepo 時，由於標籤的原因，這正是 JAK 抑製劑的轉折點。我認為我們的觀點是面對非常令人信服的數據，正如您在克羅恩病和許多其他跡像中所指出的那樣，那裡的競爭格局使得 JAK 標籤可能成為難以克服的劣勢。我認為，如果以克羅恩病為例，我認為這是一個有趣的問題，因為我們繼續非常積極地研究 IBD 中的 RINVOQ，而且潰瘍性 TYK2 在那裡也遇到了一些困難。

So I think we'll get some more data on that later. I think we'll continue to reevaluate those questions. That said, I'd say the other thing about our view is, I think with the data that, frankly, the TL1A class is putting out in IBD, we're not sure exactly where JAK will fit in the future treatment paradigm understanding the obvious benefits of being oral. But anyway, look, I think the affirmative bet we're making here is that orphan indications where the JAK liabilities won't be a problem with the unmet need is highest is sort of the place where it makes the most sense for us to pursue -- first pursue brepo.

所以我想我們稍後會獲得更多相關數據。我認為我們將繼續重新評估這些問題。也就是說，我想說的是，我們觀點的另一件事是，坦率地說，根據 TL1A 類在 IBD 中發布的數據，我們不確定 JAK 在未來治療範式中的確切位置，了解口頭表達的好處顯而易見。但無論如何，我認為我們在這裡做出的肯定的賭注是，孤兒跡象表明 JAK 負債不會成為未滿足需求最高的問題，這對我們來說是最有意義的追求——首先追擊布雷波。

Yes. I mean I think just to add to that. Look, I think we're always going to be, I think, kind of dynamic in our evaluation and really sort of -- this sort of comes down to you in a certain sense, an embarrassment of riches in terms of just the clinical data set and the breadth of potential indications we can go after. I think as Matt said and articulated on the call, our sort of primary thrust as it were is in these orphan indications for which I think we feel like our ability to separate versus other options as great as the competitive intensity is believed, et cetera, and that really allows us to kind of have this specialty rheumatology and in that area for ourselves.

是的。我的意思是我想補充一下。聽著，我認為我們的評估總是充滿活力，從某種意義上說，這取決於你，僅就臨床數據而言，這是一種財富的尷尬設定以及我們可以追踪的潛在跡象的廣度。我認為，正如馬特在電話會議上所說和闡明的那樣，我們的主要推力就在於這些孤兒適應症，我認為我們認為我們有能力將其與其他選擇區分開來，就像人們相信的競爭強度一樣，等等，這確實讓我們能夠擁有風濕病學專業以及該領域的專業知識。

And so I think we've got a lot of different -- different options here. And then I think to conceptualize over the next couple of data sets that we get in both lupus and NIU and then DM coming right this time. In terms of your question on Sotyktu. So look, I mean, I think obviously, this is sort of the -- the sort of the inherent, sort of uncertainty is around just relatively small and point estimates as well as just sort of lupus clinical trial readouts generally. I think that our own view is that there's not, not really likely -- the truth is not an inverted dose response in that Sotyktu study. I think there are reasons to believe that in essence this could be like a little bit of a reflection of just like slight imbalances -- imbalances between the various dose arms.

所以我認為我們這裡有很多不同的選擇。然後我想對我們在狼瘡和 NIU 中獲得的接下來的幾個數據集進行概念化，然後這次是 DM。關於你對 Sotyktu 的問題。所以，我的意思是，我認為顯然，這是一種固有的、不確定性，存在於相對較小的點估計以及狼瘡臨床試驗讀數中。我認為我們自己的觀點是，在 Sotyktu 研究中，事實並非是反向劑量反應。我認為有理由相信，本質上這可能有點像輕微的不平衡的反映——各個劑量組之間的不平衡。

So for example, we think that the 3-milligram bid on the that produced sort of highest [sprint head] more subjects receiving sort of triple combination standard of care baseline compared to other arms and then that the 12-milligram once daily arm had higher dropout rates, et cetera. And ultimately, if you look through sort of Sotyktu just generally, it seems like they're quite close to saturation at the 3 mg -- there's not really kind of like a true reason to believe that they're sort of more juice in there at the higher basis. And then finally, it seems like mid-teens kind of blended across these 3 values -- it seems to be consistent with how (inaudible) themselves seem to be [barring] Phase III as well.

