Welcome everyone to the 20-- not 22nd, 42nd J.P. Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at J.P. Morgan. I'm joined by my squad, Malcolm Kuno, LaRhea Hall, and Priyanka Grover. Our next presenting company is Sage Therapeutics, and presenting on behalf of the company, we have CEO, Barry Greene. Sorry, I was just a little flustered with that music. Yes, my bad, man. Don't be flustered, Anupam. Not great delivery. And look, Anupam, thanks for having us, and I'd like to thank the organizers of J.P. Morgan for having us here today. It's great to be back with all of you in San Francisco, and it's not raining for those of you that aren't, that aren't here. As Anupam said, I'm Barry Greene. Got that? The CEO of Sage Therapeutics, and it's really my pleasure to provide an update on the progress we're making in advancing innovative brain health medicines with deep biologic insight. I will be making forward-looking statements, and I refer you to our SEC filings for our latest risk factors. I joined Sage just over three years ago with the belief that brain health was the next frontier of innovation. To me, it felt like oncology did 20, 30 years ago, where there were drugs. They worked, but a lot needed to be done, and the belief in oncology 20, 30 years ago is that deep, with deep biologic insight, we could make a lot more progress. We surely haven't cured cancer, but we have made a lot of progress over the decade or so. When we think about the brain and the understanding of the brain, I believe we're at a part or a place right now with deep biologic understanding, we can have new therapy interventions that work in very specific ways, and we're certainly seeing that at Sage. If we think about the expansion of brain health diseases across the globe and the fact that we're in a brain health pandemic, new approaches certainly are required. At Sage, we have an opportunity to be the leaders in brain health and a top-tier biopharmaceutical company. Obviously, we're excited to herald in a whole new approach to treating postpartum depression with Zurzuvae, the first and only oral medicine specifically approved for PPD. I'm certainly going to talk about Zurzuvae and the great progress we're making there in a moment. But I also think it's important to note that Zurzuvae is a really important exemplar of the Sage product engine. Sage was founded on the belief that we could deeply examine the brain's neuronal networks, in our case, GABA and NMDA. And when these regulatory functions that are inhibitory and excitatory are operating in balance, and normally we have normal, healthy brain function, at least for many of us, maybe not all. When we see dysregulation, and that's what the Sage product engine is set out to understand. Set out to understand dysregulation in GABA and NMDA receptor systems, and then look for natural endogenous molecules that modulate these receptor systems, and then using our brain scaffolding, our chemistry scaffolding capabilities, neuroactive steroids, oxysterol chemistries, mimic these natural endogenous molecules with new chemical entities. I believe we've done that with Zulresso and zuranolone, and we certainly will demonstrate how we're doing that with other molecules like SAGE-718. And importantly, we have a strong balance sheet and financial discipline to execute on our product engine. I hope you can see here on slide 5 that we have a robust pipeline of brain health medicines really dedicated to looking at areas of big unmet need and global issues. We really need new approaches to tackle many of these diseases. Now, when I think about 2024, it's an incredibly exciting and catalyst-rich year for us at Sage. We have 4 drivers this year that I believe have an opportunity to create near, medium, and long-term value, and of course, I will talk about each of these in the presentation moving forward. Let's start with Zurzuvae, the first and only medicine, specifically oral medicine, specifically approved for postpartum depression. 2023 was a really exciting year for us as we made Zurzuvae commercially available mid-December. So we had about 10 days in 2023 where healthcare provider offices were open and patients could access Zurzuvae. And I believe that we have got very broad potential there. Our belief is that Zurzuvae is the key to unlock the blockbuster potential of PPD and offer a new treatment option to many women suffering from postpartum depression. We're certainly excited that Zurzuvae is in the market. Why do I talk about Zurzuvae being the key to unlock the PPD blockbuster potential? You know, as I mentioned, we are in a brain health pandemic, and one of the diseases impact is the greatest, in fact, is postpartum depression. The world today is that about one in eight live births results in PPD depressive, depression symptoms. Unfortunately, less than half of those are diagnosed and