Good afternoon, everyone. Thank you for joining our Piper Sandler Healthcare Conference. Excited to have the team from Sage Therapeutics here with us. Lots to cover in the next 25 minutes, but would love to just get started on sort of the every time I feel like every time I say the not name. Zurzuvae. Zurzuvae, yes. Yes. Walk us through, as obviously the product, is it on track to get launched in December, which is tomorrow? So give us an idea- Yeah. What will be happening tomorrow? Yeah. No, a very exciting time, obviously. Yeah. It used to be weeks away. Yeah. Now it's days away. Yeah. So, you know, we are on track to have ZURZUVAE commercially available- Yeah in December, and then the broader commercialization- Yeah Efforts will take place early next year. Okay. Yep. Maybe could you walk through what has been done to get the product ready in the right distribution channels for this month? So what has been completed, so far, and what are some of the activities that are gonna really kick off further in the first quarter of next year? Well, I'll... Why don't I start and then I'll, I'll turn it over to Chris. But just from, the distribution model, right? Mm-hmm. The most important thing here is to make sure that- Mm-hmm It's easy and available for moms, right? Yeah. They have a lot going on, so we- Mm-hmm wanna make sure that we make this as easy as possible. So we're really looking at a specialty pa- Mm-hmm -specialty, distributor to, specialty pharmacy- Mm-hmm -to patient model- Yeah which we think will be faster Yeah -and easier for patients. And, so I'll let Chris walk through a little bit more- Mm-hmm of the thinking that we have there. Yeah. So, as Kimi said, SP to patient is the way that we're thinking about- Mm-hmm distribution here. Really, this is designed to make sure that- Mm-hmm as rapidly as possible, that the medication can get prescribed, and it can move from the SP into the hands of the patient as we move forward. What we have said is that, historically, we wanna make sure that this medication- Yeah is not only accessible, but it's also affordable. Yeah. Being able to deliver this through a specialty distribution model enables us to provide really strong patient- Yeah -support services- Mm-hmm -as well as financial assistance. So no patient, regardless of their- Yeah ability to pay, insurance coverage, can actually get the medication and do so affordably. Oh, wow! Okay. So, like, there is that accessibility that you... And how is-how long will that channel be open to? As long as pretty much any, you work with them, you get them as quickly on the product, and that will be available for, I guess, given that the price of the cost and it's a one-time product, how many patients do you hope to have the channel eligible for or available for? Yeah. So this is our distribution model from now into the future, right? Okay. This is the most effective way that we have to get the medication rapidly- Yeah into the hand of the patients, to do the benefits investigation. Yeah to do the financial assistance programming. So again- Yeah Patients can actually get it in, and get it effectively and rapidly. For patients that are commercially insured, what is the prior authorization protocol for them? Do they just have to have a diagnosis of postpartum depression to be eligible, or what are the things that they have to have a checklist before they can get accessibility? Yeah. So, we're squarely amidst conversations- Yeah with payers right now at a national and regional level. Yeah as well as government payers Yeah because that's an important part of this Yeah as well, too. You know, in terms of the way that we think about Mm-hmm the medication, to be truly transformational, you have to be accessible, and you have to be affordable. Mm-hmm to the broad range of patients, as I noted. So conversations with payers right now Mm-hmm around, you know, access and affordability and prior authorizations- Mm-hmm and how they think about where they'll position this medication on the formulary Yeah -are critical. With respect to prior authorizations- Mm-hmm Given that we're in these conversations. Mm-hmm We don't anticipate, you know, very complex Yeah prior authorizations. You know, this being a woman with PPD. Yeah -and, in effect, that kind of PA- Yeah Is something that we would anticipate. We also don't anticipate step edits. Yeah. But again, a lot of this work is being done right now. Okay. So, how soon could you come back to us and kind of communicate that you had