Roivant Sciences Ltd (ROIV) 2025 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Roivant fourth quarter 2025 earnings call. (Operator Instructions) Please be advised that today's conference is being recorded. I would like now to turn the conference over to Stephanie Lee. Please go ahead.

各位女士、先生，感謝您耐心等候。歡迎參加 Roivant 2025 年第四季財報電話會議。(接線員指示) 請注意，今天的會議將被錄音。現在我想把會議交給 Stephanie Lee。請開始。

Good morning, and thanks for joining today's call to review business updates from Roivant's fourth quarter and fiscal year ended March 31, 2026. I'm Stephanie Lee with Roivant. Presenting today, we have Matt Glein, CEO of Roivant, and Drew Prompkin, CEO of Pomovance. For those dialing in via conference call, you can find the slides being presented today, as well as a press release announcing these updates on our IR website at www.investor.roivant.com.

各位早安，感謝您加入今天的電話會議，一同回顧 Roivant 截至 2026 年 3 月 31 日止第四季與會計年度的業務最新進展。我是 Roivant 的 Stephanie Lee。今天出席簡報的有 Roivant 執行長 Matt Glein，以及 Pomovance 執行長 Drew Prompkin。對於透過電話撥入的各位，您可在我們的投資人關係網站 www.investor.roivant.com 上找到今天簡報所使用的投影片，以及公布這些更新的新聞稿。

We'll also be providing the current slide numbers as we present to help you follow along. 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 have filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties.

我們也會在簡報過程中提供目前的投影片頁碼，方便您跟上進度。我想提醒各位，我們將在今天的簡報中作出若干前瞻性陳述。我們強烈建議您查閱我們向美國證券交易委員會（SEC）提交的文件，以取得更多關於這些前瞻性陳述以及相關風險與不確定性的資訊。

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

那麼，接下來我把時間交給 Matt。

Thanks, Stephanie. Thank you, everyone, for dialing in this morning. I'm glad to be talking. We have an unexpectedly busy agenda with a bunch of topics, I'm looking forward to going through all of it, including obviously, what we announced this morning, which is the preliminary open-label period data from the 1402 study in DTRA as well as a planned spotlight, we've been planning to do for a while on mostly getting into that data, which we will take us through, and some smaller updates on the brepocitinib program, although exciting, so a lot to cover.

謝謝你，Stephanie。也謝謝各位今天早上撥入參與。很高興能與各位交流。我們的議程出乎意料地繁忙，涵蓋許多主題；我很期待逐一說明，當然也包括我們今天早上宣布的內容：1402 研究在 DTRA 的初步開放標籤期數據，以及我們規劃已久的重點專題，主要會深入解讀這些數據；另外也會提供 brepocitinib 計畫的一些較小更新，雖然篇幅不大但同樣令人振奮，所以今天要談的內容很多。

I want to -- before I get involved that is one small bit of executive privilege and wish my father Jerry, a happy 75th birthday, today it's his 75th birthday. So happy birthday dad. He sometimes listen in on these calls. I don't know if it's listening in. Now if now he will be catch it on the replay.

在我開始之前——我想先行使一點小小的「管理層特權」，祝我的父親 Jerry 今天 75 歲生日快樂，今天是他 75 歲生日。爸爸，生日快樂。他有時候會收聽這些電話會議。我不知道他現在是否正在收聽。如果沒有，他之後也會在重播中聽到。

Okay, into the important topics now, starting on important business topics now. Starting on Slide 5. Look, this has been a pretty wild 12 months for Roivant. And we continue to see just tremendous execution momentum across our development portfolio.

好的，現在進入重要議題，先從重要的業務主題開始。請看第 5 頁投影片。坦白說，過去 12 個月對 Roivant 來說相當「瘋狂」。我們在整個研發產品組合上，持續看到非常強勁的執行動能。

An update that will get drawn on some of the other things for today, but it's actually pretty great is that brepocitinib was awarded breakthrough designation -- breakthrough therapy designation or continue sarcoidosis, which just underscores indication selection and development there in terms of what that could mean for those patients.

有一項更新會與今天其他內容有所呼應，而且其實相當令人振奮：brepocitinib 已獲授予突破性認定——突破性療法認定，用於（持續性）結節病（sarcoidosis），這也再次凸顯我們在適應症選擇與開發上的方向，以及這對患者可能代表的意義。

Obviously, also in this quarter, we announced LPP as an indication for brepo, and that study is already enrolling. We're excited about how it's going. And then a ton of work ongoing in commercial prep for the launch in DM, which assuming FDA goes as we expect it to, we'll launch by the end of September.

當然，在本季我們也宣布將 LPP 納入 brepo 的適應症，而該研究已開始收案。我們對進展感到振奮。此外，針對 DM 的上市準備工作也在大量推進；若 FDA 的進度如我們預期，我們將在 9 月底前完成上市。

Obviously, the biggest data update for today in the FcRn franchise is what I mentioned earlier, which is that 1402 showed, we think clinically meaningful, pretty exciting basically on response rates across ACR20, 50 and 70 in the TTR study in the open-label portion. We'll talk more about that, but that's obviously encouraging data that we're looking forward to spending some time on.

當然，今天在 FcRn 產品線中最重要的數據更新，就是我先前提到的：1402 在 TTR 研究的開放標籤部分，於 ACR20、50 與 70 的反應率上，呈現我們認為具臨床意義、相當令人振奮的結果。我們會進一步說明，但這顯然是令人鼓舞的數據，我們也期待花些時間深入討論。

We're also fully enrolled on CLE with top line data expected on that study in the second half and earlier in this quarter, we announced the failure of the [bitokamab] studies in TED, but also the hyperthyroid patients show normalization, which is supportive of our grade studies, which are ongoing and continue to enroll well also.

我們在 CLE 研究也已完成全數收案，預計下半年公布主要（top line）數據；而在本季稍早，我們宣布 [bitokamab] 在 TED 的研究未達標，但甲狀腺機能亢進患者出現指標正常化，這支持了我們正在進行且持續順利收案的 Graves 研究。

And then finally, partially, it was this quarter, but earlier this quarter, we also announced our $2.25 billion settlement with Moderna, and we expect to receive the first portion of that payment, the $950 million upfront in July. So just an incredibly busy quarter of execution for us and an incredibly busy fiscal year for us. It's really hard to believe how much has changed in a year for Roivant.

最後，部分是在本季、但更早在本季初，我們也宣布與 Moderna 達成 22.5 億美元的和解，我們預期將於 7 月收到第一筆款項，也就是 9.5 億美元的預付款。因此，對我們而言這是一個執行面極其繁忙的季度，也是非常忙碌的會計年度。Roivant 在一年內發生了如此多的變化，實在令人難以置信。

None of that, though, is to say on Slide 6 that we're done. And the next 12 months are also incredibly exciting. Obviously, one of the most important things we're going on, we will hopefully be launching brepocitinib (inaudible) by the end of September. The Phase III study in cutaneous sarcoidosis, we expect to begin this year as well, and we expect the NIU Phase III top line data in the back half of this year. So a transformative year for brepo as all of that comes around.

不過，這並不代表在第 6 頁我們就已經完成任務。接下來 12 個月同樣令人非常期待。顯然，我們最重要的事項之一，是希望在 9 月底前推出 brepocitinib（聽不清）。皮膚結節病（cutaneous sarcoidosis）的第三期研究預計也將於今年啟動，而 NIU 第三期研究的主要（top line）數據預計在今年下半年公布。隨著這些里程碑到來，對 brepo 而言將是具轉型意義的一年。

We'll spend time on this today, but mostly [phl] Phase IIb top line data is expected in the second half. That also will potentially underscore that as a really important program, and hopefully (technical difficulty) going forward to that data, I just talk more about it.

我們今天也會花時間談這個，但（[phl]）第二期 b 的主要（top line）數據預計在下半年公布。這也可能進一步凸顯該計畫的重要性；並且希望（技術問題）在取得該數據後，我能再多談一些。

Obviously, DDTRA, some of the data is around today, but we're providing a pretty significant update later this year with a little bit more data as well as detailed analysis we're doing at a patient level and hopefully, there's some feedback from FDA on a go-forward plan given what we've now seen. And then, obviously, we'll get the CLE POC top line data as well.

當然，關於 DDTRA，今天會先提供部分數據；但我們將在今年稍晚提供更重大的更新，包含更多數據以及我們正在進行的、以患者層級為基礎的詳細分析；並且希望在目前所見結果的基礎上，能獲得 FDA 對後續推進計畫的回饋。此外，我們也將取得 CLE POC 的主要（top line）數據。

And then next year is a huge year with 1402 data in Graves' and MG coming in and a ton to look forward to, and frankly, as in the -- as much in the windshield in the rear view mirror. I think I've got the car analogy right there.

而明年也將是重要的一年，因為 1402 在 Graves 與 MG 的數據將陸續出爐，還有許多值得期待的事項；坦白說，前方的路徑就像——就像擋風玻璃裡看到的，甚至比後照鏡裡看到的還要多。我想我這個汽車的比喻應該講對了。

Great. Okay. I want to go in now without spending more time with the (inaudible) and talk a little bit about this DTRA data, which I would call surprisingly good. We were pretty excited to see what we saw here. It is been only a little bit hard to process just how exciting this data is.

很好。好的。我想現在直接切入，不再花時間談（聽不清），來稍微談談這份 DTRA 數據；我會稱之為「出乎意料地好」。我們看到這些結果時相當興奮。要消化這份數據到底有多令人振奮，其實有點不容易。

And so we're still doing a lot of work on it. As a reminder, on Slide 8 of what we're talking about today. So this was a unique study design in a few ways. First of all, as I think everyone is aware, this was a study in heavily refractory patients. Every patient in this study in addition to failing steroids and DMARDs also had to fail at least two advanced lines of therapy.

因此我們仍在做大量的分析工作。提醒各位，請看第 8 頁投影片，這就是我們今天要討論的內容。這項研究設計在幾個方面相當獨特。首先，如同我想大家都知道的，這是一項針對高度難治（heavily refractory）患者的研究。本研究中的每位患者，除了對類固醇與 DMARDs 治療失敗外，也必須至少對兩種進階治療線失敗。

So most commonly, that's to, for example, TNS JAKS and IL-6s. And we'll talk a little bit about that. There's obviously some other things that could be in that bucket as well. The study also had a pretty strict entry criteria on auto antibody positivity. We had a criteria on [actpile] positive above a certain level, and that was also specific to the study the design.

最常見的情況是，例如 TNF、JAK 與 IL-6 類療法。我們會稍微談談這點。當然，這個範疇裡也可能包含其他治療。本研究在自體抗體陽性方面也有相當嚴格的入組標準。我們設定了 [actpile] 陽性需高於某一門檻的標準，而這也是本研究設計所特有的。

And then the other way I was just selling was unique is it was a randomized withdrawal study with two periods: first, an open-label active treatment period of 16 weeks at high dose 1402, 600 milligrams, followed by a Period 2 12-week rerandomization where ACR20 responders at week 14 and 16 both are rerandomized into a 12-week randomized withdrawal period where some of them stay at 600 and some go down to 300 and some of the non-placebo.

然後，另一個我剛才提到的、比較獨特的設計是：這是一項隨機化撤藥研究，包含兩個期別：第一期為16週的開放標籤主動治療期，使用高劑量1402、600毫克；接著進入第二期為期12週的再隨機分派：在第14週與第16週皆達到ACR20反應的受試者，會再隨機分派進入12週的隨機化撤藥期，其中一部分維持600毫克，一部分降至300毫克，還有一些為非安慰劑。

What we have to share today is preliminary data. We're still actually cleaning and finalizing it all, but it shouldn't move very much from here on the top line treatment effect from Period 1. Period 2 is still ongoing with more than half of patients still being dosed in the study. So we've not any data or information about Period 2 to share today.

我們今天要分享的是初步數據。我們其實仍在清理並完成最終定稿，但從現在起，第一期的整體主要治療效果（top line treatment effect）應該不會有太大變動。第二期仍在進行中，超過一半的病人仍在研究中持續給藥。因此，我們今天沒有任何第二期的數據或資訊可以分享。

And then even for Period 1, there's whole 1 of data like IgG, for example, that we haven't analyzed fully and are not ready to share. So nothing to say about it other than we're going to be sharing a pretty limited subset of this data today. On Slide 9, you can see based on characteristics for the patients in the study, going with 165 evaluable patients, I'm not going to go through all of this in detail, I would say this is quite a sick patient population.

另外，即使是第一期，也還有整整一類數據（例如IgG）我們尚未完整分析，還沒準備好分享。所以除了說我們今天只能分享這些數據中相當有限的一個子集之外，沒有更多可說的。在第9張投影片，你可以看到研究受試者的特徵；本次共有165位可評估受試者。我不會逐一細講，但我會說這是一個病情相當嚴重的受試者族群。

Obviously, by design, it's refractory, and we'll talk more about that in a second. But for example, if you look at the DSAH28 CRP score of 6.1, that's quite high for a study like this. There's a bunch of measures on here that suggest a quite sick population, which was the goal, right? This is the population that we set out to enroll.

顯然，依研究設計，這是一群難治（refractory）的病人，我們等一下會再多談。但例如你看DAS28-CRP分數為6.1，對這類研究來說是相當高的。這裡有多項指標都顯示這是一個病情很重的族群，而這正是目標，對吧？這就是我們一開始就設定要納入的族群。

And so we feel good about who's in the study on prior lines of therapy, specifically on 10, so you can see on the right-hand side, we succeeded with our entry criteria that is basically all of these patients have failed more than two advanced therapy mechanisms. And that's very different than either the [Nippo] study or really any of the later line RA studies that have been run.