even less are treated. Now, outside of the humanistic and societal consequences of an untreated mom, the impact to her baby, and the downstream of potential effects to the family unit, there's also huge socioeconomic effects associated with an untreated mother with PPD. We know that PPD moms have absorbed more healthcare dollars, more hospitalizations. There was also a socioeconomic study done examining the mother-child base for five years, and it was seen that the direct cost absorbed in that family home was over $30,000. So we certainly have, obviously, the humanistic need to treat PPD as well as the economic need across the United States. Now, let's step back and actually just think about the impact that COVID has on PPD. We know that COVID exacerbated depression worldwide.... We also know that a leading indicator of a mom getting PPD symptoms in her third trimester or a month or two after giving birth is a prior history of depression. So we'll have to see, and we're hearing about this from experts in Boston, in Chicago, in Texas, and in California, so really across the United States, that this prior incidence of depression may actually change the epidemiology of PPD in the years to come. That's just something we'll have to work out for. Is that incidence of PPD actually gonna grow because of COVID and the exacerbation of depression? Something we have to watch out for. Now, we're not the only ones who believe that we've heralded in a new age of maternal mental health or looking at PPD. Many of you saw this, the amount of media attention that the approval of Zurzuvae and PPD received was extreme. Not only did we see thousands of unique press ads run, we saw Zurzuvae and PPD highlighted on Good Morning America, on CNN every morning and every night. And importantly, this was not a proactive push by us, there were 2,000,000,000 people that viewed Zurzuvae's social media. That's 2,000,000,000 people. So the excitement and enthusiasm heralding in a new approach to treating PPD certainly is out there. I actually think it's going to continue. Now, the media got many things right. This media attention, number one, helps to destigmatize PPD, and what the media said is that PPD is a medical condition and not a moral failing. Think about that. It's not. It's a medical condition and not a moral failing. That's hugely important as we're trying to reach patients, patient advocates, and healthcare providers. The other thing the media highlighted is the rapid onset of Zurzuvae. The fact that many moms reported that they felt relief of the depressive symptoms as early as day three, and they were able to return back to their family and to their babies, giving babies the nurturing they need for healthy growth. That's hugely important to our society. And then finally, it allows patients and healthcare providers to think, "Hey, if I've got a darkened mood in my third trimester after pregnancy, added anxiety, I can't sleep, there's a medical condition, it's PPD, it's biologically driven, and there's a new treatment option." And to that end, as I mentioned, Zurzuvae, our GABA PAM, is available on the market. The features of Zurzuvae have really had significant engagement in the marketplace. What we see with Zurzuvae is it's an oral pill, taken every night with a meal for 14 days. As I mentioned in the clinical trials and reported by the media, mothers report relief of depressive symptoms as early as day 3 and the ability to return to family and child. It's a unique mechanism of action, unlike anything out there, and the product insert has important safety information. So really a monumental time for women suffering from postpartum depression, and we're excited to be driving Zurzuvae forward. Now, our commercialization strategy and launch goals here are pretty clear. We want to establish Zurzuvae as the first-line therapy for women suffering from PPD. What does that mean? That means that if a woman is appropriately screened and diagnosed, we want Zurzuvae being the first drug a healthcare provider reaches for to treat that woman. Should that prescription be written, we want that prescription sent to the mother's home as quickly as possible, without major steps and without any out-of-pocket expenses or as little out-of-pocket expenses as possible. How do we make that happen? Well, first, it comes down to significant medical education for patient, patient advocates, to healthcare providers. We're doing that through a broad omni-channel approach, using our digital tools to provide information to healthcare providers when and where they, they want it. Of course, our live field force, both, both we and Biogen's field force, are out there. In our case, of course, we've had significant experience with PPD, and I can tell you that the engagement is palpable. At a couple of the medical meetings at the end of last year, namely NEI and