Atai Beckley NV (ATAI) 2022 Q2 法說會逐字稿

Hi, everyone, and welcome, and thanks for joining us for the atai second quarter earnings call. I'm Greg Weaver, CFO of atai Life Sciences. We're very pleased to have you join us.

大家好，歡迎光臨，感謝您參加 Atai 第二季財報電話會議。我是 Atai Life Sciences 的財務長 Greg Weaver。我們很高興您加入我們。

I'm joined by our CSO, Srini Rao; our CEO, Florian Brand; and Stephen Bardin, our Deputy CFO, who joined our team last month and was most recently from BridgeBio.

我們的 CSO Srini Rao 也加入了我的行列；我們的執行長弗洛里安·布蘭德（Florian Brand）；我們的副財務長 Stephen Bardin 於上個月加入我們的團隊，最近來自 BridgeBio。

Today is my last earnings call as atai's CFO, and I'm very pleased and confident to be handing the CFO reins over to Stephen. He'll be taking on the role as of tomorrow, and I'll remain one of the adviser to the company through the end of the year.

今天是我作為 atai 財務長的最後一次財報電話會議，我非常高興也很有信心將財務長的權力移交給史蒂芬。他將從明天起接任這項職務，而我將在年底前繼續擔任公司顧問之一。

Stephen, do you want to jump in and do an introduction?

史蒂芬，你想跳進去做介紹嗎？

Yes, of course, and thank you so much, Greg. I'll keep this brief. I am incredibly honored to be selected as the next CFO of atai. My first month at atai has been incredible. And I'm thrilled to be joining this fantastic team. And I can't wait to make a huge impact in the field of mental health. Back to you, Greg.

是的，當然，非常感謝你，格雷格。我會保持簡短。我非常榮幸被選為 Atai 的下一任財務長。我在阿泰的第一個月真是難以置信。我很高興能加入這個出色的團隊。我迫不及待地想在心理健康領域產生巨大影響。回到你身邊，格雷格。

Thanks, Stephen. It's great to have you on board.

謝謝，史蒂芬。很高興您加入。

But today, the interview format will be led by 2 of our long-term analysts, Andrew Tsai from Jefferies and Judah Frommer from Credit Suisse. Over the next 30 minutes, Andrew and Judah will be asking us a series of questions on our Q2 activities, pipeline and the business update.

但今天的訪談形式將由我們的兩位長期分析師主導，他們是傑富瑞 (Jefferies) 的安德魯·蔡 (Andrew Tsai) 和瑞士信貸 (Credit Suisse) 的朱達·弗洛默 (Judah Frommer)。在接下來的 30 分鐘內，Andrew 和 Judah 將向我們詢問一系列有關第二季活動、通路和業務更新的問題。

So forgive me for this bit, but as a reminder, our discussion today may include forward-looking statements about atai's future results and performance, subject to risks and uncertainties that may cause actual results to differ. atai does not undertake any obligation to update such statements, which speak only as of today.

因此，請原諒我這一點，但提醒一下，我們今天的討論可能包括有關 atai 未來業績和業績的前瞻性陳述，這些陳述可能會受到可能導致實際結果有所不同的風險和不確定性的影響。 atai 不承擔更新此類聲明的任何義務，這些聲明僅適用於今天。

And with that out of the way and just before kicking off the interview, a brief comment on the key financial takeaways for the quarter as we reported in today's earnings release. First, our Q2 operating use of cash was $23 million and was in line with expectations. So no surprise there.

就在採訪開始之前，我們對本季的主要財務要點進行了簡短的評論，正如我們在今天的收益報告中所報導的那樣。首先，我們第二季的營運現金使用量為 2,300 萬美元，符合預期。所以這並不奇怪。

Second, in addition, let me draw your attention to the other press release from atai this morning, where we importantly announced that we've added our Hercules debt facility of up to $175 million. Third, and really the critical point, is that with the combination of $312 million in total cash and the addition of the debt facility, it's approaching $0.5 billion. We have a very strong runway, which, in combination with the pipeline prioritization and some thoughtful cost tightening, we now forecast runway extending into 2025. That's a full year beyond the earlier guidance and an important takeaway here, and as we continue to exercise a disciplined use of cash in this challenging macro environment.

其次，請容許我提請您注意今天早上 atai 發布的另一份新聞稿，其中我們重要地宣布，我們已經增加了高達 1.75 億美元的 Hercules 債務融資。第三，也是真正的關鍵點，加上 3.12 億美元的現金總額加上債務融資，已接近 5 億美元。我們有一個非常強大的跑道，結合管道優先順序和一些深思熟慮的成本緊縮，我們現在預測跑道將延長到2025 年。執行在這個充滿挑戰的宏觀環境中嚴格使用現金。

So with that, let's move into the interview section. I'll hand the mic over to Judah from Credit Suisse to introduce himself and kick us off. Judah?

那麼，讓我們進入採訪部分。我將把麥克風交給瑞士信貸的 Judah，讓他自我介紹並讓我們開始。猶大？

Great. Thanks to the atai team for having me and inviting me to participate. Greg, it's been great working with you and best of luck in your future endeavors. Stephen, welcome to the team as well. We're excited to work with you. .

偉大的。感謝atai團隊邀請我並邀請我參加。格雷格，與您合作非常愉快，祝您未來一切順利。史蒂芬，也歡迎加入我們的團隊。我們很高興與您合作。 。

So maybe just kicking off with a financial question. This has not been an ideal time maybe outside of the last few days for some mid-cap biotechs to be raising capital. And in light of your recent news, you have reasonable runway and a broad pipeline already in clinic. So how should we think about priorities for capital allocation over the next 18 or so months? And how does your current runway factor into this?