因此，我們對研究納入的受試者在既往治療線數方面感到滿意；特別是在第10張投影片，你可以在右側看到，我們依入組標準成功納入了這樣的病人：基本上所有受試者都曾在超過兩種進階治療機轉上治療失敗。這與[Nippo]研究或其實任何已執行的後線RA研究都非常不同。

And actually, one thing that we're highlighting a particularly interesting, 65% of these patients roughly have failed specifically JAK inhibitors. And notably, and we'll highlight this elsewhere as well, basically every single one of the patients who fail the JAK inhibitor also failed the TNF. So this is a TNF and JAK refractory patient population that we're focused on.

而且我們特別強調一點很有意思：大約65%的受試者曾在JAK抑制劑上治療失敗。值得注意的是——我們也會在其他地方再強調——基本上每一位JAK抑制劑失敗的病人也都曾在TNF上失敗。所以我們聚焦的是一個對TNF與JAK皆難治的受試者族群。

So look, Slide 11 is the headline here. And the headline is, with all the appropriate caveats for an open-label study, these numbers are high. We saw 73% of patients roughly with ACR20 responses, and not just that, but we saw quite deep responses. We saw over half of patients with the ACR50 and over one third of patients with an ACR70. And notably, once you get on to the deeper end of that with ACR50 and ACR70, you just don't see a lot of placebo response in that level of responder analysis.

所以，第11張投影片是這裡的重點。重點是：在充分考量開放標籤研究的所有必要但書後，這些數字仍然很高。我們看到約73%的病人達到ACR20反應；不僅如此，我們也看到相當深度的反應。超過一半的病人達到ACR50，且超過三分之一的病人達到ACR70。而且值得注意的是，一旦進入ACR50與ACR70這種更深層的反應端點，在這種反應者分析層級，你通常不會看到很多安慰劑反應。

And so it feels to us like looking at this data, there's something going on that's meaningful and interesting with this drug and something that merits enthusiasm and a lot of further investigation, and we're certainly doing all that work now as we get ready to take the program forward.

因此，從我們對這些數據的觀察來看，這個藥物似乎確實有一些具意義且有趣的作用，值得令人振奮並進一步深入研究；我們也確實正在做這些工作，為推進整個計畫做準備。

I'll highlight on Slide 12 the one other bit of interesting data from the study that we're able to present today, which is we pulled out the subset of patients who are JAK experience, remember those patients, 107 of them on both JAK and TNF experienced all of them. Some of them have also failed something else as well. And one of the things that I think is maybe most exciting about this data is it's basically fully preserved in that subset.

我也想在第12張投影片強調今天能呈現的另一個有趣數據：我們抽出曾使用JAK治療的受試者子集；記得這些病人——其中107位同時有JAK與TNF用藥經驗，而且全部都曾在這兩類治療上失敗。其中一些人也可能另外在其他治療上失敗。而我認為這份數據最令人興奮的一點是：在這個子集中，療效基本上完全被保留。

And so as you think about that opportunity where these patients have really failed all of the most advanced options available to them, we're able to deliver in an open-label setting pretty exciting response rates for those patients, which I think bodes well for the exact biological thesis with which we ran the study to begin with that autoantibody positivities and orthogonal mechanisms, some of the other anti-inflammatory options and then for acropositive patients, this could be an effective treatment option.

因此，當你思考這個機會點：這些病人確實已經在所有最先進、可用的治療選項上都失敗了；而我們在開放標籤的情境下，仍能為這些病人帶來相當令人振奮的反應率。我認為這也支持了我們一開始進行此研究的生物學論點：自體抗體陽性與正交（orthogonal）機轉、以及一些其他抗發炎選項；對於自體抗體陽性的病人而言，這可能是一個有效的治療選擇。

So like, I think, on Slide 13, just to reiterate what we're showing here. Look, these are sick patients, a difficult-to-treat patient population who have failed a lot or all of the available options and come in with highly active disease. We showed really great response rates in the data that we're excited to see how they evolve through the rest of the study and on deeper patient level analysis.

所以我想在第13張投影片再重申我們在這裡展示的內容。你看，這些是病情嚴重、難以治療的受試者族群，他們在許多甚至所有可用選項上都失敗，且入組時疾病活動度很高。我們呈現了非常好的反應率；我們也很期待看到在研究後續進展以及更深入的病人層級分析中，這些結果會如何演變。

And also notably, this is the largest patient population dosed with [i-514] today, were safe and well tolerated in the study, nothing new regulated from a safety signal perspective, identified. So a clean data set overall and further underscoring what we think we've got with 1402.

另外值得注意的是：這是迄今為止接受[i-514]給藥的最大受試者族群；在研究中安全且耐受性良好，從安全性訊號角度來看，沒有發現任何新的、需要關注的訊號。因此整體而言是一份乾淨的數據集，也進一步凸顯我們認為1402所具備的特性。

Path forward from here, obviously, if you look at this data and you feel pretty good about what this could be, significant potential benefit, a differentiated mechanism, a difficult-to-treat population with not a lot of options. So we're actively working right now to get ready to talk to FDA about this data and plan a path forward.

接下來的推進方向很明確：如果你看這些數據，會對它可能帶來的顯著潛在效益感到相當樂觀——具差異化的機轉、難治且選項不多的族群。因此，我們目前正積極準備與FDA就這些數據進行溝通，並規劃後續推進路徑。

The data is encouraging. I'll make one comment about it, which is the depth of responses is exactly what's exciting about the data set. It's exactly what makes us believe there is something beyond placebo happening in the data set.

這些數據令人鼓舞。我想補充一點：反應的「深度」正是這份數據集最令人興奮之處。也正是這一點讓我們相信，在這份數據中發生的效果不僅僅是安慰劑所能解釋。

But as you'll recall, the randomize withdrawal period, the primary endpoint of Period 2 is do patients taken off drug lose their ACR20 response in 12 weeks, which was a relatively short period to begin with and almost certainly would have been fine if we had seen more marginal benefit on ACR20. But the truth is, once you're looking at ACR50 and 70 responders, I think the bar has actually gotten a fair amount higher for Period 2.

但如你所記得的，隨機化撤藥期（randomized withdrawal period）中，第二期的主要終點是：停藥的病人在12週內是否會失去其ACR20反應；這本來就是一段相對較短的期間，而且如果我們在ACR20上看到的只是較邊際的效益，這樣的設計幾乎肯定是足夠的。但事實是，一旦你看到的是ACR50與ACR70反應者，我認為第二期的門檻其實已經被拉高了不少。

And so paradoxically, I think we still have a good shot of success there. But in some ways, Period 2 was less meaningful than it might otherwise have been. And I think there are plenty of scenarios where we don't see a p-value in Period 2 and continue forward with the drug given the overall quality of this data and diversely depending on FDA feedback, potentially situations where we do see a p-value Period 2, and just need to make sure we're comfortable with the plan forward.

因此有點矛盾的是，我認為我們仍然有不錯的成功機會。但在某些方面，第二期的重要性可能不如原本預期。我認為存在許多情境：即使第二期沒有看到統計學上的p值，我們仍可能基於整體數據品質而繼續推進這個藥物；而且也可能在不同情境下——取決於FDA的回饋——我們確實在第二期看到p值，但仍需要確保我們對後續推進計畫感到安心。

So I think much more interesting than the Period 2 data at this point is more patient level analysis as well as the results of those FDA discussions, and we expect to share all of that in the second half of this year. We're working on it right now, and my hope given the quality of the state is that will be kind of a with an enthusiastic update about next steps here that lay the groundwork for just a really big opportunity.

所以我認為，現階段比第二期數據更有意思的是更深入的病人層級分析，以及與FDA討論的結果；我們預期會在今年下半年分享這些內容。我們正在進行相關工作；以這份數據的品質來看，我希望屆時能以一個令人振奮的後續步驟更新，為一個非常大的機會奠定基礎。

Remember, we presented some data at our Investor Day suggesting this is at least a 70,000 patient population and some more specific revised commercial analysis, but Immunovant has now done that looks like that number could be 85,000 or higher. It's a big patient population in need.

請記得，我們在投資人日曾提出一些數據，顯示這至少是一個 70,000 名患者的族群，並且也做了更具體、更新的商業分析；但 Immunovant 現在所做的分析看起來，這個數字可能是 85,000 或更高。這是一個龐大且有需求的患者族群。

And I think underscoring that the speed with which this trial enrolled, the enthusiasm that physicians have for putting patients on study, is just further evidence that there's really something interesting here. And with that actually just want to also just give a shout out to the minima team who have continued to execute really well.

而我認為，這項試驗招募的速度，以及醫師將患者納入研究的熱忱，都進一步證明這裡確實有很有意思的東西。另外也想特別稱讚 minima 團隊，他們持續把執行做得非常好。

Obviously, the data itself is strong, but also the speed of enrolment, the (inaudible) removing study, the full enrollment on CLE. And I think that spans all of our programs. I think we're exciting about what -- obviously, what (inaudible) has been able to do with brepocitinib from a clinical enrollment perspective.

顯然，數據本身很強勁，但招募速度、（聽不清）移除研究、CLE 的全數入組也是如此。而我認為這涵蓋了我們所有的專案。我想我們對——顯然，（聽不清）在 brepocitinib 的臨床招募方面所能做到的事情感到振奮。

We're excited about the speed of enrollment, obviously the quality of that data, we'll find out soon. But look, we're really excited about what we've been able to do across the portfolio on execution, so much appreciation for the enormous number of people who are working toward those goals.

我們對入組速度感到興奮，當然也對數據品質感到期待，我們很快就會知道。但總之，我們對於在整個產品組合上的執行成果感到非常振奮，也非常感謝大量朝著這些目標努力的人。

Cool. I'm going to pivot now to mostly (inaudible) and do a little bit of a data preview their because the next time we get together, that data could potentially be very close in front of us. And so we wanted to get out ahead of that and give people a chance to just ground themselves in what's coming as we did last year around this time or a little later for brepo in dermatomyositis.

很好。我現在要把重點轉到主要是（聽不清），並先做一點數據前瞻，因為我們下次再聚在一起時，那些數據可能就近在眼前了。因此我們希望提前讓大家有機會先掌握接下來會發生什麼，就像去年這個時候或稍晚一些，我們針對 brepo 在皮肌炎（dermatomyositis）所做的一樣。

Look, I'll do a little bit of an interaction here. And then you all heard from Drew back at Investor Day in December, he's in the room with me and is going to talk through a little bit more about the program. Look intense unmet medical need. These patients, in the extreme significant proportion of them die. They're very sick.

我會在這裡做一點互動。你們也在 12 月的投資人日聽 Drew 講過，他現在就在我旁邊，等一下會更深入說明這個專案。這裡存在非常迫切的未被滿足醫療需求。這些患者中，有相當高比例會死亡。他們病得非常重。

There is currently only one approved mechanism with two therapies, and we think there's probably 200,000 patients for rest of the U.S. and Europe. And that one mechanism for (inaudible) is underscoring multiple really great launches at this point. So we're excited to see the commercial enthusiasm and excited to see these patients have access to some of the (inaudible) benefit already, and we're hoping to add to that. Mostly has a completely differentiated mechanism of action for the disease.

目前只有一種已核准的作用機制、對應兩種療法；我們認為在美國與歐洲其餘地區大概有 200,000 名患者。而那一種（聽不清）的作用機制，至今已支撐了多個非常成功的上市推廣。因此我們很高興看到商業端的熱度，也很高興看到這些患者已能取得部分（聽不清）的效益，我們希望能在此基礎上再加碼。Mostly 對於此疾病具有完全差異化的作用機制。

It's an STC activator. It's an inhaled STC activator is potentially the first nonpropropanil that could be available for these patients. We expect this to be a polypharmacy combination therapy market as PAH has been. And we think mosli has a chance to be First line has a chance to be a major part of the treatment paradigm, and we're just looking forward to getting this data moving forward there.

它是一種 STC 活化劑。它是一種吸入式 STC 活化劑，可能會是第一個可供這些患者使用的非 propropanil（非 propropanil）。我們預期這會是一個多重用藥的合併治療市場，就像 PAH 一樣。我們認為 mosli 有機會成為第一線治療，也有機會成為治療典範中的重要一環；我們非常期待接下來取得這些數據。

In our Phase I data across healthy volunteers of pulmonary potential patients and Drew will remind us of the state specifically, we saw among the best PVR reductions to date and one thing we're going to run people up today is that although we saw a 38% PVR reduction in some of those patients, that basically anything that has ever shown 20-plus percent PVR reductions has been able to deliver clinically meaningful benefit.

在我們的第一期數據中，涵蓋健康受試者、肺部潛在患者（Drew 會提醒我們具體狀態），我們觀察到迄今為止最好的 PVR 降幅之一；而今天我們要提醒大家的一點是，雖然在部分患者中我們看到 38% 的 PVR 降幅，但基本上，任何曾顯示 20% 以上 PVR 降幅的療法，都能帶來具臨床意義的效益。

I think it's true that there has not been any class of drug showing a 20-plus-percent PPR reduction that has not gone on to be a commercially successful class of drugs. And then finally, as a reminder, unsurprisingly, the top line data from that study is on track, and we expect to get it in the second half of 2026. It's a 135-patient study.

我認為確實如此：沒有任何一個藥物類別在顯示 20% 以上 PPR 降幅後，沒有繼續發展成為商業上成功的藥物類別。最後提醒一下，不意外地，該研究的主要結果數據仍按計畫推進，我們預期在 2026 年下半年取得。這是一項 135 名患者的研究。

So with that, I'm going to hand it over to [Drew], who's going to take you through the next handful of slides here on the program, and then I'll come back with a little summary at the end and the rest of the presentation.