例如，我們認為，與其他組相比，3 毫克的出價產生了最高的 [衝刺頭] 更多受試者接受三重組合標準護理基線，然後 12 毫克每日一次的組具有更高的輟學率等等。最後，如果你一般性地瀏覽一下 Sotyktu，你會發現它們在 3 毫克的濃度下已經非常接近飽和了——沒有真正的理由相信它們裡面有更多的果汁。在較高的基礎上。最後，似乎十幾歲左右的人混合了這 3 個價值觀——這似乎與（聽不清）本身似乎[除非]第三階段是一致的。

And our next question coming from the line of Robyn Kay Karnauskas with Truist Securities.

我們的下一個問題來自 Truist Securities 的 Robyn Kay Karnauskas。

Thanks, Mayukh for doing all the work for me on lupus and brepo, a fantastic presentation. A question on capital allocation. First, just on brepo. When you think about how -- whether it's spend more on these orphan drug indications, can you just remind us of the Pfizer agreement? And how much they -- if there's anything they contribute and then bigger picture, you talked about making capital decisions after seeing at least initially some of the data from 1402. And you've got so many moving parts just this year and next year with many drugs and decisions you'll have to make. Like can you just walk us through how you're going to think about that? Would you start thinking about that after SAD? And how long would it take you to come up with a game plan for what you're going to do for Roivant for spend?

感謝 Mayukh 為我完成了有關狼瘡和 brepo 的所有工作，這是一次精彩的演講。關於資本配置的問題。首先，就 brepo 而言。當你想到如何——是否在這些孤兒藥適應症上花費更多時，你能提醒我們輝瑞協議嗎？他們有多少貢獻——如果有什麼貢獻的話，然後是更大的前景，你談到了在至少最初看到 1402 的一些數據後做出資本決策。今年和明年你有這麼多移動部件您必須做出許多藥物和決定。您能告訴我們您將如何考慮這個問題嗎？ SAD之後你會開始思考這個問題嗎？您需要多長時間才能製定出為 Roivant 進行的支出計劃？

Yes. On the first question on brepo specifically, the answer is the lupus study itself was very heavily subsidized by Pfizer. So our cost there was a fraction of the total study cost. And that obviously made it an attractive setup for us. The rest of the costs associated with other indications are ours to [Bayer]. Pfizer does not contribute. They're protected from dilution of their 25% stake up to $1 cap, frankly, relatively similar to the mechanism at Telavant with the TL1A program.

是的。具體來說，關於 brepo 的第一個問題，答案是狼瘡研究本身得到了輝瑞的大力資助。所以我們的費用只佔總學習費用的一小部分。這顯然使其成為對我們有吸引力的設置。與其他適應症相關的其餘費用由我們承擔[拜耳]。輝瑞公司沒有做出貢獻。坦率地說，他們的 25% 股權不會被稀釋至 1 美元上限，這與 Telavant 的 TL1A 計劃的機制相對相似。

So in terms of other orphan indications, NIU, DM is all our costs, et cetera. Those are capital allocation isn't for us the same as any other but SLE, in particular, has been highly subsidized through the end of this current study. If we decided to run another study, that would also be ours to fund. More generally, I guess I probably -- in so far as I said, we wouldn't think about it until we saw the Immunovant data that was probably overstated. Obviously, we have spent a lot of time thinking about capital and capital decision-making as we explore the opportunity set, and I agree there's a lot of moving pieces coming. I think the SAD data will be informative. I think the MAD data will be informative. I think we're going to learn other things from the FcRn field including some RA data from J&J, from their own (inaudible) grade study, et cetera, through the balance of this year.