the discussion with payers, and now the requirements are X, Y, Z? Is that something that you just foresee as part of your disclosures, as you're gonna, we're gonna be tracking the launch? Yeah. So the way the cadence will work- Mm-hmm from a payer perspective, as we anticipate it Mm-hmm is that coverage will emerge in the first and second quarter of the year with respect to commercial payers. Okay. That's, that's virtually a function of some payers have a P&T on a- Yeah -monthly basis. Some do it quarterly. Yeah. It's about hitting the right cadence. Yeah. I think the Medicaid plans themselves- Mm-hmm will be more, and that's fee-for-service. Mm-hmm managed Medicaid, more in the middle of the year, in line with how Medicaid thinks about Mm-hmm the review of new medications. So again, Q3 and Q4- Okay for those as we go forward. So that's really how we think about the cadence of it. How do you imagine sort of the coverage to be sort of as these steps fall into place? Like, I don't know if you can assign like a numerical value of, like, coverage. We hope to be at X percent by first half and X percent into the second half. Is there a way to think about or in broad strokes, other than visualizing that it's gonna go up quarter over quarter, but what that looks like, the ramp, obviously slower in the first half, but very quite fast? Yeah. I mean, we haven't communicated- Okay an exact number, but as I said, the cadence looks like Yeah commercial in Q1 and Q2 Yeah -Medicaid in Q3 and into Q4. Yeah. What we can say is that given the clinical and economic value- Mm-hmm that ZURZUVAE delivers Yeah Right, to patients. Yeah and the new type of treatment that it is for physicians and the profound unmet need. Mm-hmm in this space and our desire to make sure that it's accessible and Yeah And affordable at the same time, you know, we anticipate that the uptake of this medication will be, will be strong, right? Yeah. No, that's, that's great. Could you maybe help us understand what percentage of women with postpartum depression fall under commercial pay versus Medicare? Like, what, what has your research concluded so far? ... Yeah, so as we look at the- Yeah the data, about 55% of the women- Mm-hmm - with PPD are commercially insured, and the remaining 45%- Mm-hmm are Medicaid patients. And again, we prioritize both of those groups- Mm-hmm because no woman should be unable to access this medication. Yeah. As we've said, we want to make sure that the medication is both accessible and affordable. Mm-hmm. Affordability means that for the vast majority of patients- Mm-hmm - In the way that we think about it, it's low to no copay- Right in terms of patient out-of-pocket. Just could you maybe talk about how you're foreseeing the reimbursement in the Medicare settings in going into 2024? Yeah. Yeah. I think given this population, it's limited around Medicare. Yeah. You know, because we don't have an aging population. Yeah. We have a woman of childbearing age. Yeah. In large part, it'll be commercially insured and Medicaid. Okay. Medicaid... Sorry, Medicaid, that's helpful. I guess the question also that comes up is, I mean, I have, as a mom to a 15-month-old, soon to be 16 months old, I actually have quite a bit of friends that are new moms, and they were actually telling me about your product, and I was bragging that—I cover you, and I know a lot about your product. So that was really the first time I've ever experienced discussing a company of mine with, in a social setting with, so Melissa. So that was very exciting. So I was really impressed how there is... And maybe you can talk about how you've already started your social media outreach, because they had already literally seen multiple of them, and already through, you know, Instagram and, you know, and social media, really already product awareness, which I was actually caught me very much by surprise. So could you talk about these activities that has occurred, are occurring, continuing to gear up? Like, and I live in a small town in Connecticut, so. Yeah. I mean, as an organization, as you might imagine- Yeah We are so incredibly proud. Yes of the traction Right that this story got Yeah in the mainstream media Yeah and online. And I think what it does is it really reflects the important work that we're doing. Mm-hmm and the impact that we have. Mm-hmm you know, the potential impact that we have- Mm-hmm - with ZURZUVAE as we move forward. Yeah. When it comes to what we've done and what we'll continue to do is, is