因此，接下來我把時間交給 [Drew]，他會帶大家看接下來幾張關於此專案的投影片；之後我會在最後做一點總結以及其餘簡報內容。

Thanks, Matt. And I can tell you there's a lot of excitement about mosli. So mosli is an inhaled SGC activator that's delivered directly to the lungs to activate SEC and restore impaired SGC function. SGC is a key enzyme in the NOCCGMP pathway, and in attentive stressed environments like PH-ILD, nitric oxide may be reduced and the SGC binding site, can become impaired, leading to sGC dysfunction.

謝謝，Matt。我可以告訴各位，大家對 mosli 非常興奮。因此，mosli 是一種吸入式 SGC 活化劑，直接送達肺部以活化 SEC 並恢復受損的 SGC 功能。SGC 是 NOCCGMP 路徑中的關鍵酵素；在像 PH-ILD 這種持續受壓的環境中，一氧化氮可能降低，而 SGC 的結合位點可能受損，導致 sGC 功能失調。

Now typically, SGC is activated when nitric oxide engages SGC in the presence of heme and CGMP is then produced. Unlike CGMP SGC stimulators that requires nitric oxide and heme to activate the SGC. Inhaled (inaudible) binds to the heme pocket independent of the need for NO and heme, producing CGMP, which results in vasodilation of the pulmonary arteries and potential reduction of fibrosis and inflammation of the lung tissue. Next slide.

一般而言，當一氧化氮在血基質（heme）存在下與 SGC 結合時，SGC 會被活化，接著產生 CGMP。不同於需要一氧化氮與血基質才能活化 SGC 的 CGMP sGC 刺激劑。吸入式（聽不清）可在不需要 NO 與血基質的情況下結合至血基質口袋並產生 CGMP，進而造成肺動脈血管擴張，並可能降低肺組織的纖維化與發炎。下一張投影片。

So we know many pulmonary diseases are heterogeneous in nature. And that fact can make patient treatment complex. To start, there's disease of the pulmonary vasculature and disease of the lung parenchyma. The combination of these two disorders is embodied in pulmonary hypertension with interstitial lung disease, which is the first indication we're exploring in our Phase II FOCUS Study.

因此我們知道，許多肺部疾病本質上具有異質性。而這一點會使患者治療變得複雜。首先，存在肺血管系統的疾病，以及肺實質（lung parenchyma）的疾病。這兩種疾病的組合體現在合併間質性肺病的肺高壓（pulmonary hypertension with interstitial lung disease）中，這也是我們在第二期 FOCUS 研究中探索的第一個適應症。

We believe mosli has the potential to address both the pulmonary vascular and the lung parenchymal diseases experienced with patients with PH-ILD. Mosli -- next slide. I want to make sure that -- I want to make sure that -- Let me just call out the slide numbers if everyone's got -- Okay. Okay. I'll call out -- let me call out the slide numbers.

我們相信 mosli 有潛力同時處理 PH-ILD 患者所面臨的肺血管與肺實質兩方面的疾病。Mosli——下一張投影片。我想確認——我想確認——讓我先報一下投影片頁碼，看看大家是否都有——好嗎？好的。我會報——讓我報一下投影片頁碼。

Let me just call out the slide numbers. Everyone has got --

讓我先報一下投影片頁碼。大家都有--

Okay. Thank you very much. I appreciate that. I want to make sure we're advancing. Both of these preclinical properties led Bayer to take mosli into Phase I trials in a total of 170 patients, including healthy volunteers and patients group 1 PAH and Group 4 CCAP.

好的。非常感謝。我很感激。我想確認我們有在往下進行。這些臨床前特性促使拜耳（Bayer）將 mosli 推進到第一期試驗，總計 170 名受試者，包括健康志願者，以及第 1 組 PAH 與第 4 組 CCAP 的患者。

In the Phase I study, BIR study most in 132 healthy volunteers and 38 PH patients. The healthy volunteers underwent studies with single and multiple dose formats, and mosli proved to be well tolerated, active and have an extended half-life of approximately 40 hours. And in the Phase Ib ATMOS study, 38 patients with PH were dosed in a single ascending dose format and mosli again proved to be very active producing deep PVR reductions and was very well tolerated.

在第一期研究中，BIR 研究納入 132 名健康志願者與 38 名 PH 患者。健康志願者接受單次與多次劑量設計的研究；mosli 證實耐受性良好、具活性，且半衰期延長，約為 40 小時。而在第一期 Ib 的 ATMOS 研究中，38 名 PH 患者以單次遞增劑量設計給藥；mosli 再次證實非常活躍，可帶來顯著的 PVR 降幅，且耐受性非常好。

On to Slide 20. So given mosli (inaudible) mechanism of action and inhaled route of administration, one would expect to see notable reductions in pulmonary vascular resistance associated with hemodynamic changes. And with 1 dose of mosli in PH patients, that's exactly what we saw.

接著看第 20 張投影片。因此，考量 mosli（聽不清） 的作用機轉以及吸入式給藥途徑，我們預期會看到與血流動力學變化相關的肺血管阻力顯著下降。而在 PH 患者接受 1 劑 mosli 後，結果正如我們所見。

A single dose of mosliciguat reduced PVR in these patients early and sustained through the 3-hour observation period with a mean PVR reduction of greater than 30% and a mean peak PVR reduction of approximately 38%. This places mosli's PBR reductions amongst the highest reduction seen in single and multi-dose trials in PH treatment space.

單次給予 mosliciguat 可使這些患者的 PVR 及早下降，並在 3 小時觀察期間持續維持；平均 PVR 降幅超過 30%，平均峰值 PVR 降幅約 38%。這使得 mosli 的 PVR 降幅位居 PH 治療領域單次與多次給藥試驗中所見的最高降幅之列。

With one dose mosliciguat, we also saw CGMP levels rise as measured in plasma with no associated clinically meaningful systemic side effects, including systemic blood pressure and heart rate. We also observed the desired impact on other hemodynamic measures, including mean reduction in NPAT of up to 20% and mean increase in cardiac output of up to 25%.

單次給予 mosliciguat，我們也看到以血漿測得的 cGMP 濃度上升，且未伴隨具臨床意義的全身性副作用，包括全身血壓與心率方面。我們也觀察到對其他血流動力學指標的預期影響，包括 NPAT 平均最多降低 20%，以及心輸出量平均最多增加 25%。

Slide 21. Mosliciguat was also well tolerated in Phase I patients in healthy volunteers and patients with PH. With treatment-emergent adverse events being mild to moderate intensity across both groups, and all doses were well tolerated, and we did not see significant cough, which is often exacerbated by inhaled (inaudible), and we did not see clinically relevant systemic side effects which we believe in great part was due to the inhaled direct delivery of mosli to the lungs and the limited bioavailability of mosli in circulation.

第 21 張投影片。Mosliciguat 在第一期試驗中，於健康受試者與 PH 患者皆具良好耐受性。兩組的治療期間出現之不良事件多為輕至中度，且所有劑量皆耐受良好；我們未見明顯咳嗽（吸入式（聽不清）常會加劇咳嗽），也未見具臨床相關性的全身性副作用；我們相信這在很大程度上歸因於 mosli 以吸入方式直接送達肺部，以及 mosli 在循環中的生體可用率有限。

Slide 22. So with mosli's of these Phase I tolerability and clinical profile, we look to take mosli into Phase II development in indication where there exists a major unmet medical need. And we felt that PH-ILD was an exciting opportunity for development.

第 22 張投影片。因此，基於 mosli 在第一期試驗的耐受性與臨床特徵，我們計畫將 mosli 推進至第二期開發，鎖定存在重大未被滿足醫療需求的適應症。我們認為 PH-ILD 是一個令人振奮的開發機會。

Given the primary site of PH-ILD, it's in the lungs, involving a pulmonary vasculature and the lung parenchyma and the currently approved treprostinil treatments have high treatment burden as well as tolerability challenges with highly variable efficacy and so mosli lines up really nicely in this moment.

鑑於 PH-ILD 的主要病灶位於肺部，涉及肺血管與肺實質，而目前已核准的 treprostinil 治療具有較高的治療負擔，且在耐受性上也有挑戰、療效變異性很大，因此 mosli 在此時點非常契合需求。

Since it was delivered directly to the lungs as a once daily dosing, that's been very well tolerated and produced limited incremental cough and systemic side effects in Phase I and has the potential to address both the pulmonary vascular and lung parenchymal diseases.

由於其以每日一次、直接送達肺部的方式給藥，在第一期試驗中耐受性良好，僅造成有限的額外咳嗽與全身性副作用，並且有潛力同時處理肺血管與肺實質疾病。

Slide 23. So to go a little deeper into PH-ILD patient populations and the opportunity, PH-ILD represents a large and underserved market, where new drugs are sorely needed for these patients. They're up to approximately 200,000 patients in the U.S. and Europe, likely underdiagnosed given the lack of treatment options in particular.

第 23 張投影片。為了更深入說明 PH-ILD 的患者族群與機會，PH-ILD 代表一個龐大且服務不足的市場，這些患者迫切需要新藥。在美國與歐洲患者數量可達約 20 萬人；尤其因缺乏治療選項，實際上可能被低估與低診斷。

And this is a sick population and severe subgroup of PH, less than a five-year median survival and the combination of PH and ILD represents an increasingly poor prognosis compared to each alone. And I mentioned previously the lack of treatment as there are currently only two approved FDA (Inaudible) drugs leaving room for significant improvement.

這是一個病情嚴重的族群，也是 PH 的嚴重亞群，中位存活期不到 5 年；PH 與 ILD 的合併相較於單獨任一疾病，預後更差且愈發不良。如先前所述，目前治療選擇不足，因為目前僅有兩項 FDA 核准的（聽不清）藥物，仍有顯著改善空間。

Slide 24. Now the core field of drugs in development for the treatment of PH-ILD is rather sparse. There are three companies, all with treprostinil treatments in different formulations and all of these treprostinil treatments continue to have a range of challenges.

第 24 張投影片。目前針對 PH-ILD 治療的在研藥物核心領域相當稀少。有三家公司皆以不同劑型的 treprostinil 治療為主，而這些 treprostinil 治療仍持續面臨一系列挑戰。

Seralutinib, with its different mechanisms, has also run into recent challenges as Gossamer's Phase III PERSERA trial in PAH did not meet its primary end points, coming off challenges in Phase 2 as well. And the result of the recent PRERSERA trial outcome (inaudible) has paused its planned studies in PH-ILD.

Seralutinib 由於其不同的作用機制，近期也遭遇挑戰；Gossamer 在 PAH 的第三期 PERSERA 試驗未達主要終點，且先前第二期也有挑戰。而近期 PRERSERA 試驗結果（聽不清）已使其在 PH-ILD 的既定研究計畫暫停。

So mosli on the other hand, with its first-in-class opportunity as an inhaled sGC activator has once daily dosing, positive tolerability and positive activity in its profile from Phase I studies, and this really positions mosli to be a leader in the treatment of patients with PH-ILD upon its approval.

相較之下，mosli 作為吸入式 sGC 活化劑，具備同類首創（first-in-class）的機會，採每日一次給藥，並在第一期研究中展現正向的耐受性與活性特徵；這使 mosli 在未來獲准後，有望成為 PH-ILD 患者治療的領導者。

I also wanted to share about -- and this is Slide 25. I also wanted to share our thoughts about how we see PH-ILD being and the market and how it's going to develop. We actually think the PAH market provides a likely road map for that development.

我也想分享我們的看法——這是第 25 張投影片。我也想分享我們如何看待 PH-ILD 的樣貌、市場以及其將如何發展。我們認為 PAH 市場很可能提供一條可參考的發展路線圖。

In the early days, supportive care was the only option for patients with PAH. And this is what we currently see, and that's the reality of PH-ILD patients in most regions outside of the U.S. where their are limited treatment options. Over time, drugs with newer mechanisms were approved, the combination therapy involving multiple mechanisms of action, became more common.

在早期，支持性照護是 PAH 患者唯一的選擇。而這正是我們目前所看到的情況，也是 PH-ILD 患者在美國以外多數地區的現實：治療選項有限。隨著時間推進，具新作用機制的藥物獲得核准，涉及多重作用機制的合併治療也變得更常見。

As a median survival of these PH patients has also steadily increased as time went on from two and a half years to where they are today at 12 to 15 years and treatment guidelines evolve alongside the data, which reinforced the evolution of the treatment paradigm.

隨著時間推移，這些 PH 患者的中位存活期也穩步提升，從 2 年半增加到如今的 12 至 15 年；治療指引也隨著數據一同演進，進一步強化了治療典範的變化。

Today, revenue in the PAH market has really reached a stellar level at $100 billion in aggregate sales and a robust $7 billion per year, with 15 drugs approved and there remains a good pricing environment and commercial opportunity for these newer therapies because this is driven by the complex nature of PAH.

如今，PAH 市場營收已達到非常亮眼的水準，累計銷售額達 1,000 億美元，且每年約 70 億美元，已有 15 種藥物獲准；由於 PAH 的複雜性所驅動，對於這些較新的療法仍存在良好的定價環境與商業機會。

And finally, a key takeaway is that today, over 40% of patients with PAH initiate their treatment with dual therapy and 15% of these patients will add a third therapy by the end of the year. This combo therapy, as Matt said, is really the norm. And so we are currently deep into our Phase II study exploring mosliciguat in our blinded Phase II placebo-controlled and randomized study in adults in PH-ILD. The study is a multicenter study across the globe. We're targeting 120 patients.