所以就其他孤兒適應症而言，NIU、DM 就是我們的全部成本等等。這些資本配置對我們來說與其他任何資本配置不同，但特別是 SLE，在本研究結束時得到了高額補貼。如果我們決定進行另一項研究，那也將由我們資助。更一般地說，我想我可能——就我所說的而言，我們不會考慮這個問題，直到我們看到可能被誇大的Immunovant 數據。顯然，在探索機會集時，我們花了很多時間思考資本和資本決策，我同意會有很多令人感動的事情即將到來。我認為 SAD 數據會提供豐富的信息。我認為 MAD 數據會提供豐富的信息。我認為我們將從 FcRn 領域學習其他東西，包括強生公司的一些 RA 數據、他們自己的（聽不清）等級研究等等，直到今年的剩餘時間。

I don't know that there's going to be like a single tipping point obvious moments where before which we can't make any decision and after which we can, I think it's more of taking the facts as we have them and trying to understand in which direction things swing over the coming months. That said, we have the best version of this problem, I think, in the sense that we just have lots of different options for capitalizing the business going forward. And so I think we're just -- we're frankly picking them on good choices at this point.

我不知道是否會出現一個明顯的轉折點，在此之前我們無法做出任何決定，而在此之後我們可以，我認為更多的是接受我們掌握的事實並試圖理解未來幾個月事情會朝哪個方向發展。也就是說，我認為，我們有這個問題的最佳版本，從某種意義上說，我們有很多不同的選擇來利用未來的業務。所以我認為我們只是 - 坦率地說，我們現在正在選擇他們的好選擇。

And our next question coming from the line of Louise Chen with Cantor.

我們的下一個問題來自 Louise Chen 和 Cantor 的對話。

Congratulations on all the progress this quarter. So I wanted to ask you on brepocitinib, one thing people have been asking us is how you think about pricing if the drug is approved? And I know it's a little bit early, but if you can't talk about specifics, maybe you could tell us the bookends and how you're thinking about it and what you might comp it to.

祝賀本季度取得的所有進展。所以我想問您有關 brepocitinib 的問題，人們一直問我們的一件事是，如果該藥物獲得批准，您如何看待定價？我知道現在有點早，但如果您不能談論具體細節，也許您可​​以告訴我們書擋以及您如何考慮它以及您可能將其組合成什麼。

And then on VTAMA, the reimbursement work you did on psoriasis, how much can that be leveraged to the atopic dermatitis opportunity so that you can move quickly on uptake on that one? And then one more here on brepocitinib. Can you be a little bit more specific on when this year, we'll see the data? Is it early, mid, early fourth quarter?

然後在 VTAMA 上，您在牛皮癬方面所做的報銷工作，可以在多大程度上利用到特應性皮炎的機會，以便您可以快速採取行動？然後是關於 brepocitinib 的另一篇文章。您能否更具體地說明今年我們何時會看到這些數據？是第四季度初、中、初嗎？

Yes. Thanks, Louise. On the 2 brepo questions on the timing. I think it's safe to assume mid- to late fourth quarter is probably the way to think about that. On pricing, I mean, I'll hand it to Mayukh, but I think my short answer to that question is at this point, there's a pretty wide breadth of possible indication spaces between SLE and DM and so on. So it's probably premature, but I'll hand over to Mayukh.

是的。謝謝，路易絲。關於時間安排上的 2 個 brepo 問題。我認為可以肯定的是，第四季度中後期可能是考慮這個問題的方式。關於定價，我的意思是，我會將其交給 Mayukh，但我認為我對這個問題的簡短回答是，SLE 和 DM 之間存在相當廣泛的可能適應症空間，等等。所以這可能還為時過早，但我會把工作交給 Mayukh。

Yes. I think the punchline is we're thinking about this principally as sort of a, call it, an orphan drug pricing band given the sort of indication set and then sort of what makes sense I think that these independent potentially compatible with pricing in lupus as well if efficacy data is really strong.

是的。我認為重點是，我們主要將其視為一種，稱之為孤兒藥定價範圍，給出了某種適應症集，然後是有意義的，我認為這些獨立的藥物可能與狼瘡的定價兼容如果療效數據真的很強的話。

And then on the VTAMA access question, I think the short answer is yes, that is a lot of that work can be heavily leveraged, and I would expect to be sort of process with payers to be significantly streamlined given that we're all on formulary. Obviously, there is still work to do. It's not like it's instantaneous and automatic but I would expect it to be a faster, more straightforward and frankly, much more predictable process where I have -- look, I think there were some real unknowns about how coverage was going to materialize prior to our launch. And I think at this point, we are pretty confident that we are going to get comfortably covered with reasonable rebates by the payers.