ACNP, which I attended, Zurzuvae was heralded in as a new approach to treating PPD. It was talked about from the stage, and I know many of us that were at these conferences received a lot of congratulations for bringing a new drug like Zurzuvae to market. So the engagement's significant. I can tell you that today, we're seeing patients stepping up, and we're also seeing prescriptions coming in, not only from psychiatry, which we expected, but also from OBGYN and from primary care. That's with 10 days in the market last year. So I'd say we're off to a really strong start. Importantly, the Zurzuvae for You program is up and running. That's our patient assistance program, where our idea is to drive out-of-pocket expenses down to zero, if possible. The specialty distribution network is up and running and delivering Zurzuvae packets directly to moms' home. Importantly, medical guidelines, clinical guidelines already exist. The ACOG guidelines were established actually before Zurzuvae was made commercially available, highlighting the need for OBGYNs to screen and diagnose PPD, and it points specifically to Zurzuvae as a treatment option. For those of you that have launched new medicines, that's incredibly rare. It can take a year or two or longer for medical guidelines to be updated to point to a new disease or a disease protocol, as well as a treatment protocol. Then importantly, as I mentioned upfront, the media attention and the attention to Zurzuvae will continue, and that helps to destigmatize. Now, we appreciate that access is key to unlocking Zurzuvae, and to that extent, the discussions we're having with payers, commercial, national, local payers, government payers, is going incredibly well. I'll characterize those discussions as going well. PPD is understood as a medical condition. The profile of Zurzuvae is seen as highly attractive. In general, the payers agree that step edits make sense. There's nothing else specifically approved that's oral for postpartum depression. And where they might use some utilization management is physician attestation to make sure that the person that's getting Zurzuvae is diagnosed with PPD and not some other medical condition. Of course, we want that, we want that, too. So we're off to a really strong start. The tailwinds are behind us, and I look forward to giving you more specific updates about the launch trajectory of Zurzuvae on our quarterly calls. Let me now turn to our second value driver, SAGE-718, or dalzanemdor. Bring out your inner Harry Potter on the generic name there. We are excited to have 5 programs up, clinical studies up and running this year with 4 top-line data readouts. What's really exciting about dalzanemdor really is the biologic hypothesis that underlines the invention of SAGE-718. And that is that we, in doing the work on NMDA, understood that a specific metabolite, 24S-hydroxycholesterol, regulated the NMDA pathway and was also associate-- its dysregulation was associated with cognitive impairment in neurodegenerative diseases, in our case, specifically Huntington's. So SAGE-718 is actually mimicking the function of a natural endogenous molecule to upregulate cognition. We're really excited by the program and the data to date. Now, we know that neurodegenerative diseases are growing worldwide. Huntington's, of course, remains a rare and orphan disease. Parkinson's is in the millions, and Alzheimer's disease is really set to overwhelm the healthcare system if new medical interventions. Cognitive impairment's a leading cause of disability and costs the U.S. economy over $100,000,000,000 a year. So clearly, the opportunity to maintain independence in these patients is critically important. Now, when I talk about cognition, I'm talking about the higher-order areas of the brain, things like executive function, learning, and memory. Just to give you example, these are the brain regions that allow us to do everyday tasks, like make a shopping list, drive to the store, find the items on our list, drive home, put them away, and remember where I put them. I mean, if you're like me, I forget one or two things, but generally, we can do that on a regular basis. Those suffering from cognitive impairment can't do tasks like that on a regular basis. That's what we're looking to change, provide improvement in cognitive ability in a short period of time. Now, before I turn to the data that is rolling out this year, I mentioned four clinical readouts, let me share some data generated early in the program. What we've done here is used important higher-order cognitive tests like the two-back test and the Digit Symbol Substitution Test. These are tests that measure higher-order cognition. What you can see on the left here in our challenge study is that subjects that received placebo had cognitive deficits. Those that received SAGE-718 had cognitive improvement above