最後，一個關鍵重點是：目前超過 40% 的 PAH 患者以雙重療法開始治療，而其中 15% 的患者會在一年內加上第三種療法。如 Matt 所說，這種合併治療確實已成為常態。因此，我們目前正深入進行第二期研究，在成人 PH-ILD 的盲性、安慰劑對照、隨機分派第二期試驗中評估 mosliciguat。本研究為全球多中心試驗。我們目標納入 120 名患者。

We ended enrollment with 135 patients. During the screening period, the investigators look hard to find patients to confirm ILD, elevated baseline PVR indicative of PH and limits on the level of fibrosis emphysema as determined by CAT scan. If eligible for the study to patients that are randomized two to one drug placebo and then they go through a rapid titration and that moves from 1 milligram to 2 milligrams to 4 milligrams.

我們最終完成收案共 135 名患者。在篩選期間，研究者會仔細尋找患者以確認 ILD、確認基線 PVR 升高以顯示 PH，並依據電腦斷層掃描（CAT scan）判定纖維化與肺氣腫程度的限制。若符合試驗資格，患者將以 2:1 隨機分派至藥物組或安慰劑組，接著進行快速劑量滴定，從 1 毫克到 2 毫克再到 4 毫克。

And Matt may have spoken about it, but we've seen really great progress there with the vast majority, over 95% of our patients achieving that 4-milligram dose and sustaining on -- well through the week 16 period. So that's been very attractive and positive. And at week 16, the primary endpoint is changed from baseline PVR, and that's determined at 16 weeks, alongside the secondary endpoint of change from baseline of 6-minute walk and change from baseline NT-proBNP.

Matt 可能已提到，但我們在這方面看到非常好的進展：絕大多數患者（超過 95%）達到 4 毫克劑量，並且在——嗯——整個第 16 週期間都能維持。因此這點非常吸引人且正向。在第 16 週，主要終點為 PVR 相較基線的變化，於 16 週時評估；同時次要終點包括 6 分鐘步行距離相較基線的變化，以及 NT-proBNP 相較基線的變化。

And then the patient moved on to week 24 secondary and exploratory endpoints and then they all go on drug if they weren't on drug into the long-term extension. Slide 27. So very importantly, and as we get closer to data in the second half of this year, we've focused very heavily in designing our Phase II study and defining our patient population.

接著患者進入第 24 週的次要與探索性終點評估，之後若先前未用藥者也將進入用藥，並進入長期延伸試驗。第 27 張投影片。非常重要的是，隨著我們接近今年下半年的數據揭露，我們在第二期試驗設計與患者族群定義上投入了非常多的心力。

And we carefully designed around the Seventh World Symposium of pulmonary hypertension, and these guidelines are crucial for PH-ILD patient selection. We targeted patients with worsening symptoms of PH mild-to-moderate impaired lung function based on pulmonary functional testing, elevated PVR and mean pulmonary arterial pressures were crucial.

我們也依據第七屆世界肺動脈高壓研討會的建議進行周密設計，而這些指引對於PH-ILD病患的篩選至關重要。我們鎖定症狀惡化、且依肺功能檢查顯示肺功能為輕至中度受損的患者；升高的PVR與平均肺動脈壓是關鍵指標。

And also we excluded severe emphysema to ensure a cleaner ILD population. The result is that the study population (inaudible) the recommended guidelines and more severe patients. And on Slide 28, as you can see, this effort is reflected in our baseline data in focus. Our mean TVR came in at 7.1 Wood units, so very elevated. Mean pulmonary arterial pressures of 39.3%, consistent with our desired thresholds and confirming we enrolled patients with significant hemodynamic involvement.

此外，我們排除重度肺氣腫，以確保ILD族群更為純粹。結果是，研究族群（聽不清）符合建議指引，且納入了更嚴重的患者。在第28張投影片，如各位所見，這項努力反映在我們聚焦的基線數據中。我們的平均TVR為7.1 Wood units，屬於非常高的水準。平均肺動脈壓為39.3%，符合我們設定的門檻，並確認我們納入了具有顯著血流動力學受累的患者。

The lung disease mix also looks well balanced and we protected from emphysema both in number of patients and level of severity as determined by the CAT scan. And this was very important from all of those learnings. And we also explored background therapy, including exploring PDE5s on background, and this is also consistent with real-world practice.

肺部疾病的組成看起來也相當均衡；我們在患者人數與依CAT掃描判定的嚴重程度兩方面，都避免了肺氣腫的干擾。這點對於上述所有經驗教訓而言非常重要。我們也評估了背景治療，包括探討是否合併使用PDE5抑制劑作為背景用藥，這也與真實世界的臨床實務一致。

So this careful patient selection and enrichment gives us confidence we've enrolled the right population to detect a meaningful treatment effect. We're very much looking forward to our Phase II data in the second half of this year. Matt, back to you.

因此，這種審慎的患者篩選與富集策略，讓我們有信心已納入正確的族群，以偵測具意義的治療效果。我們非常期待今年下半年取得第二期數據。Matt，交回給你。

Awesome. Thank you. Thanks, [Drew]. So look, a lot to be excited about on the program here. I just want to -- a couple of quick reminders and a summary on Slide 22 and 23 here -- on Slide 22. So Drew talked about this in detail, but just as a reminder, the primary endpoint of the study is PVR, that is the same as the primary endpoint for the Phase II programs across a variety of other PH-ILD studies or mechanisms or drugs.

太棒了。謝謝你。謝謝，[Drew]。所以你看，這個專案有很多令人振奮之處。我想——在這裡快速提醒幾點，並在第22與第23張投影片做個總結——先看第22張。Drew已經詳細說明過，但提醒一下，本研究的主要終點是PVR，這也與其他多項PH-ILD第二期研究（不同機轉或藥物）的主要終點相同。

And so we're doing the same thing following a well-traveled path there. We will then, in Phase III, move to a six-minute walk and other clinically relevant endpoints is the way that the trial is measured. I want to remind everybody; this study is not powered to achieve a p-value on six-minute walk. We may or may not have a p-value. What we're really looking for is affirmation of dosing, affirmation of safety, affirmation of PVR in this patient population.

因此我們採取相同作法，沿著一條已被充分驗證的路徑前進。接著在第三期，我們會改以六分鐘步行測試以及其他具臨床相關性的終點來衡量試驗結果。我想提醒大家：本研究的統計設計並非為了在六分鐘步行測試上達到p值顯著。我們可能會、也可能不會得到p值。我們真正要尋求的是：劑量的確認、安全性的確認，以及在此患者族群中PVR的確認。

And we will obviously look for interesting trends in patient level data on 6-minute walk. But I want to make sure we've been clear ahead of time. This is not a study design to achieve a p-value on six-minute walk. And that's not what we're looking for as our own criteria to go from here. That's the point I wanted to highlight. I want to highlight it now while having not seen any of that data so that I can't possibly be telegraphing anything about the study other than how it was designed.

當然，我們也會在六分鐘步行的個體層級數據中尋找有趣的趨勢。但我想事先把話說清楚。這不是一個為了在六分鐘步行上取得p值而設計的研究。而這也不是我們用來判斷下一步推進與否的內部標準。這是我想強調的重點。我現在就先強調，因為我尚未看到任何相關數據，因此不可能在暗示任何研究結果；我只能說明研究設計本身。

On Slide 23, just to recap what Drew has said here. First of all, again, with appreciation of home on that team. This study enrolled very quickly with all the patients enrolled within 12 months of the first patient being dosed. Early discontinuation rates compare favorably to what we've seen in previous PH-ILD studies.

在第23張投影片，簡要回顧Drew剛才所說的。首先，再次感謝團隊的努力。本研究收案非常迅速，從第一位患者給藥起算，12個月內即完成所有患者入組。早期停藥率與過往PH-ILD研究相比也相當有利。

Look, with this in $20, you can buy two pizzas at Domino's, but our investigators are enthusiastic about the program. They're excited. The feedback is good. I think we're feeling great about how the study is being run. And then -- and this is a great thing for safety, it's a great thing for the opportunity.

坦白說，拿20美元你可以在達美樂買兩個披薩，但我們的研究者對這個專案充滿熱情。他們很興奮。回饋也很好。我認為我們對研究的執行方式感到非常滿意。而且——這對安全性是好事，對機會也是好事。

As Drew said, 95% of the participants reach the maximum dose during their titration and all of the blinded safety reviews and the ongoing assessments by the DMC continues to affirm the safety of the program and have people to run the study. Obviously, there's lot of things that don't get revealed till the data is unblinded, but it certainly gives us comfort that the patients are achieving high dose, and the things are moving as they show basis.

如Drew所說，95%的受試者在滴定期間達到最高劑量；所有盲態安全性審查以及DMC持續進行的評估，都持續確認本專案的安全性，並支持研究得以持續推進。當然，有很多事情要等到解盲後才會揭露，但這至少讓我們安心：患者確實達到高劑量，且各項進展符合我們所看到的基礎情況。

So again, thank you to Drew. Happy to provide this update now ahead of that data. I'm really looking forward to seeing the outcome from this program in just a few months at this point. So looking forward to it. Lastly, in term of the pipeline updates today, I'm just going to give a brief recap of where we are in brepo.

所以再次感謝Drew。很高興能在數據出爐前先提供這次更新。此刻距離看到這個專案的結果只剩幾個月，我非常期待。因此非常期待。最後，關於今天的產品線更新，我將簡要回顧我們在brepo的進展。

Brepo has been the focus of so much of our conversation for the past 10 months. It's less of the focus today as we're in execution mode there. But just as a reminder, on Slide 25 here -- sorry, that's -- I'm looking at the wrong slide numbers. As a reminder on the next slide, on the first line of the brepo section, it's Slide 32, sorry, look, this is a huge opportunity for us.

在過去10個月裡，brepo一直是我們討論的重點。今天它不是那麼核心，因為我們正處於執行階段。但提醒一下，在第25張投影片——抱歉，那是——我看錯投影片編號了。提醒一下，在下一張投影片、brepo段落第一行，是第32張，抱歉；總之，這對我們而言是個巨大的機會。

There's possibly close to 300,000 patients addressable by the existing indications and just a ton of data coming over the next 12 to 24 months between the potential approval, obviously, in the random (inaudible), but also the NIU data, the potential for the NIU launch, the ongoing program that will start rolling soon and (inaudible) currently enrolling study in LPP and potentially more indications to come.

依現有適應症來看，可能有接近30萬名可觸及的患者；而在未來12到24個月之間，將有大量數據陸續出爐，包括潛在的核准（顯然是在隨機（聽不清）中），以及NIU數據、NIU上市的可能性、即將陸續啟動並推進的持續性計畫，以及（聽不清）目前正在LPP收案的研究，並且可能還會有更多適應症。

So just a lot of great, great, great stuff coming for brepo and a really exciting moment from here. On Slide 33, we've put this up a few times, but just to remind people. First of all, these are sick patients and there are really very few options for them in dermatomyositis.

因此，brepo接下來會有非常非常非常多的好消息，從現在起是一個非常令人振奮的時刻。在第33張投影片，我們已經展示過幾次，但再提醒大家。首先，這些都是病情嚴重的患者，而在皮肌炎方面，他們的治療選項其實非常有限。

As a reminder, 75% of these patients are on principally steroids, and in many cases, on very high doses of steroids, over 10 milligrams a day for a good portion of the year. And beyond that, it's a combination of IVIG, which as a reminder, the sort of established treatment paradigm for IVIG in dermatomyositis is somewhere etin4 and five days a month consecutive in an infusion center. So a really arduous path.

提醒一下，75%的患者主要使用類固醇治療，而且在許多情況下是非常高劑量的類固醇，一年中有相當長一段時間每天超過10毫克。除此之外，還會合併使用IVIG；提醒一下，皮肌炎中IVIG較為既定的治療模式，大約是每月在輸注中心連續輸注4到5天。因此是一條非常艱辛的治療路徑。

And then other than that, it's off-label stuff, much of what has not been successful in studies, but it's used because there's no other option. So we feel really great looking forward here to our ability to bring a new option to these patients.

再來除此之外，多半就是超適應症用藥，其中許多在研究中並未成功，但因為沒有其他選擇仍被使用。因此，我們對於未來能為這些患者帶來新的治療選項感到非常振奮。

And on Slide 34, further underscoring, and again, this is not new, we presented this before, further underscoring the need here. These patients are treated as we age for that matter, with polypharmacy on multiple lines of therapy, they're bouncing around.

在第34張投影片，進一步強調——而且這也不是新內容，我們之前已呈現過——再次凸顯這裡的未滿足需求。這些患者在治療上——同樣地，隨著年齡增長——往往需要多重用藥（polypharmacy），經歷多線治療，在不同療法之間來回更換。

They have accumulated organ damage with high systemic corticosteroid exposures. It's just a tough experience for these patients, and we think a new option is going to go far. We're not saying a lot on Slide 35 about our commercial progress.

他們在高劑量全身性皮質類固醇暴露下已累積器官損傷。對這些患者而言，這就是一段艱難的經歷，而我們認為一個新的選擇將會帶來很大的幫助。我們在第35張投影片上對我們的商業化進展沒有多談。

First of all, it is a -- and will become a more competitive field. And second of all, we're mostly just head down in execution mode. But I'll just say, suffice to say, we're doing all the things that you would expect us to be doing at this stage. We are in the thick of payer engagement.

