身份不明的发言人
Srinivas Rao
身份不明的参会者
Pete Stavropoulos（Cantor Fitzgerald）
欢迎参加Cantor全球医疗保健会议。我是Pete Stavropoulos，Kantor的生物技术分析师。和我们一起的是Atai Beckley。现在还系着领带，对吧。好的，很快就是Ty Beckley，很高兴介绍Srini Rayo，首席执行官。那么，我们先从您自己和公司的简要介绍开始，为那些不熟悉的人介绍一下。
是的。非常感谢Pete邀请我，也感谢大家的加入。我的名字是Srini Rao，我是ATAI的首席执行官和联合创始人。背景？医学博士，神经药理学博士。在我的博士研究中，我做了很多与相同药理学相关的工作。显然我很早就加入了。公司最初更像是一个基金，然后我加入将其转变为一个运营公司，当然我们已经做到了。所以ATAI目前有三个核心资产。其中一个，正如你所提到的，是来自Beckley的。
我们将在今年年底前与他们合并。所以那是我们的领先资产。那是BPL03，用于治疗耐药性抑郁症。我们还有VLSO1，紧随其后，也用于治疗耐药性抑郁症。然后我们有emp01，这是第三个化合物，用于社交焦虑障碍。所有这些都是迷幻药或迷幻药相关化合物。
好的，那么，开始吧，只是一个广泛的问题，你知道，你从一开始就在Atai，是联合创始人之一，你看着这个领域发展。只是好奇听听你的观点，关于人们如何看待迷幻药在精神科适应症方面的潜力，过去五年左右它是如何演变的，比如，从与广泛精神科社区的互动，比如在医学会议上的互动。兴趣增长了吗？你知道，当你五年前做演讲时与今天相比，房间里的互动是如何变化的？
是的，我的意思是，我认为即使早在2017年，甚至到2018年左右，都有很多怀疑。确实，Compass Pathways那时已经从非营利组织转变为营利性公司，以开发Compass360或psilocybin用于治疗耐药性抑郁症。他们那时无法筹集资金。事实上，这就是ATAI最初成立的方式，作为一个帮助资助Compass的工具。你知道，那是一个完全不同的时代。到2019年的时候，有更多的人出现在会议上，特别是像acnp这样的会议，那里有很多KOL作为思想领袖，同样的美国神经药理学学院会议，但从那时起就稳步增加了。
我认为，你知道，它已经更多地传播到了普通的精神科医生中。显然。在这期间，大众媒体上也有很多报道，这也有所帮助。
对。还有好奇的是，当你开始时，即使是与Compass Therapeutics，临床结构，临床试验基础设施，它是如何演变的？因为你只有一家公司，现在你有多个研究正在进行，所以你看到它演变了吗？
是的，这是一个很好的问题。所以Compass做了所有繁重的工作来启动和运行第一个迷幻药试验。我的意思是，那是他们的一大提升，部分工作是在COVID期间完成的。所以我的意思是，称赞他们启动了它。所以你绝对正确。现在有更多的基础设施，但也有更多的试验，而且这两者不一定成比例地扩展。所以肯定有更多的竞争。有趣的是，通常你想到的是同一适应症内的竞争。好吧，那是你通常想到的方式。
就像，哦，这些家伙在做两个TRD试验，或者一个是抑郁症，一个是trd，等等。在这里，你还必须考虑迷幻药本身，因为它更密集。基本上有一个房间和一些人员必须观察病人一段时间。所以你必须更广泛地看待迷幻药，而不仅仅是特定的适应症。
好的，所以在六月你宣布了Atali和Beckley的合并。请带我们了解战略理由，以及合并后的实体定位交付什么。你能详细说明这些效率转化为什麼吗？更好的执行还是更快的商业化路径？
是的，所以我们一直特别关注短效迷幻药，那是我们的领先化合物。VLSO1正是那样，或者正是那样。它是一种口服薄膜制剂，经粘膜给药的二甲基色胺或dmt。Beckley正在开发一种鼻内制剂，也是快速起效和失效的5-甲氧基，DMT或Mebufotina。所以我们也对那种化合物感兴趣。我们 broadly 喜欢他们的方法。我们实际上在去年一月，2024年，宣布了对他们的投资，5000万美元基本上让我们获得了公司约三分之一的股份。我们一直预期做点什么，所以在我们的数据读出之前宣布交易是有意义的，我们做了。