所以也許只是從財務問題開始。對於一些中型生技公司來說，除了過去幾天之外，現在可能不是籌集資金的理想時機。根據您最近的消息，您已經在臨床上擁有合理的跑道和廣泛的管道。那麼，我們該如何考慮未來 18 個月左右的資本配置優先順序呢？您目前的跑道如何影響這一點？

Judah, we are very, very confident in the measures that we've taken to extend the runway, as Greg mentioned, by 1 year into 2025 because we believe that the combination of a nondilutive financing, the debt facility of Hercules of up to $175 million, combined with a very intentional strategic and thoughtful way of reprioritizing our pipeline, puts us into the position to now really execute and focus in a focused way on all the very meaningful PoC data inflections that sit in the 7 clinical programs, and soon 8 clinical programs, that we are focused on going forward. And we believe that this will be appreciated by investors and not need -- we don't anticipate any additional funding to actually deliver on those PoC readouts. And I think that's an important takeaway for investors.

Judah，我們對我們採取的措施非常非常有信心，正如格雷格所提到的，將跑道延長一年到 2025 年，因為我們相信，非稀釋性融資、Hercules 高達 175 美元的債務融資的組合百萬美元，再加上一種非常有意的策略和深思熟慮的方式來重新確定我們的管道的優先順序，使我們現在能夠真正執行並集中精力關注7 個臨床項目中所有非常有意義的PoC 數據變化，很快就會有8 個臨床項目我們重點關注的臨床項目。我們相信，這將受到投資者的讚賞，而不是需要——我們預計不會有任何額外的資金來實際交付這些 PoC 讀數。我認為這對投資者來說是一個重要的收穫。

Okay. That's really helpful. And then should we read that as an inclination to further focus on later-stage programs, potentially at the expense of earlier ones or business development activities? Or should we continue to think of atai as in the process of further building a broader neuropsych platform?

好的。這真的很有幫助。那麼我們是否應該將其解讀為進一步關注後期專案的傾向，可能會犧牲早期專案或業務開發活動？或者我們應該繼續將atai視為正在進一步建立更廣泛的神經心理學平台的過程中？

Yes. I would like to emphasize that we have, over the last years, built a very, very strong pipeline and platform already with many clinical programs, but also many enabling technologies that, together with the clinical programs, in our perspective, have been proven very, very effective and efficient when it comes to -- in a very focused way to develop those compounds. And that puts us in a very strong position to have a great basis to execute on the current trials. And to your point, we will focus more on the clinical programs going forward, and we can go into those a little bit further in this call for sure.

是的。我想強調的是，在過去的幾年裡，我們已經建立了一個非常非常強大的管道和平台，已經有許多臨床項目，而且還有許多支援技術，在我們看來，這些技術與臨床項目一起已經被證明非常有效。這使我們處於非常有利的地位，為執行目前的試驗奠定了良好的基礎。就您的觀點而言，我們將更專注於未來的臨床項目，並且我們肯定可以在這次電話會議中進一步討論這些項目。

And on the BD side, we continue -- and you know BD or M&A is in our DNA. We have built a tie through aggressive M&A and BD. And especially in those depressed valuations that we are seeing, we continue to be very, very active and are on the lookout for assets, companies, technologies that can accelerate our existing pipeline or can be very complementary -- or complementing the existing pipeline and -- by basically adding programs with near-term value inflection points. So that is what we are active in, with a focus in the near-term future, definitely on clinical programs.

在 BD 方面，我們繼續進行——您知道 BD 或併購已經融入我們的 DNA 中。我們透過積極的併購和業務發展建立了聯繫。尤其是在我們看到的那些估值低迷的情況下，我們繼續非常非常積極地尋找能夠加速我們現有管道或可以非常互補的資產、公司和技術，或者補充現有管道和- - 通過基本上增加具有近期價值轉折點的計劃。這就是我們正在積極進行的工作，近期的重點肯定是臨床計畫。

I was just going to reiterate something that Florian said. So the programs that we selected and prioritized are all going to be [inclined] by the end of this year. And all of these will generate some meaningful clinical results, proof-of-concept type data within 2 years. So that's really the way to think about it. That's been kind of the model here in terms of prioritization in the next [level].

我只是想重申佛洛里安說的話。因此，我們選擇和優先考慮的項目都將在今年年底前完成。所有這些都將在兩年內產生一些有意義的臨床結果、概念驗證型數據。這確實是思考問題的方式。就下一個[等級]的優先順序而言，這就是這裡的模型。

Perfect.

完美的。

And so speaking of like you guys focusing a little bit more on the clinical-stage portion, maybe my question is a more holistic question is, as we think about, for instance, industry peers, COMPASS, they are technically pioneering the space, in a sense. So as you pursue later-stage studies, should we expect you to kind of follow COMPASS' footsteps in Phase II, for example, they did dose-ranging; Phase III, who knows if they do a placebo as a comparator, but could you kind of follow their footsteps, in a sense?