their baseline. While the Huntington's, Parkinson's, and Alzheimer's studies are probe studies and not the gold standard placebo-controlled studies that we're gonna unveil this year, what's encouraging about these data are the consistency between disease states and the consistency with our placebo-controlled study. So it gives us encouragement as we think about the data that we'll unveil this year. So when we think about the clinical program, we have a robust clinical program for dalzanemdor, with Huntington's, Parkinson's, and Alzheimer's studies. I'll provide some more context to these studies going forward. The way we've thought about the Alzheimer's and Parkinson's study are phase II placebo-controlled studies that give us important insight in how the drug works, what domains it works in, so that we can work with regulators to design the right phase III studies. The Huntington's program is put together with DIMENSION, SURVEYOR, and PURVIEW so that if the data here in Huntington's are positive—and data matter here—we believe we've designed the Huntington's program in a way that allows us to sit down with regulators and understand a novel path forward and maybe pave a new regulatory path for Huntington's. If you think about it, nothing exists in cognition for Huntington's disease. We're excited today to talk about the timing of our data readouts. Early this year, we'll have the PRECEDENT readout in Parkinson's disease. Midyear, we'll have the SURVEYOR readout in Huntington's. In late 2024, we'll have the LIGHTWAVE readout in Alzheimer's and the DIMENSION readout in Huntington's. I talked about the phase II for Parkinson's and Alzheimer's, but let me provide some more context on the Huntington's study. The DIMENSION study is a 178-patient study measuring HD-CAB, a composite endpoint, as its primary endpoint at three months. So a very robust study for an orphan disease. It's designed and powered to show a statistically significant difference between drug and placebo. We're talking about cognitive improvement here, so even small differences here matter a lot for these patients. The SURVEYOR study, I call it a companion study, is really designed to help validate the endpoint of HD-CAB and look at its components and how that relates to activities of daily living. It's not sized or designed to show statistical significance, but rather helpful in validating the endpoint of HD-CAB. So stay tuned. We're really excited to have these data roll out this year, and if positive, we're one step closer with dalzanemdor to helping patients suffering from cognitive impairment. Let me now turn to the third value driver of SAGE-324, and we're gonna have top-line readout mid-2024. So SAGE-324 is our designed for chronic administration to help with movement disorders, starting with essential tremor. Essential tremor has suffered from innovation. There hasn't been anything new in essential tremor for over 50 years. We hope to change that. Now, when we talk about essential tremor, because of the paucity of innovation, the nearly 7,000,000 adults suffering from essential tremor are often not diagnosed or treated. Only about 10%-15% are diagnosed and treated. Not unlike cognition, the issues that people suffer with essential tremor are challenged with activity of daily living. People with essential tremor can't button their shirts, or more broadly, can't dress themselves. Many can't put a spoon to their mouth, so more broadly, can't feed themselves. And, of course, they have trouble working on their devices, making phone calls with their smartphones or even texting. And in today's society, not being able to connect like that is truly devastating for these patients. And the cost of the healthcare system here is also very high. It's about $100,000,000,000 in direct cost to the U.S. economy. Now, we also have a very robust program for SAGE-324, with a KINETIC 2 readout mid-year. Well, let me remind you that what we were looking at in KINETIC, using a 60 mg dose of SAGE-324, was at a daily dosing for 28 days, given in the morning. What we saw at the end of KINETIC is at 28 days, we saw a statistically significant reduction in tremor amplitude, and that was associated with an improvement, statistically significant, in activities of daily living. What we're looking to do with KINETIC 2 is find a chronic dose that we can treat every day. KINETIC 2 is given in the evenings, not the morning, and we're doing a dose escalation study. We're looking at 15, 30, and then dosing up to 60 milligrams, with the idea that, of course, we want to see at the end of 3 months, reduction in tremor amplitude and improvement in activity of daily living. But importantly, we want to find a dose that's appropriate for chronic administration so that we can design our phase 3 studies. Of course, we have a rollover study for these patients as well to build