首先，這是一個——而且將會變得更具競爭性的領域。其次，我們大多數時間都埋頭在執行模式。但我只想說，簡而言之，我們正在做你在這個階段會期待我們做的所有事情。我們正深入進行與支付方的互動。

We are working with the physician community. We're partnering with specialty pharmacies to make sure distribution is effective for these patients. We've built a strong commercial team that we're really excited about, and we continue to do unbranded patient engagement. We talked about dermatomyositis.com when we got together in December. And I am super pleased with the work that team is doing.

我們正在與醫師社群合作。我們與專科藥局建立夥伴關係，以確保這些患者的藥品配送有效。我們建立了一支強大的商業團隊，對此我們非常振奮，並且我們持續進行不帶品牌的患者互動。我們在12月聚在一起時談到 dermatomyositis.com。而我對那個團隊所做的工作感到非常滿意。

I think they are executing on the commercial side with the same vigor that they executed on the clinical side, and I'm excited to see what we're able to do there later this year and beyond. We've also been moving along on the scientific and medical side.

我認為他們在商業端的執行力度，與他們在臨床端的執行力度同樣強勁；我也很期待看到我們在今年稍晚以及之後能在那裡做到什麼。我們在科學與醫學端也一直在推進。

If you look at Slide 36, this is a small subset of the presentations that (inaudible) has been presented all over at this point and continues to be presented all over both at the major medical meetings as well as at a whole host of regional myocytes meetings and otology meetings and notably in March the Phase III data was published in NEJM, which is a testament to how exciting the data is the custom of the importance of the study, the quality of the study, and we can't be more excited for that publication as well.

如果你看第36張投影片，這只是（聽不清）在各處發表的簡短子集；截至目前已在各地廣泛發表，並且仍持續在各處發表，包含主要醫學會議，以及大量的區域性肌炎（myocytes）會議與耳科（otology）會議。值得注意的是，第三期數據在3月發表於《新英格蘭醫學期刊》（NEJM），這證明了數據的令人振奮、研究的重要性、研究品質；我們也對這篇發表感到無比興奮。

Finally, just a super quick recap on LPP, which we announced just about one and a half months ago, a fourth indication for brepocitinib. It's a highly morbid disorder with no FDA-approved therapies. These patients are miserable. They are in a ton of pain. It's a really tough disease that in addition to pain causes itch burning, redness, scaling (inaudible) hair loss.

最後，快速回顧一下 LPP。我們大約在一個半月前宣布，這是 brepocitinib 的第四個適應症。這是一種高致病負擔的疾病，且沒有任何 FDA 核准的治療。這些患者非常痛苦。他們承受著大量疼痛。這是一種非常棘手的疾病，除了疼痛之外，還會造成搔癢、灼熱感、發紅、脫屑（聽不清）以及掉髮。

There's probably 100,000 or so such patients in the U.S. that's been growing in prevalence over time. And there's nothing approved so we have an opportunity to do something really interesting for these patients. Our trial design on Slide 38, we talked about when we first (inaudible) program is a sort of continuous enrolling Phase IIb/III pivotal that's designed to give us endpoint validation and is going to get us into hopefully registration there. So we're really looking forward to that.

美國大概有約10萬名左右這樣的患者，而且其盛行率隨時間推移一直在上升。目前沒有任何核准療法，因此我們有機會為這些患者做出非常有意義的事情。我們在第38張投影片上的試驗設計，我們在最初（聽不清）該計畫時談過，這是一個持續入組的第二期b/第三期關鍵性試驗，旨在提供終點驗證，並希望能讓我們進入註冊申請。所以我們非常期待。

And there's just a ton of reasons to be excited about the program on Slide 39. The high unmet need in LPP, the mechanistic rationale for brepo is strong. It's a Th1 dominant disease, where dual JAK innovation should work specifically well.

而在第39張投影片上，有非常多理由讓人對這個計畫感到興奮。LPP 的高度未被滿足需求、brepo 的機轉理據很強。這是一種以 Th1 為主導的疾病，雙重 JAK 抑制的創新應該會特別有效。

We think we've got the right trial design, and there's obviously some overlapping prescriber base and KOL community with our existing indications. So it all sort of fits together, and we're intent to see how that program continues from here. Great. Okay. I'm going to wrap up quickly with a financial update and then we'll get to Q&A.

我們認為我們有正確的試驗設計，而且與我們既有適應症之間，處方醫師基礎與 KOL 社群顯然有一些重疊。因此整體上是相互契合的，我們也很期待看看這個計畫接下來會如何發展。很好。好的。我將用財務更新快速收尾，然後我們進入問答。

So Max spent a ton of time on this. Financial quarter was relatively straightforward. We continue to be in a strong position from a cash perspective, $4.3 billion in cash and cash equivalents as of [March 31] before the Moderna settlement, no debt. We continue to retire shares we purchased a fair amount in this quarter. We continue to have an active program

Max 在這部分花了很多時間。本季財務表現相對直接明瞭。從現金角度來看，我們仍處於強勁位置；截至[3月31日]（在與 Moderna 和解之前），我們擁有43億美元的現金及約當現金，且沒有負債。我們持續回購並註銷股份，本季回購了相當數量。我們也持續有一個積極的計畫

And spend continues to be sort of as it has been, over time, R&D has grown a bit at the scope of the programs have increased, but that's all for the good and looking forward to the future. There is a couple of slides in here that I'm not going to talk to now, but we've gotten a few questions on accounting treatment as the launch gets closer.

支出也大致維持一貫水準；隨著計畫範圍擴大，研發支出隨時間略有成長，但這都是正向的，我們也期待未來。這裡有幾張投影片我現在不會談，但隨著上市時間接近，我們收到一些關於會計處理的問題。

And so there's some good reference material in here on Slides 44 and 45, if you're trying to build models or understand our financial statements in the future. And look, I've talked about this a fair amount already, but on Slide 46 and 47, we just have a great run ahead of us here. We've got a lot to do.

因此在第44與第45張投影片中有一些很好的參考資料，若你正嘗試建立模型或在未來理解我們的財務報表。另外，我已經談過不少，但在第46與第47張投影片上，我們前方確實有很棒的發展動能。我們還有很多要做。

Obviously, we've been fortunate and have that high-quality execution so far with the quality of our data. It sets a high bar for the stuff coming next, which I couldn't be more excited for, so a lot of really great data coming in our existing programs and new programs and looking forward to sharing all of it in the period to come as well as obviously getting back on the commercial arena and watching all of that play through.

顯然，我們很幸運，迄今在數據品質上展現了高品質的執行。這也為接下來的工作設下很高的標準，而我對此感到無比興奮；我們在既有計畫與新計畫中都將有許多非常出色的數據即將出爐，並期待在接下來一段時間與大家分享，同時也會重返商業化戰場，並觀察整個推進的進展。

So with that, I'm going to say thank you again. I assay thank you to, obviously, all of you for listening. Thank you to all of our teams, (inaudible) and (inaudible) for doing to run high-quality studies, executing well, generating quality data. I couldn't ask more of these drugs, could mess where these teams.

因此，最後我想再次說聲謝謝。我也要向各位——當然——感謝你們的聆聽。感謝我們所有團隊，（聽不清）以及（聽不清），能夠執行高品質研究、良好落實、產出高品質數據。我對這些藥物與這些團隊再也無所求了（原文含糊）。

And obviously, a great thank you to the investigators and the patients who work with us and make this happen. So thank you to everybody who makes this work. And I'm going to pass it over to the operator for Q&A so that we can get to it.

當然，也非常感謝與我們合作並促成這一切的研究者與患者。所以感謝所有讓這件事得以成真的人。接下來我把時間交給接線員進行問答，讓我們開始吧。

(Operator Instructions)

（接線員指示）

Corinne Johnson, Goldman Sachs Group Inc.

Corinne Johnson，高盛集團（Goldman Sachs Group Inc.）

Good morning, and happy birthday to Papa Gline as well. Maybe you could just contextualize the ACR responses you saw here at 16 weeks as first I think, more kind of typical and later stage in a 24-week reporting timeline? And how would you expect those responses to trend with more time on therapy with kind of implications set towards the randomized withdrawal phase? Thank you.

早安，也祝 Papa Gline 生日快樂。也許你可以把你們在第16週看到的 ACR 反應放在脈絡中說明一下：首先，相較於我認為較典型、較後段的24週報告時間點，這代表什麼？另外，隨著治療時間拉長，你預期這些反應會如何變化，並且對隨機撤藥階段可能有什麼意涵？謝謝。

Yeah. Perfect. I appreciate it. Look, I think the first answer to that question is we don't know. This is the first time patients have been treated with this drug and first time this patient population has been studied this way in detail. Sicker people tend to need more time to get better in general, and that's why I made the comments I made about the Phase II randomized withdrawal period.

是的。很好。謝謝，我很感激。我想對這個問題的第一個回答是：我們不知道。這是患者第一次接受這個藥物治療，也是第一次以這種方式對這個患者族群做如此詳細的研究。一般而言，病情較重的人往往需要更多時間才能改善，這也是我對第二期隨機撤藥期間所做評論的原因。

But in terms of week 16 versus week 24, I don't know. I'll say, I don't think there was anything specific about the data leading into week 16 that suggested we were done. And I think there's certainly a possibility for continued improvement with therapy over time. But we'll find out as we look at that part of the patient population. Thanks, Corrine, I appreciate the question.

但就第16週相對於第24週而言，我不知道。我會說，在進入第16週之前的數據，沒有任何特定跡象顯示我們已經到頂了。而且我認為，隨著治療時間推進，確實有可能持續改善。不過我們會在觀察那部分患者族群時得到答案。謝謝你，Corrine，我很感謝這個問題。

Yasmeen Rahimi, Piper Jaffray Inc.

Yasmeen Rahimi，Piper Jaffray Inc.

Congrats, team, and congrats to Papa Gline for also achieving a major milestone of 75 years. So happy birthday to him as well. Quick question on mostly congrats. We're very much looking forward to the data. You've been very granular on sort of the baseline as well as what you're seeing of up titration and safety?

恭喜各位團隊，也恭喜 Papa Gline 同樣達成 75 週年的重要里程碑。也祝他生日快樂。有個簡短問題，主要也是恭喜。我們非常期待看到數據。你們對於基線，以及你們所看到的加量（up titration）與安全性，都講得非常細。

Have you been able to look at whether your assumptions for standard deviation in PVR in six minutes or sort of tracking in alignment with what you're seeing? And I'll jump back in the queue.

你們是否已經能檢視：你們對於 6 分鐘內 PVR 標準差的假設，是否與你們目前看到的情況一致、或是追蹤上是否對齊？我會回到提問隊列。

Yeah. Thanks. I appreciate it. So look, I think the short answer to that question is we are largely blinded to all of that data, and we don't have a lot of information about it. So it's hard to say. But I think given the patient population we enrolled, we feel pretty good about where the study is headed. And we think we've got an efficacious strike. But we don't have a we don't have a lot of information about sort of ongoing distributions because the late study has been blinded. Thank you

是的。謝謝。我很感謝。所以你看，我想這個問題的簡短答案是：我們在很大程度上對所有那些數據仍是盲態，我們沒有太多相關資訊。所以很難說。但我想，考量我們納入的病人族群，我們對研究的走向感覺相當不錯。而且我們認為我們已經打中有效性。但我們沒有、我們沒有太多關於持續分布（ongoing distributions）之類的資訊，因為後期研究一直是盲態。謝謝

[Andrew Chin, Wolfe Research.]

[Andrew Chin，Wolfe Research.]

Hey. Thank you for taking the question. So Matt, I'm aware that you said with Immunovant. You haven't analyzed IgG reduction, but that's still my biggest question. So other FcRn drugs, they don't seem to be able to achieve this level of efficacy in RA and people blame it on fat glycosylation. Do you somehow have ACPA antibody reduction data? Or will we see that data before you unblind the Period 2 data?

嗨。謝謝讓我提問。所以 Matt，我知道你在談 Immunovant 時說過，你們尚未分析 IgG 降幅，但那仍然是我最大的問題。所以其他 FcRn 藥物似乎無法在 RA 達到這種程度的療效，而大家把原因歸咎於脂肪糖基化（fat glycosylation）。你們是否有 ACPA 抗體下降的數據？或者在你們解盲第 2 期（Period 2）數據之前，我們會看到那個數據嗎？

And do you expect ACPA reduction to be less than IgG reduction. Thank you.

另外，你們是否預期 ACPA 的下降幅度會小於 IgG 的下降幅度？謝謝。

Look, I don't have that data now, as I said, so I can't answer the question. We know from our Phase I study that IMVT-1402 suppresses IgG quite deeply relative to other drugs. And given the quality of the clinical data we've seen on ACR, I think it's like certainly a thing to speculate on that the overall profile of 1402 is part of what's contributing to our ability to deliver this data.

你看，我現在沒有那個數據，如我所說，所以我無法回答這個問題。我們從一期研究知道，IMVT-1402 相較於其他藥物能更深度地抑制 IgG。而且就我們在 ACR 上看到的臨床數據品質而言，我認為確實可以推測：1402 的整體特徵（profile）是促成我們能交出這些數據的一部分原因。

Obviously, it's also a different patient population that has been studied and it could also be partially patient selection. And I think that could certainly be playing a role here. So I think those are both important. Look, I think we will continue to analyze this data. I don't know at this stage exactly when we're going to present what data.

顯然，這也是一個不同的受試者族群，這也可能部分來自病人選擇。我認為這確實可能在此扮演一定角色。所以我認為這兩點都很重要。你看，我想我們會持續分析這些數據。我目前還不確定我們會在什麼時間點呈現哪些數據。

So I don't know a good answer like what you're going to see before or after the Period 2 was unwinded. I think we will provide more information about what we've seen, about what our analysis looks like when we're prepared to talk about the full future of the program.