因此，說到像你們更專注於臨床階段部分，也許我的問題是一個更全面的問題，例如，正如我們所想到的，行業同行 COMPASS，他們在技術上開創了該領域，一種感覺。因此，當您進行後期研究時，我們是否應該期望您在 II 期中追隨 COMPASS 的腳步，例如，他們進行了劑量範圍；第三階段，誰知道他們是否使用安慰劑作為比較，但從某種意義上說，你能跟隨他們的腳步嗎？

Yes. I would say that we're actually already following in their footsteps in many ways, right? So their first trial was, as you said, it was basically single-dose, dose-ranging. And that is exactly what we're doing with our Perception study, right, single administration and dose-ranging. And in both situations, I can say it's very definitively for Perception. We know that we're going to meet multiple doses, right? It's R-ketamine-related. If you know the monthly dose, those are required. But the idea of that first study was to really get a good handle on duration of efficacy, of course, and magnitude of efficacy. And so that's the data that we're going to take forward and to help design that next trial. And again, I imagine that COMPASS is doing something very similar.

是的。我想說，我們實際上已經在很多方面追隨他們的腳步了，對嗎？所以，正如你所說，他們的第一次試驗基本上是單劑量、劑量範圍的。這正是我們在感知研究中所做的，正確的，單次給藥和劑量範圍。在這兩種情況下，我可以說這對感知來說都是非常明確的。我們知道我們會接受多次劑量，對吧？它與R-氯胺酮有關。 如果您知道每月劑量，則需要這些。但第一項研究的目的是真正掌握療效的持續時間，當然還有療效的大小。這就是我們將繼續使用並幫助設計下一次試驗的數據。我再次認為 COMPASS 正在做一些非常類似的事情。

Understood. And before I turn it over to Judah, they are, technically, we learned, leveraging some digital tools in Phase III plus psychological support. It's apparent that FDA is on board with this. Could you incorporate these dynamics within neuro studies even as early as Phase II, for instance?

明白了。在我將其交給 Judah 之前，我們了解到，從技術上講，他們在第三階段利用了一些數位工具以及心理支持。顯然，FDA 對此表示支持。例如，您是否可以早在第二階段就將這些動態納入神經研究中？

Well, we've been working on digital technologies for a while now, right? So we actually announced Introspect, which is one of the focus areas within the company 2 years ago, over 2 years ago. So our digital technologies have matured to the point where they're in clinical testing now. So really got more user acceptability-type trials, but in ketamine clinics. So that we're getting all the data we need to really help, yes, and the content, right?

嗯，我們研究數位技術已經有一段時間了，對吧？所以我們實際上在兩年前、兩年多前就宣布了 Introspect，這是公司內部的重點領域之一。所以我們的數位技術已經成熟到現在正在進行臨床測試。所以確實得到了更多的使用者可接受性類型的試驗，但是是在氯胺酮診所。這樣我們就可以獲得真正有幫助的所有數據，是的，還有內容，對嗎？

So we're testing content as well. And we're actually going to be deploying these very soon in our Phase I trials with both Viridia and EmpathBio. So Phase I, of course, these are healthy volunteers, but they still require prep work, and there still are some support post dosing. So the digital technologies will be used there. And then, of course, we'll roll them out in subsequent Phase IIs.

所以我們也在測試內容。事實上，我們很快就會在 Viridia 和 EmpathBio 的第一階段試驗中部署這些技術。所以第一階段，當然，這些都是健康的志願者，但他們仍然需要準備工作，並且在給藥後仍然有一些支持。所以數位技術將在那裡使用。當然，我們將在後續的第二階段中推出它們。

Yes. Before Judah, you jump in, I would like to remind investors quickly actually why we think digital therapeutics are important. So if you remember, we are really about achieving clinically meaningful behavioral change in mental health patients and are intending to really achieve durable behavioral change. And we pursue this through our 3-pillar strategy.

是的。在 Judah 介入之前，我想快速提醒投資人為什麼我們認為數位療法很重要。因此，如果您還記得的話，我們實際上是為了在精神健康患者中實現具有臨床意義的行為改變，並且打算真正實現持久的行為改變。我們透過三大支柱策略來實現這一目標。

One is the focus on differentiated and more rapid-acting pharmacological interventions that we believe have all strong neuroplastic effects that induce this window of behavioral plasticity that we then want to leverage exactly through those digital therapeutics, such as our Introspect app, to really help foster new habits through a company of behavioral therapy elements and multiple other content elements that we believe can effectively be delivered through digital means. So this is the ongoing psychotherapeutic support elements of pillar 2 of our strategy.

一是關注差異化和更快速起效的藥理幹預措施，我們相信這些幹預措施具有強大的神經可塑性作用，可以誘導行為可塑性窗口，然後我們希望透過這些數位療法（例如我們的Introspect 應用程式）準確利用這一窗口，以真正幫助培養行為可塑性。這是我們策略第二支柱的持續心理治療支持要素。

And then along the way, use and harvest -- or harness that data that we're going to be collecting by digital phenotyping, for example, but also looking at biological biomarkers potentially here to move us to a more precision psychiatry approach of thinking about treating patients given the very heterogeneous nature in this patient population. So very, very excited to see the first technologies applied actually in the first clinical study now with our DMT program.

然後一路走來，使用和收穫——或者利用我們將通過數字表型分析收集的數據，例如，同時也研究潛在的生物標誌物，以推動我們採用更精確的精神病學方法來思考鑑於該患者群體的異質性，對患者進行治療。非常非常興奮地看到第一個技術在我們的 DMT 專案中實際應用於第一個臨床研究。

So we -- technically speaking, we could get some early data over the coming months with the digital tools, basically?

所以從技術上講，我們基本上可以在未來幾個月內使用數位工具來獲得一些早期數據？

That's correct.

這是正確的。

That's awesome. Okay.

太棒了。好的。

Yes.