然後，關於 VTAMA 訪問問題，我認為簡短的答案是肯定的，這其中的很多工作都可以得到充分利用，而且我希望付款人的流程能夠得到顯著簡化，因為我們都在處方。顯然，仍有工作要做。這並不是即時和自動的，但我希望它是一個更快、更直接、更坦率、更可預測的過程，我認為，在我們的覆蓋範圍之前，對於如何實現覆蓋存在一些真正的未知數。發射。我認為在這一點上，我們非常有信心我們將獲得付款人合理的回扣。

And our next question coming from the line of Dennis Ding with Jefferies.

我們的下一個問題來自杰弗里斯的丹尼斯·丁。

I just had one on Immunovant. So on the upcoming 1402 data, can you just remind us the study design and how long is the follow-up for SAD and MAD. Interestingly, how often is albumin being measured and as a follow-up, maybe given your comments around the assay variability and that there could be different time points on which albumin is measured and just also appreciating the fact that albumin reductions can go up and be down at some points and others. And I was just wondering what are some -- what's a good outcome for you guys in SAD and the MAD on the albumin front.

我剛剛服用了一張Immunovant。那麼關於即將到來的1402數據，您能否提醒我們一下研究設計以及SAD和MAD的後續時間是多長？有趣的是，多久測量一次白蛋白並作為後續行動，也許考慮到您對測定變異性的評論，並且測量白蛋白可能有不同的時間點，並且還要認識到白蛋白減少量可能會上升並可能會增加的事實。在某些點和其他點上下降。我只是想知道在白蛋白方面，對於 SAD 和 MAD 的你們來說，有什麼好的結果。

Yes. Thanks, Dennis. I appreciate these questions. And obviously, it's an area of a lot of focus, so it makes sense. Look, I think on study design, there's a fair amount about this in the Immunovant corporate deck and in ours as well. On the SAD study, it's 6 1402 plus 2 placebo patients. I forget exactly how far that it's measured, but it's at least a few weeks. .

是的。謝謝，丹尼斯。我很欣賞這些問題。顯然，這是一個備受關注的領域，所以這是有道理的。聽著，我認為在研究設計方面，Immunovant 公司的平台和我們的平台上都有相當多的相關內容。在 SAD 研究中，有 6 1402 名患者加上 2 名安慰劑患者。我忘記具體測量了多遠，但至少有幾個星期。 。

And then on the MAD study, it's 10 1402 and 2 placebo patients and it's weekly dosing for 4 weeks and again, with a several week tail at the end. We've got pretty frequent data points, I'd say, as a reasonable benchmark if you went and looked at like some of the batoclimab data we've put out, I'd say like the measurement points are pretty similar.

然後在 MAD 研究中，有 10 名 1402 名患者和 2 名安慰劑患者，每週給藥一次，持續 4 週，然後再進行一次，最後有幾週的尾部。我想說，我們有相當頻繁的數據點，作為一個合理的基準，如果你去查看我們發布的一些 batoclimab 數據，我會說測量點非常相似。

And so early -- in fact, we follow these patients out, sorry, a lot more than a few weeks. And there's sort of a number of measurements within 10 days and then it starts to get a little bit more spaced out in the SAD study. So again, there's a fair amount of data in event deck on this point. In terms of what good looks like on albumin in the SAT and the MAD against the backdrop of smaller is better. I think, again, with a 5% variability in the assay, I think we hope to be comfortably within 5% and I'd say any of the agents, frankly, that show a 5% or less impact on albumin seem to be pretty well set up from an LDL perspective.

這麼早——事實上，我們跟踪這些病人，抱歉，比幾週還要長。 10 天內進行了多次測量，然後 SAD 研究中的間隔開始變得更大。再說一次，事件甲板上有大量關於這一點的數據。就白蛋白在 SAT 和 MAD 的背景下的外觀而言，越小越好。我再次認為，由於檢測中存在 5% 的變異性，我認為我們希望能夠輕鬆地控制在 5% 之內，坦率地說，任何對白蛋白的影響達到 5% 或更少的藥物似乎都相當不錯從LDL 角度來看，設置良好。

So I think it's hard to say exactly how things would sort of compound from the SAD study to the MAD study, but in general, I'd say, it lowers better within that 5% bar is probably what I'm looking for.