longer-term safety and a bigger end. Let me now wrap up with the early-stage pipeline. I want to highlight SAGE-319 and SAGE-421, really to help demonstrate that we have a product platform that allows us to bring new molecules with differentiated pharmacologic properties forward. SAGE-319 is our extrasynaptic preferring GABA PAM that we're looking at for neurodevelopmental diseases, and SAGE-421, an NMDA PAM for things like schizophrenia. Hopefully, I've been able to share the exciting year ahead of us with multiple catalysts, with the launch of Zurzuvae, the readouts across dalzanemdor, and SAGE-324, and the progression of our earlier stage program. Our mission at Sage has not changed. We are here to pioneer solutions to deliver life-changing brain health medicine so every person can thrive. I understand that these challenges are significant. These are big, hard-to-tackle diseases, but at Sage and our collaborators, we're up for it, and I and all of us at Sage are excited to tackle these challenges. After all, patients are waiting. Thank you. Can I welcome up a few people on stage? We have Chris Benecchi, our Chief Business Officer, also responsible for commercial. Kimi Iguchi, our Chief Financial Officer. Mike Quirk, our Chief Scientific Officer. And unfortunately, Laura Gault, our Chief Medical Officer, was given the gift of COVID and couldn't join us over the holidays. Many of you heard me say this at other sessions, but there are three ways to ask a question, yeah? So there is the old school way: raise your hand, I'll call on you. There's, like, the new school way, which is you use the portal and type your question in, and it'll come up on this iPad, and I'll ask it anonymously. Or, I guess there's an intermediate strategy that you can just email me, and I'll ask you, I'll ask your question. But I will start with the questions of: Barry, can you clarify your comments around coverage and access of Zurzuvae, in particular step edits, and you mentioned prior auths, like, walk us through that dynamic. Yeah, let me start, and then I'll have Chris, and you'll need to use the microphone when you get to it. So we're having earnest discussion with payers at this point. Just what I said in my prepared remarks is that the discussions are going well. The payers understand that PPD is a medical condition. They appreciate the profile. They think that our Wholesale Acquisition Cost is value-based, and in general, they don't think steps are appropriate. And where prior auths may be used is to ensure that the prescription that's written is for someone with PPD and not some other disorder. And we want that too. Chris, you wanna talk more about how you think the payer discussions will roll out this year and sort of timing? Yeah. So the payer discussions, in truth, have already begun, right? We've been talking to payers for the better part of the last couple of years, you know, really reinforcing the unmet need in the marketplace. Talking more specifically about the data that we've demonstrated in terms of ROBIN and SKYLARK and what we showed with Zurzuvae. And finally, you know, we've been able to talk about, now that the medication is approved, what the value proposition is for Zurzuvae with respect to the label that we have. So those conversations have gone well. You know, we find that payers are aligned around the unmet need and the potential to help women with PPD with a medication like Zurzuvae. As we've, you know, in fact, introduced the Wholesale Acquisition Cost of Zurzuvae, what we've heard from payers is that they really believe in all of the discussions that we've had based on the Wholesale Acquisition Cost and the unmet need, that, you know, we have an opportunity here to make this medication available without the onerous prior authorizations and complex step edits that often go along with new medications. So we're really encouraged with the early discussions that we're having with payers and what it means for the first-line access for Zurzuvae as we go forward. ... And maybe you can comment on what the impact of guidelines will have on the uptake of Zurzuvae and PPD? Yeah, I'll start, and then I'll ask Chris to comment further. So, you know, for those of you that have launched sort of a new indication, a new drug, it can take years for the congresses to update guidelines and then appoint a specific drug. I highlighted this. Before Zurzuvae was medically available, ACOG had already updated their guidelines to ask the OBGYNs to screen and diagnose for postpartum depression, something that hadn't all necessarily been done, and specifically point to Zurzuvae as a new treatment option for PPD. That's really rare and very important. And as physicians think about following clinical guidance of their congresses, it's a really important lever. I think, you know, Chris, might you want to kind of comment on how that