是的。

Great. And maybe just sticking with COMPASS for a second here. It sounds like we'll get a detail of their Phase III trial design around October, I think, is the latest. So what would you say you're looking for in terms of trial design that could carry a read across beyond maybe the digital components for pipeline programs at atai?

偉大的。也許在這裡只是堅持使用 COMPASS 一秒鐘。聽起來我們將在 10 月左右獲得他們的 III 期試驗設計的詳細信息，我認為這是最新的。那麼，您認為您在試驗設計方面正在尋找什麼，可以超越 atai 管道項目的數位組件？

Well, I think we have hit on one, of course, digital and seeing how -- what their perspective is on that and how they want that characterized, validated testing, and I think that will be really interesting. The other piece is the one that I alluded to earlier, right? And that's the repeated dosing. How does the agency look upon that? What are the implications, potentially, for tox testing, right? What are they looking for there? What are they looking for in terms of long-term data? Are they looking for repeat dosing within that? Or do they look -- do they want to see meeting the ICH guidelines, so 100 subjects approximate at the end of the year?

嗯，我認為我們已經找到了一個，當然，數位化的，看看他們對此有何看法，以及他們想要如何進行特徵化的、經過驗證的測試，我認為這將非常有趣。另一件是我之前提到的，對嗎？這就是重複給藥。該機構對此有何看法？對於毒性測試來說，潛在的影響是什麼，對嗎？他們在那裡尋找什麼？他們在尋找什麼長期數據？他們是否正在尋求在此範圍內重複給藥？或者他們是否希望看到符合 ICH 指南，因此年底大約有 100 名受試者？

And these are the sort of questions that obviously will impact us over time. There are other things that would be interesting. I can't imagine it'll be very controversial, stuff like placebo versus dose control, I mean, there's lots of precedence from both. I can't imagine they'd be very -- that would be much of an issue. But the other ones are our repeat dosing, et cetera, would be really interesting and obviously very impactful for our studies.

隨著時間的推移，這些問題顯然會影響我們。還有其他一些有趣的事情。我無法想像這會引起很大爭議，例如安慰劑與劑量控制之類的東西，我的意思是，兩者都有很多優先權。我無法想像他們會非常——這將是一個大問題。但其他的是我們的重複給藥等等，這將非常有趣，並且顯然對我們的研究非常有影響。

Okay. That's helpful. And then just hitting on a couple of changes that have gone on at COMPASS given your minority stake there. Any quick thoughts on the anorexia nervosa indication? And have you guys interacted in a significant way with the new CEO?

好的。這很有幫助。然後，考慮到你在 COMPASS 的少數股權，就順便談談 COMPASS 發生的一些變化。關於神經性厭食症的適應症有什麼快速的想法嗎？你們與新任執行長進行過重要的互動嗎？

Yes. In fact, we have. We actually had a call, I believe, 1.5 weeks ago with Kabir. We believe it's a great choice. So I applaud the COMPASS Board for that decision. I think he's definitely the right person and has also the right skill set to now move that company through Phase III and, hopefully, to approval and then has also the requisite experience of how to effectively commercialize drugs. So I believe that is a very great setup for success for COMPASS going forward with him spearheading it, and George also staying onboard as Chairman. So I believe we have a very, very strong solution here for COMPASS.

是的。事實上，我們有。我相信，我們確實在 1.5 週前與 Kabir 通了電話。我們相信這是一個很好的選擇。因此，我對 COMPASS 董事會的這項決定表示讚賞。我認為他絕對是合適的人選，並且擁有正確的技能，可以讓該公司進入第三階段，並希望獲得批准，然後還擁有如何有效地將藥物商業化的必要經驗。因此，我相信，在他的帶領下，COMPASS 的成功是一個非常好的準備，喬治也將繼續擔任董事長。所以我相信我們有一個非常非常強大的 COMPASS 解決方案。

And we also applaud them for going after anorexia nervosa This is a really, really significant unmet need in psychiatry. So there is no approved drug, and we see a great potential for COMP360 here given the early signals that we saw based on their open-label trial and believe that this is very worthwhile to pursue from our perspective.

我們也讚揚他們對神經性厭食症的研究，這是精神病學中一個非常非常重要的未滿足的需求。因此，目前還沒有批准的藥物，鑑於我們在開放標籤試驗中看到的早期信號，我們看到了 COMP360 的巨大潛力，並相信從我們的角度來看，這是非常值得追求的。

Just one small follow-up. I was just curious if you guys think maybe the FDA deems their Phase IIb as a pivotal study potential? I guess, it's hard to say, but just asking if you have any thoughts.

只是一個小小的後續行動。我只是好奇你們是否認為 FDA 認為他們的 IIb 期研究具有關鍵的研究潛力？我想，這很難說，只是問你有什麼想法。

I mean, clearly, there's precedence for using Phase II data's supportive data, right? So if one of the Phase III trials is sort of marginal, there's been certainly precedents where the agency will accept a Phase II, though, is much more robust.

我的意思是，顯然，使用第二階段資料的支援資料是有優先權的，對吧？因此，如果其中一項第三階段試驗的效果有點微不足道，那麼肯定有先例表明該機構會接受第二階段試驗，儘管第二階段試驗的效果要強得多。

Will they truly accept it as a pivotal? I don't know. I mean, clearly, during the earnings call, COMPASS did emphasize 2, or at least more than 1, certainly, Phase III study. It's not obvious whether or not they also we're including a long-term follow-up study. So we'll get more clarity over the course of the next little bit. I'm personally a little skeptical of that, but that doesn't...