因此，我認為很難準確地說出從 SAD 研究到 MAD 研究的複合情況，但總的來說，我想說，它在 5% 的範圍內降低得更好，這可能就是我正在尋找的。

And our next question coming from the line of Corinne Jenkins with Goldman Sachs.

我們的下一個問題來自高盛的科琳·詹金斯 (Corinne Jenkins)。

This is Craig on for Corinne. So as you referenced earlier in the call, this can be a pretty tricky indication -- so on that, what do you view as the bar to support continued study in the indication?

這是為科琳代言的克雷格。正如您之前在電話會議中提到的，這可能是一個非常棘手的跡象 - 那麼，您認為支持繼續研究該跡象的標準是什麼？

In SLA, you said, yes?

在 SLA 中，你說，是嗎？

Yes, that's right.

恩，那就對了。

Yes. Look, I think the way we are currently thinking about the program, understanding that it's kind of a balance of the factors is Deucrav is the bar to beat given that they have the back [cleaner] TYK2. This would count as 1 of 2 pivotal studies, we believe, if successful. So the data from here would already make it onto the label. It's 52-week study. So it should be relatively predictive of a future study as well, given the way that it's set up.

是的。聽著，我認為我們目前考慮該計劃的方式，理解這是一種因素的平衡，考慮到 Deucrav 是要擊敗的障礙，因為他們有後衛 [清潔工] TYK2。我們相信，如果成功的話，這將被視為兩項關鍵研究之一。所以這裡的數據已經出現在標籤上。這是為期 52 週的學習。因此，考慮到它的設置方式，它也應該能夠相對預測未來的研究。

So I think we have the best possible setup understanding that there has been some complexity in SLE trials before. In terms of the bar, I think it's a balance of the factors, but I think you've heard us say that we think its effective as a mid-teens drug. And you've heard us say that we'd like to be better than SOTYKTU. So I think that gives you sort of some indication for where our head is at, but we're going to have to look at -- there's multiple -- multiple endpoints and things like that. So I'd say mid- to high teens sort of -- and whatever that trend looks into across the other places to look.

因此，我認為我們已經盡可能了解之前的 SLE 試驗存在一定的複雜性。就標準而言，我認為這是各種因素的平衡，但我想你已經聽過我們說我們認為它作為一種青少年藥物是有效的。您已經聽過我們說我們希望比 SOTYKTU 更好。所以我認為這給了你一些關於我們的頭在哪裡的指示，但我們必須看看——有多個——多個端點和類似的東西。所以我想說的是中高青少年——以及無論其他地方的趨勢如何。

Got it. That's helpful. And maybe just a quick one. You highlighted for the first time that you've achieved payer coverage with government covered lives. I guess how should we think of the, I guess, doctor adoption of these patients following this update? Is it going to be a similar timing as the commercial coverage lives -- you've kind of highlighted it's around 6 months in the past?

知道了。這很有幫助。也許只是一個快速的。您首次強調您已經實現了政府承保人壽的付款人承保。我想我們應該如何看待這次更新後醫生收養這些患者？是否會與商業報導的時間相似——您強調過大約是 6 個月前？

Yes. Look, the truth is that the psoriasis market is sort of 80%-ish commercial anyway. So even though we've got a lot of covered lives there. It's a smaller chunk of the patient population index. So I think now that we've got coverage, they're government patients, they'll sort of accrue over time to better GTN yields and so on. I think in general, I just expect to see steady improvements in GTN from here on out as we get closer and closer to that 50% bogey over the next 12 months and beyond. And I think the government lives will contribute to that, but I don't think it's sort of going to be like there's some kind of step function specifically associated with the government lives.

是的。聽著，事實是牛皮癬市場至少有 80% 左右是商業化的。所以即使我們在那裡有很多受保護的生活。它只佔患者人口指數的一小部分。所以我認為現在我們已經有了保險，他們是政府患者，隨著時間的推移，他們會獲得更好的 GTN 收益率等等。我認為總的來說，我只是希望從現在開始看到 GTN 的穩步改進，因為我們在接下來的 12 個月及更長時間內越來越接近 50% 的柏忌。我認為政府生活將對此做出貢獻，但我不認為這會像某種與政府生活專門相關的階梯功能。

And our next question coming from the line Yaron Werber with Cowen.