could impact other congresses and other societies as well? Yeah, certainly the ACOG guidelines are, you know, in effect, demonstrating the ability to improve screening and diagnosis, as well as point to treatment for women that are living with PPD. I think that as the first guidelines or first clinical practice guidelines, they're instructive for other organizations that are out there, perhaps like the APA and other organizations, as they think about the role that guidelines can play in really directing their clinicians around how to think about screening, diagnosing, and treating women with PPD. So we'll continue to do the work with those different healthcare or physician organizations to make sure that as conversations come up in and around guidelines moving forward, that, you know, they have the information that they need and that we're supportive of those as we move forward. And, just to put a fine point on it, you know, one of the things that people worried about with PP, not us, but others, is the question of, you know, OB-GYNs are there to deliver the healthy baby, ensure that that's okay. Will they, in fact, engage with mom and diagnose and treat? ACOG is suggesting they need to do that, and now with Zurzuvae, and we're actually seeing prescriptions, they are engaging to care for mom. They're not doing what they did historically, and again, we're at the very start here, which is refer them back to psychiatry or to primary care. And as I said, 500,000 a year right now, epidemiologically, have symptoms of PPD. Less than half of those are diagnosed, even less than half of those are treated. These guidelines and all of our other efforts are aimed to change that. Maybe you can expand on those other efforts, right, beyond guidelines to increase that diagnosis. Yeah. Chris, you wanna take that? Yeah. So, Barry, I think you said in your talk that, Zurzuvae is the key to unlocking blockbuster potential in PPD. And while certainly there's a lot that we can do around, talking about Zurzuvae, having a medication that's available, that's the first oral approved or indicated for the treatment of PPD, will have an impact on diagnosis. But there are so many other things that we can do to actually, you know, make sure that screening and diagnosis occurs. And certainly, with respect to internal initiatives as an organization, we're active and engaged with our field force with respect to the work that they're doing in educating clinicians around the importance of screening and diagnosis, as well as, making therapies, you know, making a therapy like Zurzuvae available to, to women with PPD. Externally, we are actively engaged with stakeholders across the ecosystem, whether they are, physician organizations or physicians, patient organizations, or even policymakers, to really make sure that collectively, we are driving a movement forward that focuses on the importance of screening and diagnosing for these women with PPD. You know, the ACOG guidelines is a really good example of the need to collaborate across the ecosystem with other stakeholder partners that are out there. We'll continue to do things like working with the media to make sure educational initiatives take place, highlighting the need to diagnose and screen, as we move forward, as well as working with patient communities that are talking about these issues online. There really are a number of things that we can do as a partner across the stakeholders that we, that we work with to increase diagnosis. Right. And, you know, not necessarily driven by Sage or Biogen, but I mentioned this earlier, at a couple of the congresses late last year, NEI and ACNP, there was tremendous enthusiasm for a new approach to PPD. Stage presentations, plenary sessions that we weren't sure were gonna happen, but happened, that weren't really driven by us. So the community themselves is picking this up and running it, 'cause they really haven't had anything like this for PPD in a long time. And you talked about unlocking the blockbuster potential, though there are still people on the street that view PPD as more of a niche opportunity. What levers do you think those folks are missing in particular? Well, yeah, let me step back, and I’ve had the great pleasure of launching novel medicines in indications where there wasn’t a market. When you’re looking in your rearview mirror, you say there’s no market there, therefore, there’s no market, therefore, it’s niche. When you’re looking forward proactively, just think about the numbers. There’s 500,000 women a year suffering from PPD. So if we can increase diagnosis rates, increase driving moms to treatment, the market here is a significant opportunity, and more importantly, it’s an opportunity to society in a society, help women suffering from PPD, which has been ignored historically. So we have to change that whole dynamic. Questions