他們真的會接受它作為關鍵嗎？我不知道。我的意思是，很明顯，在財報電話會議期間，COMPASS 確實強調了 2 項，或至少超過 1 項，當然，第三階段研究。目前尚不清楚他們是否也包括一項長期追蹤研究。因此，我們將在接下來的一段時間內更加清楚地了解這一點。我個人對此有點懷疑，但這並不......

Yes, we'll see.

是的，我們拭目以待。

We'll have the data soon. So let's just wait.

我們很快就會得到數據。所以我們就等等吧。

Sure.

當然。

All right. Maybe switching gears to PCN-101, if we could, certainly the program we get the most inbounds on lately. So with a couple of readouts expected end of this year, can you remind us of design time lines, maybe bars for success for the Phase IIa, and how its clinical expansion into the U.S. has gone, along with the drug-drug interaction study and the subcu bridging study. So a lot to unpack there.

好的。如果可以的話，也許可以切換到 PCN-101，這肯定是我們最近獲得最多訪問的程式。因此，預計今年年底將發布一些數據，您能否提醒我們設計時間線，也許是 IIa 期成功的障礙，以及其在美國的臨床擴張進展如何，以及藥物交互作用研究和subcu橋接研究。那裡有很多東西需要解壓。

That is a lot to unpack. So yes, just to level set with everybody, as I mentioned, the [double A] is -- the Phase II, the double-blind, placebo-controlled study, again, following the footsteps of COMPASS, single administration is IV. In this case, following in the footsteps of, yes, Janssen.

有很多東西需要解壓縮。所以，是的，正如我所提到的，[雙 A] 是第二階段，雙盲、安慰劑對照研究，再次追隨 COMPASS 的腳步，單次給藥是 IV。在這種情況下，跟隨詹森的腳步。

So we are looking at basically 2 doses of R-ketamine, one is sub associated, the other one is sort of a threshold associated. That's 30 milligrams and 60 milligrams, respectively. And of course, third arm is placebo. 31 subjects in each one of those arms. Primary outcome measure is [20] MADRS in 24 hours. It's also looked at over the course of the next 7 days and 14 days. So that's the outline of the trial. Recruitment is going really well. So very excited about that. And this trial, we're completely on track for readout by the end of this year.

因此，我們基本上正在研究兩種劑量的 R-氯胺酮，一種是亞相關的，另一種是與閾值相關的。分別是 30 毫克和 60 毫克。當然，第三組是安慰劑。每一組有 31 位受試者。主要結果指標為 24 小時內 [20] MADRS。在接下來的 7 天和 14 天中也會對其進行研究。這就是審判的概要。招募進展非常順利。對此非常興奮。這次試驗，我們完全有望在今年底前讀出結果。

In terms of U.S. expansion, as you -- we did, of course, announce an IND earlier this year. You can actually look at clinicaltrials.gov, it's going really well. And so far, there's 10 sites in the United States that are currently recruiting. And there's 3 others that are in the process of coming up online. So again, going really well.

就美國擴張而言，正如您所言，我們當然在今年早些時候宣布了 IND。你實際上可以看看clinicaltrials.gov，進展非常順利。到目前為止，美國有 10 個網站正在招募。還有另外 3 個正在上線。再說一遍，進展非常順利。

Now you also mentioned what -- in terms of what are thresholds as well as success look like. it's important to go back to what our premise here is, right? And that premise is at-home use. So our thoughts on that are pretty straightforward. I mean, obviously, that's had good efficacy, and we know what the MADRS MCID, the minimum clinically important difference, is at [2]. We hope to see more than that versus placebo at 24 hours. But the other element there is tolerability, specifically regarding dissociation.

現在您也提到了門檻和成功的樣子。回到我們這裡的前提很重要，對吧？這個前提是在家使用。所以我們對此的想法非常簡單。我的意思是，顯然，這具有良好的功效，而且我們知道 MADRS MCID（臨床上最小的重要差異）是多少 [2]。我們希望在 24 小時內看到與安慰劑相比更多的結果。但另一個因素是耐受性，特別是關於解離的耐受性。

And as you guys are probably very well aware, Spravato's quite dissociative at the doses required for efficacy. We hope to be much lower in that regard, if not within the normal realm. That's really going to be -- that will be an important factor for us in the decision-making process at the FDA to support at-home use. So that's kind of a big picture there in terms of what we are looking for.

正如你們可能非常清楚的那樣，Spravo 在達到功效所需的劑量下是相當分離的。我們希望在這方面的水平要低得多，即使不是在正常範圍內。這確實將是我們在 FDA 支持家庭使用的決策過程中的重要因素。這就是我們正在尋找的東西的總體情況。

Okay. And the other piece of at-home use is subcu? Yes.

好的。另一件家用產品是 subcu？是的。

Yes. So subcu, that's still in planning. We're basically moving that forward towards initiation at this point. But yes, I mean, basically, right now, it's IV. We have a subcu formulation that we'll be testing, looking for relative bioavailability of these 2 different routes of administration, understanding what the dose levels and what you need for comparability there.

是的。所以 subcu，仍在計劃中。目前我們基本上正在將其推進到啟動階段。但是，是的，我的意思是，基本上，現在是 IV。我們有一個 subcu 配方，我們將對其進行測試，尋找這兩種不同給藥途徑的相對生物利用度，以了解劑量水平以及您需要什麼來進行比較。

Got it.

知道了。

Of course, that will be what we take forward in subsequent trials. That's much more suitable, as you can imagine, for repeat dosing.