我們的下一個問題來自 Yaron Werber 和 Cowen 的對話。

Great. I have a couple of questions on brepocitinib. And just remind us, AA, alopecia areata, what are your plans sort of with that indication -- and then secondly, for HS, can you file -- can you just conduct one pivotal? Is that sort of sufficient? Or do you think you need to? And then I guess, finally, at what point can you present or as far as you're going to present the data from the studies. I mean, the studies are positive, obviously, I'm talking about Crohn's and HS, but just so we can also understand the overall profile safety-wise. I mean there's obviously a lot of data out there just so we see the full data.

偉大的。我有幾個關於 brepocitinib 的問題。請提醒我們，AA，斑禿，您針對該跡像有何計劃 - 其次，對於 HS，您可以提交 - 您可以只進行一項關鍵操作嗎？這樣就足夠了嗎？或者你認為你需要這樣做嗎？然後我想，最後，你可以在什麼時候展示或者你將展示研究中的數據。我的意思是，這些研究顯然是積極的，我說的是克羅恩病和 HS，但這樣我們也可以從安全角度了解整體概況。我的意思是，顯然有很多數據，所以我們可以看到完整的數據。

Yes. Perfect. Look, I think the first answer is on alopecia, we have no like current plans to progress in alopecia. That's an interesting indication. Our data looks promising, but our view is sort of the same as for the other slightly larger indications.

是的。完美的。看，我認為第一個答案是關於脫髮，我們沒有像目前那樣在脫髮方面取得進展的計劃。這是一個有趣的跡象。我們的數據看起來很有希望，但我們的觀點與其他稍大的指標有些相同。

So I think not sort of on our near-term road map, but obviously, with the quality of the data we have, we'll be watching everything. On the other questions, first of all, on HS specifically, look, I think it's premature. We haven't sort of discussed it with FDA in detail or anything like that. We don't have a concrete plan in there. So I'd probably rather not boxes in on a particular study design. That's probably what I'd say there. Mayukh, anything else you'd say in terms of the other points or you may be sort of slightly closer than I am to the Pfizer publication time lines.

因此，我認為這不會出現在我們的近期路線圖上，但顯然，憑藉我們擁有的數據質量，我們將密切關註一切。關於其他問題，首先，特別是在 HS 方面，我認為現在還為時過早。我們還沒有與 FDA 詳細討論過這個問題或類似的事情。我們那裡沒有具體的計劃。所以我可能寧願不拘泥於特定的研究設計。這可能就是我要說的。 Mayukh，您在其他方面還有什麼想說的，或者您可能比我稍微接近輝瑞的發佈時間表。

Yes. So I think not too much more to add. I think that Crohn's study in particular still has a maintenance portion to cover along with -- to look forward to being more at a future medical meeting. And then the HS study actually has been published at this point. So we can send that to you and Pfizer's abstraction on the publication...

是的。所以我覺得不用補充太多了。我認為克羅恩的研究尤其還有維護部分需要涵蓋——期待在未來的醫學會議上有更多內容。然後 HS 研究實際上已經發表了。所以我們可以將其發送給您和輝瑞對該出版物的摘要......

And our next question coming from the line of Douglas with HC Wainwright.

我們的下一個問題來自道格拉斯和 HC 溫賴特。

Doug, you might be on mute.

道格，你可能處於靜音狀態。

Can you hear me now, Matt, -- sorry about that.

你現在能聽到我說話嗎，馬特，——抱歉。

Yes. Perfect.

是的。完美的。

Starting with the VTAMA. I'm just curious, as you have -- you successfully added to the coverage for the product. Do you anticipate making any changes to the sort of co-pay card or the sort of access program, consumer access program as it is now. Or do you anticipate waiting until getting approval in AD before making any changes?