所以我無法很好地回答：在第 2 期（Period 2）解盲之前或之後，你們會看到什麼。我想當我們準備好談論整個項目未來的完整規劃時，我們會提供更多我們所看到的資訊，以及我們的分析樣貌。

I'll say, I think mostly this has been a blessing but also its curse. We've been a (inaudible) wondered if this data is going to also establish a leadership role for us along the lines of which others may follow.

我想說，這大多是一種祝福，但也有其詛咒。我們一直（聽不清）在想，這些數據是否也會讓我們建立起領導地位，成為其他人可能跟隨的方向。

So I do think we're going to be a little bit conservative on what exactly we say from a competitive perspective. But overall, I think the data are starting to speak for themselves here in terms of the quality of what we're able to do, and I hope we are continuing able to see that as the data mature.

所以我確實認為，從競爭角度來看，我們在具體要說什麼上會稍微保守一些。但整體而言，我認為就我們能做到的品質而言，數據開始在這裡自己說話了；我也希望隨著數據成熟，我們能持續看到這一點。

David Risinger, Leerink Partners.

David Risinger，Leerink Partners.

Yes. Thanks very much. So congrats on the phenomenal data this morning. My question is on mosli. So if the Phase II FOCUS study surprisingly shows a statistically significant benefit on six-minute walk, could it represent a pivotal study? And what would the requirements be in that scenario for a future NDA filing? And then just one other on mosli. Is the company considering development of mosli in any additional indications?

是的。非常感謝。也恭喜今天早上令人驚豔的數據。我的問題是關於 mosli。如果二期 FOCUS 研究意外地在 6 分鐘步行顯示具統計顯著的效益，它是否可能成為一項關鍵性（pivotal）研究？在那種情境下，未來提交 NDA 申請會需要哪些要求？另外還有一個關於 mosli 的問題：公司是否正在考慮將 mosli 開發到其他額外適應症？

Thanks, Dave. On that take a six-minute walk, I think it's impossible to say exactly what we would do until we saw the data. And so if the data look good enough to support a productive conversation with FDA, I think we would have a conversation with FDA, and the FDA has been aggressive lately on conversations about single pivotal designs.

謝謝，Dave。關於 6 分鐘步行，我想在看到數據之前，不可能確切說我們會怎麼做。因此如果數據看起來好到足以支持與 FDA 進行有建設性的對話，我想我們會與 FDA 進行討論；而 FDA 最近在討論單一關鍵性設計（single pivotal designs）方面態度相當積極。

So never say never is the answer. I want to clear; it's not the base case expectation and the study is not powered to show a benefit on six-minute walk. So we'll see what we see. But look, I think given where we're at, we'll certainly take that as we go. And other indications, I'll say, every sign around mosli is pointing to an effective, exciting agent with a lot of things we could do with it.

所以答案是：永遠不要說不可能。我想澄清：這不是我們的基本情境預期，而且這項研究的統計力（powered）並不是為了在 6 分鐘步行上顯示效益。所以我們就看會看到什麼。但你看，我想以我們目前的位置，我們當然會邊走邊看。至於其他適應症，我想說，圍繞 mosli 的各種跡象都指向它是一個有效、令人興奮的藥物，我們有很多事情可以用它來做。

As we watch the field around us, others are showing us good ideas all the time in terms of how these mechanisms might work. and we have some of our own that others haven't shown us yet. And so I think there are absolutely opportunities for indication expansion, although I remember we got this question about 40 times when we first unveiled mosli and our comment then, which is still our comment now is man PH-ILD is an area with a lot of unmet need.

當我們觀察周遭的領域時，其他人一直在向我們展示很好的想法，關於這些機轉可能如何發揮作用；而我們也有一些自己的想法，是其他人還沒展示給我們的。因此我認為適應症擴展絕對有機會；不過我記得我們第一次揭露 mosli 時，這個問題被問了大概 40 次，而我們當時的回覆、現在仍然一樣：PH-ILD 是一個有大量未被滿足需求的領域。

And even if it were the only thing we ever did with mosli, it's a big opportunity with a lot of value to deliver to patients. So on different ways to go there.

而且即使 mosli 我們最終只做這一件事，這也是一個很大的機會，能為病人帶來很高的價值。所以在那裡有不同的前進方式。

Yaron Werber, TD Cowen.

Yaron Werber，TD Cowen.

Great. Thanks so much. And also congrats on the difficult-to-treat study. So a question actually about that, is there any chance you can amend that protocol. And essentially run period one and then sort of get new patients completely into period two. So you're not going to have that step-down issue. And then secondly, based on our analysis, we think that about 75% of patients are ACPA positive. Is that still kind of what you think the data shows? Thank you.

很好。非常感謝。也恭喜這項難治（difficult-to-treat）研究。所以其實是關於那個的問題：你們是否有任何可能去修訂那個試驗方案（protocol），基本上先跑完第一期（period one），然後在第二期（period two）完全納入新的病人。這樣你們就不會有那個降階（step-down）問題。第二，根據我們的分析，我們認為大約 75% 的病人是 ACPA 陽性。這仍然大致符合你們認為數據所顯示的情況嗎？謝謝。

Yeah. Thanks, Yaron. Look, I think on your first question, there's a lot of things you could imagine doing. I think the truth is between this data and detailed patient level analysis of this data plus the Period 2 data, we're going to have a pretty good sense for what we've got and a pretty good sense for what we need to do going forward.

是的。謝謝，Yaron。你看，關於你的第一個問題，你可以想像有很多事情可以做。我想事實是：結合這些數據、對這些數據進行詳細的病人層級分析，再加上第 2 期（Period 2）數據，我們將會對我們手上有什麼、以及接下來需要做什麼，有相當清楚的掌握。

And so I don't know that we would gain that much from dragging this study out given the quality of the data we're seeing here. So I think we're going to do that analysis in detail. I think we're going to have the conversation with FDA. I think we're going to plot a course forward. But I think we'll have a pretty clear sense.

因此，鑑於我們在這裡看到的資料品質，我不確定把這項研究拖長能帶來多大的額外收穫。所以我認為我們會把那個分析做得很細。我認為我們會和 FDA 進行討論。我認為我們會規劃接下來的前進路徑。但我想我們會有相當清楚的判斷。

And then look, we've done some commercial analysis of the market in various settings as an update on version analysis actually in (inaudible) 10-K that was filed today. I think your number is within the range of what we have seen in the literature for (inaudible) patients generally.

然後你看，我們也在不同情境下做了一些市場的商業分析，作為對版本分析的更新，實際上已經放在今天提交的（聽不清）10-K 裡。我認為你的數字落在我們在文獻中看到的（聽不清）患者一般範圍之內。

Brian Cheng, JPMorgan.

Brian Cheng，摩根大通。

Hey, guys. Thanks for taking our question. And this area EXPLORER trial, since there's no washout period between Tier 1 and 2. I'm curious if you have some thought around the tail of the efficacy from those going from drug to placebo? You said that Tier 2 might be less meaningful. Are you saying that 12 weeks may not be enough to fully drive the separation? Thank you

嗨，各位。謝謝讓我們提問。關於這個 EXPLORER 試驗，因為 Tier 1 和 Tier 2 之間沒有洗脫期。我想了解你們是否有一些想法：那些從用藥轉到安慰劑的受試者，其療效尾端效應會是怎樣？你們說 Tier 2 可能比較沒有意義。你們的意思是 12 週可能不足以完全拉開差距嗎？謝謝。

Yeah, thanks. I appreciate the question, Brian. And just to reiterate, I guess like, Look, first of all, it's hard to know exactly what the tail will be at the end of dosing at the end of week 16. So that's like one piece of this. Obviously, Period 2 is blinded, so we don't know now anything about what's in there. So that's all a part of that.

是的，謝謝。Brian，我很感謝這個問題。我再重申一下：首先，在第 16 週末、也就是給藥結束時，尾端效應到底會是什麼樣子，其實很難精確知道。這是其中一個面向。另外，第二期（Period 2）是盲態的，所以我們現在也不知道裡面到底發生了什麼。這些都是其中的一部分。

Look, I'll say the other thing is, and just to reiterate what I said earlier, I think given that the Period 2 primary endpoint is losing an ACR20 response, if you imagine a patient who has achieved an ACR50 or an ACR70 response, even if they start worsening on the first day of Period 2, it just takes some time to give up that level of response.

另外我想說的是，也再次重申我先前提到的：鑑於第二期（Period 2）的主要終點是「失去 ACR20 反應」，如果你想像一位病人已經達到 ACR50 或 ACR70 的反應，即使他們在第二期的第一天就開始惡化，也需要一些時間才會失去那個反應水準。

And so that's where I'd say like the quality of the data in period to is the quality of the data in Period 1 is it's always counting against period 2, irrespective of the pharmacokinetic effects of withdrawal of the drug. So I think it's -- remember, every ACR70 responder is an ACR50 responder as an ACR20 responder. So it just takes time to come off that hill. We have people who we've achieved a lot of benefit. Just so that's that. Thank you.

因此我會說，第二期資料的品質，某種程度上會被第一期資料的品質所「牽制」，不論停藥的藥物動力學效應如何，都是如此。所以我認為——請記得，每一位 ACR70 反應者同時也是 ACR50 反應者、也是 ACR20 反應者。所以要從那個高點下來需要時間。我們有一些人已經獲得了很大的效益。大概就是這樣。謝謝。

Dennis Ding, Jefferies.

Dennis Ding，Jefferies。

Hi, good morning. Thanks for taking our questions. For PHILD, I'm curious where your thoughts around Phase Ib data and the interpretability of that data in the small number of patients Specifically, why did the 4-milligram cover outperformed so much relative to the 2-milligram dose on CGMP and also cardiac output.

嗨，早安。謝謝讓我們提問。關於 PH-ILD，我想了解你們對 Ib 期資料的看法，以及在病人數很少的情況下，這些資料的可解讀性。具體來說，為什麼 4 毫克組在 cGMP 以及心輸出量上，相較於 2 毫克劑量表現好這麼多？

And I wonder if you're expecting, if you should expect a big increase in cardiac output in mosli is locally delivered to the lungs and it's not really a systemic? Thanks so much

另外我也想問，如果 mosli 是局部遞送到肺部、並非真正的全身性給藥，你們是否預期（或我們是否應該預期）心輸出量會有很大的增加？非常感謝。

Thanks, Dennis. I appreciate the question. Look, I think the first answer is four is twice to, so there's just a lot more drug being delivered. The second point I'll make is remember, there are 170 patients across the healthy volunteer’s program. And so while the specific study that you're referring to may be a smaller pace, we have a large body of evidence at this point across mosli being administered in a lot of different settings.

謝謝你，Dennis。我很感謝這個問題。我想第一個答案是：4 是 2 的兩倍，所以實際遞送的藥量更多。第二點要提醒的是，在健康受試者計畫中總共有 170 位受試者。因此，雖然你提到的那個特定研究可能樣本較小，但截至目前我們已累積了大量證據，涵蓋 mosli 在許多不同情境下的給藥。

And I'd say the dose-dependent improvements in CGMP were broadly consistent across all of that data, the dose-dependent improvements in PVR will probably consistent across all that data. So I think we like generally think we know what we've gotten.

我會說，cGMP 的劑量依賴性改善，在所有這些資料中大致一致；PVR 的劑量依賴性改善，在所有這些資料中也大致一致。所以我認為我們整體上大概知道我們拿到的是什麼。

I think a single dose you saw real robust growth and immediately right away in CGMP. I think the thing that was exciting for us is it demonstrated that the inhaled approach was really buffering us from a systemic result and that was really important for us. And I think we'll see that as we go forward.

我認為在單次給藥時，你看到 cGMP 立即且非常強勁的上升。對我們來說令人興奮的是，這證明了吸入式途徑確實在緩衝、避免全身性效應，而這對我們非常重要。我想隨著我們往前推進，也會持續看到這點。

At this inhaled approach is so important because you can get the drug to the well-ventilated parts of the lung without worrying about those systemic effects. And so I think that's the biggest takeaway was we saw cardiac output. We saw NPAP reductions these are the things you want to see, but these were single-dose studies. So now we'll see the much more robust fashion in our Phase II. Thanks.

這種吸入式途徑之所以重要，是因為你可以把藥物送到肺部通氣良好的區域，而不必擔心那些全身性效應。所以我認為最大的重點是：我們看到了心輸出量。我們看到了 NPAP 的下降——這些都是你希望看到的，但這些都是單次給藥研究。所以接下來在我們的第二期（Phase II）中，我們會以更強而有力的方式來驗證。謝謝。

Thanks, Drew. Yes. The other thing I'll say, just because the Drew was answering that question is, look, I think one of the things that makes PH-ILD exciting as a commercial opportunity is it really requires inhaled therapy precisely because of this effect.

謝謝你，Drew。是的。我另外補充一點，因為 Drew 剛在回答那個問題：你看，我認為讓 PH-ILD 作為商業機會令人興奮的一點是，它確實需要吸入式治療，正是因為這個效應。

And so the competitive landscape will be thinner and the ability to develop drugs for this market will be more challenging because you need to sort of thread the needle on systemic vasodilation. And so we feel that gives us an advantage as well and frankly increases the level of need for the patients. So look, I think it's all setting up in that way.

因此競爭格局會比較稀薄，而為這個市場開發藥物也會更具挑戰，因為你需要在全身性血管擴張的風險上「拿捏得很精準」。所以我們覺得這也讓我們具備優勢，而且坦白說，也提高了病人的未滿足需求程度。所以你看，我認為整體就是朝這個方向在鋪陳。

Perfect. Thank you.