所以那基本上是两家公司的全面收购或全面合并。它取决于Phase IIB的结果。那些结果，我们会说，是 robustly positive。所以是的，我们显然已经宣布我们将推进那一点，就它为公司带来什么而言。那是我们目前最远的资产。所以我们内部的SOV LSO1大约，你知道，比bpl落后大约一年， give or take。所以我们有两种不同的方法，两种不同的化合物，但你知道，现在我们有一个进入 phase 3，一个在 phase 2B，第三个实际上在 phase 2A。
所以我们确实有一个很好的这些化合物的分布。
所以你知道，你确实有数据，如你提到的，Phase 2B数据在今年夏天早些时候读出。是的，请带我们了解细节。你知道，研究设计和疗效结果。
是的，所以试验实际上与Compass所做的非常相似。我的意思是，再次如我提到的，他们是真正，你知道，推动这个的人，他们是真正的先驱或他们是这里的先驱。这是对治疗耐药性抑郁症患者的单次给药。所以两次药物失败。在当前发作中，是单次给药。主要终点在四周，然后这些患者被额外监测四周或总共八周，以盲法方式。然后有一个开放标签扩展，如果他们选择进入，大多数 vast majority dead。
然后他们会得到额外剂量，然后会被额外随访八周。我们看了三个不同的剂量。有一个功能性安慰剂，是5-甲氧基，DMT的亚感知剂量，那是0.3毫克，中间剂量8，然后更高剂量12毫克。选择那两个剂量是因为它们都有非常 robust 的迷幻效果。但这真的是一个问题，两个的安全性是否可以区分。我们发现的是，确实在疗效方面8和12一样好，事实上数字上更好一点。
而且确实耐受性肯定比12毫克改善。所以那实际上是我们将推进的剂量。
好的，一些耐受性问题是什么？
是的，很多是类效应。所以有，你知道，一些恶心，呕吐和，你知道，头痛。那些是主要的事情。也有一些是，你知道，直接与给药途径相关。所以鼻刺激，一些鼻不适也是。所以 pretty。然后在所有这些化合物中，所有，包括Spravato，实际上，有，你知道，血压的短暂增加。我们也看到了。
所以90%的患者完成了核心研究。85，我猜，进入了开放标签。所以那与其他迷幻药和这些适应症的发展相比如何？
我不认为。我不认为我们还有很好的数据。我们很快会有Compass的。就开放标签和 rollover 而言，我猜唯一可用的是GH research。但那是一个非常不同的试验设计。他们只有一个一周的盲法期。然后基本上，我认为绝大多数，如果不是所有患者，都滚入了那里。但那是一个非常 truncated 试验。
所以剂量对于 ole 是固定的。你知道，如果你滚入，你得到了12毫克，我相信。没有触发条件，比如，达到MADRS的某个分数。你知道，那个设计和剂量的理由是什么？
嗯，那是为了更好理解12毫克剂量的耐受性，特别是重复给药。我的意思是，我们知道随着Spravato，你确实会随着时间获得更好的耐受性。所以那是部分原因。那也是为了理解对疗效的影响，尽管在开放标签背景下。你知道，关于标准是一个有趣的问题。现在，Spravato是，你知道，这里的领导者，当然，很多这些的先驱。他们确实有重给药标准，那是MADRS。你知道，你基本上必须维持缓解。
在现实中，那并不完全那样工作。我的意思是，那 mostly 医生，你知道，那 mostly 医生的判断，你知道，与病人交谈并试图理解病人需要什么。那 certainly 是支付者处理方式和看待方式。并不是他们 looking for 一个特定的MADRS cutoff。所以我的一般倾向是在重给药标准上更灵活。我们将向机构询问一些这些问题，看看结果如何。我的意思是，我宁愿有 something that it's A bit more scheduled, if you will, than strictly driven by criteria, but we'll see how it goes.