從 VTAMA 開始。我只是很好奇，就像您一樣，您成功地添加了該產品的承保範圍。您是否預計會對現在的共同支付卡類型或訪問計劃、消費者訪問計劃進行任何更改？或者您是否預計要等到獲得 AD 批准後再進行任何更改？

Yes. Thanks, Doug. It's a great question. Look, I think for the moment, we have no immediate plans to change the co-pay card. -- sort of set up in a way, as I'm sure you appreciate to work well for us as people migrate from uncovered to covered. And unlike some of the other parts that were set up initially, some of our competitor programs or the new topicals have like $10 programs or whatever, where the uncovered side of the card was low in order to attract trips at a time when coverage was spottier. We always had a slightly higher co-pay on the uncovered side. It was frankly set up to carry us into the AD launch and beyond. We evaluate this stuff constantly. And our focus right now is the high prescribing docs feel really great about the product and what we're really focused on is taking the back to right 2 scripts a month and turning them into 5 and 10 script a month box.

是的。謝謝，道格。這是一個很好的問題。聽著，我認為目前我們沒有立即計劃更改共同支付卡。 ——某種程度上是這樣設置的，因為我相信當人們從無遮蓋物遷移到有遮蓋物時，你會很高興為我們工作。與最初設立的其他一些部分不同，我們的一些競爭對手計劃或新主題有 10 美元左右的計劃或其他計劃，其中卡的未覆蓋面較低，以便在覆蓋範圍更不穩定的時候吸引旅行。我們在未覆蓋的一側的共付額總是略高一些。坦率地說，它的設立是為了讓我們進入 AD 的發布及以後。我們不斷評估這些東西。我們現在的重點是高處方文檔對產品的感覺非常好，我們真正關注的是把每月 2 個腳本變成每月 5 個和 10 個腳本的盒子。

And I think the sort of goal of whatever changes we make would be to sort of keep that process in motion. But the short answer is, I think the copay card actually works reasonably well. To be honest, if there's something I think we're sort of working on, it's -- I think at this point, the actual quality of coverage is better than the perception of coverage. I think these docs have been burned a fair amount historically on challenging coverage in derm. And we actually have quite good coverage. It's easy to obtain many, many of their patients, as you can see from the presentation will be covered. I think many derms frankly, have not like caught up with that reality yet. And so a lot of the educational work we're doing is just trying to make sure people understand that picture as well as we can possibly help them understand it.

我認為我們所做的任何改變的目標都是讓這個過程保持運轉。但簡短的回答是，我認為共付卡實際上效果相當好。老實說，如果我認為我們正在努力做某件事，那就是——我認為在這一點上，實際的報導質量比人們對報導的看法要好。我認為這些文檔在歷史上因挑戰皮膚覆蓋範圍而被燒毀了相當多的內容。我們實際上有相當好的覆蓋範圍。很容易獲得很多很多他們的患者，正如您從演示中看到的那樣。坦率地說，我認為許多皮膚科醫生還沒有意識到這一現實。因此，我們正在做的很多教育工作只是試圖確保人們理解這幅圖畫，以及我們可以幫助他們理解它。

And Matt, you sort of touched on another point, I'm just curious your perspective on how do you -- or what's the plan right now to sort of help accelerate the writing from sort of your low prescribers, right? I mean, because it sounds like your script base is fairly concentrated. And obviously, to sort of take it to the next level, you're going to need to increase that debt. What are the things that you're able to do to get people to go beyond just writing that first initial script? And -- are you aware of what is keeping them from only writing just a couple of scripts right now.

馬特，你談到了另一點，我只是好奇你對你如何看待——或者現在有什麼計劃來幫助加速你的低處方者的寫作，對嗎？我的意思是，因為聽起來你的腳本基礎相當集中。顯然，為了將其提升到一個新的水平，你將需要增加債務。除了編寫第一個初始腳本之外，您還可以做哪些事情來讓人們超越？而且——你知道是什麼阻止他們現在只寫幾個腳本嗎？

Yes. Thanks, Doug. Look, it's a great question. It's quite literally $1 billion question. So we spend a lot of time thinking about it. I think the short answer is we've already taken certain steps. We've got now DTC was something we were pretty conservative about up until we got to the sort of good payer coverage position. So within the last month or 2, we've really sort of started to ramp up the DTC campaign, and that should take months more to really fully sort of make it into the script volumes but it's something that we are watching to drive volumes that way.