很好。謝謝。

Derek Archila, Wells Fargo.

Derek Archila，富國銀行。

Good morning. This is Jacob on for Derik. Congrats on the 202 data. So real quick on safety. I just want to clarify firm, there were no LDL changes or other events of interest observed, right? And then Secondly, on the -- given the strong activity in Period 1, how does this inform your trial design strategy in the future?

早安。我是 Jacob，代 Derek 提問。恭喜 202 的數據。我快速問一下安全性。我想確認一下：沒有觀察到 LDL 的變化或其他關注事件，對嗎？第二個問題是——鑑於第一期（Period 1）活性很強，這對你們未來的試驗設計策略有什麼啟示？

I know you mentioned and this is likely one of a couple of registrational trials, but do you think this data changes that?

我知道你們提到這很可能是數個註冊性試驗中的其中一個，但你們覺得這些數據會改變那個判斷嗎？

Thanks, Derek. Great questions, both, although I'll remind you politely for the other analysts, we're trying to keep to one given the number in the queue, but I appreciate both questions, and I'll take both of them. First of all, on safety, in fact, what I can say here is not just in this study, but across now hundreds of patients dosed across 1402 studies, the DMC has been watching that issue, and we have seen no impact on (inaudible) LDL across the hundreds of patients dosed with 1402.

謝謝你，Derek。兩個問題都很好；不過我也禮貌提醒其他分析師，因為排隊的人很多，我們盡量每人一題，但我也感謝你問了兩題，我會兩題都回答。首先在安全性方面，我可以說的不只是這項研究：截至目前，在 1402 的研究中已經有數百位病人接受給藥，DMC 一直在監測那個議題，而我們在這數百位接受 1402 給藥的病人中，沒有看到（聽不清）LDL 的任何影響。

So while I don't have the very specific data to share for this study numerically, I think the answer is we've seen literally nothing on albumin or LDL from 1,402. And then, look, given the level of activity in Period 1 on trial design, I think the answer is. We're going to have to take this data when we get it.

所以雖然我沒有這項研究可分享的非常具體數值資料，但答案是：我們確實在 1,402 上，對白蛋白或 LDL 真的什麼都沒看到。然後，關於第一期（Period 1）活性水準對試驗設計的影響，我認為答案是：我們得等拿到這些資料後再來消化。

We're going to have to look closely at it, and we're going to have to have a conversation with FDA about where we stand and what we need to do. Obviously, the stronger the data from the first study or from this study overall, the more compelling that conversation is.

我們必須仔細檢視這件事，並且必須與 FDA 討論我們目前所處的位置以及我們需要做什麼。顯然，第一項研究或本研究整體的數據越強，那場對話就越有說服力。

And so I think we're excited about this data. Our belief is that we should be able to run a lean program from here given the patient population we're focused on given the level of need in this patient population, but that's a conversation we're going to have to have together with FDA in the months to come.

因此我認為我們對這些數據感到振奮。我們相信，鑑於我們聚焦的病患族群，以及該族群的需求程度，我們應該能從這裡開始以精實的方式推進計畫；但這是我們在未來幾個月必須與 FDA 一起進行的對話。

Awesome.

太棒了。

Samantha Semenkow, Citi.

Citi 的 Samantha Semenkow。

Hi, good morning. Thanks for taking the question. And Congratulations on the data this morning and all the progress. Now that you have this first data in RA for 1402, I'm wondering also how we should be thinking about the CLE data coming up in the second half?

嗨，早安。謝謝讓我提問。也恭喜今天早上的數據以及所有進展。現在你們已經拿到 1402 在 RA 的第一批數據，我也想請教我們應該如何看待下半年即將公布的 CLE 數據？

Will that readout include the entire 52-week study? Or will that just be the 12-week randomized portion? And what magnitude of treatment effect do you think would be meaningful here? Thank you very much.

那次讀出會包含完整的 52 週研究嗎？還是只會是 12 週的隨機分配部分？另外，你們認為多大幅度的治療效果在這裡才算有意義？非常感謝。

On the first question -- thank you, I appreciate the questions. On the data, that will just be the 12-week period. And that's what we'll have by that. So that's what we'll be able to share. And in terms of what treatment effective meaningful, look, I'll say two things.

先回答第一個問題——謝謝，我很感謝這些問題。關於數據，那將只會是 12 週期間的結果。到時我們手上就會有這些。所以我們能分享的就是那部分。至於什麼樣的治療效果才算有意義，我想說兩點。

One is we will have an opportunity to continue to talk about what we expect to see from that study over time, and we'll probably do a little preview of that data before it comes. Secondly, CLE is a little bit different than some of these other indications. I mean it is commercially more competitive and there's other mechanisms coming. And so I think the bar for us is not just sort of per se clinical meaningful.

第一，我們會有機會隨時間持續談論我們預期在那項研究中會看到什麼，我們可能也會在數據出來前先做一點預告。第二，CLE 和其他一些適應症有點不同。我的意思是，它在商業上競爭更激烈，而且也有其他作用機制的產品正在進來。因此我認為對我們而言的門檻不只是單純的臨床上有意義。

I think the bar is like do we think our data is good enough to support a program in the face of where the landscape is headed. And so we're going to look closely at that data. We're going to look at what we see, and we're going to make a decision based on the totality of the data. But I think the bar there is pretty high, and I think we knew that going in. Thanks for the question.

我認為門檻在於：面對未來市場版圖的走向，我們的數據是否足以支持我們推進一個計畫。因此我們會仔細檢視那些數據。我們會看我們看到的結果，並根據整體數據的全貌來做決策。但我認為那裡的門檻相當高，而我想我們在一開始就知道這點。謝謝你的提問。

Thomas Smith, Leerink Partners LLC.

Leerink Partners LLC 的 Thomas Smith。

Hey, guys. Good morning. Congrats on the really stellar RA data here for 1402. Just wanted to ask one, if I could, on the pivotal Graves' program. Any updates you can share with respect to patient enrollment? I think you were initially kind of gating some of the scale-up activities and trying to get a sense for how the early enrollment trends were going.

嗨，各位。早安。恭喜 1402 在 RA 的數據真的非常亮眼。如果可以的話，我想問一個關於關鍵性（pivotal）Graves 計畫的問題。在病患收案方面有沒有可以分享的最新進展？我記得你們一開始在某些擴大規模的活動上有點設門檻，想先了解早期收案趨勢如何。

But just wondering if there's anything that you could share there in terms of pace cadence and maybe patients being enrolled, anything different from initial expectations?

但想請教你們是否能分享一些節奏、速度，或是收案病患數等資訊？有沒有和最初預期不同的地方？

Thank you. Yeah, i's a good question. Look, I think the short answer is we have a pretty high bar for ourselves when we started the study, and we didn't exactly know because there hadn't been a lot of development in Graves' disease. I think we can now say enrollment is going great.

謝謝。是的，這是個好問題。我想簡短回答是：我們在啟動研究時對自己設了很高的標準，而我們當時也不完全確定，因為 Graves 氏病的開發並不多。我想我們現在可以說，收案進展非常順利。

We're on track. We'll have the data in 2017, as we previously discussed, and a lot of enthusiasm and a growing amount of enthusiasm as we continue to add sites, as docs continue to get comfortable with the study. So I think overall, really happy with how that program has evolved.

我們進度如期。如同先前討論，我們會在 2017 年拿到數據；而且隨著我們持續增加研究中心、醫師對研究越來越熟悉，熱度很高且正在升溫。所以整體而言，我們對這個計畫的發展非常滿意。

And I'll again take the opportunity to say, I think all of our main teams at this point are executing at a really high level from clinic enrollment perspective. And I think that's been a real driver of value for us.

我也再次藉此機會說明，我認為目前我們所有主要團隊在臨床收案的執行上都達到非常高的水準。而我認為這一直是我們價值的重要驅動因素。

Alex Thompson, Stifel Nicolaus & Company Inc.

Stifel Nicolaus & Company Inc. 的 Alex Thompson。

Hi, guys. Congrats on the data. This is Patrick Colton on for Alex. I guess, just kind of building on the path forward here in RA, looking at period 2, I guess if you were 300-milligram ROm performs just as well as 600-milligram, how are you guys thinking about your dosing strategy going forward in Phase III?

嗨，各位。恭喜這些數據。我是代 Alex 發問的 Patrick Colton。我想在 RA 的後續路徑上延伸問一下，著眼於第二期（period 2），如果 300 毫克 ROm 的表現和 600 毫克一樣好，你們在第三期往前推進時會如何思考劑量策略？

I -- it's fun to sit here and think about like what has in the Phase II study, we see as good -- first of all, it's a randomized withdrawal study, so I was like trying to figure out exactly what it would look like for the 300 and 600 to perform equivalently. But look, I think overall, it's just too early to say. We've got to look at the data. This is a patient population with extremely significant unmet need.

我——坐在這裡去想第二期研究裡會看到什麼其實挺有意思的——首先，這是一個隨機撤藥研究，所以我也在試著理解 300 和 600 表現等同時，具體會呈現什麼樣子。但總之，我認為現在下結論還太早。我們必須看數據。這是一個未被滿足需求極其顯著的病患族群。

And without -- I mean, to say without a lot in development is an understatement. I think like basically, we are following a new course for this patient population. So I think we've really got to look at that at that data and get an outcome from it. I think the inclusion of 300 and 600 in the study was important because FDA, especially in new indications, especially in new indication s like RA is likely to want some dose-ranging information.

而且——我的意思是，說「開發中的東西不多」其實還算保守。我認為基本上，我們是在為這個病患族群開闢一條新的路徑。所以我們真的必須仔細看那份數據並從中得到結論。我認為在研究中納入 300 與 600 是重要的，因為 FDA，尤其是在新適應症、特別是像 RA 這樣的新適應症上，很可能會希望看到一些劑量探索（dose-ranging）資訊。

But I think we're going to have some flexibility and we're going to get to see. Historically, there has been a separation in IgG reduction, obviously, between 300 and 600. So we'll see how that translates in this population. But I think we have options here. Thanks for your question.

但我認為我們會有一些彈性，也會有機會觀察。過去在 IgG 降幅上，300 和 600 之間顯然是有差異的。所以我們會看看這在這個族群中如何轉化。但我認為我們在這裡有選項。謝謝你的提問。

Thanks.

謝謝。

Prakhar Agrawal, Cantor Fitzgerald LP.

Cantor Fitzgerald LP 的 Prakhar Agrawal。

Hi. Thanks for taking my questions, and congrats on these impressive data. So maybe on the RA front, given the sample size is quite large, but ultimately, this trial was open-label and some of the ACR responses can be susceptible to open-label nature of the trial.

嗨。謝謝讓我提問，也恭喜這些令人印象深刻的數據。那麼可能在 RA 方面，雖然樣本數相當大，但最終這項試驗是開放標籤（open-label），而一些 ACR 反應可能會受到開放標籤設計的影響。

So maybe just if you can expand if you have any data on some of these secondary endpoints, which might be less susceptible to open-label design of the trial? And what gives -- how much efficacy degradation would you assume as you move from an open label to more of a placebo-controlled trial in a registration trial? Thank you.

所以想請你們多談談：是否有一些次要終點（secondary endpoints）的數據，可能較不容易受到開放標籤設計影響？另外，當你們從開放標籤走到註冊用、較偏安慰劑對照（placebo-controlled）的試驗時，你們會假設療效會衰減多少？謝謝。

Yeah. Thanks. This is -- it's a great question. It's obviously what was on our mind from the day we first saw the data, I think it is certainly helpful that we're talking about ACR50 -- ACR50 and ACR70 response and ACR20 responses, I think once you get to that level, sort of spontaneous placebo style like information, and those kinds are less frequent.

是的。謝謝。這——這是個很好的問題。顯然從我們第一次看到數據的那天起，這就是我們一直在思考的事情；我認為談的是 ACR50——ACR50、ACR70 反應以及 ACR20 反應，這點當然有幫助。我認為一旦到那個層級，那種自發性的、類似安慰劑效應的資訊（以及那類反應）就比較不常見。

We don't have any of the secondaries or additional markers to share. We've been looking at that data hard, and we feel excited about the data based on what we've seen in terms of everything hanging together, but that's about all we're able to say at this point because it's about all we know at this point.

我們沒有任何次要終點或額外指標可以分享。我們一直在仔細研究那些數據，從我們目前看到的各項結果彼此一致的情況來看，我們對這些數據感到很振奮，但就目前而言，我們能說的大概也就到這裡，因為我們目前所知道的也就這麼多。

One other thing is, we have -- the way the study is designed, the people doing the joint assessments are blinded so they are doing the assessments without knowing anything about the study, what patients are on, where the study they are or whether they're under placebo.

另外一點是，我們——依照研究設計，進行關節評估的人員是採盲的，因此他們在進行評估時並不知道任何與研究相關的資訊，包括病人使用的是什麼治療、在研究中的哪個階段，或是否為安慰劑。

That's obviously only one component of the total here, but it is one way for us to get a little bit of a little bit of objectivity into a study that is otherwise at this stage open label, and that is helpful and pretty objective. Thank you.

這顯然只是整體中的一個組成部分，但它確實是在目前這個其他方面仍屬開放標籤的研究階段，讓我們能夠在研究中加入一些客觀性的方式之一，而且這很有幫助，也相當客觀。謝謝。

William Pickering, Bernstein.