患者 tend to, you'll notice this, the patients, their scores, their severity goes up when there's any question of getting a redose because they start to get anxious, whether or not they should get it, they want to redose and they don't, you know, there's a question about it. So you see this little kick at the end if there's a question about a redose. If you don't give them that option, which is what we did, you know, which is what happened in this trial, you don't get that kick.
好的。
是的，那是严重性的增加。有趣。
所以我猜当涉及到迷幻药时，一个重要的问题是治疗和长度。治疗是治疗会话的长度，你知道，所以一次旅行或会话需要多长时间？
是的。所以再次，退一步看 spravato 每标签是两小时在诊所。那是由，在那个案例中， dissociation 决定的。那是你与 ketamine 得到的主观效果。那也是由血压和其他一切驱动的。正如我们在这里与 BPL03 讨论的，迷幻或主观效果，我应该那样说，似乎在绝大多数患者中完全解决。好吧，在大多数患者中 by 90 分钟，绝大多数患者约 85% by 两小时。所以那是我们 looking for 的。我们想要基本上能够匹配那个标签。
所以那真正驱动了最初对短效迷幻药的兴趣。我们 anticipated back in the day that there would be infrastructure that JJ would set up for it. We were fortunate to be correct on that because they've done a great job. It took a lot of marketing might and a lot of capability to set that up. Again. It's great to be able to ride their coattails on this.
只是，我猜， sort of, 你知道，一个问题是，你知道，你看到，你知道，当你与你的 kols 和同事交谈时，你看到对介入性精神科的更大兴趣吗，你知道，从既定的，你知道，临床医生以及年轻的。
Ones coming in, Particularly the younger ones coming in. 对。所以它 has, 你知道，精神科在过去几个，我的意思是，过去十年左右改变了很多，因为新的介入范式变得可用。我的意思是，总是有 ect，但那很少做。然后 rtms，经颅磁刺激来了。那是第一种真正的，你知道，介入性精神科方法，静脉 ketamine 或肌肉注射 ketamine 作为一种 off label 方法肯定被许多精神科医生采用。然后当然在 2019 年，一旦 Bravado 上市，你知道，那改变了事情 pretty significantly。
所以是的，有更多兴趣 that we're in, in talking to younger docs. We're seeing that we have three through a philanthropy type thing with mgh. I mean, we've, you know, sponsored some folks, you know, fellows and things coming through. Definitely a lot more enthusiasm for it.
好的。好吧，现在回到。所以，你知道，你提到大多数患者 were, 你知道，准备在给药后约 90 分钟出院。你知道，能从运营角度谈谈这意味着什么吗，你知道，这如何影响站点吞吐量成本，你知道，支付者潜在支付者讨论。
是的。所以，你知道，基本上我们从大多数医生那里听到的是他们希望有能力每天让不止一个患者通过。对。所以有 something that's sort of in the two hour time frame, theoretically in normal workday gets you up to four patients in a day. Most docs don't really do that. It is useful to have some additional time at the end. I mean, we talked about the fact that, you know, it's a two hour paradigm. For Spravato, what that means is people are dosed after being monitored for two hours per label.