當然，這將是我們在後續試驗中繼續前進的內容。正如您可以想像的那樣，這更適合重複給藥。

Sure.

當然。

And you mentioned the DDI study as well. So the DDI study is really focused on 3A4 inhibitors and 2C19, and looking at the impact of those compounds on the PK of R-ketamine. And so that trial is the clinical basis. All the clinical dosing have been -- is completed at this point. So it's under analysis now, and again, expecting top line certainly before the end of this year.

您也提到了 DDI 研究。因此，DDI 研究的重點是 3A4 抑制劑和 2C19，並研究這些化合物對 R-氯胺酮 PK 的影響。因此，該試驗是臨床基礎。至此，所有臨床給藥均已完成。因此，現在正在一次又一次地進行分析，預計在今年年底之前肯定會達到頂線。

Great.

偉大的。

And I'm curious, 2 points, technically, is the fundamental approvable, I guess, delta, in a sense. But maybe the market or the Street prefer something more similar to esketamine, or [what esketamine] traditionally shows. Is that fair to think about as we think about the top line data in terms of the delta of drug versus placebo?

我很好奇，從技術上講，2點是基本面可批准的，我想，從某種意義上說，是三角洲。但也許市場或華爾街更喜歡類似艾氯胺酮的東西，或[艾氯胺酮]傳統上表現的東西。當我們考慮藥物與安慰劑的增量數據時，這樣的想法公平嗎？

Yes. I mean, I think, it's a very valid point. So just kind of thinking through what the approvability package for esketamine, one was -- I mean, esketamine was. It was basically -- they had 3 trials, TRANSFORM-1, 2 and 3, and then they have this long-term [bet]. Really, the only truly positive trial was the TRANSFORM-2, right. TRANSFORM2 had a 4-point delta on the MADRS. And that's -- I think that was the 28th day. So that's a good bar.

是的。我的意思是，我認為這是一個非常有效的觀點。因此，只要思考一下艾氯胺酮的批准方案是什麼，我的意思是，艾氯胺酮是。基本上，他們進行了 3 項試驗，TRANSFORM-1、2 和 3，然後他們進行了長期[賭注]。確實，唯一真正積極的試驗是 TRANSFORM-2，對吧。 TRANSFORM2 在 MADRS 上有 4 點的增量。我認為那是第 28 天。所以這是一個很好的酒吧。

But of course, that was a lot of going into the clinic, right? So the minimum bar, for me, it's not great. But the minimum bar would certainly be 2-plus, but a rapid onset, right? So that differentiates you completely from an SSRI. SSRIs are weeks, if not a month or months, to get at. Because if you can get that same level of efficacy in 24 hours, that's a win, right?

但當然，進入診所需要花很多時間，對吧？所以對我來說，最低標準並不是很好。但最低標準肯定是 2 以上，但起效很快，對嗎？因此，這與 SSRI 藥物完全不同。 SSRIs 需要幾週甚至一個月的時間才能達到。因為如果您能在 24 小時內獲得相同程度的功效，那就是勝利，對吧？

And with esketamine, you go in there every -- you're going there twice a week for 4 weeks. You're going there once a week for the subsequent 4 weeks. That's a lot of travel. That's a lot of time in commute, right? So if we can do this all at home, I think we [all may want] about. So I mean, I think that remains a very strong win for the [the center].

對於艾氯胺酮，你每週都會去那裡——你每週去那裡兩次，持續 4 週。在接下來的 4 週內，您每週都會去那裡一次。這是很多旅行。通勤時間很長，對嗎？因此，如果我們能夠在家裡完成這一切，我想我們[所有人都可能想要]。所以我的意思是，我認為這對[中間]來說仍然是一個非常強大的勝利。

And how reliable -- "reliable" or "translatable" do you think this data set would be, assuming it was successful? Because my -- I'm presuming it's done in an inpatient setting, whereas, eventually, you want to go at-home. So do you have any color around that, around how you think about this?

假設該資料集成功，您認為該資料集的可靠性如何？ “可靠”或“可翻譯”？因為我的——我假設它是在住院環境中完成的，而最終，你想回家。那麼你對這個問題有什麼看法嗎？

Yes. I mean -- well, there's 2 elements to that. So the first is the PK piece, right? So there's a -- changing the route of administration, so there will be an impact on PK. So we're obviously generating data with our current administration protocol, which is 40 minutes continuous infusion. So of course, we need to understand what the PK of the subcutaneous formulation is, and we've got some parameters that we want to match there, right? So the AUC, the Cmax are all things that we want to look at. And of course, that's where -- that will be driven by the Phase I.

是的。我的意思是──嗯，有兩個要素。那首先就是PK部分，對吧？因此，改變給藥途徑，會對 PK 產生影響。因此，我們顯然是根據目前的給藥方案產生數據，即連續輸注 40 分鐘。當然，我們需要了解皮下製劑的 PK 是什麼，我們有一些想要匹配的參數，對嗎？因此，AUC、Cmax 都是我們想要查看的內容。當然，這就是第一階段驅動的地方。

So that will have some impact on efficacy. And of course, you're right, in-house may have a different effect. It should impact placebo on drug sort of similarly, I mean, generally going to a clinic is going to drive up your response. It's going to drive up your placebo response. So we may actually have a better signal-to-noise ratio if we're at home. Purely speculation, we'll have to see how this plays out.