from the audience? What are some of the launch metrics that we're gonna be tracking or, or being provided on a quarterly basis to just kind of understand the health of the launch? Yeah, look, we look forward to providing updates on our quarterly calls about how Zurzuvae is going and giving you as much color as possible. Kimi, you wanna?... Take that? Yeah. Thanks, Barry. So we are working with Biogen and still aligning on exactly what that would look like. But we're what we're thinking about right now to really provide more color beyond revenue, which, of course, matters, it are metrics like prescriptions, number of shipments, color on what HCPs are writing, what is the breadth there? And also, you know, the progress that we're making with payers. So we think that those are really important metrics to be looking at early in the launch, in addition to looking at revenue. One other note that I'll make is that IQVIA and Symphony are tracking the shipment data. I'll say that it looks directionally correct, but it's not precise. There are some variability because of things like free goods that might not be captured or, specialty pharmacies that we have contracted with that aren't in their database as well. So, it's directionally correct, but they will be tracking that data. Yeah, and just, Anupam, to kinda loop back to the niche versus big potential, one of the niche theses is that OB-GYNs aren't gonna diagnose and aren't gonna write. So in our quarterly updates, let's see if that's the case or our case is we actually think they're gonna engage in a big way. We talked a lot about SAGE-718, but just only briefly touched on SAGE-324. Sort of given the difficulty in developing in essential tremor, what has given you some confidence in KINETIC 2? Yeah. So, SAGE-324 is our GABA PAM designed for chronic administration and movement disorders. As I mentioned, we're, you know, we're starting in essential tremor. Essential tremor is at a paucity of innovation, so it isn't diagnosed or treated as it needs to be. And again, we hope to change that. What we saw with KINETIC was we saw at a 60-milligram dose, we saw significant, clinically meaningful and statistically significant change in tremor amplitude that was associated with activities of daily living in a stat sig way. So really important. What gives us confidence in KINETIC 2 is that out at 3 months, we wanna see that same kind of beneficial impact, improvement in tremor amplitude, as well as activities of daily living, and then make sure that we have a dose suitable for chronic administration. I'll ask Mike to comment, but this is not the only kind of GABA approach we've used, and we've seen evidence before. Yeah. Yeah, thanks, Barry, and, and that's exactly right. When you look at essential tremor in the context of the GABA receptor mechanism, this is an area that we've invested in pretty much since the earliest days of Sage, where we've seen consistent evidence across early probe trials with brexanolone. We saw evidence of tremor reduction with some probe trial studies that we ran with zuranolone, and then continuing to see with SAGE-324. And I think the key element of that is that because we have sufficient data with the GABA receptor mechanism, we're really starting to understand the pharmacokinetic, pharmacodynamic elements that drive sort of the efficacy signal. And that really allows us to design purposely what a chronic medication such as SAGE-324's profile should look like, and has led us to the design of the KINETIC 2. We're really testing that hypothesis with the multiple doses, as well as the nighttime dosing that Barry mentioned in his presentation. Yeah, well, and to be clear, what success looks like is the kind of efficacy at three months that we talked about, and enough, enough evidence that we have a go-forward dose to then work with regulators to design the Phase III studies. Questions from the audience? Not everybody at once. Maybe last question from me then. Just on your cash position, what is assumed in terms of next steps for 718 and 342? 324. 324. That's okay. Kim, you wanna take that? Sure, sure. We have a strong financial foundation right now. At the end of the third quarter of last year, we had $875,000,000 in the bank, so in a good position there. We said that our cash plus our revenue and milestones would support our operations into 2026. I'm happy to say that we earned our $75,000,000 dollar milestone from Biogen for the first commercial sale of Zurzuvae, and we should expect that money in the first quarter of 2024, so we're excited about that. So we have a strong balance sheet to get us through 2024 and the exciting catalyst that we have ahead and also the progress in the launch of Zurzuvae. We feel very confident in the balance sheet where we stand today. Okay. Thank you, Barry and team. Thanks, Anupam. Thanks, everybody. Thank you.