They're medically assessed at that point to decide whether or not they should go home. So even with Spravato you will get anxiety reactions that require someone to be settled down. Their blood pressure may take a little longer to come back to baseline. So you want a little bit of cushion. And so docs like that, so even if it's two or three administrations per day, certainly that was well received by the doctors. It's well received by the patients as well. It's a much shorter experience. 对。就支付者而言，你知道，那里的问题是，你知道，他们有，基本上有。
现在有代码用于报销某人陪伴患者的时间。越少越好，只要你不必一遍又一遍地做。我们通过那个 phase 2b 试验证明的是，这个短效迷幻药具有与 longer one like psilocybin 相同程度的疗效，但也有相同的持久性。所以我们不 anticipate 更频繁的重给药与短效化合物。所以我认为那是一个很大的好处，应该被支付者 beneficially 看待。
然后在 stage 研究设计和你在未来期望的方面，每次会话有多少监测员，他们的功能是什么？
是的，所以 FDA 几年前发布了迷幻药开发指南，他们规定房间里两个人， so to speak，其中一个有某种高级学位。所以他们可以是医学博士，你知道，他们可以是护士，他们可以是不同类型的治疗师。如果他们不是医学博士，必须有医学博士在场。所以另一个人可能更初级，你知道，学士学位加其他东西。这真正是由约翰霍普金斯和其他地方的旧文献规定的。
这是由 Maps, Lycos 倡导的，部分原因，有一个 long sordid history on why that came to be. Now the agency, you know, again, it's an unusual thing if you think about it. I mean, people develop. Well, they develop Spravato. Spravato is a dissociative anesthetic. You're not worried about all this stuff, you know, particularly things like assault and things. In the case of that compound, you can develop an anesthetic. And no one's worried about all these things there either. So it's a very unusual sort of phenomenon that has a long history and is driven by that.
所以在我们的案例中与 BPL 或 Beckley，他们有一个 pre ind meeting about a year prior to VLS01. Beckley did so there. They did require two people in the room. Ours, they had actually softened the criteria. So they needed someone around one, you know, as long as there was a video monitor and then one person in the room. But that could be the more junior one. So I think the FDA's position is slowly changing. There's recognition now that this is not therapy. It's not that dissimilar to what you see with Spravala. The patients are kind of doing their own thing.
It's sort of an internal experience. And you see that with all these psychedelics, whether it's psilocybin, LSD or the compounds that we're developing.
你监测患者的血压等等吗？
是的，我们做。
只是出于好奇，他们实际上是 hooked up 还是他们有可穿戴设备？
不，我们有，我们有遥测 for that. So, you know, it's an automated cuff, typically Usually you have, you know, pulse ox as well, just to make sure that you, you can track blood pressure and everything else that is not that dissimilar to ketamine clinics. Most of the ketamine clinics certainly that I visited the sites and things do just put up, you know, one of the pulse ox monitors on and a cuff. So pretty much the same thing.
所以你在 phase IIB 中使用的其他方法和协议是什么，你知道，你计划在 phase three 中使用以减轻各种形式的偏见？
是的，一个经常出现的是功能性揭盲。有一个担忧，随着迷幻化合物，你知道，每个人都会知道什么药物，无论他们得到了药物还是安慰剂，这实际上并不真实。许多人在安慰剂上，许多 being, 你知道，20, 25% 实际上会有 full robust 迷幻效果 just because of being in. 是的，它只是，它是那些事情之一。它确实发生。我的意思是，有 suggestibility, I mean suggestibility is pretty strong. And there's a percentage of people that do get the drug, even a higher dose, for example, with psilocybin, that didn't have a psychedelic effect.
所以，你知道，我认为那是一个有趣的部分。当然在神经精神科中，功能性盲法是相当常见的。我的意思是，无论是 lans. I mean, think about olanzapine, which is the antipsychotic. Give you that drug and then two weeks later you come back and you gain, you know, 14 pounds. Well, we, you know, and you're sedated. Both the patient and the doctor know what, what drug you were on in all likelihood. So but regardless, the couple of things to mitigate that are, you know, making sure the patients are naive, ideally naive, or at least have very distant history of psychedelic use.