所以這會對功效產生一定的影響。當然，你是對的，內部可能會產生不同的效果。它應該對藥物的安慰劑產生類似的影響，我的意思是，通常去診所會提高你的反應。它會提高你對安慰劑的反應。因此，如果我們在家的話，實際上可能會有更好的信噪比。純粹是猜測，我們必須看看結果如何。

And maybe one more question is, I noticed in the press release the bridging study could complete within the next few quarters. So as we think about the next steps afterwards, that technically is the gating step before you move to a subsequent study after this Phase II?

也許還有一個問題是，我在新聞稿中註意到，橋接研究可能會在接下來的幾個季度內完成。因此，當我們考慮之後的後續步驟時，從技術上講，這是第二階段之後進入後續研究之前的選通步驟？

Well, there's also some additional talks and other things that are also in [process]. So there are a few pieces that have to come together. That is one of them, certainly. But yes, of course, you got -- we need those results. I'll -- think of it as support the next trial.

嗯，還有一些額外的會談和其他事情也在[進行中]。因此，必須將一些部分組合在一起。當然，這就是其中之一。但是，是的，當然，我們需要這些結果。我會將其視為對下一次試驗的支持。

Okay. If I could move us over to RL-007 and CIAS. So there have literally been dozens of compounds in CIAS that have failed, some with similar pathways even to 007. And In your view, how much of that can be attributed to chemistry or target selection of those compounds versus trial design?

好的。如果我可以把我們轉移到 RL-007 和 CIAS 就好了。因此，CIAS 中實際上有數十種化合物失敗了，其中一些甚至與 007 具有相似的途徑。

Well, let's focus on the chemistry but for the moment. In general, over the last several decades, there's been this concept of being really a reduction in some of the pharmacology, right? Trying to find that piece of pharmacology that's driving the efficacy and make very clean drugs for it.

好吧，讓我們暫時關注化學反應。總的來說，在過去的幾十年裡，確實存在一些藥理學減少的概念，對吧？ 試圖找到推動療效的藥理學部分，並為其製造非常乾淨的藥物。

Certainly, that's true where the SSRIs is a good example, but also relating to -- psychotics to some degree. But the reality is that dirty drugs tend to work a little bit better in most of these indications. The nice thing or the interesting thing about RL-007 is its polypharmacology. It's absolutely got a GABA-mediated activity, GABA-B-mediated activity, I mean, but it also has neurotransmission and cholinergic effects. So that is a point of differentiation compared to some of the other things that are currently in development. which are much more focused.

當然，SSRIs 就是一個很好的例子，但在某種程度上也與精神病有關。但現實是，骯髒藥物在大多數適應症中往往效果更好。 RL-007 的優點或有趣之處在於它的多重藥理學。我的意思是，它絕對具有 GABA 介導的活性，GABA-B 介導的活性，但它也具有神經傳遞和膽鹼能作用。因此，與目前正在開發的其​​他一些東西相比，這是一個區別點。哪些更加集中。

So I think that's an interesting angle. Of course, it's consistent with our model, right? We have existing clinical data, albeit in different groups. So we have one in diabetic peripheral neuropathic pain. That is a population that probably, in general, has some degree of subclinical kind of impairment, right? They are vascular paths. That's why they have diabetic peripheral neuropathic pain. They presumably have some central or vascular [tissue] compromised as well. So we saw a signal there.

所以我認為這是一個有趣的角度。當然，這和我們的模型是一致的，對吧？我們有現有的臨床數據，儘管是在不同的組別。所以我們有一個關於糖尿病週邊神經病理性疼痛的研究。一般來說，這個族群可能存在某種程度的亞臨床損傷，對吧？它們是血管路徑。這就是他們患有糖尿病週邊神經性疼痛的原因。 他們可能也有一些中樞或血管[組織]受損。所以我們在那裡看到了一個訊號。

We saw it in normal healthy volunteers. We saw some signaling in our [inverted] mechanism type trial. We saw an inverted u-shaped curve, which is consistent with the hypothesis vis-a-vis cognitive effects. We saw a change on quantitative EEG that was sort of mirroring that as well. So again, consistent with our hypothesis. So we got a lot of things going in our favor with this compound, not disputing the fact that it's a challenging indication, not trying to walk away from that at all.

我們在正常健康的志工身上看到了這一點。我們在[反向]機制類型試驗中看到了一些訊號。我們看到了一條倒 U 形曲線，這與認知效應的假設是一致的。我們看到定量腦電圖的變化也反映了這一點。再次，與我們的假設一致。因此，我們對這種化合物做了很多有利於我們的事情，沒有質疑它是一個具有挑戰性的適應症這一事實，也沒有試圖擺脫這一事實。

In terms of the clinical trial design, it's an interesting question. So there's been a lot of development for an extended period of time on endpoints for this, right? It's this MCCB. This is the broad recognition of the unmet medical need with this indication, right? The FDA has been all over this for a very long time. Other industry partners have been involved with this entire thing. Academics have been involved. So there's been -- we have a nice consensus battery on what the endpoints should look like.

就臨床試驗設計而言，這是一個有趣的問題。因此，在很長一段時間內，在端點方面已經進行了大量的開發，對吧？就是這個塑殼斷路器。這是對該適應症未得到滿足的醫療需求的廣泛認可，對吧？ FDA 長期以來一直在關注這個問題。其他產業夥伴也參與了整件事情。學者紛紛參與其中。因此，我們對端點應該是什麼樣子有一個很好的共識。

There has been evolution on that a little bit in terms of being more focused on some of the endpoints. So that's something that's been -- or subsets, it's been ongoing. So I think, overall, though, it's probably a lot to do with the pharmacology, to some degree, around the endpoints and particularly the ability to now focus on subsets of those endpoints.