we have an excellent communications- Mm-hmm team that is really plugged in to the Mm-hmm various media outlets. Yeah media sources that are out there. In some senses, it's being prepared to react. Mm-hmm. In others, it's finding opportunities- Yeah to communicate the story as we go forward. Mm-hmm. In the grand scheme of things, I think there's an opportunity for us as an organization- Mm-hmm to really lead the way in elevating the ability to diagnose and treat PPD- Mm-hmm in such a meaningful way that- Mm-hmm I think we can make a profound difference. Thank you. And just to add to that, there are so many tailwinds- Mm-hmm - With regards to the launch of ZURZUVAE, some of which Chris just alluded to. Mm-hmm. But there's also things like policy- Yeah That's happening at the state level on maternal mental health. Mm-hmm. There's, you know, all the media that we've seen, there's advocacy that's- Mm-hmm That's making a lot of are interested in talking more about it. Mm-hmm. So there's a lot of HCPs are very interested- Mm-hmm In talking about it. So there's a lot of tailwinds across the board with postpartum depression. That's great. And team, could you maybe also talk about what is currently Biogen's commitment been to really helping you and lift this commercial footprint and work on it so you could? Yeah. Yeah, absolutely. Yeah, we, we have a very strong- Mm-hmm relationship with, with Biogen. I think that really comes from the deep, relationships across the organization, up and down, and sideways. Mm-hmm. So, that's really how we get things done. Even though there's a formal governance structure- Yeah Of course, that exists. I think a lot has to do with the relationships- Mm-hmm - that we have in place, that it really make it, make it work. With regards to the split, you know- Yeah This is a 50/50. Yeah. All the decisions and the strategy- Yeah and even the efforts themselves. Mm-hmm. So, the field force and, you know, the marketing efforts- Mm-hmm - Those are all 50/50. There might be one area or another that one party takes the lead- Mm-hmm versus the other because it's more efficient that way. But for the most part- Mm-hmm It's a 50/50 split. That's great. Team, could you maybe talk about how many OB-GYNs, like, NCPs and psych docs you're hoping to target? What is gonna be the breakdown, and how are you gonna quantify them sort of as you think about various geographies? Yeah, so we haven't communicated the exact number of targets, but- Mm-hmm but what I can say is, overall, when you look at the totality- Yeah - of the community, there's about 35,000 to 40,000 OB-GYNs. There's about 60,000- Mm-hmm or so psychiatrists that are out there. We've also mentioned in the past that some primary care physicians will be- Mm-hmm a part of the way that we think about- Mm-hmm engaging from a sales force perspective as we move forward. Obviously, you can't target every one of those- Yeah with a sales representative. Right. Yeah. But in effect, we have a very well thought out and prepared omni-channel strategy- Mm-hmm inclusive of digital efforts, that will broaden our reach and deepen- Mm-hmm our frequency beyond what our sales representatives are gonna be able to do. Again, we are living in and amongst a maternal mental health pandemic, and there's an opportunity for us- Mm-hmm by virtue of the breadth of everything that we do Mm-hmm - to communicate the importance of- Yeah diagnosing and treating, to reach a broad number of patients through the physicians that I talked about. That's very helpful. And Kimi, what metrics do you plan on providing on the launch? You know, as we obviously know, with a large number of panels covering you, like, how do you visualize- Yeah sort of the next, the cadence? Yeah. Yeah. So with the launch of ZURZUVAE, we'll certainly be talking about it at our- Mm-hmm - earnings calls, that are coming up. And so certainly, we'll be talking about things like revenue- Yeah - and number of women on drug- Mm-hmm - or prescriptions. So those are the kinds of metrics we'll be talking about. Mm-hmm. The specifics, we're working out. Mm-hmm. That's helpful. Would love to also spend time. Just one quick question before we talk about the pipeline is, this is, MDD, like, have you had a chance to engage with the agencies? What is your update there in regards to the path forward? Yeah, you know, the guidance we're giving there is really that our focus right now- Mm-hmm. -is on the launch of ZURZUVAE. Yeah. In postpartum depression. Mm-hmm. Okay, so