所以在 phase 2b 的案例中是 95% 是迷幻 naive。所以那 certainly 有帮助。而且那，你知道， kind of increases the suggestibility. So, you know, you get a response with placebo, you want to get dose response. I think that's an important element. So Compass did a really great job there. They had the 10 milligram dose and they demonstrated that despite being robustly psychedelic, it didn't have very good efficacy. So it's demonstrated that some sort of, of different, you know, there was a disconnect there. So we'll do that. And then of course, durability is really critical as well.
The long duration of blinded follow up is a really critical Element. All the programs have, you know, certainly all the phase three programs have that embedded in them.
好的。而 phase IIB 是作为单药治疗进行的。你知道，我猜他们必须让患者停用他们的抗抑郁药。你知道，那背后的理由是什么？单药治疗是你目前对 phase three 的思考方式吗？
是的。所以有文献，而且 mostly 是观察性文献，表明 SSRI 的存在，当然一个非典型抗精神病药，会减少迷幻效果的幅度。而且也有文献表明迷幻效果，迷幻效果的深度和强度，与疗效相同。所以进入 phase two 试验时 certainly 有担忧 about that。而且你知道，再次，你想要它是，如果你在考虑不良事件，等等，你想要它是一个相对清晰，干净的人群。所以那真正驱动了很多这个。
目前没有双盲安慰剂对照数据 on add on therapy at this point. There's a lot of open label data that suggests that the suppression or diminution of the psychedelic effects does not seem to happen. But it's just a risk thing at this point. So a couple of companies are doing add on, like Cybin, I believe is doing, you know, adjunctive therapy. Other companies like Compass are not. So it's a bit of a mixed bag where it's one of those things that we're discussing at this point internally how we want to proceed.
你认为这个。我的意思是，它是小数据集，但你确实有。是的，你确实有一个，所谓的队列，你知道，在 SSRIs 上。所以看起来，你知道，只是 visually looking，可能有一点更多疗效。
是的，数字上 that's been the case in these open label data sets. It does look like it's increased and I think that's really intriguing. Compass, I believe, showed something very similar. There was one other data set that also suggested as much. You know, just again, it's not double blind placebo control. Then there's the adverse event thing. So it's certainly something that we're looking into and we'll explore and it's a point of discussion with the agency as well.
所以，你知道，对于 phase 2B，它在六个国家的 38 个站点进行。是的，你知道，我只是好奇知道是否有 consistency，你知道，跨所有站点和所有地理区域。
所以我们至今进行的分析更有限，但它确实显示美国和 us 之外，那是澳大利亚，英国，欧洲的几个公司国家， broadly，那两个桶是相同的。所以那 encouraging。
你在东欧吗？
不是东欧，是德国，葡萄牙和一个地方，我相信我。你必须。不要引用我哪个国家它除了德国。那个我 certain of。
好吧，所以我猜从临床角度，持久性在八周后观察到 with a single dose. 所以你对 phase three 的维持剂量是如何思考的？我知道你提到或你提供了你的想法为什么你有 phase two as is.
是的，我们仍然 kind of pondering that. I mean, somewhere between eight and 12 weeks is probably where we'll net out in terms of redosing frequency. But again, it's a discussion point. And the eight weeks is supported by the data, of course. 对。有 robust efficacy from a placebo controlled perspective, you know, that persisted from four weeks all the way out to eight. So that's where our head is at at the moment.
所以你确实有， the Open Label Phase 2A, three cohorts and now we're waiting for one more. We are cohort of data. 只是，你知道，描述不同的队列和每个的理由。
是的，所以第一个只是单药治疗，并且是 with a intermediate dose of 10 milligrams. It was single administration, just like the Phase 2B but monitoring out to 12 weeks. This was 11 patients evaluable. We basically saw pretty robust response and remission rates, roughly 50% from day two. That persisted out to the last, you know, to week 12. We had the SSRI study, the adjunctive that you had mentioned. Same thing. In this case there was a limited set of SSRI only that the SSRIs that the patient could be on showed essentially the same thing.