在更關注某些端點方面，這方面已經有了一些進展。所以這就是一直在進行的事情——或者說它的子集。所以我認為，總的來說，在某種程度上，圍繞著終點，特別是現在關注這些終點子集的能力，這可能與藥理學有很大關係。

That makes a lot of sense. And then just where do we stand on potentially improving the dosing profile? And what's the latest in terms of next steps on the decision about whether to pursue a Phase IIb and go for an end-of-Phase II meeting or do you have an additional Phase IIa? And what could preferred endpoint selection be? You touched on it there.

這很有意義。那麼我們在改善劑量方面的潛力又在哪裡呢？關於是否進行 IIb 階段並召開 II 階段結束會議，或者是否還有額外的 IIa 階段的決定，下一步的最新進展是什麼？首選端點選擇是？你在那裡觸及了它。

Okay. Well, let me take that last bit first. So we are indeed prepping for our Phase IIb at this point. And the endpoint is going to be the MCCB. So you may recall in the last study, we saw a simple [coating] , which is very positive in that trial. Simple coating has very good overall correlation with the MCCB. So we take comfort in that in terms of some degree of proof of concept. And in fact, a simple coating is part of the MCCB. So happy that's why we've decided to move forward with that. The trial will be robust and would certainly support an end-of-Phase II meeting, assuming, of course, positive results.

好的。好吧，讓我先講最後一點。所以我們現在確實正在為 IIb 階段做準備。端點將是 MCCB。所以你可能還記得在上一項研究中，我們看到了一種簡單的[塗層]，這在該試驗中非常積極。 簡單塗層與塑殼斷路器具有良好的整體相關性。因此，我們對某種程度的概念證明感到放心。事實上，簡單的塗層就是 MCCB 的一部分。很高興這就是我們決定繼續前進的原因。該試驗將是強有力的，並且肯定會支持第二階段結束會議，當然前提是取得積極的結果。

Now in terms of posology, this is one where -- this is an area that we have to improve on. We've got some angles there. Right now, we're dosing TID. There is a good argument to be made that you can make it BID. We could, of course, use formulation technology that make it QD. And of course, that would be great, particularly keeping in mind this patient population. So that's another thing that we are trying to look at. We could bridge to that at a later point.

現在就劑量學而言，這是我們必須改進的領域。我們在那裡有一些角度。現在，我們正在服用 TID。有一個很好的論點表明您可以出價。當然，我們可以使用使其成為 QD 的配方技術。當然，那太好了，特別是考慮到這群患者。這是我們正在努力研究的另一件事。我們可以稍後再解決這個問題。

That's helpful.

這很有幫助。

And with that, we are unfortunately already out of time. So I would really like to thank you, Andrew and Judah, for dialing in today. I found this very, very insightful and interactive. Thank you so much for asking these inquisitive questions today.

不幸的是，我們已經沒有時間了。因此，我非常感謝安德魯和猶大今天撥通電話。我發現這非常非常有洞察力和互動性。非常感謝您今天提出這些好奇的問題。

And I would also like to express my gratitude to Greg for your service as CFO of atai and to drive forward our mission with so much passion. So we're really, really thankful for your service. You have been an instrumental part of our leadership team. And I'm also very grateful that you stay another couple of months until the end of the year to ensure a smooth transition when you're handing over your CFO job to Stephen.

我還要對格雷格表示感謝，感謝您作為 atai 財務長所提供的服務，並以極大的熱情推動我們的使命。所以我們非常非常感謝您的服務。您一直是我們領導團隊的重要組成部分。我也非常感謝您在年底之前再待幾個月，以確保在將財務長職位移交給史蒂芬時順利過渡。

And Stephen, really thrilled to have you here. You bring with you a lot of expertise and experience with that model that we are pursuing, so this decentralized way of developing drugs, and couldn't be more happy to have you on board. So a warm welcome for you, and looking very much forward to work with you going forward.

史蒂芬，很高興你能來到這裡。你帶來了我們所追求的模式的大量專業知識和經驗，因此這種分散的藥物開發方式，我們非常高興有你的加入。熱烈歡迎您，並非常期待與您繼續合作。

And ultimately, I would like to reemphasize, I guess, the key takeaways from my perspective to our investors. We have taken very, very strong and thoughtful measures to extend our runway by 1 year into 2025. We believe this has been the right strategic decision by adding nondilutive debt financing of up to $175 million and a very intentional and thoughtful reprioritization of our pipeline. Because, in our perspective, this puts us into a position to really focus on the key value inflection points in our programs, and 7 out of 8 are in the clinic right now. We assume to have 8 in the clinic in -- by end of this year. And there's a lot of proof of concept data sitting in there that we intend to report out over the next 2 years.

最後，我想再次強調我對投資人的看法。我們採取了非常、非常強有力和深思熟慮的措施，將我們的跑道延長一年，直至2025 年 我們相信，這是正確的戰略決策，增加了高達1.75 億美元的非稀釋性債務融資，並對我們的管道進行了非常有意和深思熟慮的優先順序調整。因為，在我們看來，這使我們能夠真正專注於我們專案中的關鍵價值拐點，而目前八分之七的專案正在臨床中。我們預計到今年年底，診所將有 8 名患者。其中有大量概念驗證數據，我們打算在未來兩年內報告。

And with that, I thank everyone to dial in, and wish everyone a very great day. Thank you.

在此，我感謝大家撥通電話，並祝大家有個愉快的一天。謝謝。