William Pickering，Bernstein。

Hi. Congrats on the updates, and thanks for the question. On mosli, you also have a Phase II open label with patients on background Epoprostenol. What are you hoping to see in that study? And then how are you thinking about broader evidence generation strategy to support reimbursement and mosli in combination with [Epoprostenol]? Thanks.

嗨。恭喜你們的最新進展，也謝謝讓我提問。關於 mosli，你們也有一項第二期開放標籤研究，納入在背景治療使用 Epoprostenol 的病人。你們希望在那項研究中看到什麼？另外，你們如何思考更廣泛的證據生成策略，以支持給付/報銷，以及 mosli 與[Epoprostenol] 聯合使用？謝謝。

Yes. So I think in the combo study, we have patients on background [Epoprostenol]. Obviously, in the main Phase IIb, we don't have patients on background [Epoprostenol] . And the reason we set this up this way is because we know that polypharmacy is going to be a part of the landscape. And so in the phase -- in the subsequent study that we run, we're likely to have some proportion of patients on background [Epoprostenol] as well.

是的。我想在這個聯合用藥研究中，我們納入的是在背景治療使用[Epoprostenol] 的病人。顯然，在主要的第二期 b 試驗中，我們沒有納入背景治療使用[Epoprostenol] 的病人。我們之所以這樣設計，是因為我們知道多重用藥將會是這個治療領域的一部分。因此在我們後續進行的研究中，很可能也會有一定比例的病人同樣在背景治療使用 [Epoprostenol]。

And it felt like going into that state study with no experience treating patients on both drugs was, for a variety of pretty obvious reasons, a liability. And so I think the combo study is, in part, really a safety study. It's just designed to make sure these things can be administered safely together.

而且我們覺得，在沒有任何同時使用兩種藥物治療病人的經驗下就進入那個狀態/後續研究，基於一些相當明顯的原因，會是一個風險。所以我認為這個聯合用藥研究，某種程度上確實是一項安全性研究。它的設計就是要確認這些藥物可以安全地一起給藥。

We will learn from it, the information that will help us designing the stratification rules, help us understand better who's going to be on what in the subsequent study. But I think beyond that, it's hard to say at this point. And that's -- the [Epoprostenol] still in pretty early days, so we don't have much to say about it. Drew, anything to add to that?

我們也會從中學到一些東西，這些資訊將有助於我們制定分層規則，並幫助我們更了解在後續研究中哪些人會使用哪些治療。但除此之外，目前很難再多說。而且——[Epoprostenol] 仍處於相當早期的階段，所以我們也沒有太多可以補充的。Drew，你要補充嗎？

I think that's exactly the case. We decided not to go on top of [Epoprostenol] in the first FOCUS study, but we were initially looking at our drug in single agent activity in PH-ILD, and we wanted to have some time to understand that population, understand mosli. Also, as you know, [Epoprostenol] do have a sticky issue with cough.

我想情況就是如此。我們決定在第一個 FOCUS 研究中不在 [Epoprostenol] 之上加用，但我們最初是在 PH-ILD 中觀察我們藥物的單藥活性，我們希望有一些時間去了解那個族群、了解 mosli。另外，如你所知，[Epoprostenol] 確實有一個棘手的咳嗽問題。

And we wanted to make sure that our drug would have a clear path to be able to demonstrate its tolerability profile, which I think has been relatively impressive. So with that, in the later days, we decided with the team to go a little deeper and look at mosli on top of inhaled [Epoprostenol] given the confidence we had in mosli after seeing it in our FOCUS study, of course, in an aggregated setting.

我們希望確保我們的藥物有一條清晰的路徑，能夠展現其耐受性特徵；我認為這點一直以來都相對令人印象深刻。因此在後期，我們與團隊決定再深入一些，在我們對 mosli 更有信心之後——當然這是基於我們在 FOCUS 研究中看到的匯總結果——來評估 mosli 加在吸入型 [Epoprostenol] 之上的表現。

So with that as a backdrop, as Matt said, we're only in the days, but we actually don't expect there to be much of an issue there, but we definitely want to understand that from a dosing and safety perspective.

在這樣的背景下，如 Matt 所說，我們目前還在早期階段，但我們其實不預期會有太大的問題；不過我們確實希望從劑量與安全性的角度把這件事弄清楚。

Douglas Tsao, H C Wainwright & Co LLC, HC Wainwright.

Douglas Tsao，H C Wainwright & Co LLC，HC Wainwright。

Hi, good morning. Thanks for taking the questions and congrats on the data progress. Matt, I'm just curious in terms of the RA data, if you've had a chance to sort of talk with some of the KOL physicians on the data. I'm just curious what their sort of feedback is.

嗨，早安。謝謝讓我們提問，也恭喜數據進展。Matt，我只是好奇，就 RA 的數據而言，你是否有機會和一些 KOL 醫師談過這些數據。我想了解他們大致的回饋是什麼。

And they were more focused on yet the response that you saw the breadth of the stock. And obviously, you've got that both so you necessarily have to choose, but if there's anything that would strike for the initial days then? Thank you.

以及他們是否更聚焦在你看到的反應深度，或是反應的廣度。顯然你們兩者都有，所以不一定需要二選一，但如果在初期階段有什麼特別突出的觀察？謝謝。

Thanks, Doug. Thanks, Doug. So we have obviously a bunch of KOLs involved with the study, therefore, we have those conversations continuously and with some of the important ones for the field who have been on multiple of these studies as well. I think in general; the answer is they're super impressed. I think one KOL our team roughly as a quote you can't fake ACR70s like this. That the opinion of one physician.

謝謝，Doug。謝謝，Doug。我們當然有許多 KOL 參與這項研究，因此我們一直持續進行這些對話，也包括這個領域中一些重要的專家——他們也參與過多項同類研究。我想整體而言，答案是他們非常印象深刻。我想有一位 KOL，我們團隊大致引用他的一句話是：「像這樣的 ACR70 你是造不了假的。」這是一位醫師的看法。

I think it's true at sublevel, but ultimately, we'll have to see what the rest of the studies show. But look, I think docs are excited. They're excited about the depth of responses. They're excited about what this could mean. And look, I think the most important thing is these are physicians who they're treating these patients.

我認為在某個層面上這是對的，但最終我們還是得看其餘研究會顯示什麼。不過你看，我認為醫師們很興奮。他們對反應的深度感到興奮。他們對這可能意味著什麼感到興奮。而且我認為最重要的是，這些醫師正在治療這些病人。

They have no options. Many of these patients are very uncomfortable with a lot of pain. I think they see a new option for this population. And they were hoping for something that worked even a little. And obviously, this is beating that for handling. So I think there's a lot of enthusiasm. Thanks.

他們沒有選擇。許多這些病人非常不舒服、疼痛很嚴重。我想他們看到了這個族群的一個新選項。他們原本只希望能有一個哪怕稍微有效的治療。而顯然，這些結果遠遠超出那個期待。所以我認為大家非常有熱情。謝謝。

Dina Ramadane, Bank of America Securities.

Dina Ramadane，美國銀行證券（Bank of America Securities）。

Good morning. Congrats on the data this morning and thanks for taking our questions. Just a quick one from us. On the nonresponders, could you provide maybe more color on these nonresponders in Period 1? Was there anything you can maybe point to such as prior failed therapy or baseline characteristics, such as maybe antibody levels that were the reason for not responding to 1402? Thank you.

早安。恭喜今天早上的數據，也謝謝回答我們的問題。我們這邊只有一個簡短問題。關於未反應者（nonresponders），你能否就第一期（Period 1）的這些未反應者提供更多細節？是否有任何你能指出的因素，例如既往治療失敗，或基線特徵（例如抗體水準），導致對 1402 沒有反應？謝謝。

Yeah. So we're looking at that in detail now just to try and get some further comfort and understanding about what's going on. I don't have anything to say about it now, but that's exactly the kind of analysis that we're running. And you said nonresponders, just a reminder, 72% or 73% were ACR20 responders. So we're also looking at some of who got to the 20, but not 50, just like trying to get a better sense of what happened there. Thank you.

是的。我們現在正在詳細檢視，試著對正在發生的事情取得更多把握與理解。我目前沒有什麼可以補充，但這正是我們正在做的那類分析。你提到未反應者，提醒一下，72% 或 73% 是 ACR20 反應者。所以我們也在看一些達到 20 但沒有達到 50 的人，想更好地理解那裡發生了什麼。謝謝。

Iris Gao, Guggenheim, Guggenheim Partners.

Iris Gao，Guggenheim，Guggenheim Partners。

Good morning. This is Iris on Seating. Congratulations on the data. My question is on not. Are there any more colors on what proportion of patients were refractory to rituximab and maybe anti-IL-6s amid are relevant enteroplasty patients. So (inaudible) that with you.

早安。我是 Iris，代 Seating 發言。恭喜這些數據。我的問題是關於 not。想請問是否能提供更多細節：有多少比例的病人對利妥昔單抗（rituximab）屬於難治（refractory），以及可能也包括抗 IL-6 類藥物；另外，是否與相關的腸成形術（enteroplasty）病人有關。所以（聽不清）想跟你確認一下。

Thank you.

謝謝。

Yeah. Thanks. I don't have that in front of me. It's a good question. We have cleaned some of that data. We had a bunch of IL-6 about six refractory patients for rituximab, I don't know. And so look, overall, we don't have that share right now. But I think the answer is that the population is consistent with a heavily pretreated population. They've been on multiple lines of therapy.

是。謝謝。我手邊沒有那個資料。這是個好問題。我們已經清理了一部分相關數據。我們有一批 IL-6 的資料，大概有六位對利妥昔單抗屬於難治的病人，我不確定。所以整體來看，我們目前沒有那個占比可以分享。但我想答案是：這個族群與「高度既往治療」的人群一致。他們接受過多線治療。

Many of them have failed things in addition to JAK and TNF. So all of those different mechanisms are in. We may eventually share more data on sort of what those different subsets look like, but I think we're particularly enthusiastic about the JAK and TNF combined failures. Remember that over 10% of these patients have failed more than three lines of these advanced therapies. Thank you.

其中很多人除了 JAK 與 TNF 之外，也在其他治療上失敗過。所以各種不同機轉的治療都涵蓋在內。我們之後可能會分享更多數據，說明不同子族群的表現，但我們特別看好同時在 JAK 與 TNF 上治療失敗的族群。請記得，超過 10% 的這些病人，在這些進階治療上失敗的治療線數超過三線。謝謝。

Sam Slutsky, LifeSci Capital.

Sam Slutsky，LifeSci Capital。

Hi. Good morning. This is Kate on for Sam. So I know the strength of Period 1 data has made period to all the more challenging, particularly on ACR20. But looking to period 2, is there a delta versus placebo potentially on other endpoints that would excite you commercially?

嗨。早安。我是 Kate，代 Sam 發言。我知道第 1 期數據的強度，讓第 2 期變得更具挑戰，特別是在 ACR20 上。但展望第 2 期，在其他終點上是否可能相較安慰劑出現差異（delta），讓你們在商業上感到振奮？

I don't think Phase 2 was really about commercial value at this point. I think Phase 2 is about better understanding the characteristics of the patients seeing erosion of efficacy, starting to understand to separate out drug effect from other things. So I think it's not so much that we're looking for some commercial bar in Phase II.

我認為第 2 期在這個時間點並不是在談商業價值。我認為第 2 期是為了更好地理解那些出現療效衰減（erosion of efficacy）的病人特徵，並開始釐清藥物效應與其他因素的影響。所以我們在第 2 期並不是在尋找某個商業門檻。

I think the quality of this headline data is such that even if it degrades, we're happy with it. And I think even in subsequent studies, I don't know if we're like shooting for this bar per se. This is just a great foundation from which to build something pretty exciting in RA.

我認為這份重點數據（headline data）的品質很好，即使後續有所下降，我們也會滿意。而且我想即便在後續研究中，我也不確定我們是否會以這個門檻作為目標。這只是個很好的基礎，讓我們能在類風濕性關節炎（RA）領域打造一些相當令人興奮的東西。

Makes sense. Thank you.

了解。謝謝。

And that will conclude today's Q&A session, and I will now turn the call back over to Matthew Gline for closing remarks.

以上為今天的問答環節，接下來我將把電話交回 Matthew Gline 作結語。

Great. Look, thank you, everybody, again. Appreciate it. There were a lot of questions there. So I appreciate everyone's forbearance and helping us get through it all and then limiting a number of questions, which is a great favor to the people lower in the queue.

很好。各位再次感謝。非常感激。剛才問題很多。所以也感謝大家的包容，協助我們把所有問題都回答完，並且限制提問數量，這對排在後面的朋友是很大的幫助。

We need to come up with questions if this has already been asked. So thank you again to everybody for playing along with that. An exciting day for us and exciting data to be able to put out. So thank you again to everybody who makes that happen from the Vance Roivant team for the patients and investigators. It takes a village, and it's a great outcome.

如果某個問題已經被問過，我們就需要想新的問題。所以也再次感謝大家配合這個安排。對我們而言是令人振奮的一天，也很高興能發布這些令人振奮的數據。因此再次感謝所有促成這一切的人，從 Vance Roivant 團隊到病人與研究者。這需要眾人齊心，結果也非常好。

It's something that we can really go firm from here. And once again, happy birthday to my dad. Thank you, everyone, for listening, and we'll talk again soon. Have a good day.

這是我們接下來可以真正穩健推進的基礎。另外，再次祝我父親生日快樂。謝謝各位收聽，我們很快再聊。祝大家有美好的一天。

This concludes the conference call. Thank you for participating. And you may now disconnect.

本次電話會議到此結束。感謝各位參與。您現在可以掛線。

Goodbye.

再見。