We then are now we're doing the two dose induction as well. So we did have some two dose induction. That data is forthcoming at this point and then looking at potentially other cohorts. But right now up in the air.
对于两个剂量，半小时 apart, 两周 apart.
所以这是，你知道，再次，诱导是一个 really interesting approach. So if you look at the label for Spravato, it does involve induction and then maintenance. Induction is eight administrations over four weeks and then maintenance is currently, you know, for the second four weeks it's once a week and then after that it's sort of as needed most. Well, many Patients get it every week and the vast majority of patients get it every week to two weeks. So that's a lot, I mean, that's just a lot of administrations. So yeah, that's kind of what we're, you know, I like the induction approach because you do get some additional benefit.
So that's something that is something that we're doing with VLSO1. Our phase 2B does have two dose induction. So we'll get some data there and then, you know, we'll have this open label data set as well. But again, not sure how we're going to proceed with how to implement this yet. In phase three, Compass did the same thing. One of their, you know, one of their phase three is currently a single dose for induction. The other one is two dose induction. So we'll see.
你如何选择两周 apart? 为什么不是一周 apart?
所以有一些担忧 about how quickly you should do that in terms of the experience itself. 你知道，我们的是一个 much shorter experience, so we probably could have pushed it to one week. But certainly in the case of psilocybin, it was like, yeah, maybe you shouldn't be doing it so close to. There were also some questions about receptor downregulation and changes such that doing it too frequently, certainly doing it day after day would be very problematic from a receptor perspective and intensity of psychedelic experience. There's some literature around that basically a little bit further apart is reasonable.
So going back to Spravato, they had a primary at four weeks, as I mentioned, two weeks. Obviously spurred splits up pretty cleanly.
好的。你知道， sort of zooming out with respect to your phase three planning. 你知道，什么 are the, 你知道，什么 are the key discussion points that you plan to have with the regulators?
是的，我的意思是，我们通常不深入很多细节 there, but I mean, I've alluded to a lot of things that we're certainly contemplating at this point. I mean, big picture, all of the phase three trials look very similar to one another. 对。所以 irrespective indication, we have mindmed with gad, we have Cybin, with mdd, we have Compass, obviously. So all these trials are pretty similar. One or two doses, six weeks ish of blinded, follow up, I mean, of primary blinded follow up out to 12 weeks and then some form of open label.
So all of that is relatively fixed. But the devil's always in the details. 你知道，the induction question, the primary endpoint, Spravato is four weeks, some of these, others have been six weeks. So just Trying to understand some of that and, and really nail that down.
而在 pipeline in a product 方面，你看到 003 除了 TRD 之外还去哪里？
是的，这是一个很好的问题。所以有一个小研究 that was done with alcohol use disorder that showed very robust effects. These compounds tend to be relatively broad based. They're impacting some network dynamics in the brain that are common across many indications. 你知道，whether it's anxiety or indeed ptsd, et cetera. There are these common networks that are disrupted at baseline, and these drugs seem to change that. So you're absolutely right. There's a lot of indications we could go for. That's something that we're still discussing right now. Our head's down on getting the phase three up and running.
We also have VLSO1. That's another place that we could. We could experiment. So we're looking at a couple different options here.
好吧，时间不多了。如果我们一年后坐在这里，你想说什么 accomplished?
我们得到了 phase 3 结果。我的意思是，我们得到了 phase 3 试验 going and, 你知道，we'll have the EMP results, the phase 2a results in hand, and then phase 2b will be, 你知道，either in hand or very shortly forthcoming. So that's what we anticipate getting through the next year.
好吧，嗯，Trinity，非常感谢你加入我们。很高兴见到你，一如既往地提供更新，并期待进展。
非常感谢，Pete。
非常感谢。