是的。謝謝，道格。聽著，這是一個很好的問題。這確實是一個價值 10 億美元的問題。所以我們花了很多時間思考這個問題。我認為簡短的答案是我們已經採取了某些步驟。在我們達到良好的付款人承保範圍之前，我們對 DTC 一直非常保守。因此，在過去的一兩個月內，我們確實開始加大 DTC 活動的力度，這應該需要幾個月的時間才能真正完全進入腳本卷，但我們正在觀察如何推動卷的數量方式。

There's other things too. There's one property is these patients don't go to the doctor very often. And so frankly, if you were a -- if you were a high [driving] dermatologist, you've been waiting for the VTAMA launch for many years. If you were a low driving dermatologist is sort of showed up, maybe you wrote a few test scripts or you write a few test scripts every month, but you actually haven't seen very many patients back in your office, who you put on VTAMA a year ago. And so I think one thing that works in our favor is just time. It's just back sort of seeing repeat visits from patients who they put on earlier in the launch. And I think that will cause a compounding effect for us.

還有其他事情。有一個特點是這些病人不經常去看醫生。坦率地說，如果您是一位——如果您是一位高級[駕駛]皮膚科醫生，那麼您已經等待 VTAMA 的發布很多年了。如果您是一名低駕駛皮膚科醫生，也許您寫了一些測試腳本，或者您每個月都寫了一些測試腳本，但實際上您在辦公室裡並沒有看到很多患者，您讓他們使用 VTAMA一年前。所以我認為對我們有利的一件事就是時間。剛剛開始看到他們在推出之前安排的患者重複就診。我認為這會給我們帶來複合效應。

And then we continue to sort of keep our ear to the ground and work on whatever the questions I mentioned, the coverage question is probably one of the most important messaging questions that we're working on right now is just helping docs understand that which isn't like other topical, but it's going to make a difference for their patients, and it's going to be easy for them to use in a way that some of the other historical launches have been more challenging.

然後我們繼續密切關注並解決我提到的任何問題，覆蓋範圍問題可能是我們現在正在處理的最重要的消息傳遞問題之一，只是幫助文檔了解哪些問題與其他主題不同，但它將為他們的患者帶來改變，並且他們將很容易以其他一些歷史發布更具挑戰性的方式使用。

And so I think that's where a lot of our focus is. I'd say in the docs call that I've been closest to, frankly, the #1 point is this payer coverage point is just (inaudible) about where things are on the payer side. But we hear other things that we continue to work on. And in general, I think doctors are familiar with the product, we're pretty happy to be using it. So we're just trying to get everybody else to build some experience in muscle memory. Remember, these docs write corticosteroids in their [sleep]. So it just takes -- it takes some time. But we'd love to see faster.

所以我認為這就是我們重點關注的地方。我想說在文檔電話中，坦率地說，我最接近的第一點是付款人覆蓋點只是（聽不清）關於付款人方面的情況。但我們聽到了其他我們繼續努力的事情。總的來說，我認為醫生熟悉該產品，我們很高興使用它。所以我們只是想讓其他人在肌肉記憶方面積累一些經驗。請記住，這些醫生在他們的[睡眠]中使用皮質類固醇。所以這只是需要一些時間。但我們希望更快地看到。

And I'm not showing any further questions in the Q&A queue at this time. I will now turn the call back over to Mr. Matt Gline for any closing remarks.

目前我不會在問答隊列中顯示任何其他問題。現在，我將把電話轉回給馬特·格萊恩先生，讓他發表結束語。

Great. So look, I just want to say thank you to everybody for listening this morning. Thank you to our team for all the work this quarter and beyond. I'm really looking forward to the next couple of months here, and we're going to have some important opportunities to get back together. And yes, thanks all, and have a great rest of your summer, and we'll be back here soon to talk about some more exciting updates. So thank you, operator. Thank you, everyone, for listening, and we'll talk again soon.

偉大的。所以聽著，我只想對大家今天早上的收聽表示感謝。感謝我們的團隊本季度及以後所做的所有工作。我真的很期待接下來的幾個月，我們將有一些重要的機會重新聚在一起。是的，謝謝大家，祝您暑假愉快，我們很快就會回來討論一些更令人興奮的更新。謝謝你，接線員。謝謝大家的聆聽，我們很快會再次討論。

Ladies and gentlemen, that does conclude the conference for today. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的會議到此結束。感謝您的參與。您現在可以斷開連接。