with women in postpartum depression. So we're putting all our focus there, Biogen is as well. So you know, that, that's- Yeah really our goal. We're doing additional work on MDD, but when we can give you an update, we will. Mm-hmm. But really, I think that the plan should be, or the- Mm-hmm Investment thesis here is really about a postpartum depression drug with ZURZUVAE. Okay. Then, team, given that we're going to 2024, like, what are some of the key catalysts that could be really important for the pipelines? If you want to just kinda highlight them in chronological order, and we'll go through. Sure. each of them. Sure, happy to. So we have two other- Mm-hmm two other programs in clinical development right now. Mm-hmm -that we're focused on. That's SAGE-324 and SAGE-718. Mm-hmm. And we can talk about them- Yeah -specifically. And those two programs, across the two programs- Mm-hmm We have five clinical readouts that we're looking for in 2024. Mm-hmm. With SAGE-324, we have an essential tremor phase 2 readout- Mm-hmm -in KINETIC 2 that we're expecting mid, middle of next year. And then with SAGE-718, we have four clinical trials- Mm-hmm looking at cognitive impairment across three distinct patient populations Mm-hmm -Huntington's disease, Parkinson's disease, and Alzheimer's disease. Mm-hmm. All four of those studies are planned to read out in 2024. Mm-hmm. We haven't given specific details on the timing of those- Mm-hmm -right now, but we would be looking to get more granular on the timing. Mm-hmm as we get into early next year. Okay, very helpful. I think let's maybe spend some time on the KINETIC study, which is, you know, expected in 2024. I think the investor community has become a little bit far more familiar with, you know, Essential Tremor than maybe over the last few months and maybe this year. So I guess the question that everybody else has for us is: what do you want to see in the study, right? What is the data that could forward you or propel you to really move into a pivotal study? I'm happy to take that one. Yeah. So, just as a reminder, so SAGE-324, it is a GABA receptor- Mm-hmm -positive allosteric modulator, also partnered with Biogen. Mm-hmm. The study we're running right now is the KINETIC 2 Study. So this is in moderate to severe patients with essential tremor, and it's the follow-up- Mm-hmm -to the KINETIC-1 study. Mm-hmm. So just taking a step back, the KINETIC-1 study was our original placebo-controlled study. Mm-hmm Looking at a 60 milligram dose. Mm-hmm. Where the goal of that study was really to say: Do we see evidence for efficacy? Yeah. Or signals of efficacy, using both objective measures, such as tremor amplitude- Mm-hmm —as well as exploratory measures around Activities of Daily Living. Mm-hmm. We saw significant signals- Mm-hmm -in that study, where we dosed for 28 days. Kinetic 2 was really designed around now, having understand that there is evidence- Mm-hmm of signals in that study, can we better understand the dosing that would be the b- Mm-hmm Most appropriate to take forward into phase 3? So in KINETIC 2, we're running three different doses. Mm-hmm. We have a 15 milligram dose, a 30 milligram dose- Mm-hmm -as well as a 60 milligram dose- Mm-hmm. -but we're titrating up to the 60 milligram dose- Okay -as opposed to, giving it all at once- Mm-hmm in the first day of dosing. There, we're also dosing for longer- Mm-hmm -than 28 days. The objective is to say, having seen signals- Mm-hmm Where do we get the best dose ranging from a benefit? Mm-hmm risk, where we continue to see the types of efficacy signals- Mm-hmm -we expect to see, as well as making sure that we understand the tolerability profile. The hopes are that with robust data- Mm-hmm coming out of that study, we'd be in a better position with Biogen to design what the phase three- Mm-hmm program would look like. Okay. So is your... In your thought process, you know, like, when... Another way to ask is when you, when you ask physicians and there's a really high unmet need, what are considered clinically meaningful differences in these measures? What do they articulate, and is that the type of change you would- Yeah at a minimum, want to see to warrant Exactly right. I mean, I think it is a matter not just of changing an amplitude- Yeah But are you seeing some impacts on activities that are meaningful? Yeah -to patients? And those are the types of signals that- Mm-hmm we would be looking for. And, and clearly, we want to be as good or better than the standard of care, where admittedly Yeah There's been no innovation for Yeah -decades, almost 50 years, since the last approved product. Okay. And could you remind us, I don't know if you guys talked about the powering of the primary endpoint and what you wanted to see? If you could remind us of that? Um- Not in there- Not, not, not, not- But do you want to talk about the endpoint? Yeah. I mean, we're, again, we're looking at both the objectives- Yeah as well as Activities of Daily Living Okay as the next different measures. Okay, perfect. So, your thought process, you report the data. At that junction, you and your collaborator will probably engage with the agency and come back to us in terms of the design and pivotal program. Yep. For the second program that you highlighted, too, right? The DIMENSION, the SURVEYOR, the PRECEDENT, and the LIGHTWAVE studies all are expected in 2024. Is there a cadence on how enrollment started? Like, what's the sequence of these studies are going to be? Like, which one are more likely to read out ahead of another? Do we have any idea? So we haven't given guidance on exactly- Yeah the order in which they would read out. Mm-hmm. Excuse me. And they've all started at different times, but they also- Yeah have different recruitment trajectories. Right. Right? One is an Alzheimer's trial- Yeah One's a rare disorder. Yeah. So they're going to have different times- Yeah of trajectory. We do expect them to all read out in 2024. Yeah. Now, from the perspective of the program- Yeah We've articulated that Huntington's is our lead indication. Mm-hmm. We're running two phase 2 trials there. Mm-hmm. The SURVEYOR trial- Yeah and the DIMENSION trial. The DIMENSION trial is a placebo-controlled- Mm-hmm You know, well-powered study. Mm-hmm to look at cognition Mm-hmm -as its primary endpoint. The SURVEYOR Study is more of a calibration- Mm-hmm type of study, where we do have drug and placebo Mm-hmm but we're, we're less interested in necessarily the difference between drug and placebo. Yeah but understanding more of the linkage between measures of cognition and other types of measures Mm-hmm -that may be more tied to function. So that we can calibrate what would a meaningful cognitive score change in dimension be, so that we can make sure that we have the most robust package in a orphan condition where there have been no approved therapies for treating- Mm-hmm cognitive deficits. Okay. So it's fair to assume that as we go into 2024, you're gonna fine-tune the guidelines of guidances in terms of which data comes out, and also probably that junction will also come up as sort of, again, similarly with the positive POC study that you wanna see to warrant larger development. Is that fair, that sort of it's gonna follow in that sequence of steps? Yes. Okay. Early next year, we'll talk about the cadence of the- Okay -the readouts. Okay. And team, I guess, how soon after these readouts could you actually start engaging with the agency? And what is the capital needed to really both bring both of these, several of these pipeline products to the finish line? So how will you kind of make the decision, prioritization across these two different distinct products? Yeah. Yeah. Well, so the data will tell the story, right? Yeah. That will certainly be it. Yeah. But we'll wanna see the data- Mm-hmm And then decide where to go from there. But, you know, as part of the work we did back when we- Mm-hmm ... We did the reorganization- Mm-hmm really worked hard to bring down our operating expenses. Mm-hmm. All of that was in mind, to make sure that we had the runway and the flexibility- Mm-hmm to make decisions, the right decisions on these bigger programs. What is the current cash and cash runway? At the end of the last quarter, we had $875 million in cash. Mm-hmm. So, we're a strong financial foundation. Mm-hmm feel good about that. And we've talked about the fact that, you know, with the work that we did- Mm-hmm With the reorganization, we have runway into 2026. Mm-hmm. And that includes both product revenue- Mm-hmm And milestones as well. Okay. Great. Well, team, we have covered quite a bit of great content in a really short period of time. Just wanna say congrats, and really look forward to a, you know, a successful launch and a really strong pipeline creation opportunities with numerous readouts. So just wanna say thank you on behalf of us here at Piper Sandler. So let's thank the team. Thank you, Barry. Thank you so much. Thank